Edgewise Therapeutics Announces Initiation of GRAND CANYON, a Global Pivotal Study of EDG-5506 in Becker Muscular Dystrophy (Becker)

– GRAND CANYON is the first pivotal study of an investigational therapy for Becker –
– CANYON, the initial Phase 2 cohorts, is fully enrolled –

BOULDER, Colo., September 26, 2023--(BUSINESS WIRE)--Edgewise Therapeutics, Inc. (Nasdaq: EWTX), a leading muscle disease biopharmaceutical company, today 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. To learn more, go to clinicaltrials.gov (NCT05291091) or the GRAND CANYON microsite: https://www.beckergcstudy.com.

"Based on the strength of safety, functional and biomarker results from our ARCH open label study, we have rapidly initiated this ground-breaking clinical study," said Joanne Donovan, M.D., Ph.D., Chief Medical Officer of Edgewise. "This study is critical for the Becker community, as there currently are no approved treatments for Becker, a condition that for far too long has been neglected."

"It is exciting to move to the next stage of testing of the clinical hypothesis that a reduction in contraction-induced muscle damage has the potential to benefit people living with muscular dystrophies," said Alan Russell, Ph.D., Co-Founder and Chief Scientific Officer of Edgewise. "Having seen promising preclinical results with EDG-5506 translate clinically, I am thrilled we are entering into a pivotal study."

Edgewise will host a community webinar with Parent Project Muscular Dystrophy on October 18, 2023, at 1:00 pm ET to share details about the trial and answer questions from the community. The registration page will be available on the PPMD website in early October.

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. ^{1, 2}

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. Go to clinicaltrials.gov to learn more about this study (NCT05160415).

About Becker Muscular Dystrophy

Becker is a genetic, progressive neuromuscular disorder that imposes significant physical, emotional, financial, and social impacts predominantly on males and their caregivers. Genetic mutations in the dystrophin gene resulting in Becker lead to contraction-induced muscle damage, which is the primary driver of muscle loss and impaired motor function in muscular dystrophies. Functional decline can begin at any age, and once that muscle loss occurs, the decline in function is irreversible and continues throughout the individual’s life. Some individuals living with Becker experience heart failure from cardiomyopathy, which may result in heart transplantation or early death. Currently there is no cure for Becker; early and long-term multidisciplinary care from neuromuscular specialists, cardiologists, physical therapists, and other specialists is critical for optimized disease management. Novel therapies are in development for Becker, including muscle targeted interventions, aimed at positively impacting disease trajectory.

About EDG-5506 for Becker and Duchenne Muscular Dystrophies

EDG-5506 is an orally administered small molecule designed to prevent contraction-induced muscle damage in dystrophinopathies including Duchenne and Becker. EDG-5506 presents a novel mechanism of action designed to selectively limit the exaggerated muscle damage caused by the absence or loss of functional dystrophin. By minimizing the progressive muscle damage that leads to functional impairment, EDG-5506 has the potential to benefit a broad range of patients suffering from debilitating genetic neuromuscular disorders. It is anticipated to be used as a single agent therapy, but it may also provide an additional benefit in combination with available therapies and therapies currently in development. In August 2021, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to EDG-5506 for the treatment of individuals with Becker.

The Company has completed a Phase 1 clinical trial of EDG-5506 designed to evaluate safety, tolerability, PK and pharmacodynamics of EDG-5506 in adult healthy volunteers (Phase 1a) and in adults with Becker (Phase 1b) (NCT04585464). In ARCH, an open-label, single-center trial (NCT05160415) assessing long-term safety and PK, decreases in biomarkers of muscle damage and trends toward improvement in NSAA have been observed following 12 months of treatment with EDG-5506. The Phase 2 trial of EDG-5506 in Becker (CANYON) has been expanded to include an additional 120 adult participants in a pivotal cohort called GRAND CANYON. CANYON is fully enrolled; GRAND CANYON is currently enrolling. LYNX, an ongoing Phase 2 trial (NCT05540860), is assessing safety, PK and biomarkers of muscle damage in participants with Duchenne. The Company is also continuing to recruit the DUNE Phase 2 exercise challenge study, to evaluate the effect of EDG-5506 on biomarkers of muscle damage following exercise in adults with LGMD2I, Becker or McArdle disease at a single site in Denmark.

About Edgewise Therapeutics

Edgewise Therapeutics is a leading muscle disease biopharmaceutical company developing novel therapeutics for muscular dystrophies and serious cardiac conditions. The company’s deep expertise in muscle physiology is driving a new generation of first-in-class therapeutics. EDG-5506 is an orally administered skeletal myosin inhibitor in advanced clinical trials in patients with Becker, Duchenne, and Limb-Girdle muscular dystrophies as well as McArdle Disease. EDG-7500, currently in a Phase 1 trial, is a novel cardiac sarcomere modulator for the treatment of HCM and other disorders of cardiac diastolic dysfunction. The entire team at Edgewise is dedicated to our mission: changing the lives of patients and families affected by serious muscle diseases. To learn more, go to: www.edgewisetx.com or follow us on LinkedIn, X (formerly Twitter), Facebook, Instagram and Threads.

References

[1] Bello L, et al., Functional Changes in Becker Muscular Dystrophy: Implications for Clinical Trials in Dystrophinopathies, Scientific Reports, 2016.

[2] van de Velde et al., Selection Approach to Identify the Optimal Biomarker Using Quantitative Muscle MRI and Functional Assessments in Becker Muscular Dystrophy, Neurology, 2021.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the potential of, and expectations regarding EDG-5506 and statements regarding Edgewise’s expectations relating to its clinical trials, including the GRAND CANYON study and enrollment of such study. Words such as "believes," "anticipates," "plans," "expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon Edgewise’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company including the potential for Edgewise’s product candidates to cause serious adverse events; Edgewise’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; the timing, progress and results of preclinical studies and clinical trials for EDG-5506; Edgewise’s ability to enroll and maintain patients in clinical trials; Edgewise’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; the timing, scope and likelihood of regulatory filings and approvals; the potential for any clinical trial results to differ from preclinical, interim, preliminary, topline or expected results; Edgewise’s ability to develop a proprietary drug discovery platform to build a pipeline of product candidates; Edgewise’s manufacturing, commercialization and marketing capabilities and strategy; the size of the market opportunity for Edgewise’s product candidates; the loss of key scientific or management personnel; competition in the industry in which Edgewise operates; Edgewise’s reliance on third parties; Edgewise’s ability to obtain and maintain intellectual property protection for its product candidates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled "Risk Factors" in documents that Edgewise files from time to time with the U.S. Securities and Exchange Commission. These forward-looking statements are made as of the date of this press release, and Edgewise assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

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