Design Therapeutics (DSGN) 2025 Conference Transcript

Summary of Design Therapeutics Conference Call Company Overview - Company: Design Therapeutics (DSGN) - Focus: Development of a new class of small molecules called GeneTACs that modulate gene expression for treating monogenic disorders [2][3] Key Points on GeneTAC Platform - Mechanism: GeneTACs can increase or decrease the expression of specific genes by recognizing DNA sequences and recruiting transcriptional machinery [2] - Targeted Diseases: - Friedreich's ataxia (FA) - Fuchs' endothelial corneal dystrophy - Myotonic dystrophy - Huntington's disease [2][3] Friedreich's Ataxia (FA) Insights - Gene Target: The frataxin gene, where low expression leads to FA [3] - Current Expression Levels: - Carriers have about 50% frataxin expression; patients have 20-25% of wild-type levels [9] - Clinical Benefit: Potential to increase frataxin expression could provide significant clinical benefits [3][10] - Clinical Trials: Two programs are currently in clinical investigation [4] Clinical Development of DT216 - Clinical Trials: DT216 was taken into the clinic in 2022-2023, showing the ability to upregulate frataxin expression [16] - Challenges: Previous formulation faced issues like injection site thrombophlebitis and short duration of exposure [17] - New Formulation: DT216P2 has shown improved pharmacokinetics and resolved previous issues [19][20] - Next Steps: Currently in Phase II studies (RESTORE FA trial) with multiple ascending doses [24] Fuchs' Endothelial Corneal Dystrophy Program - Prevalence: Approximately 2 million diagnosed cases in the U.S. [34] - Mechanism: Caused by a mutation in the TCF4 gene leading to toxic RNA production [35] - Treatment Approach: DT168 aims to reduce toxic RNA levels through eye drops, potentially modifying disease progression [36] - Phase I Study: Confirmed tolerability and safety of DT168 in healthy volunteers [37] Biomarker Development - Splice Markers: Identified splice defects as potential biomarkers for assessing treatment efficacy [38] - Study Design: Patients scheduled for corneal transplants will be treated with DT168 to evaluate splicing effects [39] Regulatory Considerations - Endpoints for Registration Trials: Evaluating visual quality measures, corneal edema, and imaging endpoints for future trials [44] - Unmet Need: Any treatment that slows or stops disease progression would be highly valuable [46] Other Programs - DM1 Program: Expected to select a development candidate this year [48] - Competitive Positioning: GeneTACs may offer advantages over existing therapies due to their mechanism and administration routes [49] Financial Position - Capital: Company ended the quarter with $216 million, sufficient to advance clinical programs [51] Market Potential - Market Validation: Skyclaris from Biogen is annualizing around $500 million, indicating a significant market opportunity for therapies targeting the root cause of FA [31]