– Announced positive two-year topline results of sevasemten ARCH open label trial and advanced GRAND CANYON pivotal cohort in Becker –

– Positive interim topline data for DUNE trial of sevasemten in Becker –

– Expanded Phase 2 LYNX trial of sevasemten in Duchenne –

– Anticipated to overenroll Phase 2 FOX trial in Duchenne boys previously treated with gene therapy –

– Initiated Phase 2 CIRRUS-HCM trial of EDG-7500 in patients with obstructive HCM –

BOULDER, Colo.--(BUSINESS WIRE)-- Edgewise Therapeutics, Inc., (Nasdaq: EWTX), a leading muscle disease biopharmaceutical company, today reported financial results for the first quarter of 2024 and recent business highlights.

“2024 is off to a great start with tremendous progress on our skeletal and cardiac muscle programs,” said Kevin Koch, Ph.D., President and Chief Executive Officer of Edgewise. “Most recently, we initiated our Phase 2 CIRRUS-HCM trial of EDG-7500 and announced positive 2-year topline data from our ARCH open label trial in Becker. We expect significant catalysts on our programs throughout this year including data from the CANYON and CIRRUS studies.”

Recent Highlights

Musculoskeletal Program / Sevasemten

Becker Muscular Dystrophy (Becker)

Sevasemten 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.

ARCH open-label trial in Becker: The Company announced positive two-year topline results from the ARCH trial, an open label, single-center trial assessing safety, tolerability, impact on muscle damage biomarkers, pharmacokinetics (PK) and functional measures with sevasemten in adults with Becker. The ARCH trial evaluated sevasemten administered daily over two years in adults with Becker. Sevasemten was well-tolerated in all 12 participants with no discontinuations or dose reductions due to adverse events. During two years of sevasemten treatment, participants’ North Star Ambulatory Assessment (NSAA) scores stabilized and continued to diverge relative to declines reported across multiple Becker natural history studies.1, 2,3 In addition, significant decreases in key biomarkers of muscle damage including creatine kinase (CK) and fast skeletal muscle troponin I (TNNI2) were observed in participants treated with sevasemten, which are consistent with prior observations. The positive results from the two-year ARCH trial further support the hypothesis that a reduction in contraction-induced muscle damage has the potential to preserve and improve muscle function and disease progression in Becker.

CANYON Phase 2 placebo-controlled trial in adults with Becker: CANYON, the largest interventional Becker trial to date, includes 40 adults and 29 adolescents with a sevasemten treatment period of 12 months. The primary endpoint of CANYON is change in CK over the treatment period with additional measures collected, including NSAA, 100-meter timed test, biomarkers of muscle damage and MRI. The Company expects to report CANYON data in the fourth quarter of 2024.

GRAND CANYON, a global pivotal cohort in Becker:GRAND CANYON, an expansion of the CANYON placebo-controlled trial, is a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of sevasemten in adults with Becker. The primary endpoint of GRAND CANYON is change in NSAA. In addition, other functional assessments, biomarkers of muscle damage and safety will be assessed. GRAND CANYON is an 18-month cohort anticipated to recruit approximately 120 individuals with Becker, aged between 18 and 50 years old and a NSAA score between 5 and 32, at up to 50 sites in 10 countries. Data from GRAND CANYON, if positive, could support a marketing application. To learn more, go to clinicaltrials.gov (NCT05291091) or the GRAND CANYON microsite: https://www.beckergcstudy.com.

DUNE Phase 2 Exercise Challenge trial in adults with Becker, LGMD2I or McArdle disease: The Company continues to advance the DUNE Phase 2 Exercise Challenge study. This 16-week randomized, double-blind, placebo-controlled study with an open label extension to 78 weeks, assesses safety, PK, and biomarker response to exercise in adults with Becker, limb-girdle muscular dystrophy type 2I (LGMD2I) or McArdle disease. Unlike Becker, LGMD2I is a muscular dystrophy caused by a dysfunctional dystroglycan complex while McArdle is caused by deficiencies in glycogen mobilization leading to metabolic crisis and injury of skeletal muscle.

The study was designed with a 3-week screening period, which included a controlled exercise challenge and subsequent biomarker analysis, principally CK and TNNI2, followed by a 16-week double-blind period in which participants were randomized 2:1 to receive once-daily treatment with sevasemten (15 mg) or matching placebo. At week 12, participants underwent a second controlled exercise challenge to determine whether treatment with sevasemten conferred protection against exercise induced muscle damage.

Topline interim results showed that sevasemten was well tolerated across all 21 participants (Becker (n=9), LGMD2I (n=9) and McArdle (n=3)). Biomarker reductions in the Becker cohort were consistent with results observed in the ARCH trial, including statistically significant decreases in TNNI2 and CK versus patients on placebo; sevasemten treatment significantly reduced mean CK by 45% (p