Belite Bio (NASDAQ:BLTE) Chief Medical Officer Hendrik Scholl said the company is advancing its lead compound, Tinlarebant, as a potential treatment for Stargardt disease and geographic atrophy secondary to age-related macular degeneration, two severe retinal diseases with overlapping features.
Speaking during a company news event, Scholl described Belite Bio as a biotech company focused on “unmet medical need in severe retinal diseases.” He said Tinlarebant has completed a Phase 3 clinical trial called DRAGON in Stargardt disease, an inherited retinal disorder that he described as “the leading cause of blindness in adolescents and juveniles.”
Tinlarebant’s mechanism targets vitamin A availability in the eye
According to Scholl, a similar accumulation of bisretinoids occurs in geographic atrophy, a late-stage form of age-related macular degeneration. He said the two diseases can appear “very similar, sometimes indistinguishable” on imaging such as optical coherence tomography, autofluorescence imaging and fundus photography, despite affecting different age groups.
Tinlarebant is a small-molecule antagonist of retinol binding protein 4, or RBP4. Scholl said the therapy is intended to reduce vitamin A availability in the retina while avoiding broader vitamin A deprivation in the body. He said Belite Bio has shown that a 5-milligram daily dose can reduce RBP4-bound retinol available to the eye by about 80%, leaving about 20% available.
FDA discussions focused on structural endpoints
Scholl said the U.S. Food and Drug Administration has been involved in discussions around clinical endpoints for Stargardt disease from early in the development process. He pointed to the ProgStar natural history study, which used definitely decreased autofluorescence, or DDAF, as a primary endpoint to measure lesion progression.
Scholl said DDAF progression can be measured precisely by reading centers and progresses in a predictable fashion, though more slowly than geographic atrophy. He said Belite Bio has remained in “constant discussions” with the FDA, including submission of interim results that led to breakthrough therapy designation for Tinlarebant in Stargardt disease.
Asked whether the company expects priority review following its completed rolling new drug application filing, Scholl said, “Given that we received breakthrough designation as a company for Tinlarebant for the development of a treatment for Stargardt disease, we believe it is fair to assume that we will receive a priority review for our submission.”
European filing considerations and endpoint validation
Scholl also discussed the European regulatory pathway, noting that Belite Bio has an approved pediatric investigation plan with the European Medicines Agency. He said the agency’s historical view of structural endpoints in geographic atrophy should be considered in the context of risk-benefit, particularly for treatments requiring monthly eye injections and showing modest treatment effects.
He contrasted prior geographic atrophy trial results, which he cited as showing 12%, 21% and 14% reductions in growth rate, with a 37% reduction for Stargardt disease. Scholl said Tinlarebant’s oral administration and “favorable tolerability and safety profile” could support a different risk-benefit assessment, though he emphasized there is “no guarantee.”
Scholl also said additional evidence is emerging on the relationship between structural endpoints and visual acuity in Stargardt disease. He noted that visual acuity declines slowly in Stargardt patients over the time frame of a typical clinical trial, citing ProgStar data showing an average decline of 0.55 letters per year on an ETDRS chart.
DRAGON II designed to support approval in Japan
Belite Bio is also running DRAGON II, a study Scholl said was originally designed to enable approval in Japan after Japanese patients could not participate in DRAGON I. Tinlarebant has received Sakigake, or pioneer drug, designation from Japan’s Ministry of Health, Labour and Welfare for Stargardt disease.
Scholl said DRAGON II is fully enrolled and includes patients from Japan, the United States and the United Kingdom. He said the trial has a similar design to DRAGON I, using the same 5-milligram daily dose. The main differences are a 1-to-1 randomization in DRAGON II, compared with 2-to-1 in DRAGON I, and a broader visual acuity cutoff that allows more patients to participate.
Scholl said the 1-to-1 design provides greater statistical power, and that enrollment accelerated after data from DRAGON I were presented. He did not provide a specific timeline for top-line DRAGON II data during the discussion.
Safety discussion centers on visual adaptation effects
Scholl said the safety profile observed in the trial included visual adaptation-related events such as xanthopsia and delayed dark adaptation. He said most of these events were mild and resolved while patients remained on study. There were no serious ocular treatment-emergent adverse events, and four treatment-emergent adverse events led to study drug discontinuation, with two leading to study discontinuation.
Scholl described xanthopsia as a temporary yellowish discoloration of the visual scene that can occur during light adaptation. He said acuity is not affected and that patient education will be important.
Delayed dark adaptation, he said, reflects a longer time needed to adjust from bright light to darkness. Scholl said this is also part of Stargardt disease itself and was reported by some patients in the placebo group, though it was more common in the treatment group due to Tinlarebant’s mechanism of action. He characterized the effect as manageable with education, such as avoiding abrupt changes between bright and dark environments.
“We do not believe that this is a big issue,” Scholl said.
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.
