Design Therapeutics (DSGN) Jefferies London Healthcare Conference 2024 summary

Strategic vision and platform differentiation

• Pioneering small molecule genomic medicines that modulate gene expression for monogenic disorders.

• Genomic medicine platform aims to surpass gene editing and gene therapy in efficacy and safety.

• Four lead programs target Friedreich ataxia, Fuchs endothelial corneal dystrophy, Huntington's disease, and myotonic dystrophy type 1.

• GeneTAC molecules offer broad tissue distribution and act without altering the genome.

• Platform designed for allele-specific targeting and modulation of disease-causing mutations.

Pipeline progress and clinical updates

• FECD program in phase 1 with healthy volunteer data expected in the first half of next year.

• Friedreich ataxia program to enter clinic in 1H 2025, starting with healthy volunteers and moving to patients.

• Huntington's and myotonic dystrophy programs advancing toward development candidate declaration.

• DT216P2, a new FA drug product, developed to improve injection site safety and sustain exposure.

• DT168 for FECD formulated as an eye drop, showing potent reduction of toxic RNA foci in patient-derived cells.

Scientific and clinical rationale

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

• GeneTACs restore frataxin expression in FA patient cells to normal levels in a dose-dependent manner.

• New excipient in DT216P2 resolves prior injection site issues and enables sustained drug exposure.

• Consistent potency of FA GeneTACs observed across diverse patient genotypes and repeat lengths.

• FECD caused by CTG repeat in TCF4 gene, with DT168 targeting toxic RNA and improving cellular function.