Hello, and thank you for joining us to discuss Belite Bio's recent announcement on its DRAGON trial. Joining the call today are Dr. Tom Lin, Chairman and CEO of Belite Bio; Dr. Hendrik Scholl, Chief Medical Officer; Dr. Nathan Mata, Chief Scientific Officer; and Hao-Yuan Chuang, Chief Financial Officer. Before we begin, let me point out that we will be making forward-looking statements that are based on our 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, and please note that you can submit questions throughout the call by clicking on the Q&A box at the bottom of your screen. We'll respond to questions following our prepared remarks. Now I'll turn the call over to Dr. Lin.
Thanks. Thanks, Judy. Good afternoon, and thank you for joining us on today's update call to discuss the interim analysis from our phase III DRAGON trial of Tinlarebant in adolescent Stargardt disease patients. I am pleased to share that the DSMB has completed its interim analysis based on all subjects having completed the one-year assessment period and recommended that the trial proceed without sample size increase or modifications, maintaining the sample size at 104 subjects. In addition, the DSMB recommended to submit the data for further regulatory review for drug approval based on strong positive outcome. For the DSMB review, completion of the trial is now on track for Q4 2025, including a three-month follow-up period. I'd like now to turn this to our CSO, Dr. Nathan Mata, to guide the interim analysis.
Thank you very much, Tom, and thank you, everyone, for joining the call today. Just a little bit of background about the drug. The drug is Tinlarebant. It is an oral, once-a-day, small molecule antagonist of retinol-binding protein 4. Retinol-binding protein 4 is the sole carrier for vitamin A delivery from the liver to the eye. The reason we're targeting this protein is because we've seen from clinical and non-clinical data that the accumulation of toxic byproducts of vitamin A is implicated in the disease progression of Stargardt disease in addition to geographic atrophy so we reason that because these byproducts are formed from circulating vitamin A, by reducing the amount of vitamin A going into the eye, we have a very good opportunity to slow the accumulation of these compounds and therefore slow the progression of the disease.
What you have before you is a slide showing you the trial design for DRAGON, which is our pivotal phase III trial in Stargardt disease. This trial enrolled 104 subjects. All of these subjects have atrophic lesions at baseline. These are called definitely decreased autofluorescence lesions, or DDAF. Slowing the growth of these lesions over time is the primary endpoint for approval in Stargardt disease. This is a global study. We have great representation of the disease across the planet. The randomization is 2 - 1 favoring Tinlarebant. It is a double-blind study conducted for two years. As Tom just mentioned, we have an interim analysis that we're talking about today. So that was triggered when all patients had completed their 12-month visit. Efficacy, as I mentioned, is looking at this atrophic lesion growth, the DDAF lesion growth. We're also looking at safety and tolerability.
In terms of other measures, we're also looking at the autofluorescent lesion growth, best-corrected visual acuity. We're looking at retinal anatomy and structure by spectral-domain optical coherence tomography and retinal sensitivity by microperimetry. You can see at the very bottom there are the key inclusion criteria. These are subjects aged 12 years - 20 years of age with molecularly and clinically confirmed Stargardt disease. The lesion size was capped off at three disc areas, which is approximately 7.62 sq mm. Patients had to have a BCVA of at least 20/200 or better. Next slide. Here are the baseline demographics and characteristics for our study. These are largely school-aged children, mean age of 15.4 years of age, average height and weight, and BMI. On the right-hand side, you can see the breakout for male and female, approximately 60% male, 40% female.
And as I said before, a good representation of races across the planet. Majority are Asian and white. Next slide. Here are the conclusions from the DSMB's interim analysis. They have recommended no modification of this study, that we continue the study without a sample size increase. I failed to mention that the dosage of Tinlarebant is 5 mg daily. This dose has been shown to be safe and well tolerated in these adolescent Stargardt patients. And at the time of the interim analysis, we had very good outcomes in terms of withdrawal rate, only 9.6% overall, with 3.8% dropout due to ocular adverse events. Importantly, visual acuity was stabilized in a majority of subjects with a mean change from baseline of less than three letters under both standard and low luminance throughout the two-year study.
And most importantly, the additional DSMB comments were that they recommend that we submit the interim data for further regulatory review for drug approval. Next slide. Here are the treatment emergent adverse events. The predominant ones that you see here, xanthopsia and delayed dark adaptation, are features of this therapeutic approach. We actually want to see these outcomes because they're telling us we're having the intended biological effect on the retina. Xanthopsia is an aberration of color vision, which is triggered by onset to light. Typically, these kids are experiencing this when they wake up from sleep. It's basically a hue of color, in this case, yellow, in the visual field, which lasts seconds to minutes, and it's reported as mild. And you can see on the right-hand side the frequency and number of patients that have experienced this ocular AE. The other ocular AE is delayed dark adaptation.
It is the opposite manifestation of xanthopsia. That is, this is a delay in the ability to accommodate dim light sensitivity, so it is not night blindness. It is simply a prolongation of the dark adaptation time. Typically, it's gone from anywhere between 10 minutes- 15 minutes. In cases where it's gone past 20 minutes, we refer to it as night vision impairment, but in either case, all reports are mild and transient, and you can see, again, the frequency and number of patients on the right-hand side. The other AE that we've seen is headache. These are essentially visual migraines. We believe that patients can experience these when they strain to use their visual acuity while they were experiencing the ocular AEs.
Perhaps most importantly, though, is that there have been no clinically significant findings in relation to vital signs, physical exams, cardiac health, or organ functions, and no severe or serious treatment emergent AEs have been reported. Next slide. In this slide, you see the visual acuity outcomes. On the left is shown the visual acuity under standard luminance. And on the right, we have essentially the same type of data, but under low luminance. And you can see over the treatment period of two years, these lines, both of the standard and low luminance, show essentially stabilization of visual acuity under both lighting conditions. So this is a very promising outcome. It shows stabilization of disease. Thank you very much. And with that, I think I'll throw it back to Tom for conclusions and Q&A.
Thanks, Nathan. Shall we move forward to Q&A?
Thanks, Dr. Lin. If anybody has a question, could you please raise your hand? Jennifer, I'm not seeing your hand raised, but I know you did indicate that you wanted to participate in Q&A. So, operator, could you kindly unmute her for a minute?
Oh. I think Jennifer.
Okay. Jennifer, go ahead.
Hi. Can you hear me?
Yes.
Okay. Hey, guys. Thanks for the update. Maybe a question on the DSMB's recommendation to submit the data for, I think the press release is for the regulatory review for drug approval. I guess, what is a fair way to interpret that? And in terms of the data being submitted, what exact data is being submitted, when and to whom? And if you're submitting interim data, how would that affect the blinding of the trial? Thanks. I'm sorry. That's a lot of questions.
Nathan, you want to?
Yeah, sure. So, Jennifer, it's obvious that the DSMB has seen positive safety and efficacy signals at the interim. You know, this was an adaptive trial design with a sample size re-estimation. The fact that they did not recommend the inclusion of additional subjects, but at the same time also recommended that we submit the data for further regulatory review tells us we're probably on the positive side of that, what we call promising zone. So I think this is a very, very positive outcome. In terms of how the data will be transmitted, that will have to be done operationally through our CRO and any regulatory authorities. We don't have a design on that right now. This is sort of, we're still fleshing that out. But again, the CRO will communicate directly with a regulatory agency to make sure that data is transmitted.
I think you may have had one other question I may have missed.
Oh, just thinking about timelines. Oh, and maybe so this will remain, I guess you guys will remain blinded to the trial. Is that correct?
Yes. The study team will always remain masked to the data. We will be applying for breakthrough designations. So there will be members on our team that will be unmasked, that will be able to prepare the document and submit it for regulatory review.
So let me add to that answer. So the study team or the sponsor will still remain masked, but our regulatory head would have the overall data from both groups. But we'll still be remained masked to who's been taking a study drug or who's on placebo. So.
Could we address your?
That's the address of the question.
Okay. Thank you. Our next question is from Yi Chen at H.C. Wainwright. Yi, please go ahead.
Hi. Thank you for taking my questions. Can you hear me?
Yes.
Yeah.
Oh, sorry.
So my first question is the press release says that the visual acuity was stabilized in the majority of subjects and then says was maintained from baseline of less than three letters lost at both standard and low luminance throughout the two-year study. But was that referencing prior observations? I mean, that particular sentence regarding throughout two-year study?
No, Yi, that's referring to the 24-month mean, if you will. If you look at all data points across 24 months, the deviation is less than three letters.
24 months mean observed in DRAGON I study. That's what you.
Yes, at the interim. So basically, the data that I just showed on the visual acuity side, I don't know if we can go back to it, Julie. Right here. So if you look under standard luminance, for instance, you look across all data points and you take the mean from all of those data points, the variance about that mean is less than three letters.
Got it. Okay. Right. Sure. And one question regarding DRAGON II, because DRAGON I, as you mentioned, has enrolled patients in 11 jurisdictions. DRAGON II are only enrolling patients in U.S., U.K., and Japan. Is that correct?
That is correct.
For those jurisdictions that are not included in DRAGON II trial, are the complete data set going to be able to be sufficient to submit a regulatory submission for Tinlarebant?
We do have consultation from a regulatory expert that tells us that yes, in fact, that would be used as a confirmatory study. It would be useful as a confirmatory study as designed.
Okay. Okay.
Right.
At this point, can you provide an update on the DRAGON II trial progress?
Yeah. DRAGON II is still recruiting. I believe we're somewhere around 10 subjects recruited thus far. I haven't got an update in about a week, but I think that's approximately right. We just began recruiting over the past month.
Okay. Got it. Thank you.
Thank you.
Thanks. Our next question is from Marc Goodman at Leerink.
Hi. Good afternoon. Thank you for taking our question. This is Basma on for Marc. Our first question related to the visual acuity data. So these are data from placebo and treated subjects, right? Collapse together. And so is that, given the lack of details about which placebo, which arms, enough to actually give you confidence that there's no effect on the visual acuity?
Yes. I mean, when you consider that 66% of these data points are from the Tinlarebant treatment arm and 1/3 are from placebo, the lines are largely driven by, we believe, the treatment arm, the Tinlarebant treatment arm.
Okay. I see that. Thank you. And the other question we have is, again, I'm sorry, we're going back to the DSMB question, which is, so how would you, is there a possibility you can go for an accelerated approval? And if so, how does unblinding or the fact that you need to stay blinded, how would that work if there is an option for you to go for an accelerated path?
Yes. As mentioned, this will be coordinated through our CRO directly to the regulatory authority. We will have, as mentioned, one member of our team that is our regulatory head have access to the data so that one person will be unmasked. The rest of the study team will be remained masked, so most of the operational and procedural detail will take place from the CRO directly to the regulatory authority with our regulatory head sort of managing the process.
I know this question has been asked before. Is the timeline for all of this process, can you give us any idea how roughly we can get an update about the CRO and their interaction with the FDA? Like over time?
I don't know.
Yeah, I don't know. We have a clear timeline yet. So we'll just have to see how it goes, and at the same time, I think, yeah, we'll just update the market when we have any update.
Thank you so much. And the last question is, DRAGON I still remains on track to report the topline data in the early 2026?
Yes.
Yes, that's correct.
Thank you. That's it. Thank you so much.
Thank you, Basma.
Thank you.
Thanks. Our next question is from Bruce Jackson at Benchmark.
Hi. Good afternoon, and thanks for taking my questions. Just going back to the intent to pursue an accelerated approval with the FDA, was this built into the trial design? And did you have any prior conversations with the FDA about this process potentially and what they might like to see?
Maybe first clarify that we don't know what the regulators, and we're not talking about only the FDA here, right? So we don't know what they're going to respond to this. It is a very pleasant surprise recommendation from the DSMB. It is not required in the protocol that they provide additional comments like this unless they see something, right? So we don't have an idea about what the regulators is going to say, but I think we can clarify that it's not, it does not need to be a regulatory approval, right? Regulatory approval have their own procedure and definition, right? You need to have a surrogate endpoint, et cetera. So I think the DSMB just telling us that they think this is positive. They think we should show it to a regulator and see what they come back.
If they come back with approval, right, that's good, but that's not within our control. But we'll just do the recommendation and see how the regulators respond to that, not just the FDA.
Okay. Okay.
So, Bruce, may I add that the responsibility of the DSMB, one of the responsibilities of the DSMB, is to monitor the study ethically. And if they see a clear meaningful clinical meaningful outcome, it is their responsibility to recommend this. If they see this is clinically benefiting the patients, then it wouldn't be fair for the placebo patients to stay on placebo. And that's why they're recommending the regulatory authorities to take a deeper look at it to see if they agree with the DSMB. And that is why we will be submitting this to the regulators and await for their review and their guidance after this.
Okay. Great. That's it for me. Congratulations on the progress.
Thank you so much.
There are no further questions. Dr. Lin, did you want to say a few things in closing?
No. Thank you. Well, thank you so much. Thank you, everyone, for participating in this call. We will be updating further the public of further information. This is all very overwhelming that we just received this recommendation from the DSMB right today. So we don't have any further information. And if we do, we'll update the public as soon as possible. Thank you so much. And have a good day.