Edgewise Therapeutics - EWTX (Nasdaq)
Unique expertise and singular focus on muscle science to develop novel therapeutics for serious skeletal and cardiac muscle diseases.
Disclosure: HELD
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 novel therapeutics. Sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor in late-stage clinical trials in Becker and Duchenne muscular dystrophies. EDG-7500 is a novel cardiac sarcomere modulator for the treatment of hypertrophic cardiomyopathy and other diseases of diastolic dysfunction, currently in Phase 2 clinical development.
“Closing out 2024 with positive Phase 2 CANYON results, completing enrollment in GRAND CANYON and advancing CIRRUS-HCM, we are well positioned in 2025 across our muscular dystrophy and cardiovascular portfolio,” said Kevin Koch, Ph.D., President and Chief Executive Officer of Edgewise Therapeutics. “In the first half of this year, we look forward to announcing additional data from EDG-7500 in HCM as well as regulatory and clinical program updates on Sevasemten in Becker and Duchenne.”
Muscle biology is exciting and complex. The Company explores the vast potential of this organ, which plays a critical role in movement, metabolic regulation, inflammation, human growth, and other important systems within the body. Their goal is to bring muscle-targeted therapeutics to the lives of those who need them most.
Platform
Guided by their approach to targeting the muscle as an organ, they have combined their foundational expertise in muscle biology and small molecule drug discovery to build a proprietary, muscle-focused platform.
This knowledge informs their therapeutic development across serious musculoskeletal, cardiovascular and cardiometabolic diseases. The Company’s team has broad experience in these disease areas, with great appreciation of the patients’ unmet needs, which their science aims to address.
Muscular Dystrophies/Contraction-induced muscle injury - Sevasemten
Sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor designed to preserve and protect unstable muscle against contraction-induced injury in individuals living with rare skeletal muscle disorders, including Becker and Duchenne.
The Company has developed Sevasemten with the aim to address the root cause of muscle breakdown in muscular dystrophies, contraction-induced muscle damage.
In muscular dystrophies, the muscle lacks protective components including the fully functional protein dystrophin. When muscle fibers are not protected and unstable, contraction-induced injury starts a repetitive cycle that ultimately leads to fat and scar and fibrosis in the muscle, and loss of function.
Cardiovascular Disease - EDG 7500
EDG-7500 is a novel oral, selective, cardiac sarcomere modulator, intended to slow the excessive rate of early contraction and improve impaired cardiac relaxation associated with obstructive and non-obstructive HCM, and with other diseases of diastolic dysfunction.
The Company is developing EDG-7500, a selective cardiac sarcomere modulator, with the aim to slow early contraction velocity and address impaired cardiac relaxation associated with hypertrophic cardiomyopathy (HCM).
Two major forms of HCM include obstructive (oHCM) and non-obstructive (nHCM), each leading to impaired cardiac performance. In oHCM, as the left ventricle (LV) contracts (systole) to eject oxygenated blood from the heart into systemic circulation, the mitral valve makes physical contact with the hypertrophied septal wall. This contact underlies the basis of the obstructed ejection of blood through the LV outflow tract (LVOT) creating a pressure difference, or gradient (LVOT-G) between the LV cavity and systemic circulation. In nHCM, the hypertrophy is more symmetrically distributed in the LV walls, therefore the patient does not develop LVOT obstruction nor pressure gradient. However due to LV hypertrophy and stiffness, LV relaxation is impaired and LV filling with blood (diastole) is significantly reduced.
Recent Development Highlights
Muscular Dystrophy Program - Sevasemten
Sevasemten - Becker
Sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor designed to protect muscle against contraction-induced muscle damage in muscular dystrophies including Becker and Duchenne.
Becker is a rare, genetic, life-shortening, debilitating and degenerative neuromuscular disorder. Genetic mutations in the dystrophin gene result in contraction-induced muscle damage, which is the primary driver of irreversible muscle loss and impaired motor function. The disease predominantly affects males with functional decline beginning at any age, and once that muscle loss occurs, the decline in function is irreversible and continues throughout the individual’s life.
Currently, there are no approved therapies on the market to treat Becker.
CANYON Phase 2 placebo-controlled trial in adults with Becker:
In December 2024, the Company announced positive topline results from CANYON, the largest interventional Becker trial that evaluated 40 adults and 29 adolescents with a Sevasemten treatment period of 12 months. Data from CANYON will be presented at the 2025 MDA Clinical and Scientific Conference. The Company plans to engage the U.S. FDA in the first half of 2025 to discuss marketing authorization filing strategies for Sevasemten in Becker.
GRAND CANYON, a global pivotal placebo-controlled cohort in Becker:
In February 2025, the Company completed enrollment in GRAND CANYON, an expansion of the CANYON placebo-controlled trial. The 18-month GRAND CANYON study is active at 51 sites in 12 countries, including the United States, United Kingdom, Netherlands, Denmark, Belgium, France, Spain, Germany, Italy, Israel, New Zealand and Australia. GRAND CANYON enrolled 175 adults, reflective of the Becker community’s enthusiasm to work toward a therapeutic option. Data from the study are expected in Q4 2026.
MESA Phase 2 open label extension trial in adults with Becker:
The Company is advancing MESA, an open-label extension trial to assess the long-term effect of Sevasemten in individuals with Becker. MESA provides continued access to Sevasemten to participants who were previously enrolled in ARCH, or completed CANYON, GRAND CANYON, or DUNE. To date, MESA has enrolled 99% of eligible participants completing these prior trials.
Sevasemten - Duchenne
Duchenne, a severe degenerative muscle disorder, is the most common type of muscular dystrophy with a median life expectancy of around 30 years. Genetic mutations in the dystrophin gene result in contraction-induced muscle damage, which is the primary driver of irreversible muscle loss and impaired motor function. While there are approved therapies on the market aimed to treat the disease, there remains a high unmet need for additional therapies.
LYNX and FOX Phase 2 trials in boys with Duchenne:
LYNX is an ongoing multi-center, dose-finding Phase 2 trial to evaluate the effect of Sevasemten on safety, biomarkers of muscle damage and function in children with Duchenne treated with oral, once-daily Sevasemten.
FOX is a Phase 2 ongoing placebo-controlled trial to assess the effect of Sevasemten on safety, biomarkers of muscle damage and function in children and adolescents with Duchenne who have been previously treated with gene therapy.
Based on collective dose finding observations from both LYNX and FOX, the Company will form its Phase 3 strategy for Sevasemten in Duchenne including patient and dose selection. The Company expects to report data from LYNX and FOX as well as its future clinical trial plans in the first half of 2025.
The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8–4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4–7.8 per 100,000 people). Source: here
Cardiovascular and Cardiometabolic Programs - Hypertrophic cardiomyopathy (HCM)
HCM - EDG-7500
EDG-7500 is a novel oral, selective, cardiac sarcomere modulator, specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with HCM and other diseases of diastolic dysfunction. HCM is the most common form of genetic heart disease, affecting approximately one in 500 people, and is associated with reduced quality of life and an elevated risk of heart failure, abnormal heart rhythms, and sudden cardiac death. There are two major forms of HCM: obstructive and non-obstructive. Despite advancements in treatment options for some HCM patients, there remains a significant unmet need for additional therapeutic approaches for patients.
CIRRUS-HCM Phase 2 trial in adults with HCM:
The Company is advancing CIRRUS-HCM, a multi-part, open-label trial, in individuals with HCM at up to 20 clinical sites in the U.S. Part A of the trial was designed to evaluate the safety and tolerability of a single oral dose of EDG-7500 in obstructive HCM. In September 2024, the Company announced positive topline data from Part A showing that treatment with EDG-7500 led to robust left ventricular outflow tract gradient reductions without meaningful changes in left ventricle ejection fraction. Parts B and C of CIRRUS-HCM are evaluating safety and efficacy of multiple doses of EDG-7500 over 28 days in individuals with either obstructive or non-obstructive HCM. The Company expects to report topline CIRRUS-HCM 28-day data in the first quarter of 2025. Further, the Company expects to report data from the 12-week CIRRUS-HCM trial in individuals with obstructive HCM and non-obstructive HCM in the second half of 2025.
Preclinical programs:
During 2025, the Company expects to file an investigational new drug application for a novel candidate for the treatment of heart failure, and select a proprietary cardiometabolic drug candidate based on preclinical proof-of-concept data.
Pipeline
Please note: Sevasemten is an investigational therapy that has not been approved for use in Becker muscular dystrophy or Duchenne muscular dystrophy by any regulatory agency, as its safety and effectiveness have not been established for the treatment of these diseases.
EDG-7500 is an investigational therapy that has not been approved for use in HCM by any regulatory agency, as its safety and effectiveness have not been established for the treatment of these diseases.
Stock Performance
Main Shareholders - Active Funds
Leadership
Kevin Koch, Ph.D. - President, Chief Executive Officer and Director
Kevin Koch, Ph.D., has served as the President, Chief Executive Officer and a member of the board of directors since 2017 and has been in the life science industry for over 30 years with a focus on drug discovery, translational medicine and clinical development. Since 2016, he has also served as a Venture Partner with OrbiMed. Dr. Koch previously served as the Senior Vice President of Drug Discovery, Chemical and Molecular Therapeutics at Biogen where he managed global drug discovery and biomarker development. Dr. Koch was a co-founder of Array BioPharma, serving as President, Chief Scientific Officer and board member from the company’s inception in 1998 to 2013. While there, he built a fully integrated research and development team that oversaw the invention of over 20 clinical development candidates across multiple therapeutic areas, several of which are now marketed medicines. Prior to Array, Dr. Koch held senior positions at Amgen and Pfizer Central Research. Dr. Koch received a B.S. in Chemistry and Biochemistry from State University of New York, Stony Brook, and his Ph.D. in Synthetic Organic Chemistry from University of Rochester.
Alan Russell, Ph.D. - Co-Founder, Chief Scientific Officer and Director
Alan Russell, Ph.D., serves as the Co-Founder, Chief Scientific Officer and a member of the board of directors. Previously, Dr. Russell served at GlaxoSmithKline as VP and Head of the Muscle Metabolism Discovery Performance Unit, leading a broad discovery and development effort focused on patients for whom muscle function is compromised. Prior to this, he worked at Cytokinetics Inc, and is the co-inventor of Tirasemtiv and Reldesemtiv, direct muscle sensitizers in clinical trials for Amyotrophic Lateral Sclerosis (ALS). Dr. Russell received a BPharm in Pharmacy and Pharmacology and Ph.D. in Cell Biology and Gene Therapy from the University of Bath in the UK and Postdoctoral training at the Stanford University School of Medicine.
Joanne M. Donovan, M.D., Ph.D. - Chief Medical Officer
Joanne M. Donovan, M.D., Ph.D., has served as the Chief Medical Officer since 2021. Most recently, Dr. Donovan served as Chief Medical Officer and Senior Vice President, Clinical Development at Catabasis Pharmaceuticals. Since 1989, she has been a staff physician at the VA Boston Healthcare System, where she was formerly Chief of Gastroenterology. Dr. Donovan has held an appointment at Harvard Medical School since 1990, most recently as associate clinical professor of medicine. From 1998 to 2011, Dr. Donovan served in positions of increasing responsibility, ultimately as vice president of clinical development, at Genzyme, a biotechnology company, which she joined through its acquisition of GelTex Pharmaceuticals. Dr. Donovan holds a Ph.D. in medical engineering and medical physics from the Massachusetts Institute of Technology, an M.D. from Harvard Medical School and an S.B. from the Massachusetts Institute of Technology. She completed residency training in internal medicine and a fellowship in gastroenterology at the Brigham and Women’s Hospital.
Robert Blaustein, M.D., Ph.D. - Chief Development Officer
Robert Blaustein, M.D., Ph.D., has served as the Chief Development Officer since January 2025. With significant depth of experience in cardiovascular drug development, Dr. Blaustein was most recently Associate Vice President at Merck, and the Atherosclerosis Section Head in the Atherosclerosis and Metabolism Clinical Research Department, leading all late phase development efforts in the Atherosclerosis space. During his 15+ years at Merck Dr. Blaustein contributed to clinical programs across a range of cardiovascular targets and led clinical development in the atherosclerosis and heart failure spaces. Dr. Blaustein obtained his undergraduate degree in mathematics from Wesleyan University. His post-graduate training included a medical residency at Brigham and Women’s Hospital, cardiology fellowship training at Massachusetts General Hospital, and a post-doctoral fellowship in the lab of Chris Miller, an HHMI investigator in the Biochemistry Department at Brandeis University. He then joined the faculty of Tufts Medical Center running an R01-funded laboratory studying ion channel proteins. At Tufts he served as an attending cardiologist in the Cardiology Division, was a faculty member in the Neuroscience and Biochemistry Departments and was co-director of the medical school's MD-PhD Medical Scientist Training Program.
R. Michael Carruthers - Chief Financial Officer
Michael Carruthers has served as the Chief Financial Officer since September 2020. Mr. Carruthers has over 20 years of experience serving as Chief Financial Officer for publicly-traded biopharmaceutical companies, with extensive experience across corporate finance and strategic planning including IPOs, secondary offerings and M&A transactions. Most recently, Mr. Carruthers consulted as Chief Financial Officer for several private and public companies. Previously, Mr. Carruthers served as Interim President of Nivalis Therapeutics, a publicly traded company acquired by Alpine Immune Sciences, in 2017 and Chief Financial Officer and Secretary from 2015 to 2017. From 1998 to 2015, he served as Chief Financial Officer for Array BioPharma Inc., a publicly traded company acquired by Pfizer Inc. Prior to this, he served as Chief Financial Officer of Sievers Instruments, Treasurer and Controller for the Waukesha division of Dover Corporation and Accountant with Coopers & Lybrand. Mr. Carruthers serves on the boards of Elevation Oncology (Nasdaq: ELEV) and OnKure, Inc., . Mr. Carruthers received a B.S. in accounting from the University of Colorado and a M.B.A. from the University of Chicago.
Behrad Derakhshan, Ph.D. - Chief Operating Officer
John Moore - General Counsel
Website: https://edgewisetx.com/
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