Earnings Call Transcript - BLTE Q3 2024

Operator, Operator

Hello, and thank you for joining us to discuss Belite Bio's Third Quarter 2024 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. Please note that you can submit questions throughout the call by clicking on the Q&A box at the bottom of your screen, and we will respond to questions following our prepared remarks. Now I'll turn the call over to Dr. Lin.

Tom Lin, CEO

Thanks, everyone, for joining our third quarter conference call. Before diving into the details of this quarter's performance and the status of our pipeline, I would like to introduce an exciting addition to our leadership team. It is my pleasure to welcome Dr. Hendrik Scholl, our new Chief Medical Officer, to the call. Professor Scholl is the world's foremost expert in Stargardt disease and age-related macular degeneration. He has pioneered some of the most significant advancements in ophthalmology and retinal disease, including the world's largest natural history study of Stargardt disease. We're thrilled to have him lead our clinical program at such a pivotal time. Certainly, his expertise and dedication will be instrumental in advancing our efforts to bring much-needed treatments to patients living with Stargardt disease and dry AMD. Dr. Scholl, welcome.

Hendrik Scholl, Chief Medical Officer

Thank you, Tom. I'm honored to be joining Belite Bio at a time when the company's clinical programs are showing such promise. Having served as the chair of the data and safety monitoring board for Belite's Phase II and Phase III Stargardt disease trials, I feel immensely confident in Tinlarebant's potential. I have dedicated my career to improving the lives of people suffering from serious retinal, and specifically macular diseases, which are almost always debilitating and have a profound negative impact on quality of life. I'm deeply impressed by Belite Bio’s pioneering approach to Stargardt disease and late dry AMD, which have historically lacked effective treatment options. Having seen firsthand the toll these diseases can take, I look forward to working with our talented team to drive our clinical programs forward and, hopefully, bring transformative therapies to patients in need.

Tom Lin, CEO

Thanks, Hendrik. Now moving on to our quarterly update, we continue to make strong progress towards advancing Tinlarebant in patients living with Stargardt disease and geographic atrophy. For those who are new to our story, Tinlarebant was developed from our retinal binding protein intellectual property portfolio. Tinlarebant is a novel oral therapy intended to reduce the accumulation of toxic vitamin A byproducts in the retina. This approach is intended to slow or stop the formation of toxic retinal-derived byproducts, which are generated in the visual cycle and implicated in the progression of Stargardt’s disease. We believe that early intervention directed at emerging retinal pathology, which is not mediated by inflammation, is the best approach to potentially slowing the progression of these diseases. 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., as well as SAKIGAKE designation in Japan, which translates to pioneer drug designation. Tinlarebant has also been granted orphan drug designation in the U.S., E.U., and Japan. We believe this speaks to the significant unmet need for both indications, as there is currently no approved treatment for Stargardt disease and no approved oral treatment for geographic atrophy. We are uniquely positioned, as we are already in global Phase 3 trials for both indications. Allow me to provide a high-level overview of the progress we have made in Q3. We have two studies underway with Tinlarebant in people living with Stargardt disease: the Phase 3 DRAGON trial and the Phase 2 DRAGON trial. The DRAGON 2 trial is fully enrolled with 104 patients, with an estimated interim analysis expected by the end of 2024 or early 2025. The DRAGON trial is expected to enroll 60 subjects across the U.S., U.K., and Japan. For geographic atrophy, we have the Phase 3 PHOENIX trial, which is expected to enroll 429 subjects. In summary, for this quarter, the DRAGON 2 trial continues to progress rapidly. We have successfully dosed the first patient in the Phase 2-3 portion and have completed the Phase 1B study in Japanese subjects at the Tokyo Medical Center. Enrollment is now also underway at sites in the U.S. and U.K. In geographic atrophy, we also continue to progress in our pivotal global Phase 3 PHOENIX trial, which has already enrolled more than 280 subjects to date. That concludes my part of the update and I will now turn over the presentation to Hendrik.

Hendrik Scholl, Chief Medical Officer

Thank you, Tom. So I'll be happy to go over aspects of the Phase 2 trial. The first is actually looking into lesion growth of patients with Stargardt disease. The data that was obtained in the Phase 2 study with Tinlarebant can be compared with natural history data collected in the ProgStar study. As Dr. Lin mentioned earlier, I led a multicenter worldwide natural history study called ProgStar, where patients were investigated over two years every six months. They ended the study with lesions defined as so-called decreased autofluorescence. The lesion growth was measured over time and was compiled into a growth curve. There is inevitable loss of tissue that is measured as the growth of EDF lesions over time. In the study, among the subjects that developed such lesions, the lesion growth rate was significantly smaller than when compared with a subset from the ProgStar study, namely 51 patients of matched age to the Phase 2 study. The growth rates indicate that the lesion growth could be slowed under the treatment with Tinlarebant, as the treatment effect was significant—halving the lesion growth rate from 1 sq mm per year to only 0.5 sq mm per year. This difference was highly statistically significant, and clinically, it is also highly significant. Next, there is inevitable loss of visual acuity, clinically measured. The typical visual acuity chart has 100 letters. Patients affected by macular diseases, such as Stargardt disease, will lose vision over time. In Stargardt disease, when lesions develop that affect the macula, patients will inevitably lose vision. In the Phase 2 study, it was shown that visual acuity loss could be stabilized in patients treated with Tinlarebant, with an average loss of about five letters over two years, compared to a loss of ten letters a year in the untreated population. It’s significant to observe that, during treatment, they only lost about three letters per year. Therefore, we conclude that visual acuity loss was stabilized under treatment with Tinlarebant. Next slide please. The safety results of the Phase 2 clinical trial showed that Tinlarebant at a daily dose of 5 mg continues to be safe and well-tolerated in adolescent Stargardt patients. The treatment produced a mean of an 80% reduction of retinal binding protein 4 from the baseline throughout the study. Adverse events such as delayed dark adaptation and xanthopsia were the most common drug-related ophthalmic adverse events and are anticipated because they relate to the mechanism of action of Tinlarebant, namely reducing the amount of retinal entering photoreceptors. Such changes were well tolerated by patients. There were no severe drug-related AEs reported and no AEs that required discontinuation of treatment. Overall, there were no clinically significant findings related to vital signs, physical exams, cardiac health, or organ functions.

Nathan Mata, Chief Scientific Officer

Thank you, Dr. Scholl. I would like to move forward with describing the clinical trial designs in our two Stargardt studies, the DRAGON study and the DRAGON 2 study. It's important to note that in both Stargardt studies and in our geographic atrophy study, we are looking at the growth rate of atrophic lesions—these lesions are the ones the FDA considers as a surrogate marker for eventual visual acuity loss. So we're examining the growth of these lesions as an endpoint for approval in all our trials. In all our studies, we are implementing a 5 mg dose, achieving an approximately 80% reduction in retinal binding protein 4. This level of reduction has been shown to lead to the slowing of lesion growth in prior clinical studies. In terms of trial designs, our DRAGON study has 104 subjects recruited, while DRAGON 2 aims for enrollment of 60 subjects. The DRAGON phase 3 study is a global study, while the DRAGON 2 study is recruiting subjects from Japan, U.S., and the U.K. The third difference is the randomization: DRAGON has a 2:1 randomization favoring Tinlarebant, while DRAGON 2 has a 1:1 randomization of Tinlarebant to placebo. All other aspects of the trial design remain consistent, including masking, treatment duration, and primary as well as secondary measures.

Hao-Yuan Chuang, Chief Financial Officer

Thank you, Nathan. In Q3 2024, we had R&D expenses of $6.8 million compared to $8.7 million for the same period in 2023. The decrease was mainly attributable to fewer CRO milestone payments related to the DRAGON trial, partially offset by an increase in the DRAGON 2 trial expenses. Our G&A expenses in Q3 2024 were $2.9 million compared to $2.2 million for the same period in 2023. This increase was primarily due to a rise in share-based compensation granted in Q3 of 2024. Our net loss amounted to $8.7 million in Q3 2024, compared to $10.9 million for the same period in 2023. Despite this, we maintain a strong balance sheet with a total of $109 million in cash, money market funds, time deposits, and U.S. Treasury bills. With the funds raised year-to-date and our recent warrant exercise, we expect about a four-year cash runway to execute all our key milestones. Thank you. Back to you, Tom.

Tom Lin, CEO

Thanks, Hao. We have had an exciting year so far, and we continue to make meaningful strides in advancing Tinlarebant in clinical trials for Stargardt disease and geographic atrophy across several countries. Now we're open for questions.

Basma Radwan, Analyst

This is Basma on for Mark. Thank you for taking our question. We would like to ask if you have done any market research to assess the tolerance of GA patients to the ocular adverse events. Would you expect those AEs to actually impact the uptake in this patient population, or do you think they're going to be resilient to these particular AEs? Thank you.

Tom Lin, CEO

Thanks. Nathan, do you want to take this one?

Nathan Mata, Chief Scientific Officer

Basma, thank you for the question. I assume you're referring to ocular AEs in the GA study?

Basma Radwan, Analyst

Yeah, which is basically the same ocular AEs in the Stargardt.

Nathan Mata, Chief Scientific Officer

Right. I just want to make sure. Yes. So in GA, we would expect probably a little bit higher incidence and severity of these adverse events because the retina is much more disease-ridden. Right? These patients have had their disease for decades versus the Stargardt adolescent subjects who have had it for years. So, yes, we would expect perhaps a higher incidence of low luminance visual acuity issues. There should be no effect on best-corrected visual acuity that is in ambient light. But in low-level light, GA patients first of all, have a problem with low-level visual acuity. The reduction of vitamin A locally within the macula would make that a little bit worse for patients that have more extensive macular involvement. So, yes, the short answer is we would expect a higher incidence of low luminance visual deficits in the GA patient population under Tinlarebant treatment.

Basma Radwan, Analyst

And would you expect that to be tolerated by the patients?

Nathan Mata, Chief Scientific Officer

Oh, yes. I mean, we're recruiting that study now. I think we're up to about 288 subjects. We certainly have seen instances of low luminous visual acuity, but it’s a minority of subjects, not the majority. So, clearly, patients are dealing with it. The majority of patients are managing quite well.

Operator, Operator

Thank you. Our next question comes from Jennifer Kim with Cantor. Please proceed.

Jennifer Kim, Analyst

Hi. Thanks for taking my questions. Maybe to start off similar to the last question, for the patients in PHOENIX who have been enrolled to date, do you have any comments on the discontinuation rates you've seen?

Tom Lin, CEO

Nathan, do you want to come in?

Nathan Mata, Chief Scientific Officer

I believe we're right around 15% right now, but that's overall. That's not just ocular AEs, but the total number. We're somewhere around 15%. I believe that was the last number.

Jennifer Kim, Analyst

Okay. And then going to DRAGON, can you walk through what's left to prepare for the interim analysis? What is your latest thinking around how you'll provide that update?

Nathan Mata, Chief Scientific Officer

When you say what's left, I mean, really, all the patient data are in. The trigger for the interim analysis is when all subjects have completed their month 12 visit. There will be some at 18 months and some that have already completed the study. What has to be done is that the data has to be cleaned, provided to the DSMB, and the DSMB then has to schedule a meeting to review that data. We predict that this timeline will be around December, at the very latest early January. Nothing more needs to be done other than data cleaning and providing the data to the DSMB followed by the DSMB meeting.

Jennifer Kim, Analyst

And in terms of disclosure on your end, would that come in the form of a press release, a call, or something else?

Hao-Yuan Chuang, Chief Financial Officer

What will happen is that we will be informed by the DSMB whether we need to increase the sample size. We will announce that to the market as soon as we know. Additionally, we'll host a press release to discuss what the DSMB has communicated to us and what that means for us. Another moving factor regarding the interim analysis will be the new DSMB chair as Dr. Scholl was our DSMB chair. We are making progress to find a replacement for that position. Once the new DSMB chair is on board, we will schedule their meeting, and given the holiday season, we may not have a clear timeline about when that meeting will occur.

Jennifer Kim, Analyst

Okay. And if I could fit one more question in. On DRAGON 2, I know you've announced the first patient dose in the phase 2, 3 portion. Can you say anything about how many patients have been enrolled in total so far? And do you have an estimate on when that enrollment could complete?

Hao-Yuan Chuang, Chief Financial Officer

I don't have a specific number on top of my mind now, but I believe that most of the Japanese subjects who passed the Phase 1B should be enrolled into Phase 2. We have started enrolling some patients in the U.S. and U.K. as well. I anticipate we could fully enroll for DRAGON 2 by Q2 next year.

Operator, Operator

Our next question comes from Yi Chen with H.C. Wainwright. Please proceed.

Yi Chen, Analyst

Thank you for taking my questions. My first question is for the PHOENIX trial. This trial has enrolled more than 280 subjects. Could you tell us whether these subjects have similar baseline characteristics compared to subjects enrolled for the approved GA therapy, which are the complement inhibitors? Thanks.

Tom Lin, CEO

I'll refer this to Hendrik. Nathan, you can add on the baseline characteristics.

Hendrik Scholl, Chief Medical Officer

This is about geographic atrophy, which is typical GA. Patients would have drusen and a thickened Bruch membrane, leading to trouble seeing in the dark. When it comes to specific inclusion-exclusion criteria, compared to trials run with injectables targeting C3 or C5 in the complement system, the main difference is that the lesion size we are targeting is somewhat smaller than that of the injectables. That is the only obvious main difference between the two larger trials and the PHOENIX trial, which targets retinal decomposition in the RPE.

Yi Chen, Analyst

Doctor Scholl, in your experience, should patients with smaller lesion sizes find it easier to observe efficacy in terms of slowing lesion growth compared to patients with larger lesions at baseline?

Hendrik Scholl, Chief Medical Officer

That's not so easy to say. When smaller lesions are targeted, there will be a subpopulation where the fovea has not been reached by atrophy. When the drug becomes available on the market, those patients may benefit the most because they could save vision. When atrophy encompasses the foveal center, significant vision loss typically occurs, often reducing vision to a level of 20/100 or lower. For patients, it’s difficult to experience progression when vision worsens at a slower pace. Physicians can measure atrophy progression precisely and compare this with natural history data under therapy. Patients will understand that their vision will worsen but at a slower rate due to Tinlarebant, which they can verify through their physicians.

Tom Lin, CEO

To add, regarding lesion size, theoretically, the anti-complement inhibitors target the inflammation process. Nathan, perhaps you can elaborate on early and late-stage lesions in geographic atrophy.

Nathan Mata, Chief Scientific Officer

Yes. The lesions in the studies with injectables have higher inflammation driving their growth, hence their efficacy. In our cohort, there is less inflammation since the targeted lesions are smaller, meaning they are probably less involved with the fovea and less driven by inflammation. Our focus with Tinlarebant is on early-stage disease, where inflammation is less pronounced compared to the larger lesions seen in other studies.

Yi Chen, Analyst

Got it. Thank you for that clarification. And for the interim analysis of the PHOENIX trial, is it just a DSMB meeting, or will there actually be some efficacy readout?

Tom Lin, CEO

Yes, it would be a DSMB meeting; I don't believe the ethics will be involved.

Operator, Operator

Our next question comes from Michael Okunewitch with Maxim Group. Please proceed.

Michael Okunewitch, Analyst

Hey, guys. Thank you for taking my questions today. First off, could you talk a bit about DRAGON 2 and whether you expect it to be required for an FDA filing, or could you file for Stargardt with DRAGON 1 alone?

Tom Lin, CEO

We've discussed with the FDA, and they indicated it will be a review issue. The DRAGON 2 study is primarily for our Japanese filing due to the SAKIGAKE designation. However, it could serve as a second well-controlled study if necessary.

Michael Okunewitch, Analyst

Alright. Thank you. And to follow up on the previous question, given the differences in your target patients for the Phase 3 PHOENIX study in GA, do you expect a segmented strategy? Or will you pursue a broader label that competes with injectable complement inhibitors?

Tom Lin, CEO

I believe we have a broader label, and it's certainly an oral treatment that offers convenience compared to injections, as not many people want to get a needle in the eye.

Michael Okunewitch, Analyst

Yes, certainly. One last question for me. I'd like to touch on Alkeus in geographic atrophy earlier this year. You both target a similar pathway, but could you discuss differences and where Tinlarebant could be better positioned for success?

Tom Lin, CEO

Nathan is the best person to answer this question.

Nathan Mata, Chief Scientific Officer

Yes, there are similarities, but also significant differences. The key difference is in how we approach vitamin A. With Tinlarebant, we lower vitamin A, reducing the accumulation of toxic all-trans-retinal, which is more harmful than the bisretinoids. Our method aims to make broader reductions across the visual cycle, while synthetic vitamin A treatments increase all-trans-retinal levels. Thus, we aim for a more favorable toxicity profile compared to other strategies.

Michael Okunewitch, Analyst

Thank you very much for taking my questions today.

Nathan Mata, Chief Scientific Officer

Thank you.

Operator, Operator

This concludes our Q&A session. I will turn it back to Tom Lin for closing remarks.

Tom Lin, CEO

Thank you all for joining our call. We'll be in San Francisco during the J.P. Morgan Healthcare Conference week in January. We hope to see some of you there, introduce you to Dr. Scholl, and have a great day. Thank you very much.

Operator, Operator