Design Therapeutics (DSGN) Corporate Presentation summary

Platform and pipeline overview

• GeneTACⓇ small molecules modulate gene transcription to treat monogenic disorders, offering broad tissue distribution and simple drug delivery compared to gene therapy or oligonucleotides.

• Four main programs target Friedreich Ataxia (FA), Fuchs Endothelial Corneal Dystrophy (FECD), Myotonic Dystrophy Type 1 (DM1), and Huntington's Disease (HD), each addressing significant unmet needs and large market opportunities.

• GeneTACⓇ molecules are designed for allele-selective modulation, sparing healthy gene expression while targeting disease-causing mutations.

• The platform enables lower R&D spend and overcomes distribution challenges seen in traditional genomic medicines.

• $206 million in cash as of September 30, 2025, supports ongoing and planned operations.

Friedreich Ataxia (DT-216P2)

• FA is a severe, multi-organ monogenic disorder caused by GAA repeat expansion in the FXN gene, leading to reduced frataxin and mitochondrial dysfunction.

• DT-216P2 increases FXN levels in patient cells without affecting healthy cells and restores FXN in patient-derived neurons at low concentrations.

• Phase 1 MAD study showed dose-dependent increases in muscle FXN mRNA, with improved exposure and tolerability for the new DT-216P2 formulation.

• RESTORE-FA Phase 2 trial is ongoing, with 12-week frataxin data expected in 2H 2026.

• Current approved therapy (SkyclarysⓇ) does not address the genetic root cause or increase endogenous FXN.

Fuchs Endothelial Corneal Dystrophy (DT-168)

• FECD is a progressive corneal disease mainly caused by CTG repeat expansion in TCF4, leading to corneal edema and vision loss.

• DT-168 eye drops selectively block mutant TCF4 RNA, reduce nuclear foci, and improve spliceopathy in patient-derived cells without affecting wild-type transcripts.

• Phase 1 SAD/MAD study in healthy volunteers showed DT-168 was well-tolerated with no serious or ocular adverse events.

• Phase 2 biomarker study is underway, with data expected in 2H 2026; splicing biomarkers from surgical samples are being used as proof-of-concept.

• Observational study of ~250 patients supports endpoint selection and may expedite future trial recruitment.