Edgewise Therapeutics, Inc. announced the start of enrollment of GRAND CANYON, a global pivotal study of EDG-5506 in individuals with Becker. GRAND CANYON is an expansion of the CANYON study. CANYON, which was over-enrolled, includes 39 adults and 24 adolescents.

EDG-5506 is an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies including Becker and Duchenne muscular dystrophy. There are currently no approved therapies for individuals with Becker, a serious genetic, progressive neuromuscular disorder with significant unmet need. GRAND CANYON is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EDG-5506 in adults with Becker.

Data from GRAND CANYON, if positive, could support a marketing application. The primary endpoint of GRAND CANYON is North Star Ambulatory Assessment (NSAA). In addition, other functional assessments, biomarkers of muscle damage and safety will be assessed.

GRAND CANYON is anticipated to recruit approximately 120 individuals with Becker, aged between 18 and 50 years old, at up to 50 sites in 10 countries. The treatment period for participants will be 18 months. Positive 12-Month Results from the ARCH Open Label Study of EDG-5506 in Adults with Becker.

The ongoing ARCH study is an open label, single-center study assessing the safety, tolerability, impact on muscle damage biomarkers, function and pharmacokinetics (PK) of EDG-5506 in adults with Becker. The ARCH study is evaluating varying doses of EDG-5506 administered daily over 24 months in 12 adults with Becker. The Company reported data at the end of 12 months of treatment with EDG-5506.

EDG-5506 was well-tolerated in all participants with no dose reductions or discontinuations due to adverse events. Consistent with prior observations, significant decreases in key biomarkers of muscle damage were seen with treatment with EDG-5506. Importantly, creatine kinase (CK) and fast skeletal muscle troponin I were reduced by an average of 37% (p=0.001) and 79% (p<0.0001) from baseline, respectively, at the participants?

12-month visit. After 12 months of EDG-5506 dosing, North Star Ambulatory Assessment (NSAA) scores continued to trend in a positive direction. Nine of the twelve participants showed either a functional improvement (n=6) or exhibited stability (n=3) on NSAA scores relative to their baselines.

NSAA scores showed a consistent positive trend that diverges from trajectories observed in the natural history studies reported by Bello et al. (2016)1 and van de Velde et al. (2021)2 in which the yearly decline was -1.2 NSAA points.

Overall, after one-year, there was a +0.4-point trend toward improvement on the NSAA compared to the -1.2-point decline observed in natural history studies in Becker patients. The encouraging results from the 12-month ARCH study support the hypothesis that a reduction in contraction-induced muscle damage in muscular dystrophies has the potential to preserve and improve muscle function while preventing disease progression in dystrophinopathies. Observations from ARCH identified key factors, including the dose of EDG-5506, for the design of a potentially registrational trial.