Belite Bio Inc Q1 2023 Earnings Call

Speaker 1: And joining me today is our CSO, Ned Mehta, who will be updating our recent clinical trial progress, and our CFO , Haoyuan, who will be updating our Q1 financial results.

Speaker 1: They still as significant are made for both indications. As currently, there is no improvements for starvation disease. And currently, no improvements or no improvements for geographic atrophy, which is predominantly thin and elderly patient population. We are currently in color phase three for both indications. And so far, we have been granted fast-track designation, rapid pediatric disease designation and often tracked as nations. As mentioned, we are currently in phase three development, and we have composition of metapedence until at least 2035. And we have pattern term extension and new patterns to be filed, which will take us well into the 2040s. So we still have a very long pattern life on the strut. So for the starvation indication, the phase three is already 213-roll with estimated interim readouts by mid-2024. We've also just recently presented very promising 80-month treatment results from our phase two, which our CSO will be presenting the results later on.

Speaker 1: We also expect to have the clinical month-final data readout for the Phase II study in Q4 This for Phase II test early.

Speaker 1: For the geographic entropy in dry and V indication, the Phase III is expected to start in running subjects in May 2023.

Speaker 1: And now I'd like to pass it on to our CSO to keep an update on our clinical trials. Nathan, thanks Tom. Hello everyone, I'm Nathan Monter. So as Tom mentioned, this is oral Wednesday treatment. The drug is called Tim Lerovant. This drug is a retinobinine protein for antagonist. So our approach.

Speaker 2: is to use this drug to limit the delivery of retinol to the eye as a means of reducing the toxic retinoids, vitamin B byproducts, that have been implicated in disease progression of both Stargardt disease and advanced RIMD. So in both these studies, we are trying to slow the growth rate of retinal lesions. That is the FDA primary exception.

Speaker 2: presented those data at international ophthalmology conferences, A-A-O and Arvo. We just recently presented the 18 month data at Arvo. You can see here the overview of the study of the Phase II outline 13 subjects. These subjects came in with no atrophic retinal lesions, but they had very prominent autoflorescence lesions, which are the lesions that precede.

Speaker 2: the atrophic lesion growth in Stargardt's disease. These subjects came predominantly from Australia and Taiwan. It is an open label set as I mentioned at two year in duration. We're looking primarily at safety and tolerability. We've already established the optimal dose at five milligrams daily. In fact that dose is effective to achieve the same pharmacodynamic response in both adolescent Stargardt patients and elderly healthy patients.

Speaker 2: see the growth of H1 pleases and in fact are where the dysretinoids are sort of residing. You can see the key inclusion criteria at the bottom. The phase three study that we call drag-in is actually enrolling. We're up to about, I believe, 58 patients out of 90 that we're targeting. These subjects will all have DDAF baseline because again, this is a pivotal study. It will have a placebo.

Speaker 2: here 2 to 1 favorings in lyrmant, 2-year treatment duration was 1-year intraminalysis, and of course we're looking at the same efficacy measures and safety measures as we looked at in phase 2. The inclusion criteria are a little different. You can see there at the bottom. We've increased the upper age range to 20. We've increased, we also put in a size stipulation for the

Speaker 2: lesion size, so there is an upper end of the lesion, but that's not because Teleripat won't work with larger lesions, but in a two-year study that gives us the best opportunity to observe a treatment effect versus placebo. Next slide, please.

Speaker 2: So as I mentioned before, this drug targets retinal binding protein 4, which is the sole carrier for delivery of retinal from the liver to the eye. Important to note that this protein is not needed for retinal delivery to other tissues the body because the whole joint is a little tight.

Speaker 2: They don't require RBP4. They lack a receptor that the eye possesses in sufficient quantity. So the eye has this dependence on delivery of retinal bound RBP4. This is why this is a fairly site-directed approach. You can see here that over periods of dosing in the ongoing phase 2, up to 18 months, we're getting a sustained reduction of retinal binding protein form of at least 70% or more.

Speaker 2: you as we move forward. As I mentioned before, this dose, daily dose, is five milligrams and you can see here approximate 80% reduction, mean reduction of RB3,4 throughout the treatment trial. There's no tachyphylaxis, that means rebounding of the pharmacodynamic effect. Next slide.

Speaker 2: I want to now share with you some of the lesion data from our 18 month open label study, the phase two. But before we do that, I need to sort of give you an orientation of what we're looking at. We're looking at two different lesion types. The first one you can see here on the left is known as a quest complete decreased autoforescent lesion. You can see the boundaries there outlined in glue. This is what ophthalmologist referred to as QDAF lesion. It's visualized here.

Speaker 2: issue and we'll talk about that more in a moment. And now as we transition to the right, you can see how the autofluorescent lesion converts into an atrophic retinal lesion. This is what optimologically virtue has definitely decreased autofluorescence. I prefer to it as dendretna because that in fact is the indication of irreversible loss of photoreceptor cells. There's no coming back from that.

Speaker 2: So when investigators look at the growth rate, they look at it in a couple of different ways. One way is to look at the aggregate growth of both the autofluorescent and atrophic retinal lesions. That's referred to as decreased autofluorescence or DAF. Another way to look at the lesion growth is independently the autofluorescent lesion growth versus the dead retina growth. And of course the dead retina growth is what the FDA is most interested in in terms of a primary and...

Speaker 2: The EAS lesion, the auto-force, this plus the atrovic, they see a growth rate of about 0.7 millimeter square per year. When we do that same analysis in our cohort at 18 months and analyze the data, we see a growth rate of about 0.28 millimeter square per year. This represents approximately a 60 percent reduction in the growth rate of the aggregate retinol lesion is both the...

Speaker 2: an ophthalmologist to better characterize the natural history of disease progression in stargart patients. They looked at both adolescent and adult patients, but it was skewed more heavily towards adults. What we have in our cohort, our phase two cohort, are subjects that are 18 years or less, and they have no DDF at baseline. Well, it turns out, subjects with that exact baseline characteristic.

Speaker 2: We're present in the Progstar cohort. And when we look at the growth rate of lesions, both the aggregate lesion, the DAF, shown on the left, and the atrophic retinolision by itself on the right. We see the growth rate fairly linear. That's the gray or blue line you see. That's the Progstar data, roughly anywhere from about 0.8 to 1, a millimeter squared change of those retinolisions per year.

Speaker 2: 50% reduction growth compared to natural industry. Here we're seeing about a 50% reduction looking at both the primary endpoint measure as well as the aggregate lesion growth rate measure. Another important point to measure is that not all of these subjects converted to an atrial footprint lesion. In fact, the majority did not. Seven of 12 subjects did not develop any atrial footprint lesions at the 18-month time, but that's roughly 60% of the cohort.

Speaker 2: Next slide, please. Now we're looking at the visual acuity data. We have what we're very happy to see. This shows a stabilization of vision, most ophthalmologists who see adolescents, stargart patients, tell us that we should be seeing a more significant loss of vision just based upon the natural progression of the disease. Here we're seeing a stabilization. We're not losing any more than about three letters over 18 months, which is well within the test, retest variability of BCVA. So really there's nothing to be said with respect to BC, other than we are stabilizing it, which is...

Speaker 2: finding signs in relation to vital signs, physical exams, or cardiac health. Very important point. And as I said before, this is a fairly psych-directed approach. So what we are seeing are primarily two ocular drug-related adverse events which we want to see. These are anticipated features of the drug. And they tell us we're having the intended biological effect.

Speaker 2: on the retina. The first is a form of chromatopsia, which is an aberration of color vision. This happens when patients transition suddenly from a very dark environment to a very bright environment. This activates cone-fold receptors in your retina, cone-fold receptors mediate bright light and color vision. So when you stimulate them with bright light or color, they want chromophores.

Speaker 2: Most of the subjects are reporting this as mild. No one's leaving studying because of it. And of course it's transient. So it goes away after several minutes. The other manifestation that we're noting is delayed documentation. Again, it accepted an anticipated feature of the treatment. This happens, this is mediated by rod photo receptors which mediate dim-like vision.

Speaker 2: So when patients transition suddenly from a very bright light to a very dim light this activity is rod flow receptors. Of course they only come up for it just as cones would in the bright light. They don't get it and they'll miss fire during this period. They will not have their full dim light accommodation. So patients will wait several minutes before they can actually accommodate to that dim light. We have mitigating measures for both of these AEs. They simply are to...

Speaker 2: slow patients transition from extremes of lighting environment. So in the instance of chromatopsia, you slow your transition from the dark to the light. And in the instance of delayed documentation, you slow your transition from light to dark. This is particularly important for elderly patients in our GA study. But again, all these AEs are mild and well-polarinated with respect to the delayed documentation.

Speaker 2: from a different retinal binding protein for antagonists. I call this a surrogate molecule. I did this study when I was with another company approximately 12 years ago. Trying to answer the question, would reduction of retinal delivery T.I. reduce lesion growth rate in patients with either staggart disease or geographic atrophy?

Speaker 2: At that time, we didn't know much about StarGuard's disease. There was no clinical, sorry, regulatory path to proval, but for geographic atrophy, there was. And in fact, that study was easy to do because there were lots of patients available. The drug use is called fend retinine. This drug was chosen because of all no developed as an anti-cancer drug. It has a side effect of reducing retmo binding protein for toothpicks.

Speaker 2: atrophy, including a placebo control. So there was placebo and two dosing arms, the 100 milligram arm and a 300 milligram arm. I'd now like to show you the lesion growth data over the duration of that study. We're not showing the 100 milligram cohort because there was no treatment effect whatsoever. You can see in the black bars here, it's a placebo growth from baseline group.

Speaker 2: 50% so basically a 50% increase in this area of the size of the lesions in those patients that got the placebo treatment. In the 300-milligram group there was something very interesting. There was a group of subjects that did not achieve a reduction of retlo-binding protein for 70% or more. Those subjects showed the same growth rate as placebo.

Speaker 2: But in a 300 milligram group, subjects who achieved at least a 70% reduction of retinal binding protein 4 or more had this profound reduction of lesion growth, approximately 25% reduction over the two-year study. I do get often asked from time to time, how did we find out that this treatment effect occurred? Actually, at end of study, there was no treatment effect whatsoever. But in the interim analysis, we noticed a treatment effect.

Speaker 2: At the 12-month time point, when we look at the visual acuity loss, again, we see a stabilization in those patients who had a treatment effect against lesion growth. You can see here in those patients who had at least a 70% reduction or retinobining protein form, they had a slowing right about the 12-month time point. They didn't lose any more than six letters. In the meantime, placebo and those patients in the 300-milligram group, they did not achieve that large RPP-4 reduction. They lost as much as two lines relative to the other...

Speaker 2: believe that's due to largely the lower bioavailability of the drug. We asked this drug to be taken with a high fat meal. A lot of elderly patients don't want to comply with that. So we didn't get a lot of good bioavail exposure. The other problem was a fed retinitis is not very potent. It has the same prophecy for the target as does the native ligand retinitis.

Speaker 2: Our drug can layer back overcomes all of the negative aspects of fennelite. First, it has much greater potency, 100-fold greater potency than fennelite. Two, it has much greater bioavailability, so it's much more water soluble. Patients won't have to take this drug with a high fat meal. Thirdly, maybe even more importantly, it's not a retinoid, so it has a much cleaner safety profile and we much more...

Speaker 2: adolescent subjects as well as elderly healthy adults. You're seeing here a pharmacodynamic profile obtained from adults to match the higher BMI and higher age range of geographic atrophy patients. These patients are taking these volunteers to 5 milligrams daily and you see a very nice profound reduction of retinobinane protein for following the initial doses. It stays.

Speaker 2: or long-term dosing of to learn about.

Speaker 2: Next slide. So this is the clinical trial design overview for the phase 3G-A study that we call Phoenix. This endpoint is going to be exactly the same in Starter's disease. The duration is the same. Same primary endpoint, same imaging modalities. The only real difference between these two studies, of course, is the indication.

Speaker 2: that being G.A. versus Starter disease. And of course the signs. We're looking at approximately 430 subjects to be targeted. We're actually starting that enrollment next, actually starting this month and next month. This will be a global double blind study, same randomization as we saw in the Phase 3 Starter study, 2 to 1, to Larabat, a favorite to Larabat rather.

Speaker 2: As I mentioned to your treatment duration, looking at exactly all the same primary efficacy measures.

Speaker 2: that we looked at in Stargarts and of course there will be a one year interim analysis. So with that now I think I'll pull it over back to how Yen so we can talk about the Q1 2023 financial results. Thank you Nathan and thank you everyone for joining this learnings call. So for Q1 on the income statement our R&D expenses were 5.7 million.

Speaker 3: compared to 0.9 million for the San period in 2022. The increase was primarily due to an increasing expenses related to the dragon and the Phoenix trial and an increase in wages due to our R&D team expansion.

Speaker 3: Our GNA expenses were 1.2 million compared to 0.2 million for the San Pura in 2022. The increase was primarily due to increasing professional service fee, insurance premium for B&O liability insurance and wages.

Speaker 3: In total, our net loss was 6.9 million compared to a net loss of 1.1 million for the same period in 2022. As of the end of March, we have 37.8 million cash and we expect this will take us to the end of 2024.

Speaker 3: You know, just to recap, our key milestone include that we have initiated the Phoenix Study in Q1, and we have announced the 18-month data from the Starlight Disease Phase II on April on April 27th on Arvo. Currently, we have enrolled 58 subjects for the Dragon Study.

Speaker 3: and we expect to enrol the first patient for Phoenix study around mid this year. In the second half of 2023, we expect to complete their phase 2 STAGO-DD study within the 24 month data and we expect to complete the enrollment for the graded study as well.

Speaker 3: In the first half of 2024, we expected half the interim result for the Dragon Study.

Speaker 3: This concludes our earnings co-presentation and now we'd like to turn to Tara for Q&A. Thank you.

Speaker 4: Great, thanks, Hayeon. Please hold for a brief moment while we pull for questions.

Speaker 4: Door first question comes from Jennifer Kim from Canterfitch, Darrell. Please go ahead, Jennifer.

Speaker 5: Hey, good morning. Congrats on the other quarter and thanks for taking my questions. Maybe to start off with the Dragon trial, the additional enrollment in this patient's I'm wondering so far, can you break down where those patients are coming from in terms of the clinical trial sites? Let's get in.

Speaker 5: especially that I think is 16 more patients this quarter, you know, where those patients coming from. And then my second question, more just a general question. For BCVA loss over 18 months, I'm just wondering what kind of loss would one anticipate in patients with DDAF at baseline? Thanks.

Speaker 1: Sure, I'll take the first question. I'll let Nathan answer the second question. So so far the majority of patients are coming from I would say.

Speaker 1: The majority of patients coming from to Europe . And then we'll cite that just started in China about a few months ago and given a population last population in China, then recruitment has caught up pretty fast with Asian patients from Asia, especially from China. So.

Speaker 1: I would say the bulk of the studies so far in Robins so far from Europe , especially from the UK, more fields, was the top recruiter and then from Asia and Australia.

Speaker 2: Nathan, the... Yes, sir. Yeah, I'm sure you're kidding. In terms of loss of visual acuity in stargart subjects who have atrophic retinal lesions at baseline, it really depends on where that lesion is. So most ophthalmologists will tell you if it's an opopially involved lesion, you can expect about a line of loss that is 5 letters per year.

Speaker 2: Our subjects came in with foveally involved autofluorescence which converted to atrophic lesions. So they're having lesions essentially in the fovea and yet we're having fairly stabilized vision. So we believe if you look at some of the quantitative autofluorescence data, we believe that we are actually clearing some of the autofluorescence away from the fovea.

Speaker 4: Thanks for the question, Jennifer.

Speaker 4: So our next question comes from Tim Lugo from William Blair. Please go ahead Tim.

Speaker 2: Thanks for taking the question. In the 24 month data, expected to be at AAL, is that the likely start for the update? Yeah, I'm still high.

Speaker 6: I guess what investigation is given the 18 month data.

Speaker 6: What are your expectations given the 18-month data? For that, okay.

Speaker 1: So don't quite get that. I think you're breaking off a bit.

Speaker 2: I'm sorry. And just what are your expectations for the 24 month data given the 18 month data? Are you just looking for stability? I guess improvements. Nathan, you'll take it a little. I can do it. Yeah, I mean, I can take that. So if you look at the trajectory, I don't know if we can go back to slide nine to show the lesion growth data relative to prod star.

Speaker 2: When you're asking what we can expect we're seeing a very linear linear trajectory It's just a different slope than natural history So if you look at for instance, I guess the GDF would be a good example The difference between natural history and our growth is as I said before about 50 percent So we expect to see this continued through 24 months because imagine both of these lines just basically continued outward for another six months Same thing with respect to DDAF you see here reflection downward at 12 months

Speaker 7: under that.

Speaker 2: Okay, I understand. And since you have a 24 month data, and I'm sure you've shown this to us over the past few days as well as Jeremy is saying a lot of calls. But can you remind us what the 24 month data looks like? For prox. We haven't shown the 24 month prox start data yet. Because it will but I can tell you is that again, if you just draw these lines out.

Speaker 2: When we're comparing the prom starts 24th day to our 24th day, right now we have nothing to compare to so it doesn't make much sense to show the prom starts 24th day, but I can tell you it is quite linear and during our cable event with Hendrick Scholl. He did comment in fact that he sees very linear growth throughout time points up to two years. Fantastic.

Speaker 2: And how long do you expect enrollment to last for Phoenix? That's a good question. Right now, so we're just starting to enroll this month. I'm expecting it'll take at least a year with our strong network to start getting up to the 430 subjects, but potentially up to a year and a half. If things don't go our way. Understood? Thank you for all the questions.

Speaker 1: Sure. Thanks Tim. Our next question comes to the HN from HD Wainwright. Please go ahead, Yi. Thank you for taking my questions. My first question is does the FDA require a certain percentage of the patients in a directing trial to be recruited from the US?

Speaker 2: They don't have any guidance regarding the percentage or number of patients. They want some representation in the US. Typically what we do is after we've completed enrollment we will communicate with the FDA what our patient subject composition looks like. We have regular meetings with the FDA thanks to our fast-track designation we have that access.

Speaker 2: So they will be feeding back to us information with respect to demographics, but there is nothing in the guidance and nothing certainly in a regulatory statute that says you have to have x number of patients for an international phase three study to be considered for an NDA in the US. You have to have some US representation. The percentage on that is a little vague. Yes, and if I may, I would like to add that, you know, we were not too worried about that. If then, you know, we're not like.

Speaker 2: point how young thanks for mentioning because after all what the agency looks at is the races, right? So Caucasian. The European population represents the Caucasian race which is the predominant race in America. As long as there's some distribution of African American potentially Hispanic, they like to see that but you can't always get that particularly in Stardust disease where we're not just the Stardust disease which as well.

Speaker 8: to assume that the Dragon Trail Creek complete enrollment around mid-2023.

Speaker 8: Probably by July . Yeah. Okay. Thank you. And my next question is, so you have the Phoenix PIVOTL trial starting enrollment and together with Dragon trial enrolling, how should we project the operating expenses going forward? Well, I'll say for the Dragon study, the PIVOTL trial is not a

Speaker 3: within the cost of probably around 15 to 20 million total. For the Phoenix study, we expect something about 40 to 45 million total. But very might wouldn't meet all those money on day one. It's going to be spread out in three to four years time. So we wouldn't have too much of cash pressure on the first year.

Speaker 4: Thank you. Thanks, Yee. Our next question comes from Bruce Jackson from Benchmark. Please go ahead, Bruce.

Speaker 9: Hi, thank you for taking my questions. I wanted to ask a few follow-up questions about page 9, which we have up here on the screen right now. Can you tell us about the error bars on those lines? What are the represent and how are they calculated? That is simple standard error of the mean.

Speaker 2: So basically looking at the deviation about the mean. And then as we take those bars out to the 24 month time period, what would we see on the Prague Star line? It's going to be very, very similar. I know that it looks like they're getting larger. The standard errors, especially if you look at DAF, they don't get much larger. They basically stay about that same as a 24 month.

Speaker 2: So you're seeing roughly, there will still be, if we see a treatment trend as we're seeing here, there will still be a different significant difference between LBS, CTO2, our patients and Prague star. But the Sanity VH's do not get any more large than they are here at 18 months for Prague star. Okay, great. And then just one follow up modeling question.

Speaker 9: Can we use the operating profile from the current quarter and kind of extrapolate that out for the next couple of quarters or will the start of the Phoenix trial? Have any impact on the back half of the year? Well, for this quarter we have high expenses because when you start a new file, you will have like a down payment.

Speaker 3: starting of a trial. So I do not expect, you know, you can just times it for to get an annual, you know, annual expenses. I do expect that the next three quarters will be, you know, lower than this quarter in terms of income statement.

Speaker 4: All right, perfect. Thank you very much. Thank you. Thanks for the questions, Bruce.

Speaker 4: So our next question comes from Yan Zee from B. Riley.

Speaker 8: Please go ahead, Yang. Good morning. Thank you for taking our questions. And thank you for the two recent KOL seminars. I have a layered question related to the assumptions for your phase 3 Stargardt dragon file. It would be helpful if you can summarize them for us.

Speaker 8: So first, learning from FrogStar and your ongoing fits to program, do you expect lesion girls or DDAF in the fits three placeable arms to be slower or faster than the faster in the dragon file? And then based on your 18-month data, do expect lesion girls in the fits great treatment arms.

Speaker 2: in a separate study in 53 adolescent children, we saw a 60% difference as a reduction, since that reduction in our growth rate compared to that natural history study. Here we're getting a 50% reduction. So across two different studies with pretty large numbers of patients for adolescent Stargardt's disease, we're getting pretty much the same treatment trend.

Speaker 2: So I believe that what we'll see once we do our phase three, which is actually ongoing, that the placebo growth should look something like what we saw here in Prague Star as well as what we saw in Georgia in 2020 because within those two studies it's fairly the same. And we expect that our group would be at least 40 to 50 percent better than that. Again, that's just based upon this limited data, but if we are thinking optimistically, the placebo groups that are that are shown here in natural history are looking consistent and we hope that our treatment...

Speaker 2: of the same disease. So the autofloresial lesions turn into the atrophic lesions. So if we can stop the growth rate of the combined lesions that we're doing here and we're stopping the growth rate of just the atrophic lesion, which again you're seeing here versus natural history, then it goes to say that we will have the same effect on the DBA lesion type as we're having on the conversion.

So we're looking both at conversion, but also what we're looking at right here is the growth rate of the incident DDF lesion. So this is basically looking like whatever patients had DDF at baseline, let's call 12 months at baseline, what was that growth rate over six months and then annualize that. So based on these data, we are seeing a very positive treatment effect that we believe will be somewhere around 40 to 50 percent better than the growth rate in the placebo arm.

Yeah, I'll just add so be in mind. I've heard that I've raised somewhere between like 20% I believe is a nation around 20%. That's all right. Yeah, so what we're seeing here is 50 50 50 50 60%. Even with half that's about 25%. So I think if we.

are getting these treatment effects, I think we're very comfortable. And there will very unlikely be any risk for CNV conversion as you see with the Appellus drug. Again, this is an oral once a day. It doesn't target anything but retinal delivery to the eye. Whereas these drugs that Appellus and Ivaric are developing are anti-inflammatory agents, so they're very ubiquitous, so they have their actions.

pretty much everywhere, you will get off-target effects from those drugs. So we think our drug overall will be a much more safe approach, especially for long-term dosing, which is needed in Stargardt's disease and geographic atrophy. Thanks for the helpful comment.

from those drugs. So we think our drug overall will be a much more safe approach, especially for long-term dosing, which is needed in star-resonies and geographic atrophy. Fighting, thanks for the helpful color. Yes.

Thanks, Yan. This concludes our Q&A session. I'll now turn it back over to Tom for closing remarks. Thank you, everyone. We look forward to updating everyone on our next call and the next part is how I just mentioned that...

In Q4, we should have the phase two completion, the final analysis data, as well as completing enrollment for our phase three. So looking forward to that and thank you everyone. Thanks again. Bye bye.

Thanks for watching!

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