Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

Inclusion Criteria:

• Age 4 to 16 years inclusive, at the time of informed consent/assent.

• Male with a confirmed diagnosis of DMD and with a mutation in the dystrophin genecharacterized by exon deletion amenable to exon 51 skipping.

• Upper extremity muscle group that is amenable to muscle biopsy.

• Brooke Upper Extremity Scale score of 1 or 2.

• Ambulatory or non-ambulatory. A non-ambulatory participant must have beennon-ambulatory for <2 years before enrollment.

• Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to thestart of study drug administration, with the expectation of maintaining a stabledose during the Placebo-Controlled and Open-Label Periods of the study (unless doseadjustment is required by weight change).

• Left ventricular ejection fraction of ≥50% by echocardiogram or ≥55% by cardiacmagnetic resonance imaging (MRI).

Exclusion Criteria:

• Uncontrolled clinical symptoms and signs of congestive heart failure (CHF).

• Any change in prophylaxis/treatment for CHF within 3 months prior to the start ofstudy treatment.

• History of major surgical procedure within 12 weeks prior to the start of study drugadministration or an expectation of a major surgical procedure during the study.

• Requirement of daytime ventilator assistance.

• Percent predicted FVC <40 % (applies only for participants who are age ≥7 years).

• Receipt of eteplirsen, or alternative exon-skipping/dystrophin-modifying therapy,within 12 weeks of randomization.

• Receipt of non-exon skipping investigational drug within 4 months before the startof study drug administration.

• Receipt of gene therapy at any time.

Other inclusion and exclusion criteria may apply.