Belite Bio, Inc
Q4 2022 Earnings Call Transcript

Published: 3 Apr 2023

[Operator:]

Good afternoon and welcome to the Belite Bio 2022 Full Year Financial Results Conference Call. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. [Operator Instructions] As a reminder, this call is being recorded and a replay will be made available on the Belite website following the event. I'd now like to turn call over to Tom Lin, Chairman and Chief Executive Officer of Belite Bio. Please go ahead, Tom.

[Tom Lin:]

Thank you, Tara. Thank you, everyone, for participating in this earnings call. I'd like to take this opportunity to give you an update on our current overview and milestones. So, we're currently 18th month into a 24-month open label Phase 2 study, which we will be presenting that data at ARVO by the end of the month. At the same time, we are also halfway, we recruited 41 subjects out of the 90 subjects into our global Phase 3 Stargardt study and we are expected expecting interim readouts by mid-2024 next year. We recently met with the FDA to request that we increased the sample size from 60 to 90. The reason being that after analyzing very promising top line treatment data from our Phase 2, we ran some simulations and we worked out that if we increase the sample size to 90, we would have more data going to the interim. And that will give us a very good chance of meeting that growth rate we can for efficacy. We've also initiated our global Phase 3 trial in geographic atrophy secondary to dry AMD, which is expected to start enrolling subjects by midyear this year. So with the interim analysis, coming up for the Phase 2 18-month data, we feel that this will probably give a very good reference to what does data study will look out for our Phase 3. Okay. Next slide, please. So, the market opportunity is that, today there's still no treatment for Stargardt disease and currently there's about 30,000 subjects in -- 30 subset of patients in the U.S. with Stargardt and currently there’s no treatment. In terms of AMD, it is still a very large population globally and this is still arising given the aging population worldwide. As you can see on the graph on the right, the graph shows that with more advance age, the more advance the AMD gets. And at the stage of AMD, we know about the wet AMD, the market about $10 billion a year. But geographic atrophy, we expect this to surpass the wet AMD market. Even though there is the entire complements that are getting approved or patents that's approved, we still think that there's still a very good -- there's still an unmet need given there is still a noninvasive form of treatment such as oral therapies which we think would surpass the market for AMD. Next slide please. So I hand now to Nathan to go through the scientific slides.

[Nathan Mata:]

Thank you, Tom. Hello, hi, Nathan Mata here, CSO for the company. I want to talk about the mechanism of action of tinlarebant. Before I begin that, I want to preface by saying in both these diseases that we're interested in intervening Stargardt disease and geographic atrophy, they're both associated with the presence of binding byproducts which are toxic, and actually cause retinal cell death and tissue. These toxic byproducts are derived from circulating vitamin A. So what our approach is, is to reduce the entry of retinol into the eye as a means of reducing the bisretinoids, these vitamin byproducts that would call as retinal disease and thereabout our orally available once a day drug competes with native vitamin A retinol for binding to retinol binding protein 4 and reduces or limits the amount of retinol entering the eye. When this happens the bisretinoids which are formed from retinol also are reduced because there's a reduced amount of retinoids traversing through the visual cycle. In Stargardt disease, this is the primary culprit of vision loss in these patients is the formation of A2E and related bisretinoids. In geographic atrophy, these molecules accumulate as well, but for a different reason and from a different origin, it's because of a dysfunction of the retinal pigment epithelium. I'd like to now show you clinical presentations of what these diseases look like. On the top of a series of images, retinal photographs from a patient with Stargardt disease and then on bottom series of images, you have a patient with geographic atrophy. We're looking over about a similar -- same period of time roughly 4.5 years in each patient, which you can appreciate if you compare the baseline images to the last images at 55 or 57 months is that in both cases the auto fluorescent area you see around lesions, which are these bright areas of tissue you see in the surrounding, the lesion, they actually spawn the new dead retina. So wherever the autofluorescence is, that is where the lesions grow into. The autofluorescence expands centrifugally and the dead lesion, that black retina follows. So this tells us that the autofluorescence precedes lesion growth in patients with Stargardt disease and geographic atrophy and that an approach to reduce these bisretinoids by limiting retinol should be effective to preserve vision loss in these patients. Next slide, please. I'm showing now our clinical development pathway starting with our first patient population that is our adolescent Stargardt patients. This, of course, after conducting our requisite SAD and MAD studies, we established safety and tolerability of this drug. In the Phase 1b/2 study, we enrolled initially 11 Stargardt subjects and determined in those subjects in the one month Phase 1b that a 5 milligram dose was effective to drive the retinal vitamin protein level down to roughly more than 70% from baseline. We enrolled those subjects then into an open label two-year Phase 2, and we added two additional Stargardt subjects for a total of 13 subjects participating in the ongoing two-year study. I have one year data, safety and efficacy data to share with you today from this Phase 2 study. We also initiated, as Tom mentioned, begun recruiting for our Phase 3 adolescent Stargardt study. Out of a total of 90 subjects, we have recruited roughly 42 subjects to-date. This can be a randomized double-masked global study. Primary endpoint will be looking at the lesion growth rate. Secondarily, we will be concerned with our best corrected visual acuity. We are also now initiating a Phase 3 trial in geographic atrophy. This again will be a two-year study with a similar trial design that of Stargardt, in that the same endpoints are the same, same treatment duration and we will get interim analysis at one year, except this study will have 430 subjects randomized in the same manner as the Stargardt study with 2

[Hao-Yuan Chuang:]

Thank you, Nathan. So, in 2022 our R&D expenses increased $1.5 million from $7.4 million in 2021 to $8.9 million in 2022. The increase was primarily due to an increase in wages and salaries due to our R&D team expansion and increased share-based compensation expenses. Our G&A expenses increased by $1.6 million from $2.4 million in 2021 to $4 million in 2022, which was primarily due to an increase in professional service fees and also an increase of our D&O insurance expenses and increase of wages and salaries. In terms of cash, we received $38 million IPO net proceeds in 2022. And as of year-end of 2022, we have cash of $42.1 million, which can last until the end of 2025 and it's enough for us to complete our Phase 2 and Phase 3 Stargardt trial if we do not spend any money on GA. However, considering the promising data that we have seen in the prior time Phase 2 study, our old Phase 2 study and market potential of GA, we do want to start a GA Phase 3 trial with the limited contractual liability in certain countries that we've already received broad interest from the PI and the size, such as in the U.S. and Australia. And with that, we will have cash runway until end of 2024 and be able to complete Phase 2 Stargardt disease trial and obtain the interim result in Phase 3 Stargardt disease trial. And we expect to only expand GA study to more countries when we secure more funding. With that, I'll turn it back to Tom.

[Tom Lin:]

Thank you, Hao-Yuan. So the key anticipated milestones for the year. In Q1, we've initiated the PHOENIX Phase 3 study in GA. We've also enrolled 42 subjects into the DRAGON study. And I believe that by I think this month there's probably about 6 to 10 subjects that qualify for the study. And so that will bring you up to 50 by the end of the month. For Q2, we have an ARVO presentation that we will be presenting the 18 month treatment data for the Phase 2 for Stargardt disease. And shortly after that we have a KOL event to discuss this 18-month Phase 2 efficacy and safety data for Stargardt disease. We also expect to initiate enrollment for the PHOENIX Phase 3 study in GA by late Q2. And then in the second half of the year, we'll have the top line 24-month Phase 2 treatment data, which will be expected efficacy and safety data for the two-year study. We will complete the enrollment for the DRAGON study by the end of the year. Hopefully, we'll work -- with the recruitment rate picking up, we should be able to reach that target enrollment by the end of the year. With this, this ends my presentation and I hand it off to Tara to moderate the Q&A.

[Operator:]

[Operator Instructions] So our first question comes from Basma Radwan from SVB Securities. Please go ahead, Basma. Basma, you might be on mute? All right. We'll go to the next question. So our next question comes from Jennifer Kim from Cantor Fitzgerald. Please go ahead, Jennifer.

[Jennifer Kim:]

Hi. Thanks for taking my question, and this is very helpful update. And thanks for that. I have a few questions here. First, I know you talked about the reasoning for increasing the size of the Stargardt trial to 90. I just want to clarify, is that to increase the probability for a successful outcome in the study overall? Or is this thinking that it could increase the probability of a positive readout at interim? And then related to that, does the mid-2024 interim assume -- I know you said enrollment completion by the end of the year. But can you remind me of that mid-2024 interim, is that a one year interim readout based on the total patients? Thanks.

[Tom Lin:]

Yes. So thanks, Jennifer. So the first question was on -- sorry. You asked three questions over there. The first question -- what was the first question, may I ask?

[Jennifer Kim:]

Just the rationale behind increasing size of trial, yes.

[Tom Lin:]

That's right. Yes. So it's actually for both. So number one, that increases probability for interim. And for the final, if we missed out on the intro, but we still have a positive trend that gives us a pretty good opportunity for the final analysis as well. So actually, it's for both.

[Jennifer Kim:]

Okay. And then the timing of the interim in mid-2024. How does that work with -- so is it the enrollment completion is year end, and then the interim...?

[Tom Lin:]

Yes. So we would have majority of the patient completing 12 month by that time. I know some patients will be in the six month -- will be six month. But the first quarter or 1/3 of patients would have 18 month data by then. So on average, we will have 12 month data, majority of patients, yes.

[Jennifer Kim:]

Okay. Great. And then my second part of the question is for PHOENIX. Is there a way we can think about, I guess, the pace of enrollment when you start out in those specific targeted countries? And then how that will ramp up once you, I guess, expand into other sites? Or in terms of numbers, like, is there a way to think about that?

[Tom Lin:]

Yes. So we started off in Europe, recruiting patients in Europe. So the first batch or the bulk of patients come from Europe.

[Nathan Mata:]

So she is asking about PHOENIX. So it's a GA study, not a Stargardt.

[Tom Lin:]

Oh, sorry. Sorry. So what's the question again? Regarding GA study?

[Jennifer Kim:]

Since the GA study, I think you said you'll target enrollment in specific countries and sites. And then later down the line, you'll expand it to other sites. So is there a way to think about, yes, enrollment before and after?

[Tom Lin:]

So we started -- so it’s a global study, right, where we are starting with U.S. And then we will look ourselves to go hopefully to other sites as we complete our financing. So we can have open about 50 sites globally.

[Jennifer Kim:]

And then of those 50 sites, how many sites come from I guess that first -- those first steps into enrollment?

[Tom Lin:]

I think it's evenly spread. I don't have the list of sites right here in my hand, but I think its evenly spread between U.S., Europe and Asia.

[Operator:]

Our next question comes from Lachlan Hanbury-Brown from William Blair.

[Lachlan Hanbury-Brown:]

This is Lachlan for Tim Lugo. We noticed that you've recently increased the upper age limit for enrollment from 18 to 20 years in DRAGON. I was just wondering if you could talk about the rationale for that, I guess also the rationale for how you chose the original age bracket of 12 to 18 and then why you've expanded that?

[Tom Lin:]

Yes, so -- Nathan, you want to take the question?

[Nathan Mata:]

Yes. Let me just go ahead and take that. So initially, Lachlan, the age range was really sort of capped off by the ODD designation and the Rare Pediatric Disease designation because they categorize adolescents of up to 18 years of age. And so for those designations, we kept that age restriction above for the Phase 2, the open label Phase 2. But after going to the agencies of ODD and the RPD office, we found out that as long as you don't completely transition outside of your adolescent patient range to just primarily get adults and try to get an indication for adults, then you're fine, you still have the ODD status. So the real rationale for going to the -- adding the 19 and 20 years is from investigators that have reached out to us and told us that they have searched at their sites that would meet all qualification criteria for inclusion, except the age range. So we wanted to do two things. One is to satisfy these investigators and get those patients into study. And two, it helped us reach that additional 30 subjects we wanted to get to, to go from 60 to 90 and it didn't hurt any of our orphan drug or RPD designations in the FDA or EMA.

[Operator:]

So our next question comes from Yi Chen from H.C. Wainwright.

[Yi Chen:]

Just to clarify, could you give us some additional coloring on the enrollment criteria in terms of lesion size QD versus DD in the Phase 3 Stargardt disease trial? And also, could you give us the same for the upcoming GA Phase 3 trials as well in terms of enrollment criteria of the lesion size?

[Nathan Mata:]

Yes. Good question, Yi. Thank you. I will go ahead and take this. So for the Stargardt disease study, actually for both studies, what we know, again, based upon prior clinical experience is that lesions above a certain size and that roughly is greater than 10 millimeter square, are not that responsive to this type of treatment. We knew that from the fenretinide study. We also knew that from the recently failed tinlarebant study with a mix of stat where they found that their Stargardt disease patients didn't have any treatment effect. But when they did, a post-hoc study looked at patients that came in with smaller lesions at baseline, they had a 40% treatment effect. So we know and there's other published data that show that lesions that are larger, grow slower. I know there's some contention in the field about if that's actually the truth, but I'm convinced by the data I've seen in the literature that larger lesions whether you have Stargardt disease or you have geographic atrophy, they just grow slower. So we're capping off the lesion a small size of 0.05 millimeter square and the upper size would not be any greater than 8 millimeter square. Those will be the size ranges for DDAF lesion. We have no requirement for QDAF lesion size whatsoever.

[Yi Chen:]

Okay. So are the patients in the ongoing Phase 2 trial -- is the requirement the same for the patients in ongoing Phase 2 trial and the Phase 3 DRAGON trial?

[Nathan Mata:]

No. In fact, that's one of the big differences is that those adolescent Stargardt subjects in Phase 2 did not have any DDAF lesion at baseline. And we're sort of -- again this was more proof-of-concept. So we want to see if our drugs have an effect on the conversion from the autofluorescent to the DDAF lesion and also, what is the growth rate of the lesion once it actually happens. In Phase 3, these subjects will be required to have a measurable DDAF lesion of at least 0.05 millimeter square in order to enter the trial, again, because we have to have a baseline measure of atrophy as a sort of a reference point to measure subsequent lesion growth.

[Yi Chen:]

I see. And what's the requirement for the dry AMD patients?

[Nathan Mata:]

It’s going to be the same lesion size range.

[Operator:]

Our next question comes from Bruce Jackson from Benchmark.

[Bruce Jackson:]

I have a follow-up question on the PHOENIX trial, the Phase 3 for AMD. You're going to start enrolling during Q2. How long do you think it's going to take to enroll 430 subjects?

[Nathan Mata:]

So my prior experience tells me 18 months to 24 months.

[Operator:]

Our next question comes from Yuan Zhi from B. Riley.

[Yuan Zhi:]

Thank you for taking our question. I have three of them. First, Nathan, can you share additional color regarding the change of enrollment for Stargardt disease? What was the assumption you used for the statistical analysis?

[Nathan Mata:]

Yes, so for that, you mean for the initial 60% or 60, that one?

[Yuan Zhi:]

Yes, so from 60 to 90 patients, and you mentioned that the interim analysis will have a better chance to reach statistical significance.

[Nathan Mata:]

Right. So when we initially targeted 60 patients for enrollment, the treatment effect that was postulate, there was a 35% treatment effect. We felt that was a little bit too robust, given, so -- even though we saw very positive data at six months and one year, what we wanted to do was really compare and be more conservative. And so we used the treatment effect that we saw from the Stargardt -- sorry, from the Phase 2 GA study, which is roughly about a 25% treatment effect. So with that treatment effect, a lower treatment effect again being more conservative and optimistic, even though we believed we're going to have something greater than that, we wanted to power our study with much greater power. And so we posited a lower treatment effect, which of course triggered a higher sample size, a larger sample size to meet the power of at least 80% with 90% confidence, and, of course, an alpha of 0.05.

[Yuan Zhi:]

That's very helpful. And the second question. Hao-Yuan, can you run us you're thinking around the strategy to develop GA programs?

[Hao-Yuan Chuang:]

Well, I think in terms of the strategy, we will be more looking for our income result on the Stargardt trial, and then we will be open to maybe find a partner for this entire pipeline. I think it's going to be art that you separate the two indications in Stargardt, remains the same drug. So it more likely does -- if we find a partner, they're going to take over both indications. And I think for the potential of the second GA trial, that probably will be run and paid by that pharma.

[Yuan Zhi:]

Got it. And my last question is regarding the FDA's usual requirement announcing safety. Can you remind us, how many patients are required to be enrolled in the Phase 3 trial for GA, of course, adjusted by the duration of treatment?

[Nathan Mata:]

So this question is really a on a case-by-case basis. The hard sort of log if you will that the FDA takes, is they have a hard requirements for the safety database. So they are required for a safety database which is really the only requirement you have to have in addition to showing statistical significance in your trial. So the safety database that agency wants at least 300 subjects at or above the intended clinical dose for at least one year. And that doesn't mean, it has to be your indicated patients. They can be any patients with any ophthalmic disorder just as long as they have some ophthalmic disease. So you can use those patients to establish a safety database. In terms of what you put into your Phase 3, the agency does not ever opine that maybe you don't have enough or maybe you have too little -- or sorry too much, because it really is a sponsor's decision. You have to understand what the agency is looking for in terms of statistical significance and the safety database. So those are the two requirements that we look to, and everyone should know that we are a very cautious and conservative company. All of our trial designs are vetted before the agency in Type C meetings, before we solidify and move forward towards recruiting.

[Operator:]

Great. Thanks for the questions, Yuan. This concludes the question-and-answer session for today's call. I'll now turn it over to Tom for closing remarks.

[Tom Lin:]

Thank you, everyone. Thank you for your time and your interest in the Stargardt and AMD program. We will look forward to everyone, keeping up to-date with our data, of our presentation at our KOL meeting. Hao-Yuan, and [Tara] will send out the invite and the information regarding these two events. And thank you again. Thanks.