Belite Bio (NASDAQ:BLTE) Chief Medical Officer Hendrik Scholl outlined the company’s approach to treating Stargardt disease and reviewed top-line results from its Phase 3 DRAGON trial during a conference session hosted by Leerink analyst Marc Goodman.
Stargardt disease: prevalence and unmet need
Scholl described Stargardt disease as a recessively inherited retinal condition caused by mutations in the ABCA4 gene that affects the center of the retina and “leads to blindness in almost all cases.” He said Stargardt is the most prevalent inherited retinal disease gene, accounting for about 30% of all inherited retinal disease cases.
Tinlarebant mechanism: targeting vitamin A delivery to the eye
Scholl said Belite’s investigational drug Tinlarebant is designed to reduce the formation of toxic retinal byproducts that accumulate due to ABCA4 dysfunction. He explained that ABCA4 normally helps remove a toxic visual-cycle intermediate (all-trans retinal) from photoreceptors; when ABCA4 is mutated, all-trans retinal can accumulate and form “bisretinals,” which then build up in the retinal pigment epithelium and cause toxicity.
The company’s strategy is to reduce retinal (vitamin A) delivery to the eye without broadly reducing vitamin A delivery to the rest of the body. Scholl said this is possible because the eye expresses a retinol binding protein (RBP) receptor that mediates vitamin A uptake. Tinlarebant is an antagonist of RBP4 that binds retinol and promotes elimination through the kidney, lowering the amount of substrate available to enter photoreceptors.
In early clinical work, Scholl said 5 mg once daily reduced circulating retinol and RBP by about 80%, leaving about 20% remaining. He emphasized Tinlarebant is an oral therapy that treats both eyes simultaneously, which he contrasted with the injection- and procedure-based approaches common in retinal disease.
Earlier evidence and the role of DDAF as an endpoint
Scholl cited preclinical work in a double knockout mouse model (RDH8 plus ABCA4) suggesting that an ~80% reduction in RBP4 could rescue disease features and “stop photoreceptor degeneration completely” at an exposure equivalent to the 5 mg daily dose.
He also discussed an open-label Phase 1b/2 study in adolescent Stargardt patients in Taiwan, where he said vision was stabilized over two years and progression of a key lesion type was slower versus natural history data from the ProgStar study. That lesion type—definitely decreased autofluorescence (DDAF)—was described as an FDA-acceptable endpoint that can be measured by tracking lesion growth rates over time.
Phase 3 DRAGON trial: primary and secondary outcomes
Scholl said the Phase 3 DRAGON trial was a multicenter, randomized, double-masked, placebo-controlled study enrolling 104 patients across geographies including the U.S., U.K., Europe, China, Taiwan, and Australia. Patients were randomized 2:1 to Tinlarebant 5 mg daily or placebo and followed for two years, with assessments every three months. Eligibility included a clinical Stargardt diagnosis, at least one ABCA4 mutation, a trackable DDAF lesion, and minimum visual acuity of 20/100.
According to Scholl, the company presented top-line data on December 1 following trial completion, reporting that the study met its primary endpoint. He said Tinlarebant reduced DDAF lesion growth rate by 36% over two years, with a P value of 0.0033. He added that applying a structured covariance matrix recommended by the DSMB yielded a P value < 0.0001.
Scholl said a key secondary endpoint—DAF, which includes both definite and questionably decreased autofluorescence—showed a similar effect size of 34% and reached statistical significance. He also highlighted a “fellow eye” effect consistent with systemic treatment: the fellow eye showed an effect size of 33% and also reached statistical significance, despite the study being optimized for the designated study eye.
Safety profile, regulatory timing, and pipeline updates
On safety, Scholl said the trial recorded six serious adverse events (four on placebo and two on Tinlarebant) and that none were considered related to the study drug. He said treatment-emergent adverse events were primarily ophthalmic and consistent with the mechanism—reducing substrate for visual pigment—leading to longer dark adaptation and transient visual discoloration. Scholl said about one-third of patients reported discoloration (including xanthopsia/dyschromatopsia) lasting seconds to minutes, and about one-third reported longer dark adaptation; most events were rated mild and many resolved over time.
Scholl said Belite was finalizing the clinical study report and remained on track to submit to the FDA in the first half of the year, adding the company anticipated FDA approval feedback in the first quarter of next year with a plan to reach the U.S. market thereafter. He said the company is also preparing filings for regulators including the EMA and the MHRA, and described Japan as a likely next major market. Belite has initiated the DRAGON II study to satisfy Japanese regulatory requirements, noting the trial had enrolled 72 patients total, including 15 Japanese patients, and that the PMDA requested a PK/PD component that showed no differences versus non-Japanese patients.
Scholl also discussed Belite’s ongoing PHOENIX trial in geographic atrophy (GA) secondary to age-related macular degeneration. He said the study enrolled 530 patients and is testing the same 5 mg daily dose against placebo, with an interim analysis planned. He compared the treatment effects of existing GA therapies cited from complement-targeting trials (13%, 21%, and 14% in OAKS, DERBY, and GATHER2) and said the company believes the bar is low, while noting efficacy in GA cannot be assumed from Stargardt results.
On commercialization, Scholl said Belite has hired key U.S. commercial leadership and is focused on expanding access to genetic testing, which he said will be important for confirming ABCA4 mutations and enabling patients to qualify for treatment.
About Belite Bio (NASDAQ:BLTE)
Belite Bio, Inc (NASDAQ: BLTE) is a clinical-stage biotechnology company focused on discovering and developing small molecule therapeutics for metabolic and inflammatory diseases. Leveraging a proprietary drug-discovery platform, the company aims to address conditions such as nonalcoholic steatohepatitis (NASH) and obesity by targeting pathways involved in fibrosis, inflammation and metabolic regulation.
Belite Bio’s pipeline includes multiple candidates in preclinical and early clinical development stages.
