Belite Bio Shares Phase 2 Tinlarebant Stargardt Study Analysis at ARVO Meeting

Belite Bio, Inc., a clinical-stage biopharmaceutical company, shared additional findings from a 24-month Phase 2 trial of Tinlarebant in adolescent patients with Stargardt disease (STGD1) at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. Tinlarebant is an oral medication designed to slow the progression of STGD1 and Geographic Atrophy (GA) in advanced Dry Age-related Macular Degeneration (Dry AMD).

Genetic profiling was conducted on 13 adolescent STGD1 patients enrolled in the study, revealing that 85% of them carried severe pathogenic ABCA4 variants. Despite these severe mutations, 42% of the participants did not develop new atrophic retinal lesions and showed no change in questionably decreased autofluorescence (QDAF) over the 24-month treatment period. Incident atrophic lesions appeared in seven subjects at different intervals within the 24 months, with four subjects developing definitely decreased autofluorescence (DDAF) lesions after the first year. The average DDAF lesion growth at month 24 was significantly lower than what is typically seen in natural history studies of the disease.

Moreover, six patients who had experienced a mean bilateral best corrected visual acuity (BCVA) loss of 10 letters per year prior to the study showed a reduced mean BCVA loss of 1.9 letters per year during the treatment period. Analysis of genotype-phenotype relationships indicated that patients with the same ABCA4 mutations exhibited different rates of lesion growth and BCVA loss, suggesting that identical genotypes do not always predict the same disease progression.

A novel method of lesion size quantification that reduces subjective bias was employed to reassess retinal imaging data. This method revealed that eight subjects had atrophic lesions within the macula at baseline. Over 24 months, the growth of these lesions into the macula halted after 16 months, correlating with the stabilization of visual acuity.

Dr. Nathan Mata, Chief Scientific Officer of Belite Bio, emphasized the continued efficacy of Tinlarebant based on the Phase 2 trial results, particularly noting the stabilization of visual acuity in patients with significant prior vision loss and the absence of new atrophic lesions in 42% of subjects. Professor John Grigg, Principal Investigator and Head Specialty of Ophthalmology at the University of Sydney, highlighted the precision and accuracy of the new lesion quantification method, which confirmed the halt in lesion growth into the macula after 16 months of treatment.

These findings reinforce Tinlarebant's potential as a promising oral treatment for STGD1. The data suggest that Tinlarebant may prevent healthy retinal cells from A2E damage and potentially halt the progression of the disease.

Tinlarebant's mechanism involves reducing the accumulation of vitamin A-based toxins known as bisretinoids, which are by-products of the visual cycle. By modulating serum retinol binding protein 4 (RBP4) levels, Tinlarebant aims to decrease bisretinoid formation and thereby slow disease progression. The drug has received several designations, including Fast Track and Rare Pediatric Disease designations in the U.S., as well as Orphan Drug Designation in the U.S., Europe, and Japan for STGD1 treatment.

Stargardt Disease (STGD1) is the most common inherited retinal dystrophy, leading to central vision loss due to ABCA4 gene mutations. The disease shares a similar pathophysiology with GA in advanced Dry AMD, characterized by bisretinoid accumulation, retinal cell death, and progressive vision loss. Belite Bio is currently evaluating Tinlarebant's safety and efficacy in GA patients through a Phase 3 study.

Belite Bio focuses on developing novel therapeutics for retinal degenerative diseases and has significant clinical programs targeting unmet medical needs, including atrophic age-related macular degeneration and autosomal recessive Stargardt disease type 1.