BLTE - NASDAQ

Ladies and gentlemen, thank you for joining us, and welcome to the Belite Bio First Quarter 2025 Earnings Call. After today's prepared remarks, we will host a question-and-answer session. [Operator Instructions] I will now hand the conference over to Julie Fallon. Please go ahead.

Hello, and thank you for joining us to discuss Belite Bio's first quarter 2025 financial results. Joining the call today are Dr. Tom Lin, Chairman and CEO of Belite Bio; Dr. Hendrik Scholl, Chief Medical Officer; Dr. Nathan Mata, Chief Scientific Officer; and Hao-Yuan Chuang, Chief Financial Officer. Before we begin, let me point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. We encourage you to consult the risk factors discussed in our SEC filings, for additional detail. Now I'll turn the call over to Dr. Lin.

Thank you for joining today's call to discuss our first quarter 2025 financial results. We continue to make good progress in this quarter towards advancing Tinlarebant in patients living with Stargardt's disease and geographic atrophy. For those who are new to our story, Tinlarebant is a first-in-class oral therapy intended to reduce the accumulation of toxic vitamin A byproducts, which is implicated in the progression of retinal lesions in patients with Stargardt's disease and geographic atrophy. We believe this approach will be effective in slowing, or halting lesion growth, which would ultimately preserve vision. To give you some perspective on the importance of this potential therapy, Tinlarebant has been granted Rare Pediatric Disease and Fast Track designations in the U.S. and Pioneer Drug designations in Japan. It has also been granted Orphan Drug designation in the U.S., Europe and Japan. We believe this speaks to the significant unmet need for both indications as currently, there is no approved treatment for Stargardt's disease and no approved oral treatment for geographic atrophy. And more importantly, we are uniquely positioned as we are already in global Phase 3 trials for both indications. So with that, let me provide a high-level overview of the recent progress we have made. We have two studies underway with Tinlarebant in patients living with Stargardt's disease. These are the Phase 3 DRAGON trial and the Phase 2/3 DRAGON 2 trial. As part of the Phase 3 DRAGON trial, we recently announced that the Data Safety Monitoring Board has completed its interim analysis, which is based on all subjects having completed the one-year assessment period. The DSMB recommended that the trial proceed without sample size increase, or modifications. So essentially maintain the sample size at 104 subjects. In addition, they recommended that we submit the data for further regulatory review for drug approval. With the DSMB's review done, completion of the trial is on track for end of this year. The DRAGON 2 trial continues to progress rapidly. We have enrolled 16 of our targeted enrollment of approximately 60 subjects, including about 10 Japanese subjects. Data from the Japanese subject is intended to expedite a new drug application in Japan to, which we have already been granted a Pioneer Drug designation. In GA, we also continue to make progress in our clinical global Phase 3 PHOENIX trial, which has already enrolled 464 subjects to-date. We expect PHOENIX trial to be fully enrolled for 500 subjects in Q3 this year. To summarize, with the excellent progress in our Phase 3 trials and promising interim results from Phase 3 Stargardt study, 2025 is off to a great start from a clinical perspective, and our balance sheet is also strong with a full year cash runway. We remain well positioned in advancing Tinlarebant as potentially the first oral treatment for people living with degenerative retinal disease. I'd like to now turn over the presentation to Nathan.

Thank you, Tom. So here, I'll talk about the DRAGON clinical trials, both DRAGON 1 and DRAGON 2, as well as the interim analysis from the DRAGON 1 study, as Tom just mentioned. Here is an overview of the clinical trial designs in the Phase 3 trials for DRAGON and DRAGON 2. These trials are designed nearly identically. There's only three differences in the trial designs, and those are highlighted in the top three rows. The first being the number of subjects, 104 in DRAGON versus 60 in DRAGON 2, the global nature of the Phase 3 design for DRAGON versus a more localized geography for DRAGON 2 in Japan, U.S. and U.K. And the randomization is 2:1 in DRAGON versus 1:1 in DRAGON 2, because of the difference in the sample sizes. Other than that, all of the other parameters of the study are identical. And of course, the endpoint is exactly the same that, is slowing the growth of the atrophic lesions as measured by FAF photography. This is the FDA accepted endpoint. The other thing I should mention is that these studies both include the same dose, which is a 5-milligram daily dose that reduces retinol-binding protein 4 to about 80% below the baseline value. And at the very bottom there, you can see the key inclusion criteria. All subjects in the DRAGON studies are 12 to 20 years old, and they have clinically and medically confirmed diagnosis of Stargardt disease. Importantly, about the DRAGON trial, as Tom mentioned, there was an interim analysis. This was a prespecified sample size reestimation in, which the DSMB would take an unmasked look at the study data to determine whether, or not there was a trend for efficacy in a so-called promising zone. This is a statistically identified window of conditional power that, tells us there's a trend for efficacy. If in fact, there were a trend for efficacy noted by the DSMB, we would then be allowed to add 30 additional subjects to the study that, would preserve and enrich the observation made at the interim so that, we would have a better chance of seeing a statistically significant difference, at the end of the second year. That analysis, the interim analysis was triggered when the last patient had met his, or her 12-month visit. The DSMB then took a look at the data, and they decided there was no modification of the study that would be required, and that we continue the study without a sample size increase. So that told us that we were not in this conditional zone of power called the promising zone. We were either on the opposite side of that, which would be futile, or we're on the very positive side, which would be the overly efficacious side or unexpected efficacy. And in fact, we knew that we're probably very efficacious because the DSMB did provide an additional comment that, they recommend we submit the data for further regulatory review for drug approval. That comment would not have been made if in fact, we were on the futile side of that promising zone. So we feel very optimistic and encouraged about this outcome. Importantly, at the time of the interim analysis, the overall withdrawal rate was less than 10%. So only 10 of 104 subjects withdrew. Of course, we don't know the breakout between placebo, and active treatment, because again, this is blended data. But to have less than a 10% dropout, when the majority of the study data has been analyzed, is quite significant. And importantly, the withdrawal due to ocular adverse events was only 3.8%. So only four of 104 subjects withdrawing, because of ocular AEs. This is particularly important, because the nature of our MOA would predict that there would be ocular adverse events. We know now from the study data that is very well tolerated and of course, mild and transient. That's very important. And then finally, when we look at visual acuity, we find that visual acuity was stabilized in the majority of subjects, with a mean change from baseline of less than three letters under both standard, and low luminance throughout the two-year study. Here's the breakdown of the treatment-emergent adverse events in the DRAGON trial. It's important to note that systemically, there was only one drug-related adverse event, and that was acne. And this can happen in teens and preteens, when vitamin A is diminished in the skin, because vitamin A does help clean pores. So if we're diminishing it, perhaps pores are not so clean, but it's a very mild AE to have systemically. Other than that, clinically significant findings in relation to vital signs, were nothing in relation to physical exams, cardiac health or organ function. What you see on the table are the outcomes from the two ocular AEs that we expected, Xanthopsia and delayed dark adaptation. As mentioned, these were reported as mild and of course, transient. You can see on the right-hand side, the frequency and number of patients presenting with those AEs. The night vision impairment you see there, which is also mild, is a more severe exacerbation of delayed dark adaptation. We had that in 15 reports of it. And then, of course, we have a non-ocular headache in some subjects, which, of course, can be manifested when subjects strain to use their visual acuity, while experiencing these ocular AEs. But overall, a very, very well tolerated and safe profile from an adverse event perspective. With respect to the visual acuity, I mentioned there was stabilization throughout the study trial. Since we have our CMO, Dr. Hendrik Scholl on the line, I'd like to get his clinical opinion on the BCVA data. Dr. Scholl?

Thank you, Nathan. The chart shows the ETDRS letter score in the study eye in orange, and the fellow eye in gray over 24 months. This is blended data, meaning the Tinlarebant group and the placebo group are shown as one group. The early treatment diabetic retinopathy study or briefly ETDRS visual acuity testing, is a standardized method used to measure visual acuity and is the gold standard in clinical trials, and research settings. The ETDRS chart includes 14 lines with five letters per line, and the maximum score on ETDRS visual acuity testing is 100. There are significant intersession variability of ETDRS visual acuity measurements in normal subjects. Test retest variability typically falls within about five letters. And in individuals with macular degeneration, variability tends to be greater, namely about eight letters. What we see on the chart is that there was not even a single letter loss on average. Clearly, this allows to conclude that there was no significant loss of visual acuity, and it is fair to say that, there was stabilization of visual acuity in the DRAGON trial. I hand back over to Nathan.

Thank you, Hendrik. So moving forward now, a few words on our Phase 3 trial in geographic atrophy, which is called PHOENIX. This is the overview of the trial design of PHOENIX. You can see on the right-hand side, the various criteria for the study. This study is enrolling up to 500 subjects. It's a global study. The design is essentially the same as that for the Stargardt trials. In fact, the dose is exactly the same, 5 milligrams daily. It produces the same pharmacodynamic effect in older, healthy adults, as it does in young adolescent children, so we can use the same dose. It has the same endpoint. There's going to be the same trial duration. We will also be including an interim analysis. The timing and specifications of that analysis, have not been worked out, but that will be conducted. And of course, that trial is still enrolling. We expect to close that enrollment sometime this summer as again, as I said, up to 500 subjects. So with that, I'll turn it over to Hao-Yuan for the financial results.

Thank you, Nathan. For Q1, 2025, we had R&D expenses of $9.4 million, compared to $6.8 million for the same period last year. The increase was primarily attributable to the share-based compensation, and slightly higher clinical trial expenses, related to the PHOENIX trial. Regarding G&A expenses, it was $6.1 million, compared to $1.6 million for the same period last year. The increase was also due to share-based compensation grade. Overall, we had a net loss of $14.3 million, compared to a net loss of $7.9 million for the same period last year. One thing to note is that as the majority of the increase of the expenses came from the share-based compensation, which was about $6.7 million and was not cash related, the operating cash outflow was only about $8.3 million. As we raised $15 million through the registered direct offering in February, and received about $5.6 million from employee stock option exercise. We had a cash increase of $12.3 million for the quarter, and leave us with $157.4 million in cash, liquidity funds, time deposit and U.S. treasury bills as end of Q1. We still expect four years of cash runway, and we expect to be able to complete all of our current clinical trials with this current cash. Thank you. Back to you, operator.

[Operator Instructions] Your first question comes from the line of Marc Goodman with Leerink Partners. Your line is open. Please go ahead.

This is Basma on for Mark. Thank you for taking our question. Could you please - our first question is about the PHOENIX trial. Could you provide us update about the discontinuation rates, and how the enrollment is ongoing in this trial? And the second question we have is about any update on the regulatory meetings for the endpoints for - I'm sorry, for the trial requirements for Stargardt disease. You mentioned that you were supposed to - were working on - you're planning to meet up with the FDA and other regulatory agencies to finalize the plan, the development plan. That's it for us? Thank you so much.

You. So I'll take those questions. So the first question is regarding the PHOENIX dropout rates. Is that, right?

Yes, correct.

So the dropout rate is approximately around about 20%. This is way below what's been reported in previous studies, such as the deuterated rate of vitamin A Phase 3 that was reported, I think, earlier this year, there's a dropout of about 30%. And I believe that Emixustat and other anticomplement inhibitors in GA, they were much, much more over 30% to 50%, I believe. Hendrik, could you shed some light on that?

Yes, that is correct. I mean it's not surprising that the injectables come with a higher risk and a higher dropout rate. And Emixustat led to severe night blindness, and there was also a higher dropout rate in the trial using Emixustat as a visual cycle modulator.

Yes. So what's more surprising is that even the deuterated vitamin A had a more than 30% dropout rate. So we're way below that. So that's pretty encouraging considering that we are conducting the trial in very elderly patients. I think the average is around about 80 year old. So compliance is an issue. But we still have it within that 20%. So we're doing pretty well. And then the second question was the Stargardt IA that we'll be discussing that with the regulators. Is that correct, if I remember correctly?

Yes, correct.

Yes. So we have been scheduling meetings with the regulators, and we are doing so right now. We will be meeting a few of those in - we've scheduled some meetings in the short-term. We'll be updating that as we go along. So right now, we don't have much to report back on.

Got it. Thank you so much.

Your next question comes from the line of Jennifer Kim with Cantor. Your line is open. Please go ahead.

Hi. Thanks for taking my questions. Maybe to start off in Stargardt. Can you just talk about the recent interactions you've had with the FDA? And any thoughts on maybe any perceived regulatory risk given the changes at the agency? And then my second question is, with the Phase 3 data, I think it's coming in early 2026. Can you just remind us what the goalpost is on efficacy and safety?

So I'll take the first one. So we haven't met up with the FDA yet. We'll be meeting up with that soon. So that's been scheduled. And then what's the other question?

If you have any thoughts on, I guess, regulatory risk given specifically the changes that have been going on at the agency?

No. I think we don't have any risk given that the data speaks for itself. So I mean, even though there's some changes within the FDA, I don't think that's going to affect us, especially, I think the division that we have met up with - well, the division that's been giving us guidance throughout the whole study, especially during the Phase 3, most of them are still there. So I don't think there's any issues with the personnel change within the FDA.

Okay. And then can I ask on the goalpost for the Phase 3 - the 24-month Phase 3 data?

24-month for the DRAGON. I think it will complete by Q3 this year. Nathan, do you want to shed some light on that to confirm?

Yes, I think Jennifer may be asking about what exactly we're looking for in terms of efficacy and safety, correct, Jennifer?

Oh okay.

Yes.

Okay. So Nathan, do you want to answer this then?

I was just going to mention that the study is powered to detect a 35% treatment effect between placebo and active. So that's what we're looking for. I mean, sometimes you get there, sometimes you don't. But based upon what the DSMB looked at and told us in terms of safety and efficacy at the interim, which, by the way, as I mentioned, the majority of data were actually available at that time. We're expecting that we'll be getting very close to our anticipated treatment effect size of 30% to 35%. Again, that's what the study is powered for. In terms of safety, I think the outlook is very positive given, again, what we see at the interim, less than a 10% overall withdrawal rate and 3.8% with respect to ocular AEs, again, because the majority of the study data had already been evaluated by the time of the interim analysis. Roughly 70% to 75% of the data was evaluated. I don't think that's going to change very much by the end of the year. So I expect those dropout rates to be fairly consistent. And as I said before, you never know about efficacy. But based upon what the DSMB saw at the interim, I'm expecting that we'll get very close to our anticipated treatment effect size.

Got it. That's helpful. Thanks, guys.

Your next question comes from the line of Yi Chen with HCW. Your line is open. Please go ahead.

Hi. Thank you for taking my questions. In view of President Trump's recent policy of most favored nation drug pricing, could you comment on your potential strategy regarding approval and launching of the drug in ex U.S. territories, particularly Japan, and whether that will affect your U.S. drug pricing and market prospects? Thank you.

Yes. Thanks for that. Well, first of all, since Tinlarebant has not launched yet, it's not going to affect us immediately. We are still observing how this is going to impact the industry as a whole, and what type of drugs are affected, Orphan Drugs, Rare Pediatric Drugs, et cetera. Right now, we are still monitoring what's going on. So we don't have an immediate answer for that. I don't think anyone has an immediate answer for that, but we're still monitoring how it goes.

Got it. Thank you. And a quick question on the financial side. Will the operating expenses continue to rise during the remainder of 2025, based on the level recorded in the first quarter?

Hao-Yuan, you want to take this?

I think it will be about slightly higher than the Q1. We did - I think we did guide the market that this year and the next year, we expect it to be higher expenses given that most of the milestone of the studies, all three studies expect to be reached in the next one, two years, yes. So the expenses will be higher this and next year. But moving forward, it will come down back to the previous level.

Okay. Thank you.

Thank you.

Your next question comes from the line of Bruce Jackson with Benchmark. Your line is open. Please go ahead.

Hi, good afternoon and thanks for taking my questions. Can you hear me, okay?

Perfect yes.

Just to follow-up on that last question. We had the increase in stock comp during the quarter. Is that also expected to be a little bit higher going forward?

Well, so it will really depend on the allocation of the expenses. So you will have part of our ESOP will be only vested based on so-called the development milestone. So it's a little bit hard to say what exactly when it will be allocated at. And for those that are going to be invested based on time, it will be allocated by the period of the duration of the option. So it's a little bit hard to really give you a figure. But I think given we did have some of the ESOP just happened in that quarter. So I don't expect it's going to be that high moving forward this year.

Okay. Great. And then last question from me is on manufacturing. Obviously, there's a push to move manufacturing to the United States for pharmaceuticals. How do you - how are you set up right now in terms of inventory? And how is your supply chain structured geographically?

Yes, good question. So Tinlarebant is manufactured in the U.S. as well as in other geographies. So tariff is not going to affect us any way.

Okay, super. All right, thank you very much.

Thank you.

Your next question comes from the line of Michael Okunewitch with Maxim. Your line is open. Please go ahead.

Thank you. Thanks for taking my questions today, guys. So I guess the first question I would like to ask, is just if you could provide any more detail on the timing, or any of the conditions that you would need to meet for that interim geographic atrophy?

So we believe that we've - so speaking on behalf of the MS team, it's probably just me and Hendrik. We are meeting with the regulators. We believe that we got what it takes to get us over the line. But until we end up having an official response from them, we're not going to disclose anything as of now.

All right. Fair enough. And then are there any additional sample size reestimations for the PHOENIX study? Or is that 500 patient count final, as it looks like we're going to wrap up enrollment in the next couple of months?

Yes. So we're expecting to wrap up the enrollment, because that enrollment is going very smoothly as of now. We're making good progress. We don't believe that we would need extra additional subjects. We're just adding it on just in case, because we are having smooth enrollments, and why not just enroll more to enroll more subjects to boost up our success. Nathan, do we have anything to add on?

No. no. In fact, right now, there's no plan to do a sample size reestimation in PHOENIX. As Tom said, we're sort of hedging our bets now that enrollment is going smoothly, to enroll as many subjects as possible at the very start, so that we won't have to do a sample size reestimation at the interim.

All right. Thank you very much.

Thanks, Michael