Duchenne muscular dystrophy (DMD) is an X-linked muscular disease caused by mutations in the DMD gene that prevent the expression of a functional dystrophin protein. Oligonucleotide-mediated skipping of DMD exons can restore the reading frame and dystrophin protein expression. 

AOC 1044 is an antibody-oligonucleotide conjugate (AOC^TM) comprised of a humanized anti-transferrin receptor 1 (TfR1) antibody conjugated to multiple copies of a phosphorodiamidate morpholino oligomer (PMO) targeting DMD44 mRNA to produce truncated but functional dystrophin protein.

EXPLORE44^TM (NCT05670730) is a randomized, placebo-controlled, double-blind phase 1/2 trial conducted in two parts. Part A assesses the effects of AOC 1044 in 5 single-dose cohorts of healthy volunteers, who are monitored for 3 months. Part B assesses the effects of AOC 1044 in 3 multiple-ascending dose-level cohorts of participants with DMD44, dosed no more frequently than once every 6 weeks for 3 months, with 3 months of follow-up.

The primary objective is to evaluate safety and tolerability of single doses in healthy volunteers and multiple doses in participants with DMD44. Secondary objectives include pharmacokinetics in part A and pharmacokinetics and pharmacodynamics with exon 44 skipping and dystrophin protein levels in part B. Exploratory objectives include pharmacodynamics with exon 44 skipping in healthy volunteers (part A) and measures of functional activity, patient-reported outcomes, and quality of life in participants with DMD44 (part B).

Part A will enroll approximately 40 healthy male volunteers (18-55 years). Part B will enroll 24 ambulatory or non-ambulatory males (7-27 years) with genetically confirmed DMD44. Eligible participants from part B will have the option to enroll in a planned open-label extension study.