Design Therapeutics (DSGN) 2024 Cantor Fitzgerald Global Healthcare Conference summary

Company overview and platform

• Focuses on small molecules that modulate gene expression for monogenic diseases.

• Targets include Friedreich's ataxia, Fuchs' corneal dystrophy, Huntington's disease, and myotonic dystrophy.

• GeneTAC platform uses heterobifunctional molecules to restore or repress transcription at specific loci.

• Small molecules offer broad tissue distribution and pharmaceutical advantages.

Friedreich's ataxia program (DT-216)

• Friedreich's ataxia caused by GAA repeat expansion in the frataxin gene, reducing protein levels and causing multi-organ dysfunction.

• GeneTAC DT-216 recruits BRD4 to mutated loci, restoring transcriptional elongation and frataxin expression.

• Preclinical and clinical data show increased frataxin RNA and protein after treatment.

• New formulation extends drug exposure and reduces injection site issues, enabling subcutaneous and IV administration.

• 2024 focus: confirm safety and exposure in GLP studies, then initiate clinical trials in healthy volunteers and patients.

Myotonic dystrophy and Fuchs' corneal dystrophy programs

• Myotonic dystrophy involves CTG repeat expansions in DMPK, leading to toxic RNA foci and spliceopathy.

• GeneTACs for DM1 recruit repressive machinery to selectively reduce mutant RNA, restoring normal splicing.

• Next milestone: declare a development candidate and plan for clinical proof of concept within current cash runway.

• Fuchs' program aims to dial down TCF4 transcription, with IND cleared and phase 1 underway.