DMD is caused by absence of functional dystrophin protein. DYNE-251, an investigational therapeutic for DMD, leverages the transferrin receptor to deliver an exon 51-skipping PMO to affected tissues with the goal of restoring dystrophin expression.

In the MAD portion of DELIVER, participants are randomized to receive DYNE-251 or placebo Q4W or Q8W for 6 months and are subsequently escalated to the highest tolerable dose in the OLE/LTE. All 54 currently enrolled participants are at the 20 mg/kg dose level. 

DYNE-251 drove dose-dependent increases in mean PMO muscle concentration and exon skipping, resulting in 3.22% and 3.72% of normal mean dystrophin in the 10 mg/kg and 20 mg/kg cohorts, respectively, at 6 months. The mean corresponding muscle content-adjusted dystrophin levels were 7.64% and 8.72% of normal. DYNE-251 led to improvements across multiple functional endpoints, including the North Star Ambulatory Assessment, Time to Rise from Floor, 10-Meter Walk/Run Test, and Stride Velocity 95^th Centile. Improvements were noted as early as 6 months in both the 10 mg/kg and 20 mg/kg cohorts; a continued effect through 12 months was observed in the 10 mg/kg cohort. DYNE-251 had a favorable safety profile as of the analysis date with most TEAEs reported as mild or moderate. Three serious TEAEs potentially related to study drug occurred in two participants in the 40 mg/kg Q4W cohort. These events had multiple confounding factors suggestive of infection or background risk that may have contributed to their presentation. Subsequently, all participants in the 40 mg/kg cohorts were lowered to the 20 mg/kg dose level.

DYNE-251 had a favorable safety profile and resulted in early improvements across multiple functional endpoints.