Belite Bio Inc. announced additional findings from the 24-month Phase 2 study of Tinlarebant in adolescent Stargardt disease (STGD1) at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. Tinlarebant is Belite Bio's orally administered tablet intended to slow disease progression in patients affected with STGD1 and Geographic Atrophy (GA) in advanced Dry Age-related Macular Degeneration (Dry AMD). Genetic profiling was performed on the 13 adolescent STGD1 patients enrolled in a Phase 2 study of Tinlarebant.

Eleven of these subjects (85%) harbored severe pathogenic/likely pathogenic ABCA4 variants. Despite these severe variants, 42% of Tinlarebant-treated subjects (5 out of 12) did not develop incident atrophic (definitely decreased autofluorescence, DDAF) retinal lesions and no change in questionably decreased autofluorescence (QDAF) was observed during the 24-month treatment period. Incident atrophic lesions appeared in seven subjects at different timepoints over 24 months; four of these subjects developed DDAF lesions after month 12.

The mean DDAF lesion growth at month 24 was 0.51 mm2 with a range of variation of 0.4 mm2, a growth rate that is significantly lower than what has been observed in natural history studies. Importantly, six STGD1 patients who had a mean bilateral best corrected visual acuity (BCVA) loss of 10 letters per year prior to enrollment in the Phase 2 study showed a mean BCVA loss equivalent to 1.9 letters per year during the 24-month treatment period. Analysis of genotype-phenotype relationships revealed that sibling subjects with identical ABCA4 mutations had different rates of lesion growth and BCVA loss indicating that identical genotypes do not necessarily predict an identical course of disease.

Notably, retinal imaging data from the Phase 2 study was reanalyzed using a novel lesion size quantification method that utilizes a mathematical classification of lesions to reduce subjective reader bias and provide enhanced accuracy and superior precision compared to the traditional method of DDAF lesion quantification. This analysis revealed DDAF lesions within the macula in 12 eyes of eight subjects at baseline. Analysis of change in atrophic lesion area within the macula of these eyes over 24 months showed a halt in lesion growth into the macula after 16 months.

This finding is consistent with the observed stabilization of visual acuity.