Belite Bio at H.C. Wainwright Conference: Strategic Focus on Eye Diseases

On Wednesday, 13 August 2025, Belite Bio (NASDAQ:BLTE) presented at the H.C. Wainwright 5th Annual Ophthalmology Virtual Conference, outlining its strategic initiatives and progress in developing treatments for Stargardt disease and geographic atrophy (GA). The company highlighted promising trial results and regulatory advancements, while acknowledging challenges in securing approvals and managing treatment side effects.

Key Takeaways

• Belite Bio’s investigational drug, tinlaribine, targets Stargardt disease and GA, with promising Phase 2 trial results.
• The company has completed enrollment for the Dragon trial in Stargardt disease and the PHOENIX trial in GA.
• Tinlaribine has received Breakthrough Therapy designation from the FDA for Stargardt disease.
• The drug’s mechanism reduces vitamin A delivery to the eye, aiming to slow disease progression.
• Belite Bio’s patent portfolio extends until at least 2040, covering tinlaribine’s composition.

Financial Results

• Tinlaribine is in various trial phases for Stargardt disease and GA, including ongoing trials in the US, UK, and Japan.
• The company holds 14 active patent families, ensuring intellectual property protection until at least 2040.

Operational Updates

• Stargardt Disease:

- The Dragon trial has enrolled 104 subjects aged 12 to 20 years.

- Interim analysis supports trial continuation without modifications.

- The FDA has granted Breakthrough Therapy designation based on trial data.

• Geographic Atrophy:

- The PHOENIX trial, a double-blind, placebo-controlled study, has enrolled 500 subjects.

- The trial aims to reduce atrophic lesion growth over a two-year period.

Future Outlook

• Strategic Plans:

- Focus on early intervention for Stargardt disease and GA.

- Seek regulatory approval for tinlaribine in Stargardt disease.

- Continue development for GA, with potential expansion to intermediate AMD.

• Potential Challenges:

- Trial outcomes and regulatory approvals remain uncertain.

- Managing side effects and ensuring patient compliance in chronic treatment.

• Opportunities:

- Significant unmet needs in Stargardt and GA markets offer substantial commercial potential.

- Breakthrough Therapy designation may expedite regulatory review.

Conclusion

Readers are encouraged to refer to the full transcript for a more detailed understanding of Belite Bio’s conference presentation.

Full transcript - H.C. Wainwright 5th Annual Ophthalmology Virtual Conference:

Eduardo Martinez, Biotechnology Equity Research, HC Wainwright: Welcome to HC Wainwright’s annual ophthalmology virtual conference. My name is Eduardo Martinez. I’m a biotechnology equity research at Wainwright, and it’s my pleasure to introduce doctor Hendrick Scholl, chief medical at Belite Bio. Doctor Scholl, please take it away.

Hendrick Scholl, Chief Medical Officer, Belite Bio: Thank you very much. I’m happy to present on early intervention with an oral treatment for macular degeneration. This is our forward looking statement. We have an experienced leadership team at Belite Bio that includes our chairman, founder, and COO, doctor Tom Lin, who is a neurologist by training, has more than

Eduardo Martinez, Biotechnology Equity Research, HC Wainwright: Welcome to HC Wainwright’s Annual Ophthalmology Virtual Conference. My name is Eduardo Martinez. I’m a biotechnology equity research at Wainwright, and it’s my pleasure to introduce Welcome to HC Wainwright’s annual ophthalmology virtual conference. My name is Eduardo Martinez. I’m a biotechnology equity research at Wainwright, and it’s my pleasure to introduce doctor Hendrick Scholl, chief medical officer at Belite Bio.

Doctor Scholl, please take it away.

Hendrick Scholl, Chief Medical Officer, Belite Bio: Thank you very much. I’m happy to present on early intervention with an oral treatment for macular degeneration. This is our forward looking statement. We have an experienced leadership team at Belite Bio that includes our chairman, founder, and COO, doctor Tom Lin, who is a neurologist by training, has more than ten years experience in executive management in biotech and was involved in over 10 new drug developments in multiple therapeutic areas That includes ophthalmology. A little bit about myself.

I have twenty five years of experience in treating retinal diseases. Was trained in Germany and The United Kingdom. Joined a large department in Germany as a vitreoretinal surgeon and led the research at the department before after worldwide search, was recruited to Johns Hopkins University and led at the Wilmer Institute retinal dystrophies. And at the time, together with Foundation Fighting Blindness, we implemented the largest natural history study for Stargardt’s disease. I will get to the disease in a moment.

That was a worldwide natural history study that allowed to establish outcome measures for this rare but still relatively prevalent disease. I participated in over 10 clinical studies both in Stagler disease and AMD and published, meanwhile, almost 300 peer reviewed papers in the field. In 2016, I returned back to to Europe, led the department in Basel. And a year ago, it speaks for my enthusiasm for Larraband, joined Belite Bio as chief medical officer. We have a very experienced chief science officer.

This is Doctor. Nathan Mata who has more than fifteen years’ expertise in ophthalmic drug development across numerous indications. But very specifically, he led the clinical development efforts for the first, retinal binding protein antagonist, RBP antagonist in advanced dry AMD, and the first visual cycle modulator in dry AMD in Stagler disease. And he’s really a pioneer in the field and introduced the first APC f four Stagler knockout mouse model in the field. And our chief financial officer, more than thirteen years experience in the capital market and closed more than 32,000,000,000 US dollar transaction.

This is Hao Chuan Chuan. So this slide shows our pipeline that includes timlaribine. You see the upper left for two indications, Stagler disease, where we run currently two phase preclinical trials. We completed a phase two clinical trial. It was a twenty four month clinical trial open label that showed to slow lesion growth.

And, currently, we are running a global registration trial named Dragon, which is ongoing, but will be completed in September that enrolled 104 subjects, adolescent subjects between 12 and 20 years old. And we are running a phase one slash phase two three clinical trial in Japan, The US, and The United Kingdom, which is the second registration trial. There’s a second indication, which is very important, obviously, geographic atrophy secondary to age related macular degeneration. In TB, we run the PHOENIX trial, which is a phase three two year randomized placebo controlled interventional trial that is ongoing. We completed enrollment a couple of weeks ago, and that was announced in a press release.

Tilarebund is a novel once daily oral tablet designed to bind serum retinal binding protein four or briefly r b p four as a means to specifically reduce retinol or vitamin A delivery to the eye, and this approach is intended to slow or halt the formation of toxic retinal derived byproducts that are generated in the visual cycle. I will explain the visual cycle in a moment and are implicated in progression of Stargardt disease and geographic atrophy. LightBio believes 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 stagler disease in GA. The market opportunity is significant. This is completely unmet medical need for Stargardt disease.

There’s no FDA approved treatment for Stargardt. There’s no treatment worldwide for Stargardt, and there are no FDA approved orally administered treatments for GA in The United in The United States And overall in the world, other than the two injectables in The United States, there’s no treatment for GA currently. We received breakthrough therapy, Fast Track, and rare pediatric disease designation in The United States and orphan drug designation in The US, The European Union, and Japan, and pioneer drug designation in Japan for Stargardt disease. LightBio has 14 active patent families, mostly composition of matter. It will last until at least 2040 without patent extension.

A little bit about tinlaraband. And before I I explain, I explain the visual cycle. This is indeed one of the best understood biochemical processes in the human in the human body. Visual the visual cycle means the regeneration of the visual pigment. We see the visual pigment on top rhodopsin.

And if there wasn’t the visual cycle, if there wasn’t the regeneration of the visual pigment in our in our eye, we would only see once at birth, and then it would be it would be dark. So this pigment needs to be regenerated, and it needs vitamin A in order to be regenerated. We see the cascade of of enzymes that are are involved such as r p 65, for example, or LRAD. And we see on the lower right, how vitamin A or ultransretinol enters the eye, specifically the retinal pigment epithelium, namely through the r b p four receptor. And it’s only the eye that expresses r b p four r b p four receptor, and and this allows the the retinal pigment epithelium to suck in vitamin A.

No other organ in the human body is dependent on that, which also means that targeting r b p four is eye specific. And by targeting r b p four that is bound to TTR and ultra trans retinol, we can reduce the level of vitamin A that would enter the eye that will be explained in a in another slide. If ABCA4 is mutated, we see that on the upper right, and this is quite a frequent disease. It belongs to the rare diseases because the threshold is under one in two thousand individuals, but it’s the second most prevalent autosomal recessively inherited disease in medicine after cystic fibrosis with a prevalence of about one in seven thousand. So if that molecule is dysfunctional, there’s a buildup of ultran’s retinal, which is very toxic and also very reactive, And it will build base retinoids, and one of the most well known is a two e, and a two e is known to be very toxic.

So this is the pathophysiology in Stager disease. In age related macular degeneration, it is very similar. We see pathology between the photoreceptors and the retinal pigment epithelium, and we see pathology underneath, the RPE between RPE and gross membrane. And we know that that pathology leads to also dysfunction of the visual cycle and buildup of toxic base retinoids in the retinal pigment epithelium. The two diseases are very similar.

We see an example of a late onset Stargardt case on the upper right and a case of geographic atrophy on on the lower right. Stargardt and GA share a similarly similar pathophysiology characterized by excessive accumulation of cytotoxic bisretenoids, retinal cell death, and, subsequently loss of vision. Vision loss occurs slowly despite peripheral expansion of dead retina until the disease reaches the center of the eye, specifically the macula. Slowing or halting the spread of that retina is the intended effect of the tinlaraband treatment. So introduction to tinlaraband, this is a novel once a day oral tablet designed to bind to serum retinal binding protein four or r b p four as a means to specifically reduce retinal delivery to the eye in order to slow or halt the accumulation of cytotoxic bisretinoins.

Belite Bio believes that intervention directed at emerging retinal pathology, which is not primarily mediated by complement activation or inflammation, would be the best approach to potentially slow disease progression in Stargardt and geographic atrophy. So how does tinlariband act? Here, we see tinlariband binding to RbB4 at underneath the retinal pigment in the peripheral bloodstream. That complex is small and will be eliminated to the kidney. As a net result, we see that less RBP4 is available to bind to ultras retinol and TTR.

Therefore, ultras retinal delivery to the retinal pigment epithelium is reduced. And as a result, we see less buildup of toxic bisretinoids in the photoreceptors in the RPE, and we see less accumulation of ultras retinal in the photoreceptors. So after, extensive preclinical research, including rescue of photoreceptor degeneration and the double knockout mouse model RDH eight and APC four. The compound went into human clinical development, and Abilite Bio conducted a phase two clinical trial that is shown here that enrolled 13 subjects in Australia and Taiwan. This was an open label two year interventional trial, that primarily measured safety and tolerability, but also, the development and growth if, there was any lesion of DDAF, QDF.

And DAF, I will explain that in a moment, best corrected visual acuity, spectral domain OCT, and microperimetry. The key inclusion criteria were adolescent patients between 12 and 18 years old diagnosed with Stagler disease carrying at least one mutation in the ABCA four gene. From the study, we have a PKPD profile of tenlariban. We see the pharmacokinetic profile in blue. We see that with onset of therapy of five milligrams per day, we see that the level of telaribund in the systemic bloodstream increases and stays at that level over the duration of the trial and obviously goes down, after cessation of the treatment.

We see a perfect mirroring, as the pharmacodynamic effect, namely our biomarker r b p four, that goes down underneath a target threshold that was defined in a interventional trial in age related macular degeneration where efficacy to slow lesions over time was shown to happen if the threshold of seventy percent was reached. With a five milligram dose, it was shown that r b four levels would be reduced at approximately 80% relative to baseline, and the r b p four levels returned to eighty seven percent of the baseline value at the end the study, and the recovery of r b p four concentration correlated very well with a decreased tindalaribond exposure. What about, endpoints in such clinical trials? It was the PROXA study that in about 2013 that I implemented at the Wilma Institute with support of the Foundation Fighting Blindness that led to the development and validation of the first endpoint for Stagler disease, namely DDAF. We see an example on the lower left.

We see the optic nerve head that is black, and by definition is black because there are no fluorophores in the optic nerve head. And then in the center of the macula, we see this lesion that is surrounded by increased fundus autofluorescence, which actually shows the cause of the problem, but we also see the consequence of accumulation of bisregionates, namely loss of retinal pigment epithelium that first becomes sick, and we see these areas of QDF, questionably decreased autoforescence, that are not as dark as the optic nerve head. And then to the left of the QDF, we see this area of DDAF, definitely decreased autofluorescence, very black, blackness level of at least 90% compared to the optic nerve head. And we can measure that DTF area over time, and we see the progression in within two years when we go to the right panel. We see that the DTF lesion has increased, and the QDF lesion has has changed its border.

Some of QDF developed into a DDF. You can also calculate the sum of the two, namely decreased autofluorescence, DAF, and that is our secondary endpoint in our registration trial. Proxstar, the Proxstar study group has shown that, these DDF progression rates can be measured over time reliably, and it was shown that in an all commerce cohort of two ninety one patients worldwide, the progression rate was pretty much exactly point seven square millimeters per year, which is compared to geographic atrophy a bit less than half what we observe in geographic atrophy. In the phase two twenty four month interventional trial, seven out of twelve subjects developed DDF lesions. It is important to note that five of the twelve subjects never developed DDF lesions.

It speaks in favor of tinlariband being able to prevent the onset of such lesions over time. Those patients that develop these lesions for those patients, the lesion size was measured by a central reading center, and we see the progression plotted in red in the left figure. And we see the the figure, the correlating figure on the right, and it was pretty much exactly half a square millimeter to two years in the interventional trial within laraband treatment. And that, could be compared with natural history, namely from the Proxstar study in order to compare apples to apples. We extracted an adolescent patient cohort out of Proxstar, namely those subjects that were aged between 12 and 18 years out of the Proxstar study that resulted in a dataset of 51 patients aged 18 and younger.

And those patients progressed at a progression rate of pretty much exactly one square millimeter per two years, and the difference between the two was highly statistically significant. So with that data, we went into a registration trial called Dragon, and there was an interim analysis, and I will speak about that interim analysis that was conducted in February by the by an independent data safety monitoring board. The Dragon trial is a registration trial that enrolled 104 subjects, which is it’s a global trial, has a randomization ratio of two to one, so twice as many patients receive tinlariband. One third receives placebo. It is stop double masked.

It’s a two year intervention trial with the primary endpoint of slowing atrophic lesions, specifically DDAF lesions, and other measures include QDF lesions, best corrected visual acuity, spectral domain OCT measures, and microperimetry. And the key inclusion criteria, this was an adolescent patient cohort aged between 12 and 20 years old diagnosed with Stagler disease and carrying at least one mutation identified in the ABCF four gene. We see to the left the demographics that are typical for such an adolescent, patient cohort, and on the right, we see further demographic characteristics, slightly dominated by a male population, over 60%, and about 40% Caucasians and a bit more than 50% Asians in the Dragon clinical trial. As mentioned, the DSMB an independent DSMB, conducted an interim analysis, in February. They concluded that no modification of the study is required.

They recommended to continue the study without sample size increase. They concluded that tinlariband at the five milligram per day dose continues to be safe and well tolerated in this adolescent Stargardt patient cohort. And at the time of the interim analysis, the overall withdrawal rate was less than ten percent, and withdrawal rate due to ocular adverse events was less than four percent. Vigilacuity was stabilized in the 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. There was an additional comment by the DSMB, namely, it is recommended to submit the data for further regulatory review for drug approval.

And we took this mandate, and presented the data to various regulatory, agencies. For example, an in person presentation in Tokyo to the PMDA in April and a submission for breakthrough designation to the FDA, and we received breakthrough designation based on the data that was submitted that the DSMB actually looked at in February in May. What about safety? Tendlariband continues to be safe and well tolerated in this adolescent patient cohort. You see the adverse events listed in this table.

Xanthopsia, which means transient yellowish of the visual scene, and delayed dark adaptation, which means that patients need a bit more time to reach their final threshold of being fully sensitive under low light conditions, are the most common drug related ophthalmic adverse events. The majority of xanthropsya delayed dark adaptation and night vision impairment were mild. Some resolved while on treatment. Headache, is the most common treatment related nonocular AE, and there were no severe or serious treatment related AEs reported. There were no clinically significant findings in relation to vital signs, physical exams, cardiac health, or organ functions.

This show this slide shows the visual acuity data. This is blended data of the study in fellow eye of the total population of these 104 subjects, we would not expect a major visual acuity decline in this stargardt cohort as was shown in the PROXTA study, but it’s still reassuring that on average, not a single letter on an EDTRS chart was was was lost over the duration of two years in the Dragon trial. Last but not least, tenerabin is being developed for geographic atrophy, which is the most common cause of blindness in the Western industrialized countries. We see the clinical trial design for geographic atrophy. We have an established efficacy endpoint, namely the reduction in atrophic lesion growth very similar to DDF in Stargardt disease, and this is accepted by the FDA as a primary and an approvable endpoint for Stargardt and geographic geographic atrophy secondary to A and D.

We believe that early intervention is important to target patients with small lesions to potentially slow the disease at an early stage. It is an oral once a day treatment. It’s identical, for both GA and Stargardt, namely the five milligram dose per day, which is well suited for a long term treatment for chronic diseases. And it has a broad potential with the primary focus right now on GA simply because there is an approvable endpoint, but it has the potential to treat earlier stages such as intermediate AMD. We see the clinical trial design to the right.

We targeted an enrollment of 500 subjects, and we reached that that target a couple of weeks ago, and that was announced by a press release ahead of time, by the way. This is a double, again, a double blind placebo controlled clinical trial with a two to one randomization of twice as many patients receiving the treatment and one third receiving placebo. Like the Dragon trial, a two year duration Primary primary measures, very similar to the DRAGON trial, namely slowing of atrophic lesions, and other measures, include best corrected visual acuity, spectral domain OCT derived outcome measures, and microperimetry. And we anticipate that there will also be an interim analysis for the PHOENIX trial. And with that, I thank you very much for your attention.

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