DT-168

DT-168 is a first-in-class GeneTAC small molecule therapy developed as an eye drop for the treatment of Fuchs endothelial corneal dystrophy (FECD). It is designed to selectively target and reduce the expression of the mutant transcription factor 4 (TCF4) gene, specifically by binding to expanded CTG repeats in TCF4. This mechanism aims to decrease pathogenic RNA foci formation and correct mis-splicing events that drive FECD progression. The drug leverages a non-invasive, topical ophthalmic formulation intended to address the underlying genetic cause of FECD—a disease with millions affected globally and no approved disease-modifying therapies. In preclinical studies, DT-168 demonstrated reduction of RNA foci and improvement in splicing defects in patient-derived corneal endothelial cells. Phase 1 clinical trials showed favorable safety and tolerability profiles in healthy volunteers, with systemic exposure below quantifiable levels. A Phase 2 biomarker trial enrolling FECD patients with TCF4 mutations is planned for late 2025[1][2][3][5][6][7][8].