Design Therapeutics, Inc. a clinical-stage biotechnology company developing treatments for serious degenerative genetic diseases, today 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 (FECD), will be presented during an oral session at the Association for Research in Vision and Ophthalmology 2023 Annual Meeting (ARVO 2023), which is being held in New Orleans from April 23-27, 2023.
FECD is characterized by progressive corneal degeneration leading to vision loss and affects millions of people in the U.S. Approximately 75% of cases are caused by a mutation in the transcription factor 4 (TCF4) gene, consisting of a CTG trinucleotide repeat expansion that leads to the formation of pathogenic RNA foci in the nucleus and the mis-splicing of multiple transcripts. 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 (CECs) 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.
The preclinical data support the potential for DT-168 to address the most common genetic cause of FECD and support the continued development of DT-168 as a potential disease-modifying therapy. 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.
About Design Therapeutics
Design Therapeutics is a clinical-stage biotechnology company developing a new class of therapies based on its platform of GeneTAC™ gene targeted chimera small molecules. The company’s GeneTAC™ molecules are designed to either dial up or dial down the expression of a specific disease-causing gene to address the underlying cause of disease. Design is currently evaluating its lead GeneTAC™ small molecule, DT-216, in an ongoing Phase 1 clinical trial in patients with Friedreich ataxia. The company is also advancing programs in Fuchs endothelial corneal dystrophy and myotonic dystrophy type-1.