Belite Bio, Inc ($BLTE)

Good afternoon. Welcome back to the Bank of America Healthcare Conference. I'm Tazeen Ahmad. I am one of the senior biotech analysts here at the bank. It's my pleasure to have our next presenting company, Belite Bio. On stage with us, we have several members from the management team. Speaking for the team today will be Tom Lin, who is Chief Executive Officer; as well as Nathan Mata, who is Chief Scientific Officer. Gentlemen, thank you for making the trip to Las Vegas. Tom, especially, I think you had a long flight over. So I really appreciate you visiting us.

Happy to be here. Pleasure to be here. Thanks for the opportunity.

So for those who may not be as familiar with Belite, I thought maybe it would be good to give a couple of minute overview of the company, the platform, and then we can go into your lead program in Stargardt.

So you want to overview -- I'm sorry, overview of the program in Stargardt disease.

Just over the company, overview of the company itself.

Overview of the company, yes.

All right. So we are an ophthalmology or retinal focused company. The company spun out from the Bioscience is a public listed company in Taiwan, but that's a company that has to do more on the oncology programs and then because this is a unique drug and unique in the sense that there's nothing out there. It is a very severe unmet need. The drug has shown very strong potentials early on. So we spun the company out in 2018, and then we listed the company in 2022. And then the clinical program has been pretty smooth. We've shown very strong data. And yes, we are very excited and we see a lot of potential in the company.

Okay. So maybe can you just give us an overview of Stargardt itself? What are the symptoms of the disease? What's the prevalence? And then we could talk about what doctors are currently prescribing for patients, if anything.

I can kick off from there. So the disease is a monogenic disease. So it's genetically inherited in an autosomal recessive manner, which means one of each parent contributes a mutant allele, if you will, and that would confer Stargardt disease upon the child. The prevalence is roughly about 1 in 6,000, so roughly about 53,000 in the United States. Of course, this is a devastating disease, especially in childhood because these kids from a very early age, have visual acuity loss and this compromises their social functions, education functions, learning, et cetera. And so this is one of the reasons that we focused on the adolescent startup patient populations because there's clearly an unmet need in the entire disease that affects adults as well. But in children, there's a much more dire need because from a socioeconomic standpoint, these children will suffer tremendously without treatment. And so we've obviously have a treatment, an oral once-a-day tablet, very easy to administer, no treatment burden whatsoever that has been shown to reduce lesion growth in these patients by as much as 36% over a 2-year period. That's never been seen before in a clinical study of Stargardt disease or geographic atrophy for that matter. So we're very, very pleased and very hopeful for an approval with the next 6 months or so.

Yes. So I maybe wanted to stay on what you mentioned for a minute about undermet need. So other companies have tried to look at Stargardt, but it's been complicated. Why do you think that is?

Yes. So I was involved with one of those companies, a company called -- formerly called Acucela now called Kubota Vision. They also had an oral once-a-day tablet that was directed at a different sort of target than what we're looking at. So they were really focused on the visual cycle per se. And this drug was a very potent drug and inhibitor of a key enzyme in the visual cycle, which although it did reduce the accumulation of toxins that are implicated in disease progression, it also had a very negative effect in terms of ocular adverse events and so ultimately, that treatment never really worked, but they ran a pretty large Stargardt trial in both -- largely adults, but it was 194 patients, I believe, Phase III trial. It did not succeed. So there was that one. And then, of course, there have been other attempts at Stargardt disease in Phase II trials that never really got off the ground. So this is really the medical of the clinical trial development in Stargardt disease with our drug, tinlarebant.

Yes. So maybe, Nathan, can you just remind everyone what the study design was for your DRAGON study?

Right. So our Phase III pivotal trial design was 104 subjects. We enrolled globally, so all over the world. It was a 2-year study where subjects took a 5-milligram tablet of our drug tinlarebant once daily over a period of 24 years, and they came in for regular assessments where we measured their lesion growth as well as visual function and safety parameters, et cetera. And of course, we had a placebo group. The study was randomized in a 2:1 manner favoring tinlarebant. So there was roughly 65 patients in the tinlarebant treatment arm and the remainder in the placebo arm. So that was really the trial design. We did have an interim analysis when all patients had reached their 12-month time point. So that triggered an unmasked look at the data by our DSMB. The DSMB looked at that data, and they made a very sort of unorthodox comment that we should submit the data for further regulatory review. At that point, no one on the Belite Bio side knew what the data looked like. Only the DSMB was unmasked to that. But because they made that strong comment, we went to the FDA and asked how can we share this data with you and potentially apply for a breakthrough therapy status, and they gave us a path, a road map to do that wherein we would unmask just a couple of members on the management team, and that would be our CEO, Tom Lin here; and our CMO, Hendrik Scholl. They would look at the data and they would prepare a dossier to submit an application for breakthrough status, and we got that breakthrough status, and we're off to the races now.

Okay. So in the discussions that you've had with FDA, have the people that have been involved in the discussions remain the same? There's been turnover at the agency. There was turnover this week, in fact. So can you talk to us about, I guess, based on the most recent change, do you expect any impact? And for the day-to-day interactions that you've had over the last couple of years, have they been the same people just for consistency purposes?

It has. So initially and probably for the last 35 years, the Director of the Division Ophthalmology was Dr. Wiley Chambers, and he had a very principled and dogmatic approach to all clinical trials, which may have been a little bit restrictive. So there's one thing that did change is the incoming director, Bill Boyd,it seems to be a little bit more lean and a little bit more willing to work with sponsors. Not that Wiley didn't work with sponsors, he did. But I think with Bill Boyd coming in, he's given us a sort of a more open window, especially in orphan diseases like Stargardt disease to apply for single study approval. You talked about the Commissioner Makary retiring under pressure, I am sure. I don't think the commissioner status really changes what we're doing on a day-to-day at Belite Bio. We were happy with Makary announced that they would be moving away from a requirement for a 2-study design for approval, and they would use a single study with confirmatory evidence. And that's exactly the path that we're taking. And in fact, that's what Bill Boyd supported as well that we should apply for the NDA with this Phase III data and the confirmatory evidence.

Okay. Yes, that was going to be my next question in that, that editorial in New England Journal that appeared from Dr. Makary and Prasad, now they're both gone from the agency. What do you think the commitment the agency still has to wanting to pursue where possible a 1-study requirement. It seems like based on what you said, you don't think anything has changed.

I don't think so. Tom, do you have anything to add to that?

No I think -- the path is one single study that understanding what the FDA was prior to that editorial already. And then, of course, the editorial came out that basically generalized the whole FDA approval landscape. But for us, it was always a clear path that we worked with the FDA very early on. We had rare pediatric disease designation. So we had that access to FDA guidance, and then we got a lot of handheld by the FDA. So it was always communicated and our clinical trial design was always to satisfy the FDA's requirements. So it has been a pretty smooth path. And I think the data speaks for itself. That's number one. And of course, satisfying FDA requirements with that data helps a lot.

Yes. And of course, this is a rare disease. So rare disease is often people are able to get 1-study.

Not just rare disease, but there's nothing out there that isn't.

Right. Okay. So where are you in the U.S. application process?

Yes. So we've begun our rolling submission. We did have a pre-NDA meeting with the FDA to align on the scheduling for submission of those modules. So we began our module submission on April 21. We expect to end that sometime early or mid-June. 60 days later, the division will opine on the appropriateness of the application. And then 6 months after that, we'll get the final decision on approval given a priority review status.

Why is this a rolling submission?

Some of our modules and specifically the nonclinical module and some of our administrative stuff was sort of lagging behind where we wanted to be. But we had to time that so those data would become available -- information would come available at the right time.

Okay. And as far as EU, is that the same requirement that FDA has asked for in terms of information that needs to be in a package?

Pretty much. There's pretty good alignment across regulatory agencies about what they're looking for. In terms of the submission time lines, we're still working on that. But we are working with various regulatory agencies almost in parallel so that we can facilitate a rapid launch across multiple territories.

Okay. What is the prevalence of Stargardt outside the U.S.? And how easy are these patients to find?

Yes, two good questions. So outside of the U.S., the prevalence is pretty much the same like in Europe, for instance, Asia. There are some pockets where it's even higher prevalence. And in terms -- I'm sorry, I think one was the.

[indiscernible] decline.

That's really a better question for the [ CMO. ] But these patients are pretty focused because even though it's an orphan disease, there are patient advocacy groups that are sort of holding these patients in sort of a registry. And I'm sure they're just all waiting for a therapy. And of course, when I go to conferences and we talk about the data, there's patients in the audience that are asking about when is this drug going to be available. So I think they're going to come out of the woodwork once the approval is announced. And I don't think they'll be coming to us. I think we have to go out and search for them.

So Stargardt it's an inherited disease that quite a lot of patients experience symptoms of declining visual acuity. They may go a long route, but majority of these patients have family members. They also have the disease. So if one patient ends up at a retinal specialist or IRD specialist, and then they have a clinical and genetic diagnosis and then basically the whole family gets going through the whole process. So I would say it's pretty centered around teaching hospitals outside of the U.S. So where there's probably less retinal specialists, but there's even probably less IRD specialists, but they manage majority of the startup patients.

Okay. Got it. Now as we think about pricing range, what would be a good comparison?

Hao.

It's probably still early to comment price range. But I think we talk about that a good reference will be the rare disease price in the U.S. which is somewhere around 350,000 a year. And we do think that we probably will do better than that, maybe up to somewhere like 500,000 without much medical exceptions. But it's not like you cannot price it higher, but if you do, you do expect probably some medical exception coming. We try to find a good balance between that.

Okay. And what type of commercial footprint do you think you'll need? Let's start with the U.S.

So probably -- we plan for maybe a diagnostic plus the sales team, somewhere like 30 people at launch and potentially get that growth to probably double the size, maybe after 2 years of the launch. Like Tom said, it's more likely the patient will come to us. So it's more about reminding the patient and the physician that, yes, there's now a treatment available, go get your testing done so you can get the coverage.

Okay. And for those that are not here, this is Hao-Yuan Chuang answering the question, CFO of the company. So as we think about the competitive landscape in Stargardt, how are you thinking about the evolution of this over the next 5 to 7 years?

Yes, that's a great question. I mean there are competitors, but we don't believe that there's a competitor that's within, let's say, 5 years of being competitive on the market with them. There's other oral therapeutics that are sort of chasing us. I think one of the problems for those companies like that have oral therapeutics will be when they're running clinical trials in the face of a launch drug, how well will they be able to recruit that trial. So they'll suffer there. But of course, there are more novel therapies. There's RNAi, which is looking at two different approaches. One is going to knock out the RBP4 protein, which, by the way, is the protein that we target because this is a protein that takes vitamin A from the liver to the eye. And in the disease eye, vitamin A turns into nasty toxins called vis-retinoids, and that's what we're trying to stop. And so there are companies sort of directing RNAi approaches and RBP4 knockout to do the same thing. With respect to RNAi that's directed to the gene, I think that's going to be more personalized medicine because very few people know this, but there's over 2,000 mutations associated with Stargardt disease. So without replacing the entire gene, you have to go after those certain mutations in the gene construct. And so that will be personalized medicine because there's so many of them. So I see a longer road for gene therapies and RNAi approaches. The small molecules are the other ones that will have a tough time recruiting if there's a launch drug at the time that they're recruiting for trials. So again, on the 5-year time horizon, I don't think that there's anyone that's going to be really competitive on the market with us.

So I'd just like to add that I think the DRAGON study demonstrated 36% efficacy. That's a pretty high bar, especially for a neurodegenerative disease. So coming from a neurodegenerative background, I was quite surprised at 36% that tinlarebant achieved is actually a very high bar because if you look at others like [indiscernible] and all that, they're like hovering around about 15%.

[indiscernible]

So 36% is very high. So for competitors coming into the space to add for that 36%, they'll probably be looking at patient numbers on the clinical side of over 1,000 you do the statistics and the number and the power calculations on the sample size. And they have to do this on the background of tinlarebant and getting approved and being the standard of care. So I think competitive landscape for next 5 years at least, seems less likely.

Okay. So based on the DRAGON data so far, can you share with us feedback that physicians have given you?

Well, I can tell you, as an oral once-a-day treatment, physicians are wildly excited about this. I mean even though most ophthalmologists, I think at their heart engineers and they like to inject things and cut things, to have a treatment for an unmet need, especially in adolescent patients really gives them something to promote to patients, right? Because patients go in and let's say they get diagnosed with the disease, which is a devastating diagnosis, there's nothing for them to do. There's no follow-up. There's nothing that they can do to slow the disease except maybe avoid bright sunlight, wear sunglasses, that type of thing. And so for a physician now to be able to say, "Hey, I've got something. And guess what, it's a pill. It's a once-a-day pill and the safety profile looks great. The treatment efficacy looks great. So yes, I mean everywhere I go when I talk about our treatment and I talk about the DRAGON study, I get nothing but positive reviews from PIs and ophthalmologists that are anxious to see this drug on the market.

Would you say that physician awareness -- and we'll get to you right after this Tom. Would you say that physician awareness is high about this drug?

It is now because now that we're hitting the circuit more with our actual data. Before this, we had open-label Phase II data where we saw positive treatment trends. But because we had no placebo group, we couldn't say anything definitive about the true treatment effect. But now with a 2-year Phase III study, 104 subjects, 36% treatment over 2 years, now there's something to sort of hang the information on. So physicians and ophthalmologists are becoming aware of that. And yes, they're reaching out and talking to us and even asking for compassionate use before we launch, which we can't do. But it's very clear that the drumbeat is getting louder and the message is becoming more resonant with these specialists.

Tom.

So yes. So when we started the Phase III or even during the Phase II, our KOLs or our principal investigators, they were actually hoping that tinlarebant if they can show a 15%, maybe even 10%, I think that's already clinically meaningful. Of course, based on [indiscernible] and all that, we thought that 20% will be approvable and we're aiming for 20% is probably where we want to be. And of course, retinal specialists think that's definitely a meaningful treatment. And then when we saw that the final data be 36%, nearly doubled that of the 20% that we expected, I think everyone was ecstatic about seeing their numbers.

So how big of an opportunity dollar-wise do you think the U.S. market is?

Hao.

Well, giving like a guidance on the price, but you know that 53,000 patients in the U.S., assuming maybe 1/3 of the patient on the drug, which we think is very reasonable and maybe conservative already. You're talking about essentially the price we say $400,000 to $500,000, plus potentially $7 billion peak sales. So it's very large.

And how long -- how easy is it to find these Stargardt patients? Could you locate them within a short amount of time just to get a sense of how long it would take for you to get to peak penetration?

Yes. So I'll start and maybe Nathan can add to it as well. So I think right now, there are probably 10,000 patients that's probably actively managed by retinal specialists, about 10,000 patients. And then I'll say 1/3 of them are early adopters where the physicians are very keen on putting their patients on to the study. And of course, if there's probably another 1/3 of retinal specialists that's probably not well informed or not updated with the new information that the treatment is just around the corner, and that's why we want to do all this reach out and letting the retinal specialists know that there's a treatment out there. And of course, with the patient advocacy group and all that they're always updating their knowledge of what's coming out, what treatments are out there and all that. So I think the patients are not hard to find -- they are there already. It is a severe disease. There's a lot of awareness in the [ ILT ] space, especially if you have young adults or kids that's going blind and that they want to get a treatment very desperately.

And the drug is coming, I think the willingness for getting the testing is going to be much, much higher as well.

Okay. Maybe let's talk about manufacturing. Where is the drug manufactured? And how ready will you be to meet demand as soon as you launch?

So the manufacturing is in China with WuXi, so probably one of the best CDMO there. And the drug itself is a small molecule drug. It's easy to manufacture and delivery. So -- and stability data is long. So any kind of supply will be easy for us to manage.

Okay. How should we be thinking about gross margin for the product?

Well, that's a good question. We probably would not be able to be in a position to know that very well yet, but we do see that this could be potentially a much lower kind of a discount rate given there's no other treatment there. So gross net probably will be pretty high.

Okay. Okay. So it looks like you have a clean runway as the launch approaches, and it looks like doctors are largely aware of the product, and it looks like demand should be high. So if you think about the speed with which you can get penetration, is there a reason to think why it shouldn't be steep, steep uptake?

Steep uptake.

I think we are expecting a steep uptake. So if there's any other reasons I can't think of. if there's any setbacks that there's probably going to be side effects of the drug, which we are not seeing. So I don't see if there's any setbacks. You think of any.

Nothing I can think of. And I think our safety profile is actually very clean. The drug is very well tolerated. The overall dropout rate in the study was less than 10% over 2 years. That was remarkable. I've been on a lot of clinical trials in ophthalmology. I've never seen dropout rates that low. So I think it's a very well-tolerated drug, and we're happy to see the data.

Okay. So we're looking forward to seeing that launch coming up. I did want to spend some time talking about geographic atrophy, which is the next area of focus. Maybe just give us a background about how you decided that, that should be your next indication.

That's a really good question. And the story goes back many, many years. I don't want to bore the audience with the history of it. But many years ago, when I was the CSO of a different company, this idea of reducing vitamin A delivery to the eye as a means of slowing lesion progression actually began in geographic atrophy with a Phase II study that enrolled 246 patients that had GA. And at that time, I used a surrogate drug, an anticancer drug known as fenretinide, which had a side effect of reducing retinal binding protein 4 in blood. And this had always been my approach. We developed that in the Stargardt animal model and shown that efficacy in the model. And so we wanted to transfer that to the clinic. We used this anticancer drug. And at the end of this 2-year study in these 246 patients, we found that patients that achieved at least a 70% reduction of this retinal binding protein 4 had a statistically significant slowing of lesion growth. And so that was sort of the proof of concept that showed that you could use a systemic treatment to reduce retinal delivery to the eye as a means of slowing lesion growth. And the pathophysiology with respect to lesion growth in GA is very similar to that in Stargardts. And so we basically transferred that whole therapeutic approach to Stargardt disease. And at the time I did this study in GA, there was very little known about the natural history of Stargardt disease. There was no regulatory path toward approval. So that's why I looked at GA rather than Stargardts as a proof of concept. And so that really gives us the impetus to do the trial. And now that DRAGON is done and we see now that we were shooting for that 70%, we got to 80%. So it was an 80% reduction of retinal binding protein 4 across the 2-year study. And as Tom noted, we have this 36% treatment effect. So I think it validates the therapeutic approach and gives us even more confidence that this is going to be effective again in GA. So that's why we came back to GA to basically go back in with a better drug. Fenretinide was a terrible drug as an anticancer drug in a retinoid that had a lot of side effects that were untoward. But now we got a drug that's not a retinoid. It's a small molecule that's very safe. The treatment effect is immediately reversible over about a month if you want to come off the drug. So superior drug, great bioavailability, great potency. And now we're going back into GA to see if we can get that same type of treatment effect in the population.

Yes. So mechanistically, do you expect it to show a visual acuity benefit?

No, we don't. And people always talk about visual function benefits. And in a 2-year study, it's just very difficult to do in patients where visual acuity loss is exceedingly slow, particularly in Stargardts, very, maybe one to two letters per year. And the bar for the FDA in terms of clinical meaningful data is 15 letter, a 15-letter difference between your placebo and your active. And in 2 years, patients just don't lose that much vision. And so other sponsors are going after, for instance, time to event hens like time to lose 10 letters or time to lose 15. We did that differently because we know that a lot of regulatory agencies now are agreeing to look at lesion growth because eventually lesion growth, which is dead photoreceptors, is going to affect your vision. And so most regulatory agencies understand that. And it's a more quantifiable reproducible metric for measuring treatment efficacy versus BCVA. And so we're sticking with that. And I think eventually, over time, if you show a trajectory of slowing of growth over time, that's going to keep happening as you take the treatment. And eventually, 3 years, 4 years, 5 years down the road, you will have an effect on slowing visual acuity loss.

So is it your view that -- well, there's two drugs that are currently on the market for GA. Both of those are injectables. So is it your view that simply replicating the type of efficacy they've shown would be the desired outcome given that you're an oral and so you wouldn't have the side effect profile of those drugs?

Yes, absolutely. And they do have terrible side effects. I'll let the audience look for themselves. But yes, if we achieved a similar level of efficacy, which is 14% to 18% slowing of growth, and we have an oral drug once a day with a very clean safety profile, I think that those injectables are in trouble because there's a really high treatment burden for patients receiving those drugs. And I think once they find out there's an oral that achieves the same treatment effect, why would you want to go to the doctor every month, every other month to get a needle in the eye where you could just wake up every morning and take a pill like a vitamin supplement or something like that?

Yes. So let me talk to you about that for 1 minute because I think there might be some people that are wondering, well, why would you -- if it's a disease of the eye, why wouldn't you want concentrated drug delivery into the eye? Why would an oral which is a systemic therapy be more ideal?

So that was intended. That's intended in the therapeutic approach. And again, we just referenced Stargardt disease. The underlying cause of Stargardt disease is toxic byproducts of vitamin A filling up in the eye. So as I mentioned earlier, vitamin A going into the eye, the diseased eye is not processed the same way as in a healthy eye, and it produces all these byproducts. So the best way to do that really is to slow the delivery of that vitamin A in a very controlled and methodical manner so that you can balance risk benefit, and that's what we're doing with tinlarebant. And so I think this is the way to go. The drug is reversible, so the tinlarebant itself really doesn't accumulate in the body. It grabs retinal binding protein for and causes to be eliminated in urine, and this is sort of the treatment effect. And so we think it's very clean, very well tolerated, very reversible if patients need to come off and just has so many benefits versus needle in the eye, and you don't need to have the drug inside the eye. And I think this therapeutic which demonstrate something people never thought of before. Just like you sort of thought, well, it has to go in the eye, if you're going to effect change in the eye, but we're showing that's not necessarily the case.

Okay. So when is the next data readout for GA?

We're aiming for end of the year for the interim.

And what would that be? Like how many patients?

They will probably be all, right, halfway for all.

We enrolled 530 patients with geographic atrophy.

And so you'll have how many shown [indiscernible]?

It will be 530 up to the 12-month mark.

We haven't confirmed the study. So you have to do the assumptions, calculation, you propose to the FDA and you talk with them. So we'll make that information available once we confirm the design.

Roughly halfway.

Okay. Perfect. Okay. With that, we are out of time. So thank you so much. Thank you so much for spending last half hour with us. And thanks, everyone, for listening.

Thank you all.