Design Therapeutics Releases Phase 1 Data For DT-168 Supporting Advancement Into Phase 2 Biomarker Trial For Patients With Fuchs Endothelial Corneal Dystrophy

esign Therapeutics, Inc. (NASDAQ:DSGN), a clinical-stage biotechnology company developing treatments for serious degenerative genetic diseases, today announced favorable data from a Phase 1 single- and multiple-ascending dose (SAD/MAD) trial of DT-168 in healthy volunteers, which will be presented on May 2, 2025 at Eyecelerator @ Park City 2025, an event backed by the American Academy of Ophthalmology highlighting industry advancements and innovative new products disrupting eye care.

DT-168 is a novel GeneTAC® small molecule, formulated as an eye drop, that is designed to selectively target and reduce the expression of the mutant TCF4 gene that causes corneal endothelial cell dysfunction leading to Fuchs endothelial corneal dystrophy (FECD).

"DT-168 represents a differentiated opportunity for FECD, a disease with millions of patients facing progressive vision loss and no approved disease modifying therapies," said Pratik Shah, Ph.D., chairperson and chief executive officer of Design Therapeutics. "Leveraging a convenient eye drop formulation, DT-168 is designed to address the underlying genetic cause of FECD by targeting the repeat expansion that drives disease progression. We are excited to initiate the Phase 2 proof-of-concept trial later this year as we advance what has the potential to be the first disease-modifying medicine for a large, underserved patient population."

Design completed a Phase 1, double-masked, placebo-controlled, randomized, SAD/MAD trial to evaluate the safety, tolerability and systemic pharmacokinetics (PK) of DT-168 ophthalmic solution. Twenty-four healthy volunteers received either placebo or single- and multiple-ascending doses of DT-168 eye drops twice daily for seven days (up to a maximum dose of two 0.5% drops twice-daily).

• DT-168 eye drops were well-tolerated in all participants.
• There were no serious adverse events, no ocular adverse events (AEs) and no treatment discontinuations due to AEs in the trial. All observed AEs were deemed not related to DT-168 by the trial investigator.
• As expected, PK analysis demonstrated systemic exposure below the limit of quantitation for all participants across all timepoints and all dose groups.
  
   

In parallel with the Phase 1 trial, Design conducted reference range studies which showed consistently different splicing in the corneal endothelium between unaffected eye donors and surgical samples from mutant TCF4 FECD patients, supporting the potential for corneal endothelium RNA biomarkers as a clinical proof-of-concept measure of drug activity.

Phase 2 Biomarker Trial of DT-168 in Patients with FECD

Based on these findings, Design plans to conduct a Phase 2 biomarker trial of DT-168 to evaluate safety, tolerability, and corneal endothelium biomarkers in patients with FECD. The trial will enroll FECD patients with the TCF4 mutation who are scheduled for corneal transplant surgery. Patients will receive 0.5% DT-168 eye drops twice-daily for approximately 4 weeks or more before corneal transplant surgery. Following surgery, tissues from the treated eyes of FECD patients will undergo testing to assess corneal endothelium RNA biomarkers, including the abnormal splicing of genes known as spliceopathy. Design plans to initiate the DT-168 Phase 2 biomarker trial in the second half of 2025, with data anticipated in 2026.

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. In addition to its GeneTAC® programs, DT-216P2, in development for patients with Friedreich ataxia, and DT-168, for Fuchs endothelial corneal dystrophy, the company is advancing programs in myotonic dystrophy type-1 and Huntington's disease. Discovery efforts are underway for multiple genomic medicines. For more information, please visit designtx.com.