Design Therapeutics (DSGN) Jefferies Global Healthcare Conference 2025 summary

Strategic vision and platform overview

• Pioneering small molecule genomic medicines to modulate gene transcription for monogenic diseases.

• Four programs in development, with clinical trials underway for Friedreich's ataxia (FA) and Fuchs endothelial corneal dystrophy (FECD).

• Platform aims to surpass gene editing, gene therapy, and oligonucleotide approaches.

• Operating runway supports clinical proof of concept data in at least one program.

Friedreich's ataxia (FA) program updates

• FA caused by GAA repeat expansion in frataxin gene, leading to reduced frataxin expression.

• GeneTAC molecules restore frataxin to normal levels by targeting DNA and recruiting transcriptional machinery.

• Previous formulation (DT-216) showed dose-dependent frataxin increases but had short tissue exposure and injection site issues.

• New formulation (DT-216P2) addresses prior limitations, showing improved PK and no injection site thrombophlebitis in early studies.

• RESTOR-FA phase 1/2 trial underway; first patient dosed with no adverse events, U.S. IND on clinical hold for non-clinical deficiencies.

Fuchs endothelial corneal dystrophy (FECD) program updates

• FECD driven by CTG repeat in TCF4 gene, causing toxic RNA and splicing defects.

• DT-168 eye drop eliminates toxic RNA foci and restores normal splicing in patient-derived cells.

• Phase 1 trial in healthy volunteers showed good tolerability and minimal systemic exposure.

• Biomarker assay developed to measure splicing correction in corneal tissue.

• Phase 2 proof of concept biomarker study to start in H2 2024, with results expected in 2026.