Belite Bio at Stifel Forum: Strategic Drug Developments

On Tuesday, 27 May 2025, Belite Bio (NASDAQ:BLTE) presented at the Stifel 2025 Virtual Ophthalmology Forum, highlighting strategic advancements in their lead drug, tinlaribat, for treating Stargardt disease and geographic atrophy (GA). The conference underscored promising trial results and strategic pricing plans, though challenges remain in navigating regulatory pathways and market competition.

Key Takeaways

• Tinlaribat is an oral treatment targeting Stargardt disease and GA, with ongoing trials showing promising interim results.
• The DRAGON trial for Stargardt disease is nearing regulatory submission, while the PHOENIX trial for GA is expected to conclude enrollment soon.
• Belite Bio anticipates premium pricing for tinlaribat upon initial approval for Stargardt disease, adjusting for a broader GA market later.
• FDA granted breakthrough therapy designation, emphasizing the drug’s potential impact.

Operational Updates

• DRAGON Trial (Stargardt Disease):

- Interim analysis indicated strong efficacy and safety.

- Data recommended for regulatory submission; report expected by year-end.

- Enrollment completed with low dropout rates.

• DRAGON 2 Trial (Stargardt Disease):

- Enrollment ongoing in Japan, US, and UK, leveraging sakigaki designation.

- Expected to close by September, with results two years later.

• PHOENIX Trial (Geographic Atrophy):

- Aiming for 500 subjects; enrollment closing in July.

- Interim analysis set for July 2026; final results in July 2027.

• Regulatory Designations:

- Orphan drug status in US, EU, and Japan.

- Breakthrough therapy designation granted by FDA.

Future Outlook

• Stargardt Disease:

- Anticipated approval of tinlaribat before GA.

- Plans to file for approval based on DRAGON trial outcomes.

• Geographic Atrophy:

- Market authorization submission planned post-positive phase 3 results.

• Pricing Strategy:

- Initial premium pricing for Stargardt due to orphan drug status.

- Adjustments expected upon GA approval for broader market.

Q&A Highlights

• Efficacy Measurement:

- Focus on slowing atrophic lesion growth in trials.

• Retinal Binding Protein 4:

- Targeting significant reduction to slow lesion progression.

• Enrollment Success:

- Oral administration has bolstered patient interest, despite injectable alternatives.

• Lesion Size and Disease Stage:

- Targeting smaller lesions and early to intermediate GA stages for optimal treatment efficacy.

For more detailed insights, please refer to the full transcript below.

Full transcript - Stifel 2025 Virtual Ophthalmology Forum:

Annabel: Hi. Good morning, everyone, and welcome to the, BeLight Bio, session. Happy to have Nathan Mata here, CSO of Vuelite, and also Henrik Scholl, chief medical officer. And maybe we can just start out, by giving everyone an introduction and overview of the company and just sort of start with that origin story and how you move into and then move into the the the the the programs themselves.

Nathan Mata, CSO, Vuelite/BeLight Bio: Hoping to do so. So I’ll kick off. So, we’re Blight Bio. We’re based in San Diego, California. We are a biotech company focused on advancing an oral once a day treatment intended for the therapeutic, intervention in two different but somewhat related diseases, Stargardt disease, which is a juvenile inherited macular dystrophy, and age related macular degeneration, which most people are familiar with, which, of course, is, associated with with with with aging.

Both of these diseases in both these diseases, the accumulation of toxic byproducts of vitamin A is implicated in disease progression. What our treatment does is reduce the amount of vitamin going into the eye as a means of slowing the accumulation of these compounds, and therefore slowing disease progression and preserving vision. So this drug is called tinlaribat. As I mentioned, it’s an oral once a day tablet. It targets a protein called retinal binding protein four.

This protein is the sole carrier protein for delivery of vitamin A from the liver to the eye. And as I mentioned before, the toxic byproducts that are implicated in disease progression in both of these diseases are derived from vitamin A. So by reducing the amount of vitamin A going into the eye, we have a chance of slowing the accumulation of these compounds and, of course, slowing disease progression. We’re focused on two indications, as I mentioned, Stargardt disease and geographic atrophy. And so if you look at the top of this overview slide, you see our trial designs in Stargardt disease.

We’ve completed a two year open label study in adolescent Stargardt disease, which we see very promising safety and efficacy data. Based upon the promising data from that, phase two study, we initiated a placebo controlled phase three study. This is a two year study, a global trial called DRAGON. This study enrolled 104 adolescent Stargardt patients aged 12 to 20 years of age, and they’re receiving the drug tinlaribat daily, once daily. This, trial actually had an interim analysis in February where we received very positive information from our DSMB, which told us essentially that we’re seeing efficacy in the dataset.

So this is very promising. In addition, we have a very, very promising safety profile. The dropout rate in this study was less than ten percent, and it’s nearly completed. It’s going to read out by the end of this year. That’s the Dragon study, the first phase three two year, study of tenorubicel.

The other study we have going, which is also a phase three two year study, is called Dragon two. This is a smaller study enrolling 60 subjects, the same age range. It’s the same adolescent Stargardt patient population. The difference with this Dragon two trial is it’s more focused on, geographic regions in Japan, US, and UK, and it really is designed to take advantage of a recent designation we got from the Japanese regulatory authority. This is called a sakigaki or pioneer drug designation.

It’s equivalent to the clinical breakthrough therapy designation that you would receive in The US, which would help you expedite, your development of of your drugs. So, hopefully, we’ll be able to get approval in Japan before any other, country in the world. So that’s pending. That trial is actually still enrolling. We expect to close that enrollment sometime around September of this year.

Then, of course, two years from that time point will be the top line readout. Our study in geographic atrophy is called PHOENIX. This is also a phase three two year trial enrolling geographic atrophy subjects. We’re going to get 500 subjects in this study. We’re almost to the enrollment number now.

We believe that we’ll we’ll be able to close that enrollment in July at 500 subjects. And, again, that is a two year treatment trial. In both of these studies, all subjects are receiving the same five milligram dose of tenlerabat because in dose finding studies, what we’ve determined is that the five milligram dose is effective to reduce the retinal binding protein four to about an 80% reduction below the baseline. And in prior clinical studies, that level of reduction has been shown to lead to a slowing of lesion growth, which is the primary endpoint in both these diseases is to slow the growth of atrophic lesions in the retina of these patients with Stargardt disease and geographic atrophy. One of the differentiators of our treatment versus the currently approved treatments for GA, the injectables, that is the intravitreal injectables, is that our treatment, of course, is oral.

That’s the first thing. But also, we’re focused on treating patients with earlier stage disease, because these molecules that are basically causing the pathology emerge early in the disease stage, and we believe we can detect the disease early before there’s really significant loss of retinal tissue or vision. Obviously, there’s no approved treatments for Stargardt and no oral approved treatments for GA, so we hope to be the first in both of these categories. We’ve received various designations, as you can imagine, being an orphan drug, various designations across The U. S, EU, and, of course, as I mentioned, in Japan.

And we have a very strong strong patent family, 14 active patent families. Both of these are a matter of composition, not expected to expire until 2040, and that’s without any patent term extension. If I can just go really quickly, I’m gonna skip the market slide. You can see very briefly what the market overview looks like in both Stargardt disease and geographic atrophy. It’s huge, to say the least.

Here’s the mechanism of action. I want to go over this very briefly just so you have an idea about exactly what we’re doing. Our drug does not intervene in the visual cycle. Actually, as I said before, what it does is it targets a protein called retinal binding protein four, shown here in the lower right hand corner. In the liver, retinal binding protein four binds to vitamin a.

This is a two. This is the chemical abbreviation for vitamin a. Once that binding occurs, another protein called transthyretin binds to that complex. So what gets liberated into the circulation is a very large molecular sized complex comprised of r p four, vitamin a, and transthyretin. And because it’s so large, it resists filtration in the kidney.

So this is a mechanism whereby you can maintain a high steady state level of vitamin A in the blood because, again, this complex is so large, it doesn’t get filtered through the kidney. But for the eye, it’s very important to note that the eye has a unique preference for uptake of vitamin A when it’s presented on retinal binding protein four, and that’s because of the presence of a retinal binding protein four receptor, which is not abundantly expressed in other tissues. So other extrahepatic target tissues do not have a reliance for vitamin A uptake when it’s presented on a retinal binding protein four. They can uptake vitamin A from other carriers or in other forms. But in the eye, it’s a receptor mediated process.

The vitamin A goes into the eye, goes through a series of enzymatic reactions where it’s eventually converted to rhodopsin. Rhodopsin then is light activated, which releases an aldehyde form of vitamin a called all transretinal. This is a very reactive species of vitamin a, and it’s actually very toxic. So if it accumulates in the eye, it could actually start destroying membranes. The way it gets out of the eye is through an active pumping process mediated by a protein called ABCA four.

ABCA four is essentially an enzymatic flip base which grabs the retina from inside the retina and flips it outward, availing it to another enzyme for further detoxification back to alcohol reentry back into the visual cycle. So this is the normal processing of vitamin a in a healthy unaffected eye. But in patients with Stargardt’s disease, there are genetic mutations that affect the function of this protein. Consequently, the aldehyde cannot be removed from the retina as efficiently, and it lingers within the retina where it condenses upon itself, forming these dimers of vitamin a that are called bisretinoids. These these are the, toxic molecules I I spoke about earlier.

The most abundant bisphenoid toxin that’s been identified in human tissue is known as a two e, and this molecule has been shown to kill retinal tissue through diverse mechanisms. So in Stargardt’s disease, it’s very widely accepted that the reason for the initial pathology and eventual blindness is because of the accumulation of a two e and related bisphenoid molecules. And, of course, because these molecules are derived from vitamin a, it stands to reason that if you can limit the amount of vitamin a going into the eye, you can limit the production or the accumulation of these bisphenoid compounds. And that’s the that’s our approach. In geographic atrophy, it’s important to note that these bisphenoid molecules accumulate similarly, but not because of a broken pump or any specific genetic mutation, but rather because of pathology beneath and above this area of tissue called the retlopin and epithelium, where all of these critical enzymes that metabolize vitamin A reside.

And when that happens, there’s an interruption of nutrient transfer across these cellular compartments, and that interferes with the processing of vitamin A in this compartment. And so these misreadnodes can actually form locally right within the retinal pigment epithelium because of dysfunction of these, different different enzymes that metabolize vitamin A. Very quickly, I just do want to mention, from a clinical perspective, ophthalmologists can view these bis retinoids because they have an intrinsic autofluorescence due to their retinoid composition that emits a light, basically, when looking through a specialized camera. So here what you see is a couple of case studies, a patient with Stargardt disease and a patient with GA, analyzed over time, looking annually at their lesion growth. And what you can see, if we start with a patient with Stargardt disease at the baseline image here, you see these two blackened areas of tissue.

This is dead retinal tissue that’s never coming back. But if you look peripheral to that tissue, you see this intense zone of autofluorescence surrounding those lesions on all sides. Those are the bisretinoid molecules. And now as you go forward in time annually through these images, what you can see is that those that dead retinal tissue actually spreads into the autofluorescent zone, and the autofluorescent zone continues to expand outward in a centrifugal manner to accommodate that dead retina. So it shows you that wherever you have this retinoids, you will soon have retinal pathology.

The same thing we see in a patient with geographic atrophy. Here the lesion is a little smaller in the lower left hand image, but you can still see it. But if you look peripheral to that lesion, you see these little punctate areas of autofluorescence. They’re a little bit more clear here at the 12 image. Those are bisrenoids.

And as you go forward now in time, what you see is those little areas of autofluorescence slowly become atrophic lesions, so that wherever you saw an autofluorescent little blip, you soon see retinal tissue. So, again, these are bisretinoins converting the retinal tissue into atrophic tissue that’s never going to be revitalized. And, because these are derived from bisretinoins that are sourced from vitamin A, by limiting the amount of vitamin A going into the eye, we believe we can slow the accumulation of these lesions and preserve vision in these patients. So I’ll stop there. That was quite a lot.

I’m sure we’ve got a lot of Q and A lined up based upon that information, so I’m happy to turn it back, to Annabel for any questions.

Annabel: Yeah. So, you know, maybe we can just start with some of the earlier phase, phase two studies that you had conducted. I guess, you know, when we think about and I’m gonna start with GA because we’re a lot more familiar with GA. But, you know, when you, are talking about, you know, GA, we’re looking at lesions, we’re looking at inflammation. What is it that you saw?

What were you measuring in phase two? Were you also measuring lesions, or were you measuring something else as far as the dysretinoids, and the accumulation of toxic material? What is it that got you, excited about your phase two data that moved you that got you moving into the phase three? So is it the same things that you were measuring as they’ve measured in past trials for GA, or was this something else since you’re moving earlier in treatment?

Nathan Mata, CSO, Vuelite/BeLight Bio: Oh, the the currently accepted endpoint for both Stargardt disease and geographic atrophy is to slow the growth of the atrophic lesions. So basically, what you’re seeing here in these images, these black blotches, is if you can statistically slow the growth of these lesions relative to placebo, that is an approvable endpoint. So in phase two, that’s exactly what we looked at, is we looked at the growth of atrophic lesions. It’s very difficult to measure the autofluorescent area, so that’s not really an endpoint. In fact, the agency is only concerned about the death of photoreceptors.

So this black area of tissue represents the death of photoreceptors, which of course leads to blindness. So that really is the endpoint that we’ve been looking at in all of our studies. Our pharmacodynamic biomarker is retinal binding protein four. So we know from a prior clinical study that a certain level of reduction, and that level of reduction is 70% or more, can lead to a slowing of lesion growth. That was done with a different, pharmaceutical product.

It was a surrogate retinal binding protein for antagonist. It it is not as effective and as potent and selective as tinlaribat, but it was used for POC, And that data was published, by Neon in 2013 in geographic atrophy. So we use that data as sort of a precedent for what we need to do in terms of slowing lesion growth. We need to reduce the retinal binding protein per level by at least 70%. And over time we believe that will lead to a slowing of the growth of these lesions, because, again, they are spread according to the accumulation of dysretinoids in the back of the eye.

So retinal binding protein four is our biomarker. We know once we get it down to a certain level we’re more likely to achieve a significant effect on slowing lesion growth in the retina.

Annabel: Okay, got it. And again, in GA you mentioned your ideal is to go earlier in treatment where they may not have as many lesions or they may not have the full you know, it it might be also a slowing slower growing stage of disease. So, have you designed the phase three so that you can really explore, the efficacy in these earlier stages of disease if you don’t have as rapid a progressing stage once you hit, you know, the the full GA with lesion growth and blinding, you know, or lesion death. So maybe you can talk about the differences between your trials and your specific stage of disease and the trials that we’ve seen in the past.

Nathan Mata, CSO, Vuelite/BeLight Bio: I think the biggest difference is the lesion size at baseline. So we’re focused on focusing on patients with smaller lesions at baseline. We’ve learned from other studies with a similar pharmacology as temlaribat that lesions that get to a certain size, let’s say, in excess of 10 to 15 millimeters squared, there’s the size of the lesion in the back of the eye, that the two year treatment trial is not effective, let’s say, a long enough time to realize the the benefits of a far pharmaceutical approach like tenlarabant. But if you go after lesions that are smaller, you have a greater chance in a two year study of realizing or observing a treatment effect. And I should mention that, thankfully, in GA, there’s been a number of natural history studies that we know predictably what the lesion growth rate will be in various lesion size categories.

I can tell you, with respect to our recruitment and our enrollment for baseline lesion sizes, we’re still in a very predictable growth range that we’re not worried about, for instance, having a slower than expected lesion growth. Because, again, we can reference prior clinical literature that tells us within a certain size range of lesion what the growth rate will be, and we feel comfortable about being able to achieve a treatment effect within a two year range with our lesion sizes as selected.

Henrik Scholl, Chief Medical Officer, BeLight Bio: Okay. Maybe if I can add, I mean, maybe you worry about smaller lesion grow not as fast, but there are ways to correct that, namely to correct for baseline lesion size. And in geographic atrophy, you actually if you do that correction, you bring the lesion growth to a linear growth rate. And the precision that you apply for measuring lesions for smaller lesions is comparable to larger lesions. So therefore, if you do this correction and you go for smaller lesion sizes, there’s no reason to worry that your drug would not be able to slow progression or that the reading center would not be able to pick up that slowing by reading the images.

Annabel: Okay. Got it. Maybe you can talk about enrollment, into the trial. I think you, in past, needed four fifty or 500 patients. How has that proceeded?

How are you finding, the patient willingness given that some of them aren’t as symptomatic, and may not be as willing to to treat? Maybe you can just talk about there of enrolling such a trial.

Nathan Mata, CSO, Vuelite/BeLight Bio: Let me talk about the enrollment, and I’ll throw it to Doctor. Scholl to talk about, for instance, how these patients present and whether or not they’re symptomatic. In fact, they’re largely symptomatic. But talking about just the enrollment of the trial, it’s actually gone very well. In fact, we thought that initially the approvals of Cifovri and Eiservay, which are the injectable treatments for geographic atrophy, we thought that those approvals may slow our enrollment, but in fact, it’s quite the opposite.

There are quite a large number of patients that are not interested in getting intravitreal injections. And in fact, when presented with the opportunity to take an oral unapproved investigational drug or an approved injectable therapeutic, they largely opt to take the oral therapeutic because of the the reduced treatment burden. Right? So these patients don’t have to come to clinic. They don’t have to get injections in the eye.

They can basically take the the the pill daily as a sort of like a vitamin supplement that they would take normally on on a day to day basis. So so enrollment has not been an issue. As I said, we’re going after 500. We expect to close that enrollment probably in July. And I think, really, there’s a lot of interest, from patients because, again, this is an oral treatment which has been shown to be relatively very safe thus far.

But I’d like to, get, Doctor. Scholl’s clinical opinion regarding how these patients present, in terms of their vision loss, or how they even come to, an ophthalmologist to get diagnosed. Hendrik?

Henrik Scholl, Chief Medical Officer, BeLight Bio: Yeah. Thank you, Nathan. A couple of considerations here. Number one, this is an elderly population. Life expectancy of patients that developed GA affecting vision is six to eight years.

So we we talk about an elderly population, and they typically are under regular care and would have had a diagnosis of intermediate AMD before they developed geographic atrophy. So this is number one why patients would learn about such treatment trials for an existing treatment for geographic atrophy. Number two, even if the lesion stays outside the fovea are in the beginning, many patients develop parafoveal lesions that would allow them to remain at twentytwenty visual acuity, but they have a scotoma that is close or a blind spot close to the very center, they may very well and typically are symptomatic because it’s still in the macula. So they visual field loss in the macula that may not affect recognizing small letters on a visual acuity chart. But when they look at newspaper, they may notice that large parts of the newspaper would not be visible.

So even if patients are at twentytwenty visual acuity, they may very well be symptomatic. In actual fact, most of the patients enrolled into these clinical trials have foveal lesions and have some degree of of vision loss.

Annabel: Okay. Got it. And and just out of curiosity, the so we were talking a lot about the intermediate stage disease. Is it only suitable for intermediate stage, or would it be also suitable for those in late stage disease, even possibly as a complement to intravitreal injections?

Henrik Scholl, Chief Medical Officer, BeLight Bio: So by by definition, right, we talk about late stage. Chillicographic atrophy is one of two late stages of AMD. Intermediate AMD would not come with any lesions. And number two, if you would like to target intermediate AMD, then you would need an approvable endpoint. And for intermediate AMD, other than visual acuity, and visual acuity typically is almost unaffected or within normal limits in intermediate AMD, there is none.

We are conducting in my academic activities so called clinical study, which is one of the largest natural history studies in intermediate AMD. I can tell you it’s difficult to agree on an endpoint that would be approvable. But tiloribund would be an ideal drug to prevent vision loss in the future, right? But right now, what we concentrate on is patients that have, let’s call it, real disease, that eventually will become symptomatic or are symptomatic, and we have an approval endpoint, namely the growth rate of geographic atrophy.

Annabel: Great. And maybe in the time we have, I’d like to touch on Stargardt’s disease, which is obviously a very similar presentation. Does this disease progress very much the same way as it does in GA, or does it have a slightly different presentation?

Henrik Scholl, Chief Medical Officer, BeLight Bio: So maybe I can I can take the questions? We we conducted the largest natural history study ever in the field called Proxstar progression of Sagar disease study. It was a worldwide international natural history study funded by the Foundation Fighting Blindness. And what we found is that, number one, there are lesions that are almost identical to what we call atrophy in geographic atrophy. We coined the term definitely decreased autofluorescence, and it’s good that Doctor.

Mehta is still projecting this image. You see on the top as he explained, these large areas, we call them definitely decreased autophorescence, which is kind of an intuitive term. And this has been approved by the FDA and other regulatory agencies as an endpoint. And what we measured over time is that the progression rate is shows pretty much the same variability. It also depends on baseline lesion size, which, again, can be mostly corrected by correcting for baseline lesion size.

And But the progression rate on average is about onethree to onetwo what we observe in geographic atrophy. Having said that, since these patients have pretty much exactly 10x the life expectancy when they develop symptoms. They’re typically ten to twenty years old instead of seventy to eighty years old. Even though the progression rate is only, let’s say, a third or half, it is very significant for, for, their visual performance for the rest of their life.

Annabel: Okay. Got it. Got it. Okay. So one one question that we would have is that Stargardt is obviously a rare disease.

Geographic atrophy is a very, very, large population. How, can you balance the advantages of one being, you know, an orphan drug with its broader development plans? And, you know, how do you how do you balance the two? And and and maybe you can talk about that dynamic.

Nathan Mata, CSO, Vuelite/BeLight Bio: Yeah. I think it’s important to note, as I mentioned earlier, that in both of these indications, we’re using the same dose. And, of course, it’s the same drug. So Right. Our our Stargardt programs are ahead of the GE program probably by about a year and a half or almost two years.

So with success in our Dragon trials, we expect to have, approval for Stargardt disease first. Because it’s an orphan disease, there’ll be premium pricing there for that drug. It’ll be in line with other orphan drugs. So that pricing will go for a period of time until geographic atrophy gets approved, which could be two or three years, four years down the road. And then at that time, we’ll have to adjust the pricing because, again, the larger, population of GA will basically sort of offset the smaller market in Stargardt, but, of course, we’ll have a smaller price.

So we don’t expect to have any problems with that. And, of course, these are sort of quality problems to have when you’re worried about pricing. Right now, we’re focused on execution in our studies and just making sure that we get through the goal line, the finish line, with our Dragon trials.

Annabel: Yeah. Great. Okay. So maybe you can talk about just the next data points in the last minute or so and, for each of the respective programs.

Nathan Mata, CSO, Vuelite/BeLight Bio: Right. So in Stargardt disease, as I mentioned, the first phase three trial will end around September, and we’ll probably have the study report available by by, end of the year or Q1. So that’s the Dragon trial. I didn’t mention, but our DSMB took an interim analysis of that trial and recommended that we share the data with other regulatory agencies to seek drug approval. That recommendation would not have been made if, in fact, the data were not efficacious.

So we, as a study sponsor, are masked, so we don’t really know the treatment effect. There’s a limited number of people on our side that do know, the treatment effect. Hendrik is one of those, and that small team is actually leading the effort to go out to other regulatory agencies to share this data. So we have a very promising outcome in Dragon. That will be a trial that we intend to file on with confirmatory evidence from other studies.

And then, of course, our Dragon two study is right behind that, roughly about a year and a half behind that, also in Stargardt disease. And then in geographic atrophy, as I mentioned, we’ll be closing enrollment sometime around perhaps July of this year. So in 2026, July of twenty twenty six next year, that’ll be around the time of the interim analysis. And then one year after that, July of twenty twenty seven, will be the top line, two year phase three readout in PHOENIX.

Henrik Scholl, Chief Medical Officer, BeLight Bio: And to make best use of the last couple of seconds, I I can add that the the interim analysis and the unmasked data were submitted to the FDA, and the FDA granted breakthrough designation last week.

Annabel: Okay, fantastic. And on that note, I think we will, close this out because we’re a little bit over. But thank you so much for, all the information. What an interesting program.

Henrik Scholl, Chief Medical Officer, BeLight Bio: Thank you very much. Thank you very much.

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