Belite Bio Inc Q1 2023 Earnings Call

Tom Lin: Joining me today is our CSO, Nathan Mata, who will be updating our recent clinical trial progress, and our CFO, Hao-Yuan, who will be updating our Q1 financial results. For those that are new to Belite's story, the company is developing a novel oral once-a-day treatment that potentially slows disease progression in Stargardt disease and geographic atrophy in dry AMD. There is still a significant unmet need for both indications, as currently there is no approved treatments for Stargardt disease, and there are currently no approved oral treatments or no approved non-invasive treatments for geographic atrophy, which is predominantly in an elderly patient population. We are currently in global Phase III for both indications, and so far, we have been granted Fast Track designation, Rare Pediatric Disease designation, and Orphan Drug designations.

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.

Tom Lin: As mentioned, we are currently in Phase III development, and we have composition of matter patents until at least 2035, with patent term extension and new patents to be filed, which will take us well into the 2040s. We still have a very long patent life on this drug. For the Stargardt indication, the Phase III is already two-thirds enrolled, with estimated interim readouts by mid-2024. We've also just recently presented very promising 18-month treatment results from our Phase II, which our CSO will be presenting the results later on. We also expect to have the 24-month final data readouts for the Phase II study in Q4 this year. For the geographic atrophy in dry AMD indication, the Phase III is expected to start enrolling subjects in mid-2023. Now I'd like to pass it on to our CSO to give an update on our clinical trials.

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.

Tom Lin: Nathan?

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.

Nathan Mata: Thanks, Tom. Hello, everyone. I'm Nathan Mata. As Tom mentioned, this is an oral once-a-day treatment. The drug is called Tinlarebant. This drug is a retinol binding protein 4 antagonist. Our approach is to use this drug to limit the delivery of retinol to the eye as a means of reducing the toxic bisretinoids, vitamin A by-products, that have been implicated in disease progression in both Stargardt disease and advanced dry AMD. In both these studies, we are trying to slow the growth rate of retinal lesions. That is the FDA primary accepted endpoint for both Stargardt disease and geographic atrophy. What you're looking at in front of you are the trial design overviews for our ongoing open-label phase II, where I'll share some 18-month data with you.

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.

Nathan Mata: In fact, we've had interim analyses at periodically six months throughout the study, and we published, or sorry, presented those data at international ophthalmology conferences, AAO and ARVO. We just recently presented the 18-month data at ARVO. You can see here the overview of the study, the Phase II outline, 13 subjects. These subjects came in with no atrophic retinal lesions, but they had very prominent autofluorescent lesions, which are the lesions that precede the atrophic lesion growth in Stargardt disease. These subjects came predominantly from Australia and Taiwan. It is an open-label study, as I mentioned, a two-year in duration. We're looking primarily at safety and tolerability. We've already established the optimal dose at 5 milligrams daily. In fact, that dose is effective to achieve the same pharmacodynamic response in both adolescent Stargardt patients and elderly healthy patients. I'll show you some of that data as we move forward.

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.

Nathan Mata: We're looking at the growth rate by an instrumentation called fundus autofluorescence photography. This allows us to visualize both the atrophic lesion, which of course we're trying to slow, as well as the precedent atrophic lesions, which are, as I said, precede the growth of atrophic lesions, and in fact, are where the bisretinoids are sort of residing. You can see the key inclusion criteria at the bottom. The Phase III study that we call DRAGON 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 at baseline, because again, this is a pivotal study. It will have a placebo control, and we need some reference point for the endpoint, which is, of course, slowing the growth of the atrophic lesions. Of course, this will be a global study, Stargardt being an orphan disease.

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.

Nathan Mata: Hard to find these subjects, especially since we're going after adolescent subjects, not adult subjects. Thankfully, the enrollment is going quite well at this point. You can see the randomization here, 2 to 1 favoring Tinlarebant, 2-year treatment duration with a 1-year interim analysis. Of course, we're looking at the same efficacy measures and safety measures as we looked at in phase II. 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 also put in a size stipulation for the lesion size. There is an upper end of the lesion, but that's not because Tinlarebant won't work with larger lesions. In a 2-year study, that gives us the best opportunity to observe a treatment effect versus placebo. Next slide, please.

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.

Nathan Mata: As I mentioned before, this drug targets retinol binding protein 4, which is the sole carrier for delivery of retinol from the liver to the eye. Important to note that this protein is not needed for retinol delivery to other tissues of the body because they don't require RBP4. They lack a receptor that the eye possesses in sufficient quantity. The eye has this dependence on delivery of retinol bound to RBP4. This is why this is a fairly direct, site-directed approach. You can see here that over periods of dosing in the ongoing phase II, up to 18 months, we're getting a sustained reduction of retinol binding protein 4 of at least 70% or more. The reason we target this particular dose is because of data from a precedent clinical study in geographic atrophy, where a different RBP4 antagonist was used.

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.

Nathan Mata: In those patients, those subjects, it was found that subjects who got to at least this 70% reduction or more had a slowing of lesion growth. I'll share that data with you as we move forward. As I mentioned before, this dose, daily dose, is 5 milligrams, and you can see here approximate 80% reduction, mean reduction of RBP4 throughout the treatment trial. There's no tachyphylaxis. That means rebounding of the pharmacodynamic effect. Next slide. I want to now share with you some of the lesion data from our 18-month open-label study, the phase II. Before we do that, I need to give you an orientation for what we're looking at. We're looking at 2 different lesion types. The first one you can see here on the left is known as a Questionably Decreased Autofluorescence Lesion. You can see the boundaries there outlined in blue.

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.

Nathan Mata: This is what ophthalmologists refer to it as QDAF lesion. It's visualized here, as you can see, as I mentioned, by fundus autofluorescence imaging. The important thing about these lesions is that they may be amenable to rescue because the tissue is not atrophic yet. It is simply filled up with all of these autofluorescent bisretinoid compounds, so it's on the verge of converting. If we get to it early enough, it's possible that we may be able to slow its conversion into dead retinal tissue. We'll talk about that more in a moment. Now as we transition to the right, you can see how that autofluorescent lesion converts into an atrophic retinal lesion. This is what ophthalmologists refer to as Definitely Decreased Autofluorescence. I refer to it as dead retina because that, in fact, is the indication of irreversible loss of photoreceptor cells.

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.

Nathan Mata: There's no coming back from that. 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 terms of a primary endpoint for efficacy. We look now to the literature to see if this data, the growth that we're seeing in our subjects, is comparable to or less than or greater than something that's published in natural history.

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...

Nathan Mata: We look at a recent study published by Georgiou in 2020, where they quantified in 53 adolescent subjects the growth rate of the aggregate, that is the DAF lesion, the autofluorescence plus the atrophic. They see a growth rate of about 0.7 millimeters square per year. When we do that same analysis in our cohort at 18 months and annualize the data, we see a growth rate of about 0.28 millimeters square per year. This represents approximately a 60% reduction in the growth rate of the aggregate retinal lesions, both the autofluorescent and the dead retinal lesions, again, compared to natural history. Next slide, please. We now look to comparisons versus ProgStar. If you're not familiar with ProgStar, this was an international effort by global retinal specialists and ophthalmologists to better characterize the natural history of disease progression in Stargardt patients.

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...

Nathan Mata: They looked at both adolescent and adult patients, but it was skewed more heavily towards adults. What we have in our cohort, our phase II cohort, are subjects that are 18 years or less, and they have no DDAF at baseline. Well, it turns out subjects with that exact baseline characteristic were present in the ProgStar cohort. When we look at the growth rate of lesions, both the aggregate lesion, the DAF shown on the left, and the atrophic retinal lesion 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 millimeter square change of those retinal lesions per year. Then we compare that to our data shown in the red line here, the DAF lesion on the left, the DDAF lesion on the right.

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.

Nathan Mata: You can see if you look at the trajectory, there's roughly about a 50% reduction in the growth rate of the combined retinal lesion and separately the atrophic retinal lesion compared to ProgStar. In the previous study, we had a 60% reduction of growth compared to Natural History. 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 atrophic retinal lesion. In fact, the majority did not. Seven of 12 subjects did not develop any atrophic retinal lesions at the 18-month time point. That's roughly 60% of the cohort. Next slide, please. Now we're looking at the visual acuity data. We're very happy to see this. Actually, this shows a stabilization of vision.

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...

Nathan Mata: Most ophthalmologists who see adolescent Stargardt 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. Really there's nothing to be said with respect to BC other than we are stabilizing it, which is always a promising treatment trend. Next slide. We're talking about the safety data. Again, this is the 18-month safety data. We look systemically for AEs, of course, in these subjects because this is an oral drug. You expect there to be systemic side effects, but in fact, we see no systemic side effects whatsoever.

Nathan Mata: No severe or moderate drug-related AEs reported, no AEs requiring discontinuation from treatment, no clinically significant finding signs in relation to vital signs, physical exams, or cardiac health. Very important point. As I said before, this is a fairly site-directed approach. What we're 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 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 photoreceptors in your retina. Cone photoreceptors mediate bright light and color vision. When you stimulate them with bright light or color, they want chromophore.

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.

Nathan Mata: Because under our treatment regimen, that chromophore will only be slowly supplied to the photoreceptors, there's a delay in their timing to fill up, and they will misfire during this period and produce these transient hues of color in the visual field. In this case, yellow has been most frequently reported by our patients. You'll note, most of the subjects are reporting this as mild. No one's leaving the study because of it. Of course, it's transient, so it goes away after several minutes. The other manifestation that we're noting is delayed dark adaptation. Again, an accepted and anticipated feature of the treatment. This is mediated by rod photoreceptors, which mediate dim light vision. When patients transition suddenly from a very bright light to a very dim light, this activates rod photoreceptors. Of course, they'll need chromophores, just as cones would in the bright light.

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...

Nathan Mata: They don't get it, and they'll misfire 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 slow patients' transition from extremes of lighting environment. In the instance of chromatopsia, you slow your transition from the dark to the light. In the instance of delayed dark adaptation, you slow your transition from light to dark. This is particularly important for elderly patients in our GA study. Again, all these AEs are mild and well-tolerated. With respect to delayed dark adaptation, this is a manifestation of the disease process. Most patients can't even discern the pharmacological added delayed dark adaptation on top of their own intrinsic disease-caused delayed dark adaptation. Next slide, Hao-Yuan.

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.

Nathan Mata: I mentioned earlier that we had clinical proof of concept from a different retinol binding protein 4 antagonist. 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 to the eye reduce lesion growth rate in patients with either Stargardt disease or geographic atrophy? At that time, we didn't know much about Stargardt disease. There was no regulatory path toward approval. For geographic atrophy, there was. In fact, that study was easy to do because there were lots of patients available. The drug used is called fenretinide. This drug was chosen because although developed as an anti-cancer drug, it has a side effect of reducing retinol binding protein 4 in the circulation. Can you go to it quick, Hao-Yuan?

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.

Nathan Mata: As shown here, this is a synthetic retinoid. It was not designed as a retinol binding protein 4 antagonist. It was designed as an anti-cancer drug. I repurposed this drug in a phase II proof of concept study with 246 patients that had geographic atrophy, including a placebo control. There was placebo and two dosing arms, the 100 milligram arm and the 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, the placebo growth from baseline grew 50%. 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.

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.

Nathan Mata: There was a group of subjects that did not achieve a reduction of retinol binding protein 4 of 70% or more. Those subjects showed the same growth rate as placebo. In the 300 mg group, subjects who achieved at least a 70% reduction of retinol binding protein 4 or more had this profound reduction of lesion growth, approximately a 25% reduction over the 2-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. In the interim analysis, we noticed a treatment effect, and I wondered where did it go. I started looking at the pharmacodynamic data, and we saw that there was an inflection of retinol binding protein 4 upward at the 12-month point.

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.

Nathan Mata: A lot of these patients either stopped taking it or it stopped having a bioavailability effect in these patients. The other point I want to point out is that at the 12-month time point, when we look at the visual acuity loss, Hao-Yuan, 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 of retinol binding protein 4, they had a slowing right about the 12-month time point. They didn't lose any more than 6 letters. In the meantime, placebo and those patients in the 300 milligram group that did not achieve that large RBP4 reduction, they lost as much as 2 lines relative to the other group, the responding group. This is roughly a 2-line gain.

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...

Nathan Mata: It's approximated to that based upon looking at the difference between placebo and the treatment arm. We have a 25% slowing of lesion growth and a stabilization of vision representing a 2-line gain at the end of the study. As I mentioned before, it's unfortunate in this study, only one of every three subjects actually met this requirement for the retinol binding protein 4 reduction, and we believe that's due to largely the lower bioavailability of the drug. We ask 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 bioavailability exposure. The other problem was fenretinide is not very potent. It has the same potency for the target as does the native ligand retinol. Our drug, Tinlarebant, overcomes all of the negative aspects of fenretinide.

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.

Nathan Mata: First, it has much greater potency, 100-fold greater potency than fenretinide. 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 will be much more tractable for long-term chronic dosing in diseases like Stargardt disease and geographic atrophy. Speaking of geographic atrophy, let's talk about our phase III study design in GA. I mentioned earlier that the 5 milligram dose was effective to achieve the same pharmacodynamic response in both adolescent subjects as well as elderly healthy adults. You are seeing here a pharmacodynamic profile obtained from adults to match the higher BMI and higher age range of geographic atrophy patients.

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.

Nathan Mata: These volunteers took 5 milligrams daily, you see a very nice profound reduction of retinol binding protein 4 following the initial doses. It stays reduced during daily dosing until we withdraw the drug. We didn't show you that in the adolescent patients, it's true for them as well. When we withdraw the drug, the retinol binding protein 4 rebounds back towards the baseline, which is a nice effect to have the reversibility of the pharmacodynamic effect should there be any untoward effects with regard to safety or long-term dosing of Tinlarebant. Next slide. This is the clinical trial design overview for the phase III GA study that we call PHOENIX. This endpoint is going to be exactly the same in Stargardt disease. The duration is the same. Same primary endpoint, same imaging modalities.

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.

Nathan Mata: The only real difference between these two studies, of course, is the indication, that being GA versus Stargardt disease, and of course, the size. We're looking at approximately 430 subjects to be targeted. We're actually starting that enrollment this month and next month. This will be a global double-blind study. Same randomization as we saw in the phase III Stargardt study, 2 to 1, favorite to Tinlarebant rather. As I mentioned, 2-year treatment duration, looking at exactly all the same primary efficacy measures that we looked at in Stargardt. Of course, there'll be a 1-year interim analysis. With that now, I think I'll throw it over back to Hao-Yuan so he can talk about the Q1 2023 financial results. Hao-Yuan.

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.

Hao-Yuan Chuang: Thank you, Nathan. Thank you everyone for joining this earnings call. For Q1, on the income statement, our R&D expenses were $5.7 million, compared to $0.9 million for the same period in 2022. The increase was primarily due to an increase in expenses related to the DRAGON and the PHOENIX trial, and an increase in wages due to our R&D team expansion. Our G&A expenses were $1.2 million, compared to $0.2 million for the same period in 2022. The increase was primarily due to increase in professional service fee, insurance premium for D&O liability insurance, and wages. 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 had $37.8 million cash, and we expect this will take us to the end of 2024.

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.

Hao-Yuan Chuang: Now, just to recap, our key milestones include that we have initiated the PHOENIX study in Q1, we have announced the 18-month data from the Stargardt disease phase II on 25 April on ARVO. Currently, we have enrolled 58 subjects for the DRAGON study, and we expect to enroll the first patient for PHOENIX study around mid this year. In H2 2023, we expect to complete the Stargardt disease phase II study with the 24-month data, and we expect to complete the enrollment for the DRAGON study as well. In H1 2024, we expect to have the interim result for the DRAGON study. This concludes our earnings call presentation, now I would like to turn to Tara for Q&A. Thank you.

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.

Tara: Great. Thanks, Hao-Yuan. Please hold for a brief moment while we poll for questions. Our first question comes from Jennifer Kim from Cantor Fitzgerald. Please go ahead, Jennifer.

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

Jennifer Kim: Hey, good morning. Congrats on another quarter, and thanks for taking my questions. Maybe to start off with the DRAGON trial, the additional enrollment in those patients. I'm wondering, so far, can you break down where those patients are coming from in terms of the clinical trial sites and especially, I think it was 60 more patients this quarter, where are those patients coming from? 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 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.

Tom Lin: Sure. I'll take the first question, I'll let Nathan answer the second question. So far, the majority of patients are coming from Europe. Then with sites that just started in China about a few months ago. Given a large population in China, that recruitment has caught up pretty fast with Asian patients from Asia, especially from China. I would say the bulk of the studies so far, the enrollment so far from Europe, especially from the UK, Moorfields, was the top recruiter, and then from Asia and Australia. Nathan.

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.

Nathan Mata: Yeah. Sure

Tom Lin: DDAF visual acuity.

Nathan Mata: Yeah, in terms of loss of visual acuity in Stargardt subjects who have atrophic retinal lesions at baseline, it really depends on where that lesion is. Most ophthalmologists will tell you if it's a foveally involved lesion, you can expect about a line of loss that is five letters per year. Our subjects came in with foveally involved autofluorescence, which converted to atrophic lesions. They're having lesions essentially in the fovea, and yet we're having fairly stabilized vision. We believe that 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. We think that's why we're getting a stabilization. To answer your question, typically you see somewhere between five to six letters per year. Roughly about a line in these types of patients when they are foveally involved.

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.

Jennifer Kim: Okay, that's helpful. Thanks, guys.

Tara: Thanks for the question, Jennifer. Our next question comes from Tim Lugo from William Blair. Please go ahead, Tim.

Speaker 4: Thanks for the question, Jennifer.

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

Tim Lugo: Thanks for taking the question. Is the 24-month data expected to be at AAO? Is that the likely spot for the update?

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.

Nathan Mata: Yeah.

Tom Lin: Yeah.

Tim Lugo: I guess what are your expectations given the 18-month data for that update?

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

Hao-Yuan Chuang: I don't quite get that. I think you're breaking off a bit.

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

Tim Lugo: Oh, I'm sorry. Just what are your expectations for the 24-month data given the 18-month data? Are you just looking for stability and I guess improvements?

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.

Hao-Yuan Chuang: Nathan, you want to take it or I can do it.

Nathan Mata: Yeah, I can take that. 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 ProgStar. When you ask what we can expect, we're seeing a very linear trajectory. It's just a different slope than natural history. If you look at, for instance, I guess the DDAF would be a good example. The difference between natural history and our growth is, well, as I said before, about 50%. We expect to see this continue through 24 months, because imagine both of these lines just basically continued outward for another 6 months. Same thing with respect to DDAF. You see here an inflection downward at 12 months.

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

Nathan Mata: These are limited numbers of patients, but generally speaking, these are fairly linear growth rates, so we expect to see that linearity continue through 24 months. I expect that we will see the same treatment trend that is roughly a 50% difference in the growth rate at 24 months versus what we're seeing here in ProgStar. Again, we do have the 24-month data for ProgStar, so we know exactly what that looks like. We believe we'll be well under that.

Tim Lugo: Okay, understand. Since you have the 24-month data, and I'm sure you've shown this to us over the past few days as well as during these KOL calls, but can you remind us what the 24-month data looks like for ProgStar?

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.

Nathan Mata: Yeah, we haven't shown the 24-month ProgStar data yet. What I can tell you is that, again, if you just draw these lines out linearly, that's exactly what the 24-month data in ProgStar shows. You can expect another roughly a 0.2 millimeter square of growth on the DAF. The same thing could be said with respect to DDAF. Again, we'll show that when we're comparing the ProgStar 24-month data to our 24-month data. Right now, we have nothing to compare to, so it doesn't make much sense to show the ProgStar 24-month data. I can tell you it is quite linear, and during our KOL event with Hendrik Scholl, he did comment, in fact, that he sees very linear growth throughout time points up to 2 years.

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.

Tim Lugo: Fantastic. How long do you expect enrollment to last for PHOENIX?

Nathan Mata: That's a good question. Right now, 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.

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.

Tim Lugo: Understood. Thank you for all the questions.

Nathan Mata: Sure.

Tara: Thanks, Tim. Our next question comes from Yi Chen from H.C. Wainwright. Please go ahead, Yi.

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?

Yi Chen: Thank you for taking my questions. My first question is, does the FDA require a certain percentage of the patients in a DRAGON trial to be recruited from the US?

Nathan Mata: They don't have any guidance, Yi, 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. 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 III 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.

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.

Hao-Yuan Chuang: Yeah. If I may, I would like to add that we were not too worried about that given we're not like some of the studies, international study, that they have the majority of the patient or even more, or even 80%, 90% of the patient coming from one Asian countries. In our study, we do have the majority still come from Europe. We don't expect we'll have run into any problem instead of having too much focus on non-US countries or race.

Nathan Mata: That's a good point, Hao-Yuan. Thanks for mentioning, because after all, what the agency looks at is the races, right? 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 Stargardt disease, where not just the Stargardt disease, which as a whole is limited, but now we're going after adolescent Stargardt disease, which is even more limiting. The agency is willing to give us some leniency with respect to demographics because of that rarity of finding these patients.

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.

Yi Chen: Got it. At this point, is it safe to assume that the DRAGON trial could complete enrollment around mid-2023?

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

Nathan Mata: Probably by July.

Yi Chen: Yeah. Okay. Thank you. My next question is, you have the PHOENIX pivotal trial starting enrollment and together with DRAGON trial enrolling, how should we project the operating expenses going forward?

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

Hao-Yuan Chuang: Well, I would say, for the DRAGON study, I think the cost is probably around $15 to 20 million total. For the PHOENIX study, we're expecting something about $40 to 45 million total. Bear in mind, we don't need all those money on day one. It's going to be spread out in 3 to 4 years' time. We wouldn't have too much cash pressure in the first year.

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.

Yi Chen: Got it. Thank you.

Hao-Yuan Chuang: Thank you.

Tara: Thanks, Yi. Our next question comes from Bruce Jackson from Benchmark. Please go ahead, Bruce.

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

Bruce Jackson: Hi. Thank you for taking my questions. Wanted to ask a few follow-up questions about page nine, which we have up here on the screen right now. Can you tell us about the error bars on those lines? What do they represent? How are they calculated?

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.

Nathan Mata: That is simple standard error of the mean. Basically looking at the deviation about the mean.

Bruce Jackson: As we take those bars out to the 24-month time period, what would we see on the ProgStar line?

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.

Nathan Mata: It's going to be 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 at the 24 month. You're seeing roughly, there will still be, if we see a treatment trend as we're seeing here, there will still be a statistical difference, significant difference between LBS-008-CT02, our patients, and ProgStar. The standard deviations do not get any more large than they are here at 18 months for ProgStar.

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.

Bruce Jackson: Okay. Great. Then just one follow-up modeling question. Can we use the operating profile from the current quarter and kind of extrapolate that out for the next couple of quarters? Will the start of the PHOENIX trial have any impact on the back half of the year?

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.

Hao-Yuan Chuang: Well, for this quarter, we have higher expenses because when you start a new trial, you will have a down payment. Usually, you have some milestone payment that is subject to the achievement of, say, select the first site, getting the contract signed, getting the first patient screened, getting the first patient dosed, et cetera. Usually, you will have slightly higher expenses on the starting of a trial. I do not expect you can just times it four to get annual expenses. I do expect that the next three quarters will be lower than this quarter in terms of the income statement.

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.

Bruce Jackson: All right. Perfect. Thank you very much.

Hao-Yuan Chuang: Thank you.

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

Tara: Thanks for the questions, Bruce. Our next question comes from Yuan Zhi from B. Riley. Please go ahead, Yuan.

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

Yuan Zhi: Good morning. Thank you for taking our question, and thank you for the two recent KOL seminar. I have a layered question related to the assumption for your phase III Stargardt DRAGON trial. It would be helpful if you can summarize them for us. First, learning from ProgStar and your ongoing phase II program, do you expect lesion growth of DDAF in the phase III placebo arm to be slower or faster in the DRAGON trial? Based on your 18-month data, do you expect lesion growth in the phase III treatment arm to be slower or faster in the DRAGON trial?

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.

Nathan Mata: I think with respect to placebo in the DRAGON study, we hope to see what we're seeing here. We hope that these natural history data are going to be exactly what we get in a placebo group. I'll remind you that the slide prior to this, where we look at DAF in a separate study in 53 adolescent children, we saw a 60% difference. There was a reduction, 60% reduction in our growth rate compared to that natural history study. Here, we're getting a 50% reduction. Across two different studies with pretty large numbers of patients for adolescent Stargardt disease, we're getting pretty much the same treatment trend.

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.

Nathan Mata: I believe that what we'll see once we do our phase III, which is actually ongoing, that the placebo growth should look something like what we saw here in ProgStar as well as what we saw in Georgiou et al in 2020, because within those two studies, it's fairly the same. We expect that our group would be at least 40% to 50% better than that. Again, that's just based upon this limited data. If we are thinking optimistically, the placebo groups that are shown here and for natural history are looking consistent, and we hope that our treatment trend will be the same as we're seeing here. We haven't changed the dose. We haven't changed the patients. The only thing we really did is cap the upper end of the lesion size and require that all patients have DDAF at baseline.

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...

Nathan Mata: We asked this question just recently to an investigator KOL, would he expect to see a difference in our lesion growth in this study where we have DDAF versus in the phase II where we only had QDAF? As he mentioned, these are evolution of the same disease. The autofluorescent lesions turn into the atrophic lesions. If we can stop the growth rate of the combined lesions, what 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 DDAF lesion type as we're having on the conversion. We're looking both at conversion, but also what we're looking at right here is the growth rate of the incident DDAF lesions.

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.

Nathan Mata: This is basically looking like whatever patients had DDAF at baseline, let's call 12 months at baseline, what was that growth rate over 6 months and then annualize that. Based on these data, we are seeing a very positive treatment effect that we believe will be somewhere around 40% or 50% better than the growth rate in the placebo arm.

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.

Yuan Zhi: Got it. Thanks.

Tom Lin: Yeah. Just to add, bear in mind, Apellis varies somewhere between, like, 20%, I believe. Is it, Nathan? Around about 20%?

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.

Nathan Mata: That's about right.

Tom Lin: Yeah.

Tom Lin: Yeah.

Tom Lin: What we're seeing here is 50% to 60%. Even with half that, it's about 25%. I think if we are getting these treatment effects, I think we're very comfortable.

Nathan Mata: There will very unlikely be any risk for CNV conversion, as you see with the Apellis drug. Again, this is an oral once a day. It doesn't target anything but retinal delivery to the eye, whereas these drugs that Apellis and Iveric 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. We think our drug overall will be a much more safe approach, especially for long-term dosing, which is needed in Stargardt disease and geographic atrophy.

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.

Yuan Zhi: Got it. Thanks. That was a helpful color.

Nathan Mata: Sure.

Tara: Thanks, Yuan. This concludes our Q&A session. I'll now turn it back over to Tom for closing remarks.

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...

Tom Lin: Well, thank you, everyone, and we look forward to updating everyone on our next call. The next milestone, as Hao-Yuan just mentioned, that in Q4, we should have the phase II completion, the final analysis data, as well as completing enrollment for our phase III. Looking forward to that, and thank you, everyone. Thanks again. Bye-bye.

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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