Design Therapeutics Releases Clinical Data for DT-216P2

Design Therapeutics announced biomarker and clinical data from the ongoing Phase 1/2 RESTORE-FA trial evaluating DT-216P2 in patients with Friedreich ataxia. DT-216P2 is a GeneTAC small-molecule therapeutic candidate designed to increase frataxin expression by targeting the GAA repeat expansion in the FXN gene, the genetic root cause of FA. RESTORE-FA is a Phase 1/2 clinical trial evaluating DT-216P2 in patients with FA, designed to assess safety, pharmacokinetics, pharmacodynamics, and exploratory clinical endpoints. As of May 17, 16 patients had completed treatment with weekly intravenous DT-216P2 across dose cohorts of 0.1, 0.3, 0.6, and 1 mpk for four weeks. After four weeks of DT-216P2 treatment at the 1 mpk dose cohort, patients demonstrated mean improvements from baseline of 6.4 points in the modified Friedreich's Ataxia Rating Scale and 2.7 points in the Upright Stability Score. Further, DT-216P2 demonstrated changes of greater than five points in patient-reported fatigue, as measured by the PROMIS Fatigue Scale, both at the end of four weeks of treatment and two weeks following the last dose. These data exceeded the three-point threshold generally considered to be a minimal important change in fatigue. Dose-dependent increases in endogenous FXN were observed following treatment with DT-216P2 across FXN mRNA and protein assays in whole blood, as well as FXN mRNA measurements in affected muscle tissue, demonstrating activity in both blood and muscle. Following four weeks of treatment at 1 mpk, whole blood FXN mRNA levels increased by 65% from baseline. Whole blood FXN-M and FXN-E protein levels increased by 22%-27% from baseline two weeks following the last dose. Muscle FXN mRNA levels increased by 42% from baseline. Together, these findings demonstrate comprehensive biomarker activity with increases in FXN mRNA and protein, as well as activity in both blood and muscle caused by DT-216P2 treatment. The biomarker data provide mechanistic support for the observed clinical improvements in FA patients. DT-216P2 was generally well-tolerated, with no serious adverse events or treatment discontinuations reported. All adverse events were mild or moderate. Adverse events considered possibly or probably related to DT-216P2 occurring in more than one patient included mild to moderate transient alanine transaminase elevations observed in three patients, all of which were asymptomatic with no associated increases in bilirubin and on background omaveloxolone. Transient ALT elevations are anticipated with enhanced mitochondrial activity, a downstream consequence of FXN restoration. Based on these data, the company intends to pursue a registrational path and provide an update on its plans in the fourth quarter of 2026.