Belite Bio (NASDAQ:BLTE) executives outlined the company’s late-stage plans for tinlarebant, an oral therapy being developed for Stargardt disease and geographic atrophy, during a Stifel meeting discussion featuring Chief Medical Officer Hendrik Scholl and Chief Financial Officer Hao-Yuan Chuang.
Scholl said Belite has completed its registration trial in Stargardt disease, known as DRAGON, and presented topline data on Dec. 1. The company is preparing to submit a New Drug Application to the U.S. Food and Drug Administration, which Scholl said is expected to be completed within a month. He said the company anticipates a potential approval in the first quarter of next year through a priority review process.
Tinlarebant’s mechanism targets vitamin A delivery to the eye
Scholl said tinlarebant is designed to reduce delivery of retinol, or vitamin A, to the eye by binding to RBP4 in systemic circulation. In Stargardt disease, dysfunction in the ABCA4 gene disrupts the visual cycle and leads to buildup of toxic bisretinoids, including A2E, which contribute to degeneration of photoreceptors and retinal pigment epithelial cells.
“This exactly correlates with blindness, because if there is no photoreceptor, there is no vision,” Scholl said.
He said tinlarebant’s oral dosing differentiates it from intravitreal therapies used in retinal disease. The company selected a 5-milligram once-daily dose after single- and multiple-ascending-dose studies. Scholl said the dose reduced RBP4 below the company’s 70% target threshold within days and maintained reductions near 80% while treatment continued. He also said RBP4 levels returned quickly to baseline after discontinuation, indicating reversibility.
DRAGON data showed slowing of lesion growth
Scholl said tinlarebant is intended to slow or potentially stop disease progression, not restore lost photoreceptors. He compared the approach to other neurodegenerative diseases, where lost neuronal cells are not regenerated.
In DRAGON, Scholl said tinlarebant showed a 36% treatment effect in Stargardt disease based on lesion progression. The primary endpoint measured growth of areas known as definitely decreased autofluorescence, or DDAF. He said DDAF reflects areas where photoreceptors and retinal pigment epithelial cells have died and can be precisely measured.
The company also assessed decreased autofluorescence, or DAF, as a key secondary endpoint. Scholl said the DAF endpoint showed a 34% treatment effect and reached statistical significance. He said this was important because it suggested tinlarebant may slow progression in areas where cells are not yet fully lost.
Because tinlarebant is systemic, Scholl said the company also evaluated patients’ fellow eyes. He said statistically significant treatment effects were observed in the fellow eye for both the primary and key secondary endpoints, which the company views as confirmatory evidence.
Company says one trial supports U.S. filing
Scholl said Belite is seeking U.S. approval based on the DRAGON trial and additional confirmatory evidence. He said the company has discussed this approach with the FDA, while noting that the agency does not commit to approval before review.
Belite is also conducting DRAGON II, but Scholl said that study is not intended as a second U.S. registration trial. He said DRAGON II originated after Japan granted the company Sakigake designation and wanted data in Japanese patients. The study also allowed patients at sites in the U.S. and U.K. to participate and enrolled 73 patients.
Scholl said DRAGON II is separate from the U.S. filing, although the integrated safety summary will include all patients exposed to tinlarebant across phase 1, phase 2, DRAGON, DRAGON II and the PHOENIX trial in geographic atrophy.
Safety profile and long-term use
Asked about safety in younger Stargardt patients who may need chronic treatment, Scholl said patient education will be important. He said tinlarebant reduces substrate for the visual cycle, which can make adaptation from bright to dark conditions take longer. He also described xanthopsia, or temporary yellowish discoloration of vision after moving from dark to light, as another key side effect.
Scholl said these effects are related to the drug’s mechanism and should be explained to patients. He said systemic safety findings were limited, with six serious adverse events reported in the registration trial, four of which occurred in the placebo group.
Geographic atrophy plans remain data-driven
Belite is also studying tinlarebant in geographic atrophy, a late form of age-related macular degeneration, through the PHOENIX trial. Scholl said the GA study includes 530 patients, many of whom have completed at least one year of treatment with the same 5-milligram daily dose.
Scholl said the GA trial includes somewhat earlier-stage patients than those studied in injectable therapy trials. He said oral tinlarebant could potentially be complementary to injectable approaches, though combination use would require future studies.
On commercial strategy for GA, a Belite representative said the company remains committed to developing treatment for both Stargardt disease and GA but needs more data before evaluating the commercial approach. Asked whether the company would keep the same dose or develop a separate strategy for GA if results are strong, the representative said it is “probably too early” to comment and that decisions will be data-driven.
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.
