Design Therapeutics (DSGN) investor relations material

Program updates and clinical progress

• Lead program DT-216 targets Friedreich ataxia by increasing endogenous frataxin using a small molecule approach, with clinical proof of concept achieved earlier than expected and a primary endpoint set as endogenous frataxin blood protein.

• The 12-week efficacy assessment for DT-216 will focus on endogenous blood protein, with data expected in Q1 2027; sample size increased to 10 patients at 1 mg/kg, with higher dose cohorts also being explored.

• Four-week data showed dose-dependent increases in frataxin mRNA and protein, with notable improvements in mFARS (6.4 points) and Upright Stability Score (2.7 points), exceeding typical results from approved therapies.

• Engagement with FDA is ongoing to validate endogenous frataxin as a surrogate endpoint, potentially enabling accelerated approval pathways.

• Additional programs include a DM1 candidate (DT-818) in multiple ascending dose studies, a Fuchs' program with data expected next year, and a preclinical Huntington's program.

Mechanistic insights and competitive landscape

• DT-216 uniquely increases endogenous frataxin, unlike other approaches that provide exogenous protein or gene therapy, and is supported by extensive natural history data linking higher frataxin to better clinical outcomes.

• Natural history studies in Friedreich ataxia show a continuous relationship between frataxin levels and disease progression, supporting the therapeutic goal of increasing endogenous frataxin.

• Regulatory precedent exists for using frataxin as a surrogate endpoint, with other programs pursuing accelerated pathways based on biomarker changes.

• DT-818 for DM1 targets toxic RNA at the DNA level, showing high potency across a range of repeat lengths and offering a differentiated, widely distributed small molecule approach.

• Ongoing studies in DM1 will inform dose selection and endpoint strategy, with a focus on translating molecular impact to clinical benefit by 2027.

Forward-looking statements and strategic plans

• Q4 update planned to share registrational strategy for DT-216 after FDA feedback on surrogate endpoint use.

• Higher dose cohorts for DT-216 are exploratory, aiming to inform long-term development and late-stage planning.

• DM1 program will leverage learnings from the field to refine clinical endpoints and maximize impact on unmet needs.

• Fuchs' program data anticipated next year, with preclinical Huntington's program progressing.

• Continued focus on innovative small molecule approaches for monogenic diseases, aiming for best-in-disease profiles.