To assess the pharmacodynamics (PD), safety, tolerability, pharmacokinetics (PK) and efficacy of GYM329 in ambulant adult patients with FSHD.

FSHD is a genetic muscle disorder characterized by asymmetric skeletal muscle weakness and muscle atrophy. Time of first symptom onset is variable, from childhood to adulthood, but typically manifests in the second or third decade of life. There is no approved therapy for FSHD; thus, there is a high unmet medical need as the disease can cause significant morbidity and reduce the quality of life of affected patients.

GYM329 (RO7204239) is an investigational, recycling and antigen-sweeping monoclonal anti-myostatin antibody. MANOEUVRE (NCT05548556) is a Phase 2, multicenter, randomized, placebo-controlled, double-blind study that will investigate the effect of GYM329 in adult ambulant patients with a genetically confirmed diagnosis of FSHD1 or FSHD2. Participants (target enrollment N~48) will complete a pre-treatment period to collect baseline movement data via a wearable device before randomization (1:1, GYM329: placebo) for the 52-week double-blind treatment period. GYM329 or placebo will be administered every 4 weeks by subcutaneous injection.

The primary endpoints are the percentage change from baseline in the contractile muscle volume of quadriceps femoris muscle as assessed by magnetic resonance imaging (MRI) at Week 52 and the safety of GYM329. Secondary endpoints include the change from baseline of muscle volume in various muscles and groups of muscles as assessed by MRI. Exploratory efficacy endpoints include assessment of motor function and strength. The MANOEUVRE study design will be presented.

This study will provide valuable information about the PD, safety, PK and efficacy of GYM329 treatment in patients with FSHD.