Earnings Call Transcript - BLTE Q2 2022

Operator, Operator

First Half 2022 Financial Results Conference Call. After today’s presentation, there will be an opportunity to ask questions. Please note, this event is being recorded. Yesterday, Belite Bio issued a news release announcing the company’s financial results for the first half of fiscal 2022, which is available on the company's investor relations website. Additionally, the presentation has been uploaded to the event section of the same website. If participants joining via webcasting find that the slide presentation is not synchronizing, please refresh the webpage and make sure to click on the play icon at the bottom left corner. Alternatively, please visit the event section of our investor relations website to view the presentation. I’d like to remind you that the statements we are about to make today may include statements relating to Belite Bio’s business plans and future prospects that are forward-looking statements as defined by the Private Securities Litigation Reform Act of 1995. These statements cover many events and matters that are subject to various risks that could cause actual results to differ materially from those expressed or implied in any forward-looking statement we make. I encourage you to review the forward-looking statement section included in our Form 6-K furnished on August 10th for a detailed description of the risk factors affecting our business that could cause those differences. Additionally, any forward-looking statement mentioned above represents our views only as of today, and we do not undertake any obligation to update any forward-looking statement except as required under law. Representing Belite Bio today are Dr. Tom Lin, CEO; Dr. Nathan Mata, CSO; and Mr. Hao-Yuan Chuang, CFO. I’d now like to turn the call over to Tom. Tom?

Tom Lin, CEO

Thanks, Chris. And thanks everyone for joining this call. I’m Tom Lin, CEO of Belite Bio, and I’d like to give a quick background on myself. I’ve trained in Medicine and Surgery and also did my PhD in Neurology, where my research focus was on developing treatments for neurodegenerative disease. For most of my career, I’ve led several novel drug developments in multiple therapeutic areas. And prior to founding Belite Bio and Lin Bioscience, I have led two startup companies to IPO. On this call with me today is our CSO, Nathan Mata; and our CFO, Hao-Yuan Chuang. Nathan, would you like to introduce yourself?

Nathan Mata, CSO

Sure. Thanks, Tom. Hello everyone I’m Nathan Mata. I am the Chief Scientific Officer for Belite Bio. My PhD is in neurobiology, and I have a Master’s degree in biochemistry as well. I’ve been in the biotech space for about 18 years. The majority of that, over 15 years, has been in ophthalmic drug development, specifically focusing on advancing therapies for neurodegenerative diseases, such as AMD and Stargardt’s disease. I’m credited with leading the development of the first RBP4 antagonist in advanced dry AMD and the first visual cycle modulator in both advanced dry AMD and Stargardt’s disease. I look forward to discussing more with you and showing you some of our data. Thank you.

Tom Lin, CEO

Hao-Yuan?

Hao-Yuan Chuang, CFO

Hi, everyone. Thank you for joining the call today. My name's Hao-Yuan. I have more than 10 years of capital market experience, including being an investment banker in Hong Kong for several years and also working for several Chinese conglomerates on their overseas listings and acquisitions. I also have an MBA from Columbia University. Thank you. Back to you, Tom.

Tom Lin, CEO

Thanks, Hao-Yuan. So the business highlights. Our goal is to deliver treatment for dry AMD and Stargardt disease, which are the leading causes of vision loss. AMD affects around 200 million patients worldwide, and Stargardt’s disease, being a rare disease, is the most common form of inherited retinal disease, affecting one in 10,000 children and adults. There is a significant unmet need and a large market opportunity, as there are currently no approved treatments for both these diseases. Our lead asset LBS-008 is in late-stage clinical development, and we have already started enrolling patients in our global Phase 3 study for Stargardt disease. We have also been granted fast-track designation, a rare pediatric disease designation in the U.S., and orphan drug designation in both the U.S. and EU for Stargardt disease. Upon a successful Phase 3, LBS-008 is also eligible for a priority review voucher, which vouchers have been sold for $80 to $150 million. The milestones to date include our completion of the Phase 1 trial in 111 healthy adults in both the U.S. and Australia. Currently, a two-year open-label Phase 2 trial is ongoing. We’ve presented promising six-month treatment data in May this year, with the 12-month treatment data expected to read out around October this year. The two-year double-blind Phase 3 trial has already commenced in the U.S., UK, Germany, Belgium, Switzerland, Hong Kong, Taiwan, and Australia, with several patients already enrolled. We expect to apply for enrollment in more jurisdictions and aim to enroll a total of 60 adolescent Stargardt patients globally. Moreover, the Phase 2/3 trial in dry AMD is also planned for the end of the year. We have a clear clinical development pathway toward approval, as the currently accepted primary efficacy endpoint for both Stargardt and dry AMD is well-known. Both the FDA and EMA have expressed a willingness to accept the slowing of lesion growth as the primary endpoint for approval. Another important point to mention is that we have a good idea of the level of RBP4 reduction required to achieve a treatment effect against lesion growth. The data I’m referring to comes from a Phase 2 proof-of-concept study led by our CSO about 10 years ago in advanced dry AMD patients treated with Fenretinide, an anti-cancer drug with some RBP4 antagonist activity. In that study, patients who achieved at least a 70% reduction in RBP4 had statistically significant slowing of lesion growth compared to placebo. From our Phase 1 study in healthy adults and our ongoing Phase 2 study in adolescent Stargardt subjects, we have identified the optimal dose to be a low dose of five milligrams that can achieve RBP4 reduction of over 70%. We’re also seeing very promising data from this Phase 2 study in adolescent Stargardt patients receiving five milligrams of LBS-008, which Nathan will present later on. Finally, we have a very strong patent portfolio with distinct patent families and IP protection until at least 2034 without patent term extension. We continue to file new patents. With that, I’ll now hand off to our CSO, Dr. Nathan Mata, to discuss the pathophysiology of Stargardt 1 and advanced dry AMD. Nathan?

Nathan Mata, CSO

Very good. Yes. Thanks, Tom. So first I’d like to outline the clinical trial design for our Stargardt studies. As Tom mentioned, we did a single ascending dose and multiple ascending dose in healthy volunteers. We then moved to our target patient population, which are adolescent Stargardt patients. We had 11 of those patients involved in a Phase 1b, where we confirmed that the five-milligram dose per day was effective to achieve at least a 70% reduction that Tom referred to, which I call the therapeutic threshold. We then added additional two patients, bringing our total to 13 participants in an ongoing two-year open-label Phase 2 study. There’s no placebo because it’s open-label. We’re primarily looking at safety, tolerability, and matching the dose with the reduction of retinol binding protein 4, along with ophthalmic assessments, such as lesion size growth as the primary measure. This is done by a parameter that ophthalmologists refer to as definitely decreased autofluorescence, so keep that in mind as I will reference it again. The precursor to DDAF is questionably decreased autofluorescence or QDAF. This leads to the lesion. I’ll show you some clinical data in a moment. The Phase 3 study will be very similar in design. It is the same patient population, but because it’s a pivotal study, there will be more participants, a minimum of 50 in this global study. As Tom mentioned, we already have patients enrolled in the UK and Europe. This is a double-blind, well-controlled study with a two-to-one randomization, meaning for every two patients receiving LBS-008, one will receive a placebo. This is a two-year study where we will look closely at safety tolerability and, more importantly, efficacy. The same efficacy measures and measurement modalities will be used. Now, I’d like to justify why we believe this treatment effect would be effective for both Stargardt’s disease and dry AMD. Next slide please. What you have here are two case studies. In the upper panel, you have retinal observations from a patient with late-onset Stargardt’s disease. In the bottom panel, you have the same data from a patient with dry AMD. These images were taken using fundus autofluorescence photography, which lights up the cytotoxicity caused by retinoids, implicated in the progression of both diseases. The hallmark feature of both diseases is the accumulation of vitamin A byproducts, called bisretinoids, that are highly cytotoxic but also fluoresce. As you look at the images from baseline to serially out to 12, 24, and 36 months for Stargardt’s disease, you’ll notice areas of blackened lesions, referred to as definitely decreased autofluorescence, indicating dead retina. Around that lesion tissue, which is irreversibly lost, there’s autofluorescence surrounding it, becoming prominent each year. In the dry AMD patient, there's a smaller, unifocal lesion, with surrounding autofluorescent areas. If you follow those areas out across the years, you will see that they eventually become lesions. By slowing the delivery of vitamin A into the eye, we aim to slow the accumulation of these compounds and thereby preserve vision. Next slide please. Now let’s focus on some clinical data from our ongoing Phase 2 study. We will start with safety data, specifically the Phase 2 results from the six-month interim analysis. These subjects have been receiving five milligrams of LBS-008 every day. We’re observing expected features, with chromatic aberrations like xanthopsia, which indicate that we’re seeing some effects on cone photoreceptors. There’s a mild and transient hue color that patients see upon waking or when transitioning from dark to bright light, which is expected. Delayed dark adaptation is noted, with a three to five-minute delay to accommodate to dim light environments, but it's essential to note that in most cases, definitely decreased autofluorescence was asymptomatic, as it’s part of the disease. Importantly, we reported no severe adverse events or significant findings concerning vital signs or cardiovascular health. Now on to efficacy data. Next slide please. We initially want to look at the distribution of change in QDAF in our subjects at six months. Remarkably, eight of 13 subjects showed a reduction or no change in QDAF. This is significant, considering that this disease is slowly progressive; it never abates or regresses. Seeing a reduction or stable autofluorescence is encouraging. Next slide please. We also need to focus on lesion growth. Only one of 13 subjects converted from an autofluorescent lesion at baseline to a retinal atrophy lesion at six months, with a growth of about 0.3 millimeters squared. Averaging across subjects, the mean lesion growth is far below the expected rate for this patient population, indicating a potential trend towards establishing our mechanism of action and efficacy. Next slide please. The best-corrected visual acuity revealed that eight of 13 subjects, or 62%, demonstrated no change or improvement in their vision, which aligns with the reduction in autofluorescence we observed. This correlation is encouraging and suggests a promising trend. So, at six months, we are observing signals of efficacy, and we look optimistically towards our next interim analysis at one year. With that, I’ll turn it over to Hao-Yuan to discuss the financial results for the first half of 2022. Thank you.

Hao-Yuan Chuang, CFO

Thank you, Nathan. On the income statement for the first half of 2022, we had R&D expenses of $2.5 million compared to $3.6 million for the same period last year. The $1.1 million decrease in R&D expenses is mainly due to having higher drug manufacturing and toxicology study costs last year for the preparation of our Phase 3 clinical trial. Regarding G&A expenses, the first half of 2022 was $1.1 million, which is about the same as the $1.2 million from the same period last year. The net loss for the first half of 2022 was $3.5 million compared to $4.7 million last year. The difference mainly arises from the decrease in R&D expenses. On the balance sheet, the majority of our total assets is cash, amounting to $48.7 million, with the increase primarily due to the IPO net proceeds of about $36.1 million. This concludes our presentation. Thank you for listening. We will now take questions if any, back to you, Chris.

Operator, Operator

Great. Operator, if you will, could you open up the call for questions from the phone dial-in?

Operator, Operator

Well, Chris, I have some questions from the webcast here. I think we can start with those?

Operator, Operator

Sure.

Operator, Operator

I think the first question I have here is when do you expect to release the first year data from the Phase 1b2 study? Tom, do you want to answer that?

Tom Lin, CEO

Yes, of course. We have patients in the Phase 2 studies that have already reached their 12-month treatment mark, and some data are coming in already. Between August and October, we expect the majority of patients to reach their 12-month treatment mark for the Phase 2. We anticipate having the majority of those data by October this year.

Operator, Operator

Thank you, Tom. The next question I have is, what is your commercialization plan, Tom?

Tom Lin, CEO

Well, at this moment, we still have about three years until the drug is approved, roughly around three years. During this time, we still have a lot to consider regarding the commercialization plan. Currently, we are open to partnerships and licensing with pharmaceutical partners.

Operator, Operator

Thank you. Operator, I think you can open up the line for the hand raise on the phone dial-in.

Operator, Operator

Certainly. Our first question comes from the line of Chaitanya Gollakota with H. C. Wainwright.

Unidentified Analyst, Analyst

Hey everyone. Congratulations. This is Chait on behalf of Lee Chen from H.C. Wainwright. I just have a few quick questions. Based on what you’ve seen so far from your Phase 2 study, what are your expectations for—? I know it’s a long way off, but what are your expectations for the pivotal Phase 3 study in STGD1 patients? Also, I know you spoke about 70% RBP4 reduction. Is that the minimum you need to see for any kind of lesion reduction? Or is that the amount you’re expected to reduce to see the target reduction essentially required for eventual approval? And also, as a quick follow-up, do you need two pivotal studies for an approval, or is just one sufficient? I have a few other follow-up questions after this. Thank you.

Tom Lin, CEO

Nathan, this is your expertise.

Nathan Mata, CSO

Yes. In terms of expectations, it's very straightforward. We expect to see what we are seeing now. You mentioned Phase 3, but let’s talk about Phase 2 first. At one year, if we see the same trends—reduction in autofluorescence, fewer patients converting to retinal atrophy, and preservation or improvement in vision—then I expect that will continue. Many things can happen between Phase 2 and Phase 3, but we have the same patients, same drug, same design, and same efficacy endpoints. I would be shocked if Phase 2 results differ substantially from Phase 3. Regarding the treatment effect and RBP4 reduction, from the bisretinoid study I led, a 69% reduction in RBP4 did not show a slowing of lesion growth. Therefore, it's clear that a 70% threshold is required for efficacy. Those with reductions below 70% did not experience any benefit in slowing lesions. In Stargardt disease, which has bisretinoids as the primary factor, I expect even better results than in advanced dry AMD. About pivotal studies, for AMD, you typically need two Phase 3 studies because of its prevalence. However, Stargardt’s disease, with a prevalence of one in 10,000, may allow for more leniency with regulatory agencies. If we conduct a robust Phase 2 and then follow with a strong Phase 3 showing efficacy trends, we could potentially justify a single pivotal Phase 3 for registration, provided we also include a post-marketing commitment to follow up.

Unidentified Analyst, Analyst

Excellent. Thank you. And last, do you have any comments on the competitive landscape? I know a few competitors have tried, but some have not been successful. Any comments on the evolving landscape in this space? And lastly, any color on the cash runway?

Tom Lin, CEO

Nathan, would you like to take that?

Nathan Mata, CSO

Yes, I can take the first portion regarding the competitive landscape. Currently, we see two main therapeutic approaches: late-stage therapies, including complement inhibitors for geographic atrophy and Stargardt’s disease, and early-stage treatments, which we aim to be. We don’t want to see lesions develop; our goal is to start treatment early enough to prevent that, specifically targeting autofluorescence in patients. Most Stargardt trials have focused on adult-onset disease, which is slower progressing. We focus on childhood-onset, which has aggressive progression. This early intervention strategy sets us apart, as we believe starting treatment while the eye is still healthy will yield better outcomes. Regarding cash runway, we expect our cash reserves to sustain operations until early 2025. By then, we hope to have completed our Phase 2 study and have at least interim results from Phase 3 trials, depending on the approval and enrollment speed. If we conduct a second Phase 3 for dry AMD, we will consider additional fundraising or licensing partnerships.

Operator, Operator

So operator, I think you can open up the next question.

Operator, Operator

Certainly. Our next question comes from the line of Bruce Jackson with The Benchmark Company.

Bruce Jackson, Analyst

Hi, good afternoon. Thank you for taking my questions. Most of which have been answered. With the dry AMD trial set to begin in Q1, are you still on target?

Tom Lin, CEO

Yes, we are currently about 80% to 90% done designing the study protocol. We are in discussions regarding the patient profile and target population. With that, we expect to initiate the Phase 3 study probably by the end of the year or the beginning of next year.

Bruce Jackson, Analyst

Okay, great. That's it for me. Sorry, I don’t have any more questions, but you guys are doing a great job. Thank you very much.

Tom Lin, CEO

Thanks.

Nathan Mata, CSO

Thank you, Bruce.

Operator, Operator

I have another question here from the webcast Q&A. What kind of criteria are you considering to select earlier dry AMD patients for the Phase 2/3 trial? Nathan, do you want to answer that?

Nathan Mata, CSO

Yes. There are two anatomical features we will focus on. First, we will look for reticular pseudodrusen. Their presence indicates impending disease progression. Second, we want to start with the smallest lesions possible. Previous studies have shown that larger lesions are less responsive to treatment. Our goal is to select patients with very early stages of advanced AMD with substantial autofluorescence but limited lesion size.

Operator, Operator

Thank you. Also, could you explain the mechanism of action of the drug again? Nathan?

Nathan Mata, CSO

Sure. LBS-008 is an RBP4 antagonist. It competes with Vitamin A for binding to retinol binding protein 4, which reduces the delivery of vitamin A to the eye. The eye expresses the RBP4 receptor, leading to a unique preference for uptake of vitamin A bound to RBP4. By knocking retinol off RBP4 with our drug, we effectively reduce the amount of vitamin A entering the eye. Other tissues are unaffected by this mechanism, making our treatment site-specific. By decreasing vitamin A levels in the eye, we reduce retinoid accumulation, notably the cytotoxic precursor bisretinoids like A2E, which have been linked to cell death in Stargardt disease and dry AMD. I hope that clarifies the MOA.

Operator, Operator

Thank you, Nathan. I don’t see any other questions here. Is there anything else? If not, we will conclude today’s earnings call. Okay. I’ll now send it back to Tom for closing remarks.

Tom Lin, CEO

Thank you everyone for listening to the call. We are excited to be listed on the NASDAQ and very pleased with the progress of LBS-008 in the clinic. We look forward to our upcoming data release in October, where we’ll discuss our one-year treatment results from the Phase 2 Stargardt disease trial. Have a great rest of your day. Thank you again, and we look forward to providing more updates on our progress.

Operator, Operator

Before we end today’s conference call, I’d like to remind everyone that this call will be available for replay via webcast about two hours after the event, lasting 30 days at the company’s IR website. Thank you for joining the call today. This concludes today’s conference call. You may now disconnect your lines.