Background: Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) are a next-generation chemistry platform in which a cell-penetrating peptide is conjugated to the PMO backbone, with the goal of increasing tissue penetration, exon skipping, and dystrophin production with less frequent dosing. SRP-5051 is an investigational PPMO designed to skip DMD exon 51. Objective: Here we report results from the Part A dose-finding phase of MOMENTUM (NCT04004065), an ongoing phase 2 study of SRP-5051. Methods: Patients amenable to exon 51 skipping (aged 7?21 years) received ascending doses of SRP-5051 (4, 10, 20, or 30 mg/kg) intravenously every 4 weeks. Primary endpoint was safety; other endpoints included exon skipping, dystrophin protein, and pharmacokinetics of each dose. Results: Eighteen patients were enrolled. At week 12, exon skipping for the 20- and 30-mg/kg cohorts was 2.57% and 10.79%, respectively (versus 0.26% and 1.62% at baseline), and mean dystrophin protein was 3.06% and 6.55% of normal (versus 0.17% and 0.92% at baseline); all patients in these cohorts experienced an increase in exon skipping and dystrophin production. Immunofluorescence results from the 30-mg/kg cohort showed correct localization of dystrophin to the sarcolemma. Overall, 17/18 (94.4%) patients experienced a treatment-emergent adverse event (TEAE); the majority were mild to moderate in severity. Ten (55.6%) patients experienced treatment-related TEAEs of hypomagnesemia (including 2 serious cases) prior to the implementation of magnesium monitoring and supplementation; most cases were mild to moderate, asymptomatic, and resolved with supplementation. No other safety concerns were identified. Conclusions: MOMENTUM Part A results show SRP-5051 increases exon skipping and dystrophin production and that the majority of TEAEs were mild to moderate in severity. All participants from Part A have been invited to enrol in Part B of MOMENTUM.