Design Therapeutics’ DT-168 molecule shows efficacy in corneal dystrophy

Design Therapeutics announced that preclinical data for the company’s novel GeneTAC small molecule, DT-168, an eye drop being developed for the treatment of Fuchs endothelial corneal dystrophy, will be presented during an oral session at the Association for Research in Vision and Ophthalmology 2023 Annual Meeting in New Orleans from April 23-27. FECD is characterized by progressive corneal degeneration leading to vision loss and affects millions of people in the U.S. There are no disease-modifying therapies approved for FECD, and advanced cases generally require ocular surgery, including corneal transplant. DT-168 is designed to selectively target the expanded CTG repeats in the TCF4 gene to reduce RNA foci formation and mis-splicing. In preclinical studies, DT-168 reduced foci in patient-derived primary corneal endothelial cells to levels seen in cells from healthy individuals with low nanomolar IC50 values. Treatment with DT-168 also significantly improved mis-splicing in patient-derived CECs across a panel of genes. Additionally, in animal studies DT-168 eye drops were well-tolerated after multiple doses and distributed throughout the cornea with micromolar levels of DT-168 observed in the cornea 24 hours after dosing. Design remains on-track to submit an Investigational New Drug application for DT-168 for the treatment of FECD in the second half of 2023.