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spk01: Thank you for joining us to discuss Beelight's third quarter 2023 financial results. Joining the call is Dr. Tom Lin, Chairman and CEO, Dr. Nathan Mata, Chief Scientific Officer, and Hao-Wan Zhang, Chief Financial Officer of Beelight Bio. Before we begin, let me point out that we will be making forward-looking statements that are based on current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. We encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Dr. Lin.
spk02: Thank you. Thank you for joining our reporting for the third quarter. I'm Tom Lim, CEO of Be Like Bio. Joining me is our CSO, Nathan, and CFO, Hao. I'd like to start off by giving an overview. So, Tadaraband is a novel once-a-day oral tablet designed to bind to serum retinal binding protein, or known as RPP4, as a means to specifically reduce retinal delivery to the eye. This approach is intended to slow or stop the formation of the toxic retinol derived by products which are generated in the visual cycle and are implicated in the progression of the Stages disease and geographic atrophy secondary to dry MD. We believe that early intervention directed at emerging retinal pathology, which is not mediated by inflammation, would be the best approach to potentially slow disease progression in stardust disease and geographic atrophy. There is still a significant unmet need for both indications, as currently there is no approved treatments for Stardust disease, and there are currently no approved oral treatments for GA, and we are already in Global Phase III trials for both indications. So far, we have been granted fast-track designation, rare pediatric disease designation, and orphan drug designation. We have several patent families and with composition of meta patents lasting until 2040 and with patent term extension and new patents to be filed, which we will have patent protection way past the 2040s. So we still have a very long patent life on this drug and we are already in late stage development. For Stargardt indication, the phase three is already fully enrolled with estimated interim readouts by second half of 2024. WE'VE ALSO JUST RECENTLY PRESENTED POSITIVE 24-MONTH TREATMENT RESULTS FROM OUR PHASE 2, WHICH NATHAN WILL BE PRESENTING THE RESULTS LATER ON. FOR GA IN DRY MD INDICATION, THE PHASE 3 IS ALREADY ENROLLING SUBJECTS. WITH THIS, I'D LIKE TO PASS THIS ON TO OUR CSO TO GIVE AN UPDATE ON OUR CLINICAL TRIALS. NATHAN?
spk00: THANK YOU, TOM. So I'd like to start by giving you an overview of our clinical trial designs in Stargardt's disease. I'd like to first start, however, just to orient everyone that it's important to note that the reduction of atrophic lesion growth rate as measured by retinal imaging is the FDA accepted primary endpoint for both Stargardt's disease and geographic atrophy. In Stargardt's disease, the atrophic lesion is called a definitely decreased autofluorescent lesion. Just keep that in mind. Whereas in geographic atrophy, it's simply referred to as atrophic lesion growth, but it is essentially the same thing. Back to the Stargardt trial design. There are two trials that, one we've recently completed and one that's ongoing, as Tom mentioned. The one shown on the left-hand side is our open-label Phase II Stargardt trial enrolling 13 adolescent subjects aged 12 to 18 years of age from Australia and Taiwan. This is a two-year study looking primarily at safety and tolerability. We had identified the optimal dose in a previous Phase Ib, that optimal dose being 5 milligrams daily, and I'll show you some of the pharmacodynamic data from that dose. We're looking primarily in terms of efficacy at the atrophic lesion growth, but in Stargardt's disease, we're also looking at a predecessor of the atrophic lesion growth, which is autofluorescent lesions that are referred to as questionably decreased autofluorescent or QDAF. In this phase two study, the 13 subjects enrolling only started with this early lesion type. They did not have atrophic lesions. So we want to measure two things in this study. One, The conversion time from the QDF lesion to the atrophic lesion, the DDF lesion, and then also once the DDF lesion is formed, we want to measure the growth rate of that incident DDF lesion. And I'll share some of that data with you in a moment. And you can see at the bottom there the key inclusion criteria, 12 to 18 years of age. All of these subjects have been both clinically and molecularly confirmed as having Stargardt's disease. The other study that we're doing in Starks disease is our pivotal phase three study called Dragon. This study, as Tom mentioned, has just recently completed enrollment at 104 subjects. It's important to note that all of these subjects in the phase three trial will have atrophic lesions at baseline because that's the only way that you can really measure the endpoint that is growth of atrophic lesion growth when you have it at baseline. So that's what we'll be doing in phase three. This is a global study. That's the only way we could get 104 subjects. In fact, this is the largest study in SARS disease in adolescent patients ever conducted. You can see the randomization there is two to one favoring to Larabant. It is a two-year study with the same efficacy endpoints that we're looking at in the phase two. We're also looking obviously at vision. We're looking at anatomic markers by spectral domain, optical coherence tomography, and we're looking at retinal sensitivity by microperimetry. At the very bottom there, you see the key inclusion criteria, very similar to the open label phase two, except we've expanded the age range another two years to go from 12 to 20 years of age. And we've also defined the upper size of the lesion at 7.62. So all of these subjects will have lesions that size or smaller. And you see there the BCA vision requirement of 2200 or better. With that, I'd like to go to the next slide and talk to you about some of the pharmacodynamic data I just mentioned earlier. What you're seeing here is a pharmacokinetic and pharmacodynamic profile of five milligrams tenlariband in those adolescent stargut subjects that were participating in the open-label phase two. The blue line shows the level of tenlariband in blood. And the red line shows our pharmacodynamic biomarker, retinal binding protein four. This is what the drug is hitting. And you can see here that there's a very nice correlation between the increase of tenlarabant in blood and the decrease of retinal binding protein four in blood until we withdraw the drug at month 24. And you see a very rapid reversibility over about 28 days of drug cessation. So we get about an 87% return that is of the baseline value at the end of study. But during study, we have approximately 80% reduction of retinal binding protein 4 in the blood. This is important to note because in a prior clinical study, not conducted with Teleribet, but a different RBV4 antagonist, we found that a dose of 70, sorry, a reduction of 70% or more of retinal binding protein 4 was effective to produce a slowing of lesion growth in patients with geographic atrophy. SO THIS HAS BECOME OUR TARGET THRESHOLD FOR RBV4 REDUCTION. WE WANT TO ACHIEVE AT LEAST A 70% REDUCTION OR MORE, AND HERE WITH A 5-MILLIGRAM DAILY DOSE, WE'RE ACHIEVING A MEAN 80% REDUCTION IN ALL SUBJECTS THAT HAVE BEEN DOSED. NEXT SLIDE, PLEASE. I MENTIONED TO YOU THAT IN THIS OPEN LABEL PHASE 2, OF WHICH YOU'RE LOOKING AT THE 24-MONTH DATA APP RIGHT NOW, THESE ADOLESCENT STARGRAPH SUBJECTS DID NOT HAVE ATROFIC LESIONS AT BASELINE, ONLY AUTOFLUORESCENT LESIONS. And we wanted to understand if we're actually having a treatment effect over 24 months of treatment. So what we did is we did a comparator study. We compared our data to data from the largest natural history study of Stargardt's conducted to date. That study is known as Prague Star. It was conducted over several years. involving 400 to 500 patients in these studies. Most of those subjects were adult Stargardt subjects. However, there was a subpopulation within that larger group of about 50 subjects that had the exact same baseline characteristics as our subjects in the open-label Phase II. That is, they were 18 years or younger, And they had no atrophic lesions at baseline. So this subgroup served as a nice apples-to-apples comparison for our analyses. And you're looking at them here on the left-hand side. What you're looking at is the growth of incident atrophic retinal lesions over the course of 24 months in each group. The ProgStar group is shown in blue, and our group, the Teleribet treatment, is shown in red. so neither group had atrophic lesions so we're measuring the time to the incident lesion growth and then we're measuring the growth of the incident of atrophic lesion over time and you can see that at every time point from six to 24 months we consistently have a lower reduction or sorry a lower ddf lesion growth compared to progstar such that by the end of this trial at 24 months we have a highly statistically difference between progstar growth and our growth that is our lesion growth being about 50 percent lower than what was published in the progstar studies this is phenomenal in fact has never been reported before the other important aspect of this study is among the subjects that we hadn't studied Five of them did not convert to any atrophic lesion. And that, again, is another important finding because it suggests that our drug is slowing the conversion of the early lesion type, the autofluorescent lesion type, to the atrophic lesion type. That's the first observation. The second observation being once those incident lesions are formed, we have a slowing of the growth rate of those lesions compared to natural history. So it's important to note that this phenomenon, what we're seeing, this slowing of lesion growth, is statistically significant at every time point that we've measured. And in fact, as I said before, has really never been demonstrated in another interventional treatment trial of adolescent Stargardt patients. Next slide, please. So now I'd like to show you our 24-month visual acuity data. What you're looking at is the visual acuity data from both the study eye, which is designated at baseline, and the fellow eye. This disease is a bilateral disease, so the disease will affect both eyes equally. And our drug, of course, is systemic, so it will affect both eyes equally. But what we're showing you here is both eyes. Just to show you, over time, we're getting stabilization of each eye of each patient over 24 months. This is significant because although this study was not powered for treatment efficacy against vision, it is important to see stabilization over 24 months because these subjects will, in fact, lose vision annually over time so the fact that we're slowing lesion growth and also stabilizing vision is a very important finding the other point i want to make is that visual acuity losses or gain within 10 letters is not considered clinically significant so what we have here really is potential test retest variability affecting these data so until you get outside of 10 letters there really is nothing clinically significant to say about the data but it's important to note that there's stabilization while we are in fact slowing lesion growth as i've showed you in the previous slide Next slide, please. Now I'd like to show you the drug-related adverse events. It's important to note that although this is a systemic drug, there have been no clinically significant findings in relation to vital signs, physical exams, cardiac health, or organ function. What we see are two anticipated ocular drug-related AEs that we would like to see because they're telling us we're having the intended biological effect on the retina. The first is a form of chromatopsia called xanthopsia. This is mediated by cone photoreceptors. This is a photoreceptor subtype in your retina, which confers bright light and color vision. So when subjects under our treatment transition suddenly from a very darkened environment to a bright environment, this activates cone photoreceptors. Cone photoreceptors will demand chromophore. Under our treatment regimen, that chromophore will only be slowly supplied to the cone photoreceptors so there'll be a delay in their timing to attain maximum bright light sensitivity during that time there will be an artificial and electrical produced hue of color in the visual field in this case yellow it can last seconds to sometimes a few minutes it's important to note that these subjects are reporting as mild and of course it's transient the majority of subjects have encountered this ae 10 of 13 but no one has left study because of them The other manifestation is called delayed dark adaptation. And this is mediated by another photoreceptor cell type called the rod photoreceptor, which confers dim light vision. So when subjects under our treatment transition suddenly from a very bright light to a very darkened environment, that activates rod photoreceptors. They will also demand chromophore to maintain dim light sensitivity. Under our treatment regimen, that chromophore will be slowly supplied. So there will be a period during which subjects will not have maximum dim light sensitivity. they will eventually gain it it's somewhere between eight to perhaps fifteen minutes delay but it will be attained this is not night blindness and once again you can see a high number of subjects having this this ae but nobody leaving study because of it because again it is mild it is transient and of course it's fully reversible So we believe this drug, 5 milligrams daily, is effective to achieve what we want in the retina with these very mild and well-tolerated AEs. It's also important to note that in our treatment overall, this has been very well-tolerated. Again, no systemic AEs and only ocular drug-related AEs, which we need to see as they are intended to have this effect on the retina. Next slide. I'll now show you our trial design for geographic atrophy. This is a phase three trial design. It's going to look very similar to our phase three trial in Stargardt's disease with two important exceptions. The indication, geographic atrophy instead of Stargardt's disease, and the number of patients, 430, to reflect the higher prevalence of GA in the population. Of course, it will be a global study, same randomization scheme as in the Phase III Stargardt trial, 2 to 1 favoring tenlariband, two years in duration. We're going to be looking at the same efficacy measures. Of course, here we're looking at atrophic lesion growth. It is the same as DDAF, but just named differently, but it is the same phenomenon. And of course, we're looking at visual acuity outcomes, anatomical outcomes by SDOCT and retinal sensitivity by microperimetry. And there will be an interim analysis at one year, as there will be in the phase three Stargardt trial. Next slide. With that, I'd now like to throw it back to Hao Yan so we can discuss the Q3 2023 financial results. Thank you. Thank you, Nathan. So in Q3, we had 8.7 million R&D expenses,
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