Belite Bio at Leerink’s Global Healthcare Conference: Promising Drug Developments

On Monday, 10 March 2025, Belite Bio (NASDAQ: BLTE) presented at Leerink’s Global Healthcare Conference 2025, unveiling strategic insights into their drug TINlarabant. The company’s Chief Scientific Officer, Nathan Mata, shared promising Phase 2 results for treating Stargardt disease and geographic atrophy (GA), while also addressing regulatory challenges and future market entry plans.

Key Takeaways

• Belite Bio’s TINlarabant showed a 50% reduction in lesion growth in adolescent Stargardt patients during Phase 2 trials.
• The Phase 3 DRAGON study received a positive recommendation from the DSMB for regulatory review.
• Belite Bio aims for potential market entry outside the U.S. by 2027, with a 50/50 chance of accelerated U.S. approval.
• TINlarabant offers an oral administration advantage over injectable treatments, with a favorable safety profile.
• The drug targets early-stage disease by reducing vitamin A levels, unlike competitors focusing on inflammation in late-stage GA.

Operational Updates

During the conference, Nathan Mata detailed the mechanism of TINlarabant, which targets retinal binding protein 4 (RBP4) to reduce vitamin A delivery to the eye. This approach aims to slow toxin accumulation that contributes to disease progression. The Phase 2 study, involving 13 adolescent patients, demonstrated a significant 50% reduction in lesion growth, with 42% of participants not developing lesions.

The ongoing Phase 3 DRAGON study, with 104 subjects, mirrors the design of the DRAGON 2 study for Japanese regulatory approval. The interim analysis led to a DSMB recommendation to submit the data for regulatory review, indicating a strong treatment effect.

Future Outlook

Belite Bio is pursuing regulatory approvals from multiple agencies, including the EMA and Japan’s regulatory body under the Sakigaki designation. The company anticipates data readout by Q1 2026 and aims for market entry in ex-U.S. countries by 2027. The FDA’s approval remains uncertain, with a 50% chance of accelerated approval.

Safety and Tolerability

The Phase 2 study reported no subject withdrawals due to adverse events, while the Phase 3 study had a 9.8% overall withdrawal rate, with only 3.8% due to ocular events. These events, such as delayed dark adaptation and chromatopsia, were transient and mild, supporting the drug’s favorable safety profile.

Comparison to Competitors

TINlarabant distinguishes itself from competitors like Syfovre and Izervay, which are injectables targeting inflammation in late-stage GA. TINlarabant’s oral administration and focus on early-stage disease provide a unique advantage. Mata powered the study for a 40% treatment effect, believing a 20% effect is sufficient for approval.

For more detailed insights, refer to the full transcript of the conference call.

Full transcript - Leerink’s Global Healthcare Conference 2025:

Unidentified speaker: Okay. Here we go. Thanks for joining us, everybody. Our next session is with Belite Bio. And I have Nathan Mata, who is the CSO of the organization.

Thanks for joining us. Obviously, a very exciting time for the company. What’s going on with TINlarabant? Maybe just give us a little step back for a second and just explain to people about the drug and, you know, what is it and what Stargardt is, you know, just just kind of the frame everything, the opportunity for us here. Yeah.

Nathan Mata, CSO, Belite Bio: So let’s let’s start with the indications that we’re going after first for Stargardt disease is inherited a juvenile macular dystrophy affects children as well as adults. But in children, the disease is much more severe because the genotypes are much more pathogenic versus versus adults. That’s one indication. The other indication is geographic atrophy in in in AMD, which is the advanced form of dry AMD. Interesting in both these diseases, the accumulation of toxins, vitamin A based toxins is implicated in disease progression.

And so what we’ve reasoned is that since these toxins are derived from circulating vitamin a, by reducing the amount of vitamin a going into the eye, we have an effect on slowing the accumulation of these these toxins and slowing the disease progression. And we do this by targeting a protein called retinal binding protein four, which is the sole carrier protein for delivery of vitamin a from the liver to the eye. That’s what our drug, telerabat, does. So telerabat is an oral once a day small molecule drug that is an antagonist of retinal binding protein four. So it competes with vitamin a for binding to RPP four and it slows the amount of vitamin a going into the eye.

And by doing this, we slow the accumulation of these toxins and slow disease progression. That’s the idea.

Unidentified speaker: And, so this mechanism works in Stargardt because why?

Nathan Mata, CSO, Belite Bio: It’s interesting. In Stargardt disease, the reason these children and adults go blind is because there’s a broken pump in the back of the eye. This pump is responsible for circulating vitamin a throughout the eye. And when this pump is broken, the vitamin a gets backed up. And when this vitamin a gets backed up, it actually starts turning into these toxins.

So this broken pump creates these toxins, which then destroy retinal tissue. And again, these toxins are derived from circulating vitamin a. So in Stargardt disease, we are confident that the only reason there’s disease pathology and eventual blindness is because the accumulation of these toxins. And we can slow them by reducing the amount of vitamin a going into the eye. It sounds counterintuitive because we all learned that vitamin a is important for your for your eye, but too much vitamin a in a diseased eye is actually very, very bad.

Unidentified speaker: Interesting. So help us size the Stargardt opportunity.

Nathan Mata, CSO, Belite Bio: Yeah. So Stargardt disease, there’s never been a true epidemiological study. So it’s estimated to be approximately one in eight to ten thousand patients or people. So that’s roughly about thirty thousand people in The US. Of course, you have much larger numbers in countries like China, where even though the prevalence isn’t higher, there’s a larger population.

So in fact, China was one of our major enrollers in our Phase three study.

Unidentified speaker: Good. So let’s talk about the data that you have so far, the Phase two data before we get into the Phase three. Talk about what you know the outcomes functionally, anatomically, you know just what you saw.

Nathan Mata, CSO, Belite Bio: So this is where we started. Once we had TINARAVAT ready to go is we enrolled an open label phase two study with 13 adolescent Stargardt patients aged 12 to 18 years of age. All of these kids had bialylic pathogenic mutations. And of course, they had the clinical presentation of Stargardt disease. We gave these patients an amount of ten larabant that reduced their circulating vitamin a by about 80%.

So they’re dealing with about 20% of the normal amount of vitamin a. What I should mention is that, you know, when we start talking about systemic vitamin a reduction, people start thinking, well, you’re gonna create vitamin a deficiency across the body. That’s not true because retinal binding protein four is only required for delivery of vitamin a to the eye. It’s not required for delivery to extra hepatic target tissues such as, for instance, spleen, muscle, fat, etcetera. Those tissues can uptake vitamin a from other carriers and other sources.

So our approach is really specific to the eye. Having said that, this 80% reduction resulted in a slowing of lesion growth over two years in these subjects. In fact, it was about a 50% reduction in the growth rate compared to natural history. And there was in fact a subgroup of subjects that never even spawned atrophic lesions throughout this study. Roughly forty two percent of the cohort never grew a lesion.

And in those subjects that did, the growth rate was significantly lower than predicted by natural history. So we were very, very excited by that. And that’s why we went forward with the phase three study.

Unidentified speaker: So just back up one second. Let’s make sure everybody understands what are the outcome measures.

Nathan Mata, CSO, Belite Bio: Yeah. So the endpoint for drug approval in both of these indications, Stargardt disease NG, is to slow the growth of the atrophic lesions because the growth of the atrophic lesions will eventually impact vision. And while that’s the most clinically meaningful outcome for a patient, that is vision loss, the vision loss in patients with STAR disease and G is exceedingly slow, whereas the lesion growth is very rapid. So it makes sense that if you really want to preserve vision, you slow the lesion growth first because that eventually will read out into stabilized or improved visual outcomes for patients.

Unidentified speaker: So this is on an OCT. We’re basically looking.

Nathan Mata, CSO, Belite Bio: Actually, it’s FAF photography. So in retinal imaging, we’re actually looking at the back of the retina and watching these lesions grow. Okay.

Unidentified speaker: So we’re watching the lesions grow. You had 13 patients that you watched for how long?

Nathan Mata, CSO, Belite Bio: Two years. Two years study. They take five milligrams of our drug daily, which reduces their vitamin a level about 80% relative to the baseline status.

Unidentified speaker: Okay. So and that was after two years. And what was baseline status? Talk about the natural history work that you’ve done.

Nathan Mata, CSO, Belite Bio: Yeah. That’s interesting. So so the natural history work was led by doctor Hendricks Scholl, who is now our CMO. But prior to becoming our CMO, he led the largest natural history study of Stargardt’s ever conducted. And he’s in fact responsible for many of the key findings that we have now in terms of the natural history and really helped us design his data, helped us design the trial because we knew from natural history how to select patients and what their growth rate would be over time based upon that work.

So that was a very critical. Those were called the prog star studies, a huge collection of reports over many years, both prospective and retrospective studies looking at the natural history of Stargardt disease.

Unidentified speaker: And you think 13 patients is enough to give you a sense of what’s really going on?

Nathan Mata, CSO, Belite Bio: You know, we would have we wanted to get more. But the fact is that for the sites that we had, they were ready to go and we just wanted to get an answer. So it was enough of a sample size for us to get a response to see are we in fact changing the trajectory of lesion growth? And I think we got our answer.

Unidentified speaker: Yeah. Yeah. Yeah. It’s interesting. It’s like, and it’s also a new outcome for people.

This this.

Nathan Mata, CSO, Belite Bio: Right. So just having an oral therapeutic by itself is is amazing that you know you would get that sort of efficacy in the eye. A lot of people think that it wouldn’t work that way but again because we are targeting that receptor in the eye, it works very very nicely. What

Unidentified speaker: about speed because you’d mentioned you looked at two years. How is it working after, you know, three months, six months? Yeah.

Nathan Mata, CSO, Belite Bio: Yeah. So so there is a sort of a latency in terms of how the drug kicks in because you have to, give some time for the systemic vitamin a level to equilibrate with the ocular level. That’s typically three to six months. But once that happens, then you’re starting to see a change in lesion growth. So six months after that, you start seeing changes.

I see.

Unidentified speaker: And so are we I guess I’m just thinking about Stargardt patients. If they have, you know this this this this problem right obviously they’re starting to see these lesions. How much time after the lesion starts to become a problem? Do we have vision problems? Like is it is it correlated completely or is it a lag effect?

Nathan Mata, CSO, Belite Bio: No, that’s a good question because in fact in children, which again have much more severe genotypes, they have a much more severe disease, they lose their vision much much more rapidly. So a kid who’s diagnosed at six years of age will be legally blind by by the time they’re 20. So that that’s a pretty rapid, loss of vision. In adults, it’s much more slowly progressive because they have more mild mutations. But in kids, and that’s why it’s so so critical, that’s why we designed our study in adolescence because these kids have a rapid disease progression.

And the other differentiator about our approach is very important is early intervention. So we we went after children that have very small lesions, but they’re very close to the fovea. So they’re very close to where the visual acuity center is and these lesions will grow into the fovea. And if we can stop those lesions growth into the fovea, we’ll preserve vision.

Unidentified speaker: Yeah. So let’s talk about the phase three DRAGON study. I know that you have some slides. Yeah.

Nathan Mata, CSO, Belite Bio: Let me just skip to that real quick. So this is just an overview just to provide the audience some, idea of the clinical studies we have going. We’ve already spoken about that phase two twenty four month study, that open label study in the 13 Stargardt kids, where we showed a slowing of lesion growth. The phase three study is one we recently got an interim readout from. This is called Dragon.

This study completed enrollment at 104 subjects. Again, it was a two year study. They’re getting the same dose that the kids in the phase two study got five milligrams per day. So again, they’re having this 80% reduction in vitamin A and that reduction actually starts right away, but it does take some time for that to have an effect in the eye. As I said, we have some interim data that’s very exciting.

We’re really, really thrilled about what the DSMB gave us over the past couple of weeks. And then of course, we’re also having another Stargardt study called Dragon two. This is to take advantage of a designation that we’ve received from the Japanese regulatory authority, PDMA, called Sakigaki designation. And we’re the first company, ophthalmology company to ever receive it. So we’re very honored.

But basically, what this designation allows us to do is get an approval in Japan based upon just one study. So basically, all they wanted to see in this Dragon two study was 10 Japanese subjects going through two years of treatment and having promising safety and efficacy outcomes. And then we get approval in Japan. And it also serves as a backup in case, the FDA or some of the regulatory agencies asked for a confirmatory study of our Dragon study. So Dragon one and Dragon two are Stargardt studies, phase three, that we’re very optimistic about.

And then of course we have a study in geographic atrophy going, a Phase three study. We’re enrolling targeting about four twenty nine subjects. We’re at about 400 now, so we don’t have too much further to go. But that’s basically the overview of the

Unidentified speaker: So before you go on, so we have 104 patients. How many sites and how many of those sites are the same? Like the 10 patients that you had in the phase two, how many sites were those? Couple sites?

Nathan Mata, CSO, Belite Bio: There was only three sites.

Unidentified speaker: Three sites.

Nathan Mata, CSO, Belite Bio: Each of those sites were involved in the track. All three are here. Okay. And how many additional sites did you have to do? An additional 22, so about 25 sites.

Unidentified speaker: And is it fair to say that that’s where all the Stargardt patients are in The United States pretty much?

Nathan Mata, CSO, Belite Bio: I would say so. I mean, we really, we went to every KOL, every ophthalmologist, these Stargardt kids that we could think of that had a sufficient number of patients and that’s all across the globe. And I think we’ve captured as many as you could potentially get, in terms of adolescent Stargardt patients. And in fact, this is the largest study of adolescent Stargardt disease ever conducted.

Unidentified speaker: Interesting. Okay. So it’s a two year study. And are we gonna are we gonna get to the interim? So yeah, you’ll talk about it.

Okay. And then just so people understand the geographic artery, it’s the same exact product?

Nathan Mata, CSO, Belite Bio: Same exact product, same exact dose because it’s the same endpoint, same trial design. Everything in all of our studies is identical except for the patient population. Right, exactly.

Unidentified speaker: And they have to have GA already. They have early GA. Is it late?

Nathan Mata, CSO, Belite Bio: That’s another important point because again, we’re after early intervention because we believe if you stop these lesions when they’re small, you have a better chance of slowing overall and eventually preserving vision. And I should mention in terms of the competition because most people who are interested in ophthalmology, if you’re here today, you must be interested in ophthalmology. You’re aware of the two approvals in geographic atrophy, a Sifovir and Izarave. These are complement inhibitors that are injected into the eye that essentially quell an inflammatory response that occurs in late stage disease. You do not have inflammation in early stage disease.

So those products would not be expected to be effective in the patients that we’re selecting for our GA study or our Stargardt study because again, the lesions are too small. So that’s another differentiator in addition to an oral therapeutic. I just wanted to provide that contrast. Talk about

Unidentified speaker: the endpoints in, I guess the endpoints are the same at both studies. So just give us, so make sure we understand the sec because I want to talk about the key secondaries in the anatomical vision you’re looking at.

Nathan Mata, CSO, Belite Bio: Right. So even so for all the studies like the approvals for for Siphofovir and Izervay and for what we’re doing, it’s all the same slowing the trajectory of lesion growth relative to placebo in a statistically meaningful way. So over two years, you want to see a divergence of growth placebo here, your treatment here. And hopefully at the end, you’ve got a delta that gives you stat sig.

Unidentified speaker: And the FDA, what have they given you as far as guidance to? So

Nathan Mata, CSO, Belite Bio: the FDA has actually been very workable with us because they’ve allowed us to build a protocol that was quite novel, to use a drug that you know is also quite novel. They weren’t concerned about the vitamin systemic vitamin deficiency for the reasons I spoke about earlier. So they gave us a lot of leniencies again because these are children going blind. And and of course, they wanna see a product approved. But at the same time, they’re the most conservative regulatory agency that we’ve confronted.

And we’re working with eight regulatory agencies right now across the globe to get approvals. Many of them have said they will grant an approval based upon one well controlled Phase three study. The FDA has not said that. They said it will be a review issue. So the only ones that are being a little bit tough in terms of the approval requirement.

I

Unidentified speaker: don’t understand how they can even I mean given all of the different diseases that we’ve seen get approved with one trial.

Nathan Mata, CSO, Belite Bio: I mean It’s the division of ophthalmologists. But not frankly. You wouldn’t see this in oncology for instance

Unidentified speaker: well division has changed leadership is Boyd any nicer than Chambers?

Nathan Mata, CSO, Belite Bio: It’s interesting you asked that because we’ve seen a pretty good consistency between what Doctor. Chambers has told us and what Doctor. Boyd is telling us now Maybe that philosophy will change. He’s new, maybe he’s still adopting some of his own principles, but right now he seems to be very Wiley esque. Wiley chambers.

Unidentified speaker: I’m gonna use that one if you’re okay with that. So talk about the secondary endpoints.

Nathan Mata, CSO, Belite Bio: Yeah. So our secondary endpoints is also another lesion growth endpoint. So I should I should mention that I talked about the growth of atrophic lesions. There’s also something called an autofluorescent lesion and the autofluorescence actually precedes the atrophy. So when you combine the autofluorescence and the atrophy, that’s their secondary endpoint is to stop the overall growth of all lesions, whereas the primary is just the atrophic lesion.

But what we found is the autofluorescent lesion actually does cause visual acuity damage, visual acuity loss. In our phase two study, all of the 13 kids had fully involved autofluorescence at baseline and they were all losing vision. They didn’t have any atrophy, but they had autofluorescence. And because our drug would primarily first reduce the autofluorescence and then the atrophy, we wanted to include that as our key secondary endpoint to slow the growth of the overall lesion. It’s called decreased autofluorescence, but it’s basically the autofluorescence and the atrophic lesion.

And then of course we have visual acuity as another.

Unidentified speaker: Did we look at all those endpoints with the 13 patients in the Phase two?

Nathan Mata, CSO, Belite Bio: We did and we saw promising results. So it yeah that’s what I

Unidentified speaker: was going to ask you like to just help quantify like what did you see?

Nathan Mata, CSO, Belite Bio: It’s tough to quantify because again it was an open label study. Yeah. But if you look at again compared to natural history we’re getting about a 50% reduction in the growth of both the atrophic lesion as well as the overall lesion.

Unidentified speaker: Yeah. Yeah. Interesting.

Nathan Mata, CSO, Belite Bio: Yeah. So very, very promising data.

Unidentified speaker: Yeah. Side effects. Talk about side effects. What we’ve seen in the phase two, what do we expect to see, what’s on target, what’s off target.

Nathan Mata, CSO, Belite Bio: Great question because people envision that because we’re reducing vitamin A delivery to the eye, we’re going to trigger all of these ocular AEs that are gonna be intolerable and patients are gonna drop out of study. What I can tell you is that the two year phase two study with those 13 kids, we didn’t lose one subject to an ocular AEs. In fact, there was no withdrawals due to any AEs and there was no drug related systemic AEs. So we were happy to see that. Now going forward into our Phase three study where we now have 104 subjects, we’re seeing exactly the same thing.

We are seeing the overall dropout by time of interim. And by the way, the interim analysis was conducted two weeks ago. By that time, more than half of the kids had already finished two years of dosing. The total withdrawal rate was nine point eight percent. So ten out of a hundred and four subjects.

And that due to ocular AEs was only three point eight percent. So four out of a hundred and four subjects. And as I said, fifty percent of them had already gone through the whole two year. So this whole idea that these these children would not be able to tolerate these ocular adverse events, it’s just not true. They’re tolerating it quite well.

And it gives us very, very high hopes for, future dosing going forward.

Unidentified speaker: So let’s talk about what are the AEs.

Nathan Mata, CSO, Belite Bio: Yeah. So when I say ocular AEs, there’s two. The first is called delayed dark adaptation. Many people may have heard of this. Sometimes it’s called night blindness.

That’s a misnomer. But basically, what this is is a delay in your ability to accommodate to dim light settings. And again, that’s due to reduced vitamin a delivery to the eye. So typically, for instance, here’s an example. So if you’re out on a bright sunny day and you walk into a movie theater, it takes you about maybe four or five minutes to find your seat because you’re accommodating to that dim light.

A patient receiving our drug will take perhaps two to three times longer because their vitamin delivery is slower, so they’ll need more time for those photoreceptors to fill up with vitamin a. That is called delayed dark adaptation. The other ocular adverse event is called chromatopsia. It’s the opposite effect, and it happens when you’re, when you’re exposed to bright light suddenly from a dark state. So almost all the kids, we have diaries from our from our studies, and when you read these diaries, what you see is all these kids are reporting it, the ones that have it, say that when they wake up from sleep, they get this hue of yellow in their visual field, which lasts seconds to minutes.

That hue of that hue of of yellow is caused by cone photoreceptors electrically misfiring because they don’t have enough vitamin a. And again, that less seconds to minutes, then the vitamin A fills up and it goes away. So these are transient mild ocular adverse events, which as I said are being tolerated quite well.

Unidentified speaker: Yeah. Yeah. So is there some type of bar that the FDA has talked about for what’s necessary for efficacy

Nathan Mata, CSO, Belite Bio: You know, they have not. So so and that’s that’s an important question because until the approvals of the GA drugs, Ciflover and Azirbay, we had no idea of what the agency was looking for. Now we look at it’s twenty percent. If you look at the overall studies, I mean, you have fourteen percent, you have twenty, twenty two percent. If you do the mean, it’s roughly about twenty percent.

So what that tells us, the fact that they approved those drugs with a twenty percent slowing of lesion go says that’s the bar. So if you can get to twenty percent or more, you’ve got an approved drug with a good safety profile. And by the way, that safety profile

Unidentified speaker: of those drugs is not that great. It’s not nearly as

Nathan Mata, CSO, Belite Bio: good as you know. Absolutely not. And it’s a needle in the eye, and we’re a pill in the mouth.

Unidentified speaker: Right. Right. Right. Right. Interesting.

And so as far as that’s concerned, I mean, what are you thinking about for the endpoint? Like, what’s what’s the number for you?

Nathan Mata, CSO, Belite Bio: Where do I predict? Yeah. So I powered the study. I was involved in designing the studies, being a lot of people know this, but I’ve been doing this for about twenty some years and we never found the right drug. And I believe telerabat was the right drug.

So I powered the study for a forty percent treatment effect at two years.

Unidentified speaker: Okay.

Nathan Mata, CSO, Belite Bio: Fingers crossed.

Unidentified speaker: Forty percent.

Nathan Mata, CSO, Belite Bio: Remember the number. Let’s see what happens. I’m not promising anything. You just ask what I think.

Unidentified speaker: Yeah. Yeah. Okay. Let’s move to the interim. What did we learn?

What did you talk about the other day?

Nathan Mata, CSO, Belite Bio: Right. So first, the trial design is just to break out Dragon one and Dragon two just so you can see. If you look at the top three lines, that’s where these studies differ. That’s the only place. Right?

So basically, the the number of subjects, the geographical location and the randomization two to one versus one to one. Everything else in these studies is is identical. The dosing and, of course, the endpoint is the same. So I just wanna give you an overview for the similarity of these two trial designs. The DRAGEN study is the one where we have the interim analysis, and that interim analysis was triggered once all subjects had reached their twelve month imaging visit.

By that time, a number of subjects had also completed month sixteen. So the DSMB, this independent DSMB, was looking at data all the way up until month sixteen. They’re looking at efficacy, that means the leisure growth, and they’re looking at safety, both systemic and ocular safety. This is a little bit about the demographics. You can see these kids are very young.

These are school age kids. Typical, you know, height and weight for for for kids that age, roughly 60% male to 40% female. And then you can see the race distribution. The reason why you see such a high, representation by the Asian population is because we did enroll in China, and China was our biggest enroller for Stargardt disease. So we got about roughly fifty five percent of our subjects coming out of Asia, and then the rest of Caucasian, European and North American subjects round out the rest of that at about forty percent.

So that’s the overview of the demographics. Here is what the DSMB provided for our interim analysis. And before I go through the data, I do wanna say that this was a sample size re estimation exercise. That’s the reason we did the interim. So the idea here was to take a look at the data to see if we see a trend in efficacy.

And if we did, that would allow us to add up to thirty three zero additional patients. And the reason you wanna do that is because if you see a trend in the middle of your study, you wanna preserve that trend. So you add more subjects to give you a greater chance for statistical power by the end of year two. So the DSMB had one thing to do, to tell us whether or not we’re gonna add subjects or not. So if we add subjects, they’re telling us there’s a trend for efficacy.

We wanna preserve it, so we’re gonna add 30 subjects. If they said don’t add subjects, you’re either on the positive side of that window, which we call the promising zone. That means we’re doing much better than we thought. There’s more than just a trend. There’s a clear signal or it’s futile.

So you you if you if it’s futile, you don’t wanna add patients. And if you’re doing way too good, you don’t wanna add patients. They told us not to add any more subjects. And they added and I’ll go right there to the bottom where it says additional DSMB comments. It is recommended to submit the data for further regulatory review for approval.

Now the DSMB would not add this note if we were on the futility side. So clearly without saying so, I believe we’re on the positive side of that promising zone, which tells me we have a pretty good treatment effect.

Unidentified speaker: So we’re all a little surprised to get that, I suppose. Is there even As were we. Is there even precedent for DSMBs to kind of do that? I hadn’t really heard

Nathan Mata, CSO, Belite Bio: I’ve done three trials in Stargardt disease. I’ve done two in geographic atrophy. Atrophy. I’ve never seen this kind of recommendation ever. It really took us by surprise.

Unidentified speaker: So what? So so your your takeaway is something good is going on here. And what now? Like, what does the FDA need? Anything different from because this is not the FDA talk and this is just the DSMB talk and that’s the quality of the study.

Nathan Mata, CSO, Belite Bio: So we’re going to do exactly what the DSMB has asked us to do is to reach out to these regulatory authorities, and there’s eight of them that we’re going after, and show them the data. And the way it’s going to happen is, everyone on the sponsor side is masked except for two individuals, our head of regulatory and our chief medical officer, Doctor. Hendrick Scholl. They will have access to all of the data that the DSMP saw so that they can engage in conversations and discussions with the regulatory authorities regarding either breakthrough therapy designation, expedited approval, conditional approval, these types of things. So within the next three to six months, we’ll have some, hopefully, harmonization amongst these eight regulatory authorities so we can understand what are they all looking for in common and then pursue that path.

So we won’t go to the FDA until we’ve had this harmonization across regulatory authorities. So we’ll need to meet with all of them to understand what they want. Because in fact, EMA has told us very clearly right after we got our approved pediatric investigational plan, which paves the way for an MAA, by the way. They told us with a completed phase three study and a pip that that would be enough for approval by their by their perspective. So that’s EMA.

Japan has said the same thing with the Sakigaki designation as I mentioned earlier. China has indicated the same thing.

Unidentified speaker: One study is enough.

Nathan Mata, CSO, Belite Bio: One study. It’s FDA that’s sort of holding that.

Unidentified speaker: They’ll come around. I honestly cannot imagine that they’re gonna make you do two. I mean, there’s nothing approved for Stargardt. It doesn’t make any sense.

Nathan Mata, CSO, Belite Bio: And that’s the reason for going out of the other agencies to see what their opinion is. Maybe that’ll shake up the FDA a little bit and help them shape their opinion.

Unidentified speaker: You’re right. So this is to do. You haven’t gone to the FDA.

Nathan Mata, CSO, Belite Bio: We’re doing it. We’re doing so all this is happening. So the FDA is pretty fast. We can get in there pretty fast and they give you an answer within thirty days. The other, agencies are three months, roughly.

So we want to do those first because they’re a longer timeline and then we’ll circle back to the FDA.

Unidentified speaker: But just to understand if the f even if the FDA says, okay, that’s wonderful, finish the study. Yeah. When will the study be finished?

Nathan Mata, CSO, Belite Bio: So the study will end at the end of this year. The data after QC and cleaning all that probably available by Q1 of twenty twenty six.

Unidentified speaker: Right.

Nathan Mata, CSO, Belite Bio: So everyone will know exactly how this study read out by Q1 of twenty twenty six.

Unidentified speaker: So if everything goes according to plan, we’ve got positive data, the DSMB is kind of leaning in that direction. First quarter, we get the data and we file soon after.

Nathan Mata, CSO, Belite Bio: Yes, sir.

Unidentified speaker: So this is presumably on the market in 2027, no later than that if that’s the scenario.

Nathan Mata, CSO, Belite Bio: At least in ex U. S. Countries.

Unidentified speaker: Right. And in The US, it’s possible they make you do another. But

Nathan Mata, CSO, Belite Bio: I think there will be so many patient advocacy groups that will bang their door down and yell at their congressmen to get the FDA to respond. They’re not always responsive.

Unidentified speaker: So now let’s be even a little more aggressive here and think about any type of accelerated approval based on where we are now. It’s like just just file now. Yeah. Like, you know, what you have, what’s the likelihood? How are you thinking about that?

Nathan Mata, CSO, Belite Bio: I’m thinking it’s fiftyfifty because again, we don’t know exactly what the DSMB saw. I certainly don’t know.

Unidentified speaker: Yeah.

Nathan Mata, CSO, Belite Bio: I’m predicting, let’s say it’s something like a 25, 30 percent treatment effect. That’s astounding because if it’s linear throughout, we’re gonna hit that forty percent number and that’s never been seen before in a degenerative retinal disease to have a forty percent treatment effect. So something like that may change the opinion of the FDA, just that alone. And of course, the safety profile, which is amazingly clean as shown here in the fourth bullet.

Unidentified speaker: It’s kind of interesting how this has played out.

Nathan Mata, CSO, Belite Bio: Yeah, it really is. I guess,

Unidentified speaker: you know, you were talking about the adverse events. I just was thinking like adverse events, anything?

Nathan Mata, CSO, Belite Bio: Yeah,

Unidentified speaker: here we go. So those are the numbers that’s from the interim. So this is new data.

Nathan Mata, CSO, Belite Bio: Right. So this is from the interim analysis looking at, again, data. Well, for safety, they looked at all available data. So I mentioned what xanthopsia is. You can see that in about twenty six percent, twenty seven percent of patients Delayed dark adaptation, same number.

And what interesting thing about delayed dark adaptation, I should have mentioned this, is that in both star disease and geographic atrophy, delayed dark adaptation is part of the disease process. So many patients are already accommodating that effect because they’ve been living with the disease for so long.

Unidentified speaker: It’s on target.

Nathan Mata, CSO, Belite Bio: Right. The chromatography, which is part of the xanthopsy, those are related. Xanathopsy is just the color yellow. That is sort of more rare. So that is definitely a pharmacological effect.

But what I always tell people, you know, when they say is, are these do these concern them? Absolutely not. As long as patients aren’t dropping up because what this tells us is that we’re having the intended biological effect on the retina. If you have these reads out readouts, it’s telling you that systemic treatment is reading out in the retina and that’s exactly what we want to see. Well, I

Unidentified speaker: mean, look, what’s the alternative? Right? The alternative is terrible. So it’s this is not, you know, the end of the world. Those are not horrible side effects.

Nathan Mata, CSO, Belite Bio: No, I think, you know, with approval with this profile, I think this is going to be a blockbuster drug. Yeah.

Unidentified speaker: And the AEs, any reason to think that they would be different in the GA population?

Nathan Mata, CSO, Belite Bio: There is, and I’m glad you brought it up because, older, damaged retinas are not going to tolerate reductions in vitamin E as well as these younger Stargardt retinas. So I predict in patients with more macular involvement of the lesion, they will have a harder time with the delayed dark adaptation. So this could result in for instance, deficits in low luminance vision over time in some subjects. Not at all, but I predict that because you know, in patients who have extensive macular involvement of lesions, they could have a harder time with delayed dark adaptation than other patients. Good.

Unidentified speaker: Good. In our last minute, what have we not hit on? What else do we need to make sure we talk about?

Nathan Mata, CSO, Belite Bio: I think we got everything except this last slide which is basically just showing you again from the interim data stabilized vision. People say, okay, so stabilized vision. So what? Actually, this is very profound because if you can stabilize vision while slowing lesions, it’s telling you over time, you’re preserving vision. You don’t have to necessarily improve it relative to placebo.

All you have to do is keep it the same. So these kids over two years, if you look at the standard luminance vision, they didn’t lose anything. Basically, the the loss was roughly about less than three letters. And if you look at low luminance vision, it’s essentially the same. There’s a little drop in the beginning, but then throughout time and again, these are blended data, meaning that you we don’t know who’s on treatment or who’s on active.

But the fact is, according to the randomization, sixty six percent of the subjects are on active. So you can look at the data that way. And once you tease out thirty three percent, it’s not going to change these lines very much. So I predict once you see the unmasking, you’re going to see exactly these these types of lines. So stabilization of visual acuity along with slowing lesion growth is a very, very positive outcome.

Unidentified speaker: Well, if you if you put the, curves for the natural history Yeah. Then I think people would understand. Yeah. Absolutely. Maybe you should do that right underneath.

Nathan Mata, CSO, Belite Bio: And that’s very important too because patients with you know, are not getting treated, they will be losing vision.

Unidentified speaker: They’re getting worse and worse. Exactly. Exactly. Good. Thank you.

Yeah.

Nathan Mata, CSO, Belite Bio: Thank you.

Unidentified speaker: Well, it’s great. Thanks for joining us.

Nathan Mata, CSO, Belite Bio: Thank you.

Unidentified speaker: Very exciting. I’ve not seen these DSMVs be that aggressive. Yeah. So I think that’s really, really good news.

Nathan Mata, CSO, Belite Bio: Well, we’re certainly the better for it. Okay. Yeah. Thank you all for attending. Yeah.

Unidentified speaker: Appreciate it. Thank you. Great to see you again. Welcome. All right.

This article was generated with the support of AI and reviewed by an editor. For more information see our T&C.