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Our science-driven culture places patients first as we start with their unmet needs and then work towards developing therapies to help address the significant challenges of serious muscle diseases.
−Removed: Since our inception in 2017, our precision medicine muscle platform has generated several programs to address a variety of muscle diseases.
−Removed: We are advancing two clinical-stage programs in muscular dystrophies and severe cardiac diseases and a number of preclinical programs.
−Removed: Our muscular dystrophy program includes sevasemten (EDG-5506), an orally administered skeletal myosin inhibitor.
−Removed: Sevasemten is currently being studied in multiple Phase 2 clinical trials, including a pivotal cohort, in patients with either Becker muscular dystrophy (Becker) or Duchenne muscular dystrophy (Duchenne).
−Removed: Our cardiovascular program includes EDG-7500, a novel oral, selective cardiac sarcomere modulator.
−Removed: EDG-7500 is currently being studied in a multipart Phase 2 trial in both obstructive and non-obstructive hypertrophic cardiomyopathy (HCM).
−Removed: We are also continuing to advance our preclinical exploration, including novel cardiometabolic targets.
−Removed: As a clinical-stage biopharmaceutical company, we are focused on the discovery, development and commercialization of innovative treatments for severe muscle diseases for which there is significant unmet medical need.
Guided by our holistic drug discovery approach to targeting the muscle as an organ, we have combined our foundational expertise in muscle biology and small molecule engineering to build our proprietary, muscle focused drug discovery platform.
Our platform utilizes custom-built high throughput and translatable systems that measure integrated muscle function in whole organ extracts to identify small molecule precision medicines regulating key proteins in muscle tissue, initially focused on addressing rare neuromuscular and cardiac diseases.
−Removed: We have developed and
−Removed: characterized a library of novel sarcomere modulators exhibiting a broad range of pharmacological and pharmacokinetic (PK) properties regulating disease-related muscle biology.
−Removed: Our most advanced product candidate, sevasemten, is an orally administered allosteric, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address contraction-induced muscle injury, the root cause of dystrophinopathies including Duchenne and Becker.
−Removed: Both of these disorders are rare and often debilitating diseases, and we estimate that in the US, EU-5 and Japan there are approximately 35,000 Duchenne patients and approximately 12,000 Becker patients.
+Added: We have developed and characterized a library of novel sarcomere modulators exhibiting a broad range of pharmacological and pharmacokinetic (PK) properties regulating disease-related muscle biology.
+Added: Based on the results of our drug discovery platform, we are advancing multiple clinical-stage programs in muscular dystrophies and severe cardiac diseases, as well as a number of preclinical programs.
+Added: Muscular Dystrophy
+Added: Our muscular dystrophy program includes sevasemten, our most advanced product candidate, an orally administered allosteric, selective, fast myofiber (type II) myosin small molecule inhibitor designed to address contraction-induced muscle injury, the root cause of dystrophinopathies including Duchenne muscular dystrophy (Duchenne) and Becker muscular dystrophy (Becker).
+Added: Both of these disorders are rare and often debilitating diseases, and we estimate that in the US, EU-5, and Japan there are approximately 35,000 individuals living with Duchenne and 12,000 individuals living with Becker.
There are currently no approved therapies for individuals with Becker.
As a selective fast myosin inhibitor, sevasemten presents a novel mechanism of action designed to selectively limit injurious stress caused by lack of dystrophin by moderating fast skeletal muscle myosin force development and thereby compensating for the absence of functional dystrophin.
−Removed: Our preclinical data with sevasemten in animal models of muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, reduced systemic fibrosis and improved measures of muscle function including strength and ability to engage in physical activities, which we believe may provide evidence of a disease modifying effect.
−Removed: A unique observation from our preclinical work is that sevasemten led to pronounced prevention of cardiac fibrosis.
−Removed: This is a highly relevant finding, particularly if replicated in clinical observations, since cardiac myopathy is a major driver of mortality in both Duchenne and Becker.
We believe sevasemten has potential therapeutic utility as either a standalone or combination therapy for patients suffering from rare muscular dystrophies, if approved.
−Removed: In Becker, we have advanced sevasemten through the clinic including completing a Phase 1 trial evaluating safety, tolerability, PK and pharmacodynamics of sevasemten in adult healthy volunteers (Phase 1a) and in adults with Becker (Phase 1b).
−Removed: In ARCH, an open-label, single-center trial assessing long-term safety and PK, decreases in biomarkers of muscle damage and trends toward improvement in function as measured by the North Star Ambulatory Assessment (NSAA) have been observed following 24 months of treatment with sevasemten.
−Removed: In CANYON, a multi-center, double-blind, randomized, placebo-controlled study to investigate the effect of sevasemten on the safety, pharmacokinetics, biomarkers, and functional measures of participants, we met the primary endpoint of reduction in circulating levels of creatine kinase (CK), a biomarker associated with skeletal muscle damage, as well as the secondary endpoint of stabilization of function as measured by the NSAA after 12 months of treatment.
−Removed: CANYON was expanded to include a pivotal cohort called GRAND CANYON that completed enrollment, including over-enrolling beyond the target 120 adult participants, in February 2025.
−Removed: The Company also completed the Phase 2 DUNE Exercise Challenge Study, in patients with Becker, Limb Girdle Muscular Dystrophy Type 2i (LGMD2i) and McArdle disease at a single site in Denmark.
−Removed: In Duchenne, we are advancing our Phase 2 studies, LYNX and FOX, both assessing safety, PK and biomarkers of muscle damage in individuals with Duchenne and for the purpose of identifying a dose of sevasemten that will reduce biomarkers of muscle damage and has the potential to provide functional benefit to patients in a Phase 3 trial.
+Added: Sevasemten is currently being studied in multiple late-stage clinical trials in Becker and Duchenne, including an ongoing pivotal cohort in patients with Becker.
The FDA granted sevasemten Fast Track designation for the treatment of Duchenne in February 2024, and Orphan Drug Designation (ODD) for the treatment of Duchenne and Becker and Rare Pediatric Disease Designation (RPDD) for the treatment of Duchenne in November 2023.
The FDA previously granted Fast Track designation for the investigation and development of sevasemten for the treatment of Becker.
−Removed: We established our cardiovascular program by evolving a second muscle-targeted initiative that focuses on the identification of novel cardiac muscle modulators.
−Removed: We are currently pursuing our other lead product candidate, EDG-7500, for the treatment of HCM in addition to exploring the potential of its novel mechanism in the treatment of disorders of diastolic dysfunction.
−Removed: In September 2024, we announced topline results of our Phase 1 trial of EDG-7500 which assessed the tolerability, PK, and pharmacodynamics of EDG-7500 in healthy adults, observing that EDG-7500 was well tolerated without meaningful changes in left ventricle ejection fraction (LVEF).
−Removed: We have also initiated the multi-part Phase 2 CIRRUS clinical trial of EDG-7500 in obstructive hypertrophic cardiomyopathy (oHCM) and non-obstructive hypertrophic cardiomyopathy (nHCM).
−Removed: In September 2024, we shared topline data from Part A of this trial in which EDG-7500 demonstrated robust left ventricular outflow tract (LVOT) gradient reductions in a single dose without meaningful changes in LVEF in patients with oHCM.
−Removed: We have also dosed the first patients in the CIRRUS-HCM 28-day
−Removed: trial (Parts B and C) and have initiated an open-label extension trial (Part D) evaluating the long-term safety, tolerability, and treatment effects of EDG-7500.
−Removed: We are currently amending Part D of the CIRRUS-HCM trial as we plan for Phase 3 in 2026.
−Removed: We continue to plan to report initial CIRRUS-HCM data from Parts B and C in the first quarter of 2025 and from Part D in the second half of 2025.
−Removed: Additionally, our EDG-003 discovery program is exploring the potential of other unique and novel mechanisms to address a variety of disorders, including cardiometabolic disease.
−Removed: We believe our programs also offer substantial opportunities for us to expand into other severe muscle diseases for which there are limited or no approved treatments.
+Added: Cardiovascular
+Added: Early in the founding of Edgewise, we identified a unique set of cardiovascular molecules as part of a skeletal muscle counter-screen.
+Added: We initiated our cardiovascular program with EDG-7500 identified as our lead candidate, a molecule with unique characteristics.
+Added: EDG-7500 is a novel oral, selective, cardiac sarcomere modulator (CSM), specifically designed to slow early contraction velocity and address impaired cardiac relaxation associated with hypertrophic cardiomyopathy (HCM) without impacting systolic function.
+Added: EDG-7500 is currently being studied in a multipart Phase 2 trial in both obstructive HCM (oHCM) and nonobstructive HCM (nHCM).
+Added: In 2023, we identified a second cardiac sarcomere modulator, EDG-15400, which is currently in a Phase 1 trial of healthy adults with the future disease target of heart failure with preserved ejection fraction (HFpEF).
+Added: In addition, our EDG-003 discovery program is exploring candidates with unique properties to address cardiometabolic diseases.
+Added: We believe our muscle-focused discovery program offer substantial opportunities for us to expand into other severe muscle diseases for which there are limited or no approved treatments.
Using our proprietary drug discovery platform, we are developing a pipeline of precision medicine product candidates that target key muscle proteins and modulators to address a broad array of muscle diseases.
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Our current pipeline is summarized below.
−Removed: Our History and Team
−Removed: We have assembled an experienced and highly motivated management team with a strong track record in the biotechnology and pharmaceutical industry.
−Removed: We are focused on building a leading, patient-centric, fully integrated global muscle disease company.
−Removed: Members of our team have extensive expertise in muscle diseases, small molecule drug discovery and development and patient advocacy with proven track records at organizations including Alexion, Amgen, Array Biopharma, Catabasis, Cytokinetics, Genzyme, GlaxoSmithKline, Parent Project Muscular Dystrophy, Pfizer, Biogen and MyoKardia.
−Removed: We were co-founded in 2017 by our Chief Scientific Officer, Alan Russell, Ph.D., Peter Thompson, M.D., who is currently a Partner at OrbiMed and Badreddin Edris, Ph.D., who is currently the Chief Operating Officer at SpringWorks Therapeutics, Inc.
−Removed: through funding provided by OrbiMed.
−Removed: Russell has extensive experience in developing novel therapeutics for diseases involving skeletal muscle, having previously served as Vice President and Head of the Muscle Metabolism Discovery Performance Unit at GlaxoSmithKline from 2010 to 2017 and as Associate Director, Muscle Biology and Therapeutics at Cytokinetics from 2002 to 2010, where he was the co-inventor of tirasemtiv and reldesemtiv, direct muscle sensitizers for Amyotrophic Lateral Sclerosis.
−Removed: We are led by Kevin Koch, Ph.D., who has been in the life science industry for over 30 years with a focus on drug discovery, translational medicine and clinical development.
−Removed: Koch previously served as the Senior Vice President of
−Removed: Drug Discovery, Chemical and Molecular Therapeutics at Biogen where he managed global drug discovery and biomarker development.
−Removed: 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.
−Removed: 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.
−Removed: Prior to Array, Dr.
−Removed: Koch held senior positions at Amgen and Pfizer Central Research.
−Removed: Our Chief Operating Officer, Behrad Derakhshan, Ph.D., our Chief Financial Officer, R.
−Removed: Michael Carruthers, our Chief Medical Officer, Joanne Donovan, M.D., Ph.D., and our General Counsel, John Moore, each have more than 15 years of experience in drug research, clinical development, regulatory affairs, manufacturing, business development and commercialization of novel medicines, particularly in a range of devastating rare diseases and cardiac disorders.
−Removed: Additionally, in January 2025, we appointed Robert Blaustein, M.D., Ph.D, a cardiac drug development expert from Merck, as Chief Development Officer (CDO).
−Removed: Further, we have built a scientific advisory board with experts in the field of neuromuscular and cardiac muscle diseases affecting both children and adults.
−Removed: Our scientific advisors include researchers who publish widely-cited articles on the skeletal and cardiac aspects of muscular dystrophy as well as on inherited forms of cardiovascular disease.
−Removed: Moreover, some of our advisors lead clinical units at some of the leading muscle disease centers in the United States and are actively involved in our drug development process and programs.
−Removed: As a private company, we raised $160.7 million from leading institutional investors which include OrbiMed, Novo Holdings A/S, U.S.
−Removed: Venture Partners (USVP), Deerfield Management, Viking Global Investors, New Leaf Ventures, Janus Henderson Investors, RA Capital Management, Cormorant Asset Management, Logos Capital, Wellington Management, CureDuchenne Ventures and an undisclosed institutional investor.
−Removed: We also raised $186.1 million in net proceeds from our initial public offering in March 2021, $129.2 million in net proceeds from our follow-on public offering in September 2022 (the September 2022 Offering), $59.4 million in net proceeds through an “at the market offering” program (ATM Program), and $231.9 million in net proceeds from our underwritten registered direct offering in January 2024 (the January 2024 Offering).
Our vision is to improve the lives of patients and families suffering from severe muscle diseases by building the world’s leading muscle-focused biopharmaceutical company.
Key components of our strategy to achieve this vision include:
−Removed: ● Engaging comprehensively with patients, their families and their physicians to develop trusted relationships, transparent communications, and become a leader in the rare muscle disease communities.
−Removed: By positioning ourselves as a trusted partner that moves with thoughtful urgency, we will continue to work to understand the needs of patients in order to inform our development of sevasemten, EDG-7500 and other programs for severe muscle diseases.
+Added: ● Engaging comprehensively with patients, their families and their physicians to develop trusted relationships, transparent communications, and become a leader in the rare muscle disease communities we serve.
+Added: By positioning ourselves as a trusted partner that moves with thoughtful urgency, we will continue to work to understand the needs of patients in order to inform our development of sevasemten, EDG-7500, EDG-15400, and other programs for severe muscle diseases.
We continue to seek to better appreciate the burden of disease from the patient perspective, understand the current standard of care and unmet needs in managing the disease and learn what is most meaningful to patients.
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Its unique mechanism of action provides the potential to establish sevasemten as a foundational therapy in dystrophinopathies, either as a single agent therapy or in combination with available therapies and those in development.
−Removed: We are advancing sevasemten through the clinic including the completion of the CANYON Phase 2 trial evaluating safety and effects on function and biomarkers of muscle damage in adult males with Becker, and the completed enrollment of the pivotal GRAND CANYON cohort, including over-enrolling beyond the target 120 adult participants, designed
−Removed: to evaluate the efficacy and safety of sevasemten over an 18-month period.
−Removed: In Duchenne, we are advancing our Phase 2 clinical trials, LYNX, assessing safety, PK and biomarkers of muscle damage, and FOX, which includes children and adolescents previously treated with gene therapy.
● Leveraging our deep expertise in muscle-disease therapeutics to expand our pipeline, advancing EDG-7500 into the clinic for the treatment of HCM and other diseases of diastolic dysfunction.
−Removed: EDG-7500 is a first-in-class oral, selective, cardiac sarcomere modulator intended for the treatment of HCM and other diseases of cardiac diastolic dysfunction.
+Added: EDG-7500 is a first-in-class oral, selective, cardiac sarcomere modulator intended for the treatment of both oHCM and nHCM.
The compound is designed to slow early contraction velocity and improve impaired cardiac relaxation.
−Removed: This novel mechanism is anticipated to have a broad therapeutic index that may facilitate fixed dosing and minimize monitoring during treatment.
−Removed: Preclinical data of EDG-7500 support beneficial activity in animal models of both obstructive and non-obstructive HCM with diastolic benefit and minimal changes in left ventricular systolic performance in a range of preclinical experiments.
−Removed: We completed a randomized, double-blind, placebo-controlled, single and multiple ascending dose Phase 1 trial evaluating safety, tolerability, PK and pharmacodynamics in healthy adults, observing that EDG-7500 was well-tolerated without meaningful changes in left ventricle ejection fraction in healthy adults.
−Removed: Further, we observed that EDG-7500 in oHCM demonstrated robust LVOT gradient reductions without meaningful changes in LVEF in Part A of our CIRRUS-HCM multi-part Phase 2 trial of EDG-7500 in individuals with HCM.
+Added: This novel mechanism is anticipated to have a broad therapeutic index that may facilitate reach to an expanded HCM market, beyond what is covered by current standard of care.
● Investing in our precision medicine drug discovery platform to fuel the development of novel targeted therapies to expand our pipeline into additional skeletal and cardiac muscle diseases.
Building upon our success in designing small molecule inhibitors of fast skeletal myosin, we are leveraging our proprietary drug discovery platform and capabilities to create precision medicines for muscle diseases with high levels of unmet need.
−Removed: In addition to sevasemten and EDG-7500, we are also advancing our preclinical program, EDG-003, directed to cardiometabolic targets.
+Added: In addition to sevasemten, EDG-7500, and EDG-15400, we are also advancing our preclinical program, EDG-003, directed to cardiometabolic targets.
● Integrating our scientific expertise, development capabilities and growing network of patient advocacy groups and collaborators to develop novel therapies addressing muscle diseases with the highest unmet need.
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● Opportunistically evaluating strategic collaborations and asset acquisition opportunities to accelerate development and commercialization timelines as well as potentially expand our pipeline within our core therapeutic areas.
−Removed: We have retained global development and commercialization rights to all of our programs and intend to maximize their commercial opportunity across global markets.
+Added: We have retained global development and commercialization rights to all of our programs
+Added: and intend to maximize their commercial opportunity across global markets.
We plan to collaborate on product candidates that we believe have promising utility in disease areas or patient populations that are better served by the resources or specific expertise of other biopharmaceutical companies.
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Sevasemten, our most advanced product candidate, is an orally administered, allosteric, selective, fast myofiber (type II) myosin inhibitor that is designed to be inactive against slow myofiber (type I) myosin present in both skeletal muscle and the heart.
−Removed: Our preclinical data for sevasemten in animal models with muscular dystrophy demonstrated that selective regulation of fast (type II) myofiber contraction protected muscle from damage, decreased systemic fibrosis and improved measures of muscle function, including strength and physical activity.
−Removed: Sevasemten was evaluated in a Phase 1 clinical trial designed to assess the safety, tolerability, and PK of sevasemten in adult healthy volunteers (HVs) (Phase 1a) and in adults with Becker (Phase 1b).
−Removed: Our Phase 1a data in HVs demonstrated that sevasemten was generally well-tolerated and amenable to daily dosing.
−Removed: Our Phase 1b (ARCH) data in Becker individuals demonstrated proof of concept by showing a significant reduction in key biomarkers of muscle damage.
−Removed: We also initiated a Phase 2 clinical trial (CANYON) in individuals with Becker in July 2022, added a potentially registrational cohort to CANYON in September 2023 (GRAND CANYON), initiated a Phase 2 (LYNX) dose-finding clinical trial in children with Duchenne in October 2022 and a Phase 2 (FOX) clinical trial in
−Removed: children and adolescents with Duchenne who have been previously treated with gene therapy in October 2023.
−Removed: Type II myosin inhibition prevents muscle damage via a blockade of the biophysical stress response during normal muscle contractile activity thus stabilizing the muscle and protecting the muscle from damage.
+Added: Type II myosin inhibition prevents
+Added: muscle damage via a blockade of the biophysical stress response during normal muscle contractile activity thus stabilizing the muscle and protecting the muscle from damage.
As such, it is a potentially complementary approach to dystrophin replacement strategies which stabilize muscle through the re-expression of a truncated but not fully functional dystrophin.
−Removed: Absence of dystrophin in Duchenne causes muscle fiber membrane stress when muscles contract, leading to myofiber damage.
−Removed: By enhancing muscle stability and decreasing muscle damage, we believe sevasemten has the potential to improve outcomes across a broad range of Duchenne patients when used as a single agent.
−Removed: Sevasemten may also provide a synergistic or additive effect in combination with available therapies and therapies currently in development, including dystrophin replacement gene therapies.
+Added: Absence of dystrophin in Duchenne and truncated availability of dystrophin in Becker causes muscle fiber membrane stress when muscles contract, leading to myofiber damage, which is referred to as contraction-induced muscle injury.
+Added: By enhancing muscle stability and decreasing muscle damage, we believe sevasemten has the potential to improve outcomes across Becker and Duchenne patients when used as a single agent or in combination with other available therapies.
+Added: A fast myofiber (type II) myosin inhibitor designed to protect against contraction-induced muscle injury
Disease Background
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We estimate that Duchenne occurs in approximately one in every 3,500 to 5,000 live male births and that the patient population is approximately 12,000 to 15,000 in the United States and approximately 25,000 in Europe.
−Removed: Becker has a much lower incidence of
−Removed: approximately 1 in every 18,450 live male births.
−Removed: We estimate there are about 5,000 patients with Becker in the United States, with similar numbers estimated in Europe.
−Removed: Duchenne Muscular Dystrophy
−Removed: Duchenne is a severe, degenerative muscle disorder with a median life expectancy of around 30 years.
−Removed: People living with Duchenne begin to lose their ability to walk without assistance by their early teens and nearly all will require the use of a wheelchair by the time they are in their mid-teens.
−Removed: Duchenne is the most common type of muscular dystrophy and 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.
−Removed: Currently, there is no cure for Duchenne;
−Removed: early, active multidisciplinary care from neuromuscular specialists, cardiologists, physical therapists, and other specialists is critical for optimized disease management.
−Removed: Current therapeutic options for Duchenne are inadequate to prevent significant morbidity and mortality;
−Removed: novel therapies in development for Duchenne, including muscle targeted interventions, aim to positively impact disease trajectory.
+Added: For Becker we estimate there are about 6,000 patients with Becker in the United States and 12,000 in the United States, EU-5, and Japan.
Becker Muscular Dystrophy
−Removed: In contrast to Duchenne, Becker results from a mutation in the dystrophin gene yielding a partially functional protein.
−Removed: Becker patients often are diagnosed at a later age in childhood (approximately 11 years old) with similar symptoms to Duchenne of symmetrical, proximal limb weakness, notable in the quadriceps, with calf hypertrophy and elevated CK.
−Removed: While certain Becker patients have mild or minimal lower limb weakness and remain relatively stable over time as measured by the NSAA, other Becker patients have a typical Becker disease course with progressive loss of lower limb function, measurable with the NSAA over a 12-month period with the majority losing ambulation at some point in their lifetime.
−Removed: Compared to Duchenne, Becker patients’ skeletal myopathy occurs later in childhood, and they maintain ambulation through age 16.
−Removed: However, Becker patients develop cardiomyopathy at a similar mean age to Duchenne (14.4 years Duchenne and 14.6 years Becker), which may result in death or the need for cardiac transplantation.
+Added: Becker is a rare, genetic, life-shortening, debilitating and degenerative neuromuscular disorder.
+Added: 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.
+Added: The disease predominantly affects males, with functional decline beginning at any age.
+Added: Once that muscle loss occurs, the decline in function is irreversible and continues throughout the individual's life.
+Added: Currently, there are no approved therapies on the market to treat Becker.
+Added: Duchenne Muscular Dystrophy
+Added: Duchenne, a severe degenerative muscle disorder, is the most common type of muscular dystrophy with a median life expectancy of around 30 years.
+Added: Genetic mutations in the dystrophin gene result in contraction-induced muscle injury, which is the primary driver of irreversible muscle loss and impaired motor function.
+Added: While there are approved therapies on the market aimed to treat the disease, there remains a high unmet need for additional therapies.
Current Treatments for Duchenne and Becker and their Limitations
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In October 2023, the FDA granted AGAMREE (vamorolone), a novel steroid therapy, approval in Duchenne patients aged 2 years and older, and Catalyst Pharmaceuticals, Inc.
−Removed: announced commercialization of this product in the United States in March 2024 following its North America exclusive license deal with Santhera.
+Added: has commercialized this product in the United States following its North America exclusive
+Added: license deal with Santhera.
The modest chronic benefit of steroids is weighed against the risks, and treatment is often discontinued after loss of ambulation.
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announced that no statistical significance in function was observed between the treatment group and the placebo group in VILTEPSO’s confirmatory study, which may affect VILTEPSO’s accelerated FDA approval.
+Added: In November 2025, Sarepta announced that AMONDYS 45 and VYONDYS 53 missed their primary endpoint in the confirmatory study.
+Added: This result may affect its drugs’ accelerated FDA approval.
+Added: As all exon-skipping therapies result in the re-expression of a truncated dystrophin protein, the best treatment outcome that Duchenne patients can expect is a Becker-like disease phenotype.
In addition, Translarna® (ataluren), a small molecule intended to promote ribosomal read-through to overcome the nonsense (stop) pathogenic mutations in Duchenne, was conditionally approved in the European Union and Brazil for ambulatory patients aged 2 years and older with Duchenne resulting from a nonsense mutation in the dystrophin gene.
−Removed: However, in January and June 2024, the Committee for Medicinal Products for Human Use of the EMA delivered negative opinions on the re-examination procedure for the conditional marketing authorization of Translarna, which may result in the withdrawal of Translarna from the EMA markets..
+Added: However, in March 2025, the European Commission adopted the negative opinions issued by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) for the renewal of conditional marketing authorization of Translarna.
+Added: While this action effectively removes Translarna’s marketing authorization in the European Economic Area, individual countries within the EU can leverage existing legislation to allow continued use of Translarna.
Phase 3 trials have not confirmed clinical efficacy and Translarna® is not approved for treating Duchenne in the United States.
−Removed: As all PMO therapies result in the re-expression of a truncated dystrophin protein, the best treatment outcome that Duchenne patients can expect is a Becker-like disease phenotype.
Gene Therapy for Duchenne
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In June 2024, the FDA granted Elevidys full approval for the treatment of ambulatory individuals aged 4 years and older, and accelerated approval for the treatment of non-ambulatory individuals aged 4 years and older.
−Removed: Other companies focused on developing genetic based therapies for Duchenne that target dystrophin mechanisms include Solid Biosciences Inc., Genethon, PepGen, Dyne Therapeutics, Avidity Biosciences, REGENXBIO, Wave Life Sciences, and Entrada Therapeutics.
−Removed: In June 2024, Pfizer announced its gene
−Removed: therapy Phase 3 trial failed to meet the primary and key secondary endpoints and is no longer under development.
+Added: However, in November 2025, the FDA revised the Elevidys indication to limit to ambulatory individuals 4 years or older and added black box warnings about risks of acute and fatal liver injuries.
+Added: Other companies focused on developing genetic based therapies for Duchenne that target dystrophin mechanisms include Solid Biosciences Inc., Genethon, Dyne Therapeutics, Avidity Biosciences, REGENXBIO, Wave Life Sciences, and Entrada Therapeutics.
Gene editing treatments that are in preclinical development are also being pursued by Vertex and Sarepta Therapeutics.
Delivery of minidystrophin or microdystrophin to muscles in Duchenne has been shown to be sufficient to reform the larger complex of proteins that make up the dystroglycan complex.
−Removed: However, the truncated nature of the shortened dystrophin protein is not capable of providing complete protection against contraction injury.
+Added: However, the truncated nature of the shortened dystrophin protein does not appear to be capable of providing complete protection against contraction injury.
As a result, we believe that the best potential therapeutic outcome is inducing a severe Becker-like phenotype (the shortest documented dystrophin protein in Becker is 50% of normal) where patients would still have significant residual skeletal muscle impairment and will thus continue to have a high degree of unmet need.
What is clear is that gene therapies currently in development for Duchenne do not represent a cure for the disease.
+Added: Non-Dystrophin Therapies
+Added: Italfarmaco Group has developed a nonsteroidal histone deacetylase (HDAC) inhibitor to reduce inflammation and slow muscle loss in patients with Duchenne.
+Added: Satellos Bioscience, Inc.
+Added: is developing an orally administered small molecule drug designed to address deficits in muscle repair and regeneration and announced functional data from a Phase 1b trial in adult patients with Duchenne in May 2025.
We believe that each of the therapeutic approaches outlined above currently have significant limitations, and that there continues to be a high unmet medical need for new disease-modifying therapies for the treatment of patients with Duchenne.
Moreover, with the biotechnology and pharmaceutical industry’s almost exclusive focus on Duchenne, little attention has been paid to drug development in Becker where there are no approved therapies for patients.
−Removed: Our Solution:
−Removed: Since the cloning of the dystrophin gene in 1986, researchers, clinicians, and pharmaceutical and biotechnology companies have worked relentlessly to advance the scientific and clinical understanding of Duchenne to accelerate finding a cure.
−Removed: At Edgewise, we have built on this foundational work through applying our understanding of muscle physiology to develop sevasemten, a molecule that we believe has the potential to change the devastating course of Duchenne.
−Removed: While many of our competitors are targeting dystrophin, our orthogonal approach is focused on protecting muscle damage induced by contractions from activities of daily living.
−Removed: Sevasemten is an orally administered, allosteric, selective, fast myofiber (type II) myosin inhibitor that is designed to be inactive against slow myofiber (type I) myosin present in both skeletal muscle and the heart.
−Removed: We believe sevasemten has the potential to overcome many of the obstacles facing other therapeutics in development for the treatment of dystrophinopathies based on the following key characteristics:
−Removed: ● Offers a novel, potentially disease modifying approach for the treatment of severe muscle diseases by blocking the structural destabilization of skeletal myofibers.
+Added: Sevasemten is an orally administered, investigational small molecule designed to selectively modulate fast muscle fiber contraction by modestly inhibiting fast skeletal muscle myosin adenosine triphosphatase (ATPase).
+Added: Sevasemten is highly selective for fast skeletal myosin as compared to cardiac or smooth muscle myosin.
+Added: We believe sevasemten has the potential to overcome many of the obstacles facing other therapeutics in development for the treatment of dystrophinopathies based on the following key characteristics and data:
+Added: ● Offers a novel approach for the treatment of severe muscle diseases by blocking the structural destabilization of skeletal myofibers.
By protecting dystrophin deficient myofibers from degeneration, sevasemten’s mechanism of action is directed towards the underlying cause of muscle degeneration in Duchenne and Becker to reduce muscle damage, prevent downstream fibrosis, allow healthy muscle contraction, and enhance physical function.
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● Offers a mutation agnostic approach with the potential to be used for disorders resulting from genetic lesions in dystrophin or the dystroglycan complex .
−Removed: Sevasemten can potentially be used to treat all populations of Duchenne and Becker, as well as many forms of LGMD, a progressive, lethal myopathy that results from mutations of key proteins in the dystroglycan complex.
+Added: Sevasemten can potentially be used to treat all populations of Duchenne and Becker, as well as many forms of Limb Girdle muscular dystrophy type 2I/R9 (LGMD), a progressive, lethal myopathy that results from mutations of key proteins in the dystroglycan complex.
● Provides a mechanistic approach to treat Duchenne that may provide additional functional benefits over genetic based therapeutics.
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An illustration of sevasemten’s novel mechanism of action
−Removed: Background and Rationale of Our Approach
Human skeletal muscle consists of three fiber types, “slow” type I and “fast” types IIa or IIx/d, defined by the specific myosin isoform that they express.
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Similar observations have also been made in all known mammalian models of Duchenne.
−Removed: The control and coordination of these fiber populations is a complex process, designed to maintain physical performance even under conditions of extreme environmental and metabolic stress.
+Added: The control and coordination of these fiber populations is a complex process, designed to maintain physical performance even under conditions of extreme
+Added: environmental and metabolic stress.
Under normal conditions, skeletal muscle contractile demand is much lower than at the maximal output.
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One of the troponin subunits, TnI has a different isoform for each type of striated muscle (fast, slow and cardiac) and can be used to explore the fiber-specific source of these proteins.
−Removed: We evaluated Duchenne and Becker patient plasma samples
−Removed: using high specificity assays for fast and slow myofiber TnI and observed that fast myofiber TnI (TnI2) plasma levels are higher than slow myofiber TnI (TnI1) levels, suggesting that fast myofibers are more susceptible to loss of dystrophin function during muscle contraction.
+Added: We evaluated Duchenne and Becker patient plasma samples using high specificity assays for fast and slow myofiber TnI and observed that fast myofiber TnI (TnI2) plasma levels are higher than slow myofiber TnI (TnI1) levels, suggesting that fast myofibers are more susceptible to loss of dystrophin function during muscle contraction.
Conversely, we observed that HVs had virtually no leak from fast muscles .
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Moreover, stabilization of the sarcomere with sevasemten via direct decreases in contractile stress potentially provides greater muscle protection than secondary inhibition of calcium release via the ryanodine receptor.
−Removed: Another corollary to our approach of selectively targeting type II fast skeletal muscle myofibrils with sevasemten is mavacamten (MYK461), a selective allosteric inhibitor of cardiac type I myosin ATPase.
−Removed: Mavacamten was approved by the FDA for HCM, a disorder characterized by excessive contractility and impaired relaxation of cardiomyocytes.
−Removed: Through selective targeting of cardiac type I myosin ATPase, mavacamten is designed to reduce cardiac muscle hypercontractility in HCM.
−Removed: Mavacamten’s mechanism of action further validates selective allosteric regulation of myofibers as a viable therapeutic approach to treating various muscle disorders.
−Removed: Interestingly, nature has carried out one of the more critical experiments to help us understand the impact of inhibiting fast fiber myosin selectively.
−Removed: There are several reports describing the human phenotype of people born with genetic loss of function (LOF) of the myosin heavy chain 2 gene, MYH2 which encodes Type IIa myosin and makes up approximately 85% of the body’s fast fibers.
−Removed: Muscle biopsies in these patients show a heavy skewing towards slow type I muscle fibers as a result of complete lack of fast type IIa muscle fibers.
−Removed: These patients have mild, proximal muscle weakness with ocular muscle involvement but remain ambulatory throughout life.
−Removed: The observations in these patients
−Removed: demonstrate an ability of the body to maintain function despite complete loss of one myofiber type.
−Removed: Given that our goal is to partially inhibit type II fast skeletal muscle myofibrils in order to modulate force development and not completely inhibit them, as is the case in the LOF patients, it is our belief that selective fast fiber regulation with sevasemten will likely be well-tolerated and may protect dystrophic myofibers from degeneration and subsequently improve and/or preserve physical function.
Preclinical Data
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Sevasemten Clinical Plan
−Removed: An updated overview of our near-term clinical development plan for sevasemten in Duchenne and Becker is shown below:
−Removed: Sevasemten Phase 1 Clinical Trial
+Added: To date, we have completed a Phase 1 trial in healthy volunteers and a small cohort of individuals with Becker, ARCH, a Phase 1, open-label, dose escalation, single-site trial of 12 ambulatory adults with Becker, and CANYON, a Phase 2, double-blind, randomized, placebo-controlled trial in adults and adolescents with Becker.
+Added: Through MESA, an open label extension trial in individuals with Becker, 36-month data is available for individuals previously enrolled in ARCH and 18-month data is available for individuals previously enrolled in CANYON.
+Added: GRAND CANYON, a pivotal adult cohort within CANYON, is currently ongoing.
+Added: For Duchenne, LYNX, a Phase 2 trial in children with Duchenne, and FOX, a Phase 2 trial in children and adolescents with Duchenne previously treated with gene therapy, remain ongoing.
+Added: An updated overview of our near-term clinical development plan for sevasemten in Becker and Duchenne is shown below:
+Added: Phase 1 Clinical Trial
In October 2020, we initiated a Phase 1 randomized, placebo-controlled, double-blind, single and multiple ascending-dose clinical trial to evaluate the safety, tolerability and PK of sevasemten in adult HVs (Phase 1a) and adults with Becker (Phase 1b), to address potential differences in safety, tolerability and PK in the background of dystrophic muscle.
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Sevasemten was well tolerated in Becker subjects.
−Removed: Seven of the seven subjects enrolled in the Phase 1b cohort experienced TEAEs and all were Grade 1.
+Added: Seven of the seven subjects enrolled in the Phase 1b cohort experienced Treatment Emergent AEs and all were Grade 1.
There were no AEs of special interest, no SAEs, and no discontinuations due to AEs.
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Moreover, sevasemten led to a robust, significant reduction in key biomarkers of muscle damage, driving CK, TNNI2, myoglobin and AST to either normal or near normal levels observed in healthy volunteers after only two weeks of sevasemten dosing.
−Removed: Sevasemten ARCH Open Label Data
+Added: ARCH Open Label Data
In December 2021, we initiated our ARCH open label, single-center trial of sevasemten in 12 adults with Becker, including all seven participants from our Phase 1b first-in-human trial (following a 3-month washout).
−Removed: ARCH was designed to evaluate the safety, PK, changes in biomarkers of muscle damage such CK and fast skeletal muscle troponin I, measures of function with NSAA/NSAD, time function tests and patient-reported outcomes.
+Added: ARCH was designed to evaluate the safety, PK, changes in biomarkers of muscle damage such CK and fast skeletal muscle troponin I, measures of function with North Star Ambulatory Assessment (NSAA)/North Star Assessment for Limb-Girdle Type Muscular Dystrophies(NSAD), time function tests and patient-reported outcomes.
The schematic below outlines the overall trial design.
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The patients in ARCH had significant functional impairment and evidence of decreased muscle mass at baseline.
−Removed: All individuals had a decreased ability to perform functional measures such as the 10-meter walk-run or rise from floor – only half of the Becker patients were able to perform the rise from the floor at baseline.
−Removed: Their creatinine, which is derived directly from muscle, was decreased.
−Removed: Their CK was elevated, consistent with ongoing muscle damage, and the DXA lean body mass was also decreased, consistent with the overall decreased function and decreased muscle mass.
−Removed: North Star scores for these individuals ranged from 4 to 31.
−Removed: Baseline characteristics are summarized below, highlighting significant functional impairment and decreased muscle mass.
−Removed: Becker Patient Baseline Characteristics in ARCH
+Added: All individuals had a decreased ability to perform functional measures such as the 10-meter walk-run or rise from floor,
+Added: decreased creatinine that is derived directly from muscle, decreased lean body mass on DXA, and elevated CK consistent with ongoing muscle damage, all consistent with decreased muscle mass and function.
+Added: NSAA scores for these individuals ranged from 4 to 31.
At 24 months, sevasemten continued to be well tolerated following escalation to the 20 mg dose, after initially receiving a 10 mg and 15 mg doses.
−Removed: An overview of the adverse events observed up to the 12 and 24-month timepoints can be seen in the table below.
+Added: An overview of the AEs observed up to the 12 and 24-month timepoints can be seen in the table below.
Summary Table of AEs Observed in ARCH (at the 24 Month Timepoint)
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Observations from ARCH identified key factors, including the optimal dosing strategy of sevasemten, for the design of a potentially registrational trial in Becker.
+Added: Through MESA, our open label extension trial, following 36 months of treatment for patients previously enrolled in ARCH, we observed sustained disease stabilization.
+Added: Notably, NSAA scores for participants who rolled over from ARCH remained stable, relative to expected functional declines seen in multiple Becker natural history studies, reinforcing prior ARCH findings.
+Added: In ARCH, Open Label Data In Becker Demonstrated Sustained Disease Stabilization At Three Years
Phase 2 Clinical Trial in Becker (CANYON trial and GRAND CANYON cohort)
−Removed: In July 2022, we initiated our CANYON Phase 2 clinical trial of sevasemten, assessing the effect of sevasemten over a 12-month period on safety, PK, biomarkers of muscle damage (e.g., CK, troponins, myoglobin), and functional measures in individuals with Becker aged 12 years and above.
−Removed: This placebo-controlled trial successfully recruited 69 individuals at approximately 14 sites in the United States, United Kingdom, and the Netherlands.
+Added: In July 2022, we initiated our CANYON Phase 2 clinical trial of sevasemten, a multi-center, double blind, randomized, placebo-controlled study, assessing the effect of sevasemten over a 12-month period on safety, PK, biomarkers of muscle damage (e.g., CK, troponins, myoglobin), and functional measures in individuals with Becker aged 12 years and above.
+Added: This placebo-controlled trial successfully recruited 69 individuals at 16 sites in the United States, United Kingdom, and the Netherlands.
In September 2023, based on the positive observations from the ARCH trial, we amended the CANYON trial and initiated GRAND CANYON, a potentially registrational cohort in individuals with Becker.
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In February 2025, we completed enrollment, including over-enrolling beyond the target 120 Becker adults, in the GRAND CANYON pivotal cohort.
−Removed: Based on the positive Phase 2 CANYON results, we plan to engage the FDA and European Medicines Agency about marketing authorization filing strategies for sevasemten in Becker.
+Added: Based on the positive Phase 2 CANYON results, we continue to engage the FDA and European Medicines Agency about marketing authorization filing strategies for sevasemten in Becker.
+Added: Through MESA, our open label extension trial, following 18 months of treatment for patients previously enrolled in CANYON, we observed sustained disease stabilization.
+Added: Notably, NSAA scores of participants who rolled over from CANYON trend toward improvement, diverging from expected functional declines seen in multiple Becker natural history studies, reinforcing prior CANYON findings.
+Added: In CANYON, Open Label Data In Becker Demonstrated Sustained Disease Stabilization At 18 Months
Exercise Challenge Study (DUNE Study)
In November 2022, we initiated a Phase 2 Exercise Challenge Study (DUNE), to investigate the effect of sevasemten on muscle injury biomarkers following exercise, studied at a single site in Denmark.
−Removed: The trial is a 16-week randomized, double-blind, placebo-controlled Phase 2 trial assessing safety, PK and biomarker response to exercise in adults with Becker, LGMD2I or McArdle disease.
+Added: The trial is a 16-week randomized, double-blind, placebo-controlled Phase 2 trial assessing safety, PK and biomarker response to exercise in adults with Becker, LGMD or McArdle disease.
At the 2024 World Muscle Society meeting, we presented topline results from the DUNE study.
showing sevasemten was well tolerated across 21 participants:
−Removed: Becker (n=9), LGMD2I (n=9) and McArdle (n=3).
+Added: Becker (n=9), LGMD (n=9) and McArdle (n=3).
In the Becker cohort, sevasemten showed significant reductions in biomarker of muscle damage including a 45% decrease in CK after 16 weeks of treatment.
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To date, 99% of eligible participants completing these trials have enrolled in MESA.
+Added: In June 2025, we announced positive data from MESA in participants previously enrolled in ARCH and CANYON, which demonstrated sustained disease stabilization, reinforcing prior ARCH and CANYON findings.
Phase 2 Clinical Trials in Duchenne (LYNX and FOX Studies)
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LYNX is designed to identify a dose of sevasemten that will reduce biomarkers of muscle damage and has the potential to provide functional benefit to patients in a Phase 3 trial.
−Removed: Additionally, we added a new cohort to LYNX to include children aged four to seven years with Duchenne who are not currently treated with corticosteroids.
+Added: Additionally, a cohort includes children aged four to seven years with Duchenne who are not currently treated with corticosteroids.
Patients within the LYNX trial are initially dosed in placebo-controlled cohorts over 12 weeks, then continue on to the open label portion of the trial for up to 48 months.
+Added: In June 2025, we announced encouraging observations from the LYNX Phase 2 placebo-controlled trial in participants with Duchenne across several functional measures, including Stride Velocity 95th Centile (SV95C), NSAA and 4 stair-climb, while identifying a dose of 10 mg for further evaluation.
We initiated the FOX trial, a Phase 2 placebo-controlled trial in children and adolescents with Duchenne who have been previously treated with gene therapy.
−Removed: The FOX trial will assess the effect of sevasemten over 12 weeks on safety,
−Removed: PK and biomarkers of muscle damage.
+Added: The FOX trial is assessing the effect of sevasemten over 12 weeks on safety, PK and biomarkers of muscle damage.
The trial will also explore changes in functional measures, such as the NSAA and self-reported/caregiver-reported outcomes.
−Removed: Approximately 48 participants, aged six to 17 years, are expected to be enrolled in the trial at multiple sites across the United States.
+Added: Participants, aged six to 17 years, are enrolled in the trial at seven sites across the United States.
Participants will then continue in an open-label extension portion of the trial for up to 36 months to gain further insights into safety, PK, function and biomarker measures.
+Added: In June 2025, we reported initial results from the FOX Phase 2 placebo-controlled trial in participants with Duchenne previously treated with gene therapy that also supported that sevasemten 10 mg has the potential to reduce the rate of functional decline.
Natural History Study
In 2022, we commenced an observational natural history study being conducted in collaboration with the GRASP-LGMD Consortium.
−Removed: Enrollment is expected to be complete in Q1 2025.
+Added: Enrollment was completed in 2025.
A Novel Molecule for the Treatment of Patients with HCM and Other Diseases of Diastolic Dysfunction with Significant Unmet Needs
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One of these agents, the small molecule EDG-7500, has unique properties that may lead to a novel therapeutic approach for patients with HCM.
−Removed: The effects of EDG-7500 on cardiac function overlap with some of the desirable attributes of the cardiac myosin inhibitors (CMIs) such as BMS’s CAMZYOS® (mavacamten) and Cytokinetics’ CK-274 (aficamten).
−Removed: However, there are differences in EDG-7500’s effects on cardiac function from those of CMIs that we believe have the potential to yield a potentially superior target product profile for the treatment of multiple phenotypes of HCM and may also have therapeutic benefit in sub-populations of patients with heart failure with preserved ejection fraction (HFpEF).
+Added: The effects of EDG-7500 on cardiac function overlap with some of the desirable attributes of the cardiac myosin inhibitors (CMIs) such as BMS’s CAMZYOS® (mavacamten) and Cytokinetics’ MYQORZO (aficamten).
+Added: However, there are differences in EDG-7500’s effects on cardiac function from those of CMIs that we believe have the potential to yield a superior target product profile for the treatment of multiple phenotypes of HCM and may also have therapeutic benefit in sub-populations of patients with heart failure with preserved ejection fraction (HFpEF).
Disease Background and Current Treatment Limitations
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HCM is caused by abnormal proteins in the heart, including cardiac myosin, that lead to excessive cardiac contraction.
−Removed: Estimates suggest there are as many as 630,000 people in the United States suffering from different forms of HCM.
Over time, abnormal proteins in the heart, many of which are inherited, lead to excessive cardiac contraction, referred to as hypercontractility.
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They may also have episodic lightheadedness and loss of consciousness (syncope).
−Removed: In addition, these patients are at increased risk of heart failure, stroke, atrial fibrillation, and sudden cardiac arrest.
+Added: In addition, these patients are at increased risk of heart failure, stroke, atrial fibrillation (AF), and sudden cardiac arrest.
HCM can be divided into patients with obstructive disease, known as obstructive HCM (oHCM) and those with non-obstructive disease (nHCM).
The pathophysiologic feature of obstruction is present in two thirds of patients with HCM, as the mitral valve comes into contact with the thickened muscle of the interventricular septum during the ejection of oxygenated blood from the heart to the systemic circulation.
−Removed: This creates an obstruction to blood flow exiting the heart through the LVOT which results in a pressure gradient between the LV cavity and the systemic circulation.
+Added: This creates an obstruction to blood flow exiting the heart through the left ventricular outflow tract (LVOT) which results in a pressure gradient between the LV cavity and the systemic circulation.
As a result, higher pressures are generated in the left ventricle than normal, and a pressure gradient develops between the LV cavity and the systemic circulation.
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This abnormal cardiac physiology, termed diastolic dysfunction leads to a decrease in cardiac output that is particularly severe when an HCM patient exerts themselves.
−Removed: oHCM patients also have LV diastolic dysfunction in addition to obstruction of blood flow in the LVOT.
+Added: oHCM patients also have
+Added: LV diastolic dysfunction in addition to obstruction of blood flow in the LVOT.
The clinical manifestations of oHCM and nHCM are generally similar though oHCM patients may experience more symptoms of lightheadedness and syncope.
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Current Management of HCM
−Removed: To determine the appropriate treatment approach, physicians use the New York Heart Association (NYHA) functional classification system to classify both obstructive and non-obstructive HCM patients into one of four categories;
−Removed: NYHA Class I-IV (least to most severe symptoms, respectively).
−Removed: The NYHA classification system is based on the degree of disease impact to the patient’s physical activity and is used to guide the physician’s choice of therapy.
−Removed: The majority of diagnosed HCM patients are symptomatic and are classified as NYHA class II-IV which requires active treatment.
−Removed: NYHA class I HCM patients generally do not require therapeutic intervention unless they meet established guideline criteria placing them at a high risk of sudden cardiac death, in which case implantation of a cardiac defibrillator may be advised.
−Removed: Class I HCM patients are generally under physician surveillance consisting of annual follow-up visits with their cardiologist.
−Removed: Current pharmaceutical treatment is intended to decrease hypercontractility and improve diastolic filling in both oHCM and nHCM and to reduce LVOT obstruction in oHCM patients in order to achieve meaningful symptom relief.
−Removed: Non-vasodilating beta blockers and non-dihydropyridine calcium channel blockers, drugs that are indicated for broader cardiovascular disorders and do not address the underlying cause of the disease, are the first-line therapies for symptomatic oHCM and nHCM patients.
−Removed: Commonly prescribed beta-blockers are atenolol, propranolol, and metoprolol.
−Removed: Verapamil and diltiazem are calcium channel blockers used in the treatment of symptomatic oHCM and nHCM.
−Removed: For oHCM patients who remain symptomatic, a sodium channel blocker may also be added, typically disopyramide.
−Removed: In April 2022, the FDA approved CAMZYOS™ (mavacamten), a CMI, for the treatment of adults with symptomatic New York Heart Association (NYHA) Class II-III oHCM to improve functional capacity and symptoms.
−Removed: Despite CAMZYOS™ efficacy, there are still limitations of this approach including a narrow therapeutic index, long terminal half-life (seven to nine days) and limited ability to rescue excessive pharmacology if it develops.
−Removed: As oHCM or nHCM progresses, patients have limited treatment options often requiring surgical or other invasive interventions including heart transplant.
+Added: Physicians classify both oHCM and nHCM patients using the New York Heart Association (NYHA) functional classification system (class I-IV), which reflects the degree of physical limitation and guides treatment decisions.
+Added: The majority of diagnosed HCM patients are symptomatic (NYHA class II-IV) and require active treatment.
+Added: NYHA class I HCM patients generally do not receive pharmacologic treatment unless they meet guideline-based criteria indicating elevated sudden cardiac death risk, in which case implantable cardioverter-defibrillator therapy may be recommended.
+Added: Otherwise, class I HCM patients will remain under routine surveillance.
+Added: From a therapeutic standpoint, current pharmacologic management is anchored in addressing two distinct clinical challenges:
+Added: relief of symptomatic LVOT obstruction in oHCM and symptom management in nHCM.
+Added: In oHCM, in addition to diastolic dysfunction (impaired relaxation and compliance), obstruction arises when a typically hyperdynamic, hypertrophied left ventricle, often with systolic anterior motion in the mitral valve, creates a dynamic outflow gradient that produces symptoms by limiting forward flow.
+Added: Accordingly, the therapies of oHCM aim to reduce LVOT gradient in symptomatic patients.
+Added: Historically, negative inotropes (beta blockers, non-dihydropyridine calcium channel blockers, and disopyramide) have demonstrated symptomatic benefit, largely in smaller and older clinical studies, and act by blunting calcium-dependent pathways and reducing cardiac contractility.
+Added: CMIs reduce obstruction through a distinct mechanism, decreasing the number of force-generating myosin heads available to interact with actin, which decreases contractile force and LVOT gradients.
+Added: In contrast, nHCM is driven by diastolic dysfunction, elevated filling pressures, microvascular dysfunction, and myocardial ischemia.
+Added: No randomized, evidence-based pharmacologic therapies have been shown to improve outcomes in nHCM, leaving a significant unmet need.
+Added: Symptom control is largely empiric;
+Added: beta blockers or non-vasodilating calcium channel blockers may reduce angina-like symptoms attributable to supply-demand mismatch by lowering heart rate and myocardial work, but fail to normalize core diastolic abnormalities (early relaxation, end-diastolic compliance).
+Added: The CMI class has validated a targeted approach in oHCM.
+Added: CAMZYOS®, approved by the FDA in April 2022, and MYQORZO, approved by the FDA in December 2025, demonstrated improvements in functional capacity and symptoms in symptomatic oHCM (NYHA class II-III), confirming both clinical efficacy and commercial viability of mechanism-based therapies.
+Added: However, CMIs present adoption constraints despite efficacy:
+Added: ● black box warning for heart failure risk;
+Added: ● echo-guided titration requirements, adding clincal and operational complexity;
+Added: ● risk evaluation and mitigation strategy (REMS) requirements, which can limit prescribing flexibility and increase administrative burden.
+Added: As oHCM or nHCM progresses, options narrow, often requiring septal reduction procedures or, in advanced cases, heart transplantation.
+Added: The dynamic highlights a clear opportunity for differentiated, targeted therapies, especially in the underserved nHCM segment with no approved, randomized, outcome directed pharmacologic options.
Unmet Need in HCM
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In addition, a significant percentage of oHCM patients do not respond to CMI and other therapies.
−Removed: efficacy of CMIs in patients with nHCM, who have impaired relaxation and diastolic dysfunction, also remains unproven.
+Added: The efficacy of CMIs in patients with nHCM, who have impaired relaxation and diastolic dysfunction, also remains unproven.
Limited Efficacy of Current Therapeutic Approaches to Treat oHCM
+Added: Our Approach and Preclinical Data
EDG-7500 is a novel small molecule discovered by our company’s scientific research efforts.
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EDG-7500 Leads to Rapid Improvement of nHCM Cardiac Structure and Function After a Single Dose
−Removed: In summary, we have observed that EDG-7500 is a first-in-class cardiac sarcomeric protein modulator that targets the underlying pathophysiology of HCM.
+Added: In summary, we have observed that EDG-7500 is a first-in-class cardiac sarcomeric modulator that targets the underlying pathophysiology of HCM.
Preclinical data in models of both obstructed and non-obstructed HCM suggest the ability to drive a broadly effective clinical response at a low risk of decreasing left ventricular ejection fraction below normal at all doses tested.
−Removed: Due to EDG-7500’s self-limiting mechanism on systolic contraction, we plan to investigate fixed-dose regimens of EDG-7500 thus potentially eliminating the echo-mediated dose titration and intense follow-up requirements of current therapies.
−Removed: As part of our IND-enabling work, we are completing the toxicity and safety pharmacology profile of EDG-7500 in standard GLP safety pharmacology studies, and in non-GLP exploratory and dose range studies.
+Added: Due to EDG-7500’s self-limiting mechanism on systolic contraction, we plan to investigate
+Added: fixed-dose regimens of EDG-7500 thus potentially eliminating the echo-mediated dose titration and intense follow-up requirements of current therapies.
+Added: EDG-7500 Clinical Plan
EDG-7500 Phase 1 Clinical Trial
In September 2023, we announced initial dosing in a Phase 1 trial of EDG-7500 which assessed the tolerability, PK, and pharmacodynamics of EDG-7500 in healthy adults.
−Removed: In September 2024, the Company announced top-line data of EDG-7500 from the Phase 1 trial in healthy subjects.
+Added: In September 2024, the Company announced topline data of EDG-7500 from the Phase 1 trial in healthy subjects.
In the placebo-controlled Phase 1 SAD trial (n=48), healthy subjects received single doses of EDG-7500, ranging from 5 to 300 mg.
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There were no meaningful changes in LVEF for all SAD and MAD subjects across a broad range of EDG-7500 exposures.
−Removed: In the MAD portion of the trial, a half-life of approximately 30 hours was observed, and steady state was
−Removed: achieved in approximately 4 days after the start of once-daily dosing.
+Added: In the MAD portion of the trial, a half-life of approximately 30 hours was observed, and steady state was achieved in approximately 4 days after the start of once-daily dosing.
Generally, dose proportional increases in exposure were observed in both SAD and MAD.
EDG-7500 Phase 2 Clinical Trial (CIRRUS-HCM)
−Removed: In April 2024, we initiated CIRRUS-HCM, a four-part, multi-center, open-label trial, in approximately 55 patients with HCM at up to 20 clinical sites in the U.S.
+Added: In April 2024, we initiated CIRRUS-HCM, a four-part, multi-center, open-label trial, in 107 patients with HCM at up to 22 clinical sites in the U.S.
The primary objective of Part A of the trial was to evaluate the safety and tolerability of a single oral dose of EDG-7500.
Other key outcome measures included PK, LVEF, and resting and provocable LVOT gradient.
−Removed: In the fourth quarter of 2024, we opened and began enrolling the 28-day arms (Parts B and C) and the 12-week open label extension (Part D) of the CIRRUS-HCM trial in patients with obstructive HCM and non-obstructive HCM.
−Removed: We are currently amending Part D of the CIRRUS-HCM trial as we plan for Phase 3 in 2026.
−Removed: We continue to plan to report initial CIRRUS-HCM data from Parts B and C in the first quarter of 2025 and from Part D in the second half of 2025.
+Added: In the fourth quarter of 2024, we opened and began enrolling the 28-day arms (Part B and Part C) and the 12-week open label extension (Part D) of the CIRRUS-HCM trial in patients with oHCM and nHCM.
+Added: CIRRUS-HCM Part D is designed to explore exposure-response correlations and assess biomarker-guided dose optimization to inform the design of Phase 3 trials expected in the second half of 2026.
+Added: We plan to report initial CIRRUS-HCM data from Part D in the first half of 2026.
In CIRRUS-HCM Part A, patients with oHCM received a single dose of 50, 100 or 200 mg of EDG-7500.
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This reduction highlights the potential of our mechanism in the treatment of diseases of diastolic dysfunction, including nHCM.
−Removed: The Company expects to report CIRRUS-HCM 28-day data in the first quarter of 2025.
+Added: In CIRRUS-HCM Part B, patients with oHCM received a once-daily dose of 50 or 100 mg of EDG-7500 for four weeks.
+Added: A 71% mean reduction in resting LVOT pressure gradient (LVOT-G) and a 58% mean reduction in provokable (Valsalva) LVOT-G were observed in patients receiving the 100 mg dose.
+Added: EDG-7500 Led to Significant Reductions of Resting and Valsalva LVOT-G in the 100 mg Cohort
+Added: Treatment with 100 mg of EDG-7500 also demonstrated a 62% mean reduction from baseline in NT-proBNP, a key biomarker of heart failure.
+Added: EDG-7500 Administration Resulted in Rapid and Robust Reductions in NT-proBNP, a Key Marker of Heart Failure in HCM
+Added: In addition, positive trends in echocardiographic parameters of diastolic function were observed following treatment with EDG-7500.
+Added: Clinically meaningful improvements were also observed on the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), with a substantial mean increase of 23 points observed at the 100 mg dose.
+Added: In addition, treatment with 100 mg of EDG-7500 over four weeks demonstrated improvements on the NYHA functional class score.
+Added: 78% of participants improved by ≥ 1 NYHA class, and 67% improved to NYHA class I (i.e.
+Added: asymptomatic).
+Added: In CIRRUS-HCM Part C, patients with nHCM received a once-daily dose of 50 or 100 mg of EDG-7500 for four weeks.
+Added: Treatment with 100 mg of EDG-7500 demonstrated a 42% mean reduction from baseline in NT-proBNP, a key biomarker of heart failure.
+Added: Like oHCM Patients, EDG-7500 Resulted in Rapid and Robust Reductions in NT-proBNP in Patients with nHCM
+Added: The results observed in Part B and Part C in patients with oHCM and nHCM were achieved without meaningful reductions in LVEF.
+Added: Importantly, there were no LVEF values <50% at any timepoint.
+Added: The most frequently reported adverse events were dizziness, upper respiratory tract infection, and AF, nearly all of which were considered mild to moderate in severity.
+Added: Gradient Relief in oHCM and nHCM Patients was Achieved Without a Meaningful Reduction in LVEF
+Added: Enrollment in Part D of the CIRRUS-HCM trial was completed in the first quarter of 2026.
+Added: For patients who completed 12 weeks of dosing in Part D (8 with oHCM and 12 with nHCM), EDG-7500 generally had a favorable safety profile and was well tolerated.
+Added: Consistent with previous observations, no clinically significant changes in LVEF or reductions in LVEF to below 50% were observed, with EDG-7500 continuing to demonstrate a differentiated LVEF profile relative to CMIs.
+Added: A Novel Molecule for the Treatment of Patients with HFpEF
+Added: Overview and Disease Background
+Added: Edgewise is developing a novel small molecule, EDG-15400, with a distinct mechanism of action for the treatment of HFpEF.
+Added: Heart failure (HF) is a growing global clinical syndrome that affects approximately 6.7 million individuals in
+Added: the United States and more than 60 million people worldwide.
+Added: Approximately half of all patients with HF are diagnosed with HFpEF, defined by a left ventricular ejection fraction of 50% or greater.
+Added: HFpEF is a heterogeneous and complex syndrome with multiple contributing factors, including advanced age, inflammation, cardiometabolic stress, lifestyle factors, and coexisting medical conditions.
+Added: This heterogeneity has historically complicated disease characterization and clinical development.
+Added: Patients with HFpEF commonly experience symptoms such as dyspnea, fatigue, and peripheral edema, which can range in severity and substantially impair quality of life.
+Added: HFpEF is associated with a high burden of hospitalization, with reported 30-day readmission rates of approximately 20–30%, as well as significant morbidity and mortality, with published estimates suggesting 5-year mortality rates of approximately 50–60%
+Added: Current Management and Unmet Need of HFpEF
+Added: HFpEF management includes non-pharmacological strategies such as sodium restriction, exercise, and cardiac rehabilitation, as well as pharmacologic therapy aimed at reducing mortality and hospitalizations, improving symptoms, and managing comorbidities.
+Added: SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRA), angiotensin II receptor blockers (ARB), and angiotensin receptor neprilysin inhibitors (ARNI) are the four components of guideline directed medical therapy.
+Added: Diuretics are used as needed to manage congestion.
+Added: Nonetheless, HFpEF remains a disorder associated with significant morbidity, mortality, and economic and healthcare burden.
+Added: Diastolic dysfunction is widely recognized as a central feature of HFpEF and a major contributor to impaired cardiac reserve in affected patients.
+Added: Despite its importance in disease pathophysiology, current therapies for HFpEF do not directly target diastolic dysfunction.
+Added: Diastolic dysfunction is a key feature of HFpEF and EDG-15400 is being evaluated for its potential to modulate pathways relevant to diastolic function, which may address an unmet medical need in HFpEF.
+Added: Phase 1 Clinical Trial
+Added: EDG-15400 is currently being studied in a Phase 1 trial of healthy adults.
+Added: The trial is being conducted in healthy adult volunteers to assess the safety, tolerability, PK, and pharmacodynamics of single and multiple ascending doses of EDG-15400.
+Added: It also includes assessments of the effect of food on drug absorption and comparisons of different formulations.
+Added: This first-in-human study aims to support future clinical development in HFpEF and is expected to report topline results in the first half of 2026.
+Added: We also plan to initiate a Phase 2 trial in participants with HFpEF in the second half of 2026.
Manufacturing
3 unchanged sentences
We maintain agreements with our manufacturers that include confidentiality and intellectual property provisions to protect our proprietary rights related to our product candidates.
−Removed: We have engaged CDMOs to manufacture sevasemten and EDG-7500 for preclinical and clinical use.
+Added: We have engaged CDMOs to manufacture sevasemten, EDG-7500, and EDG-15400 for preclinical and clinical use.
All of our product candidates are small molecules and are manufactured in synthetic processes from readily available starting materials.
−Removed: Our chemistry is a convergent synthesis of under five steps and fourteen steps for sevasemten and EDG-7500 respectively, and appears amenable to scale up and does not currently require unusual equipment in the manufacturing process.
We obtain our supplies from these CDMOs on a purchase order basis and do not have a long-term supply arrangement in place.
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If any of our product candidates are approved, we currently intend to market and commercialize them in the United States and select international markets, either alone or in collaboration with others.
+Added: There is no cure for Becker and no approved therapies on the market to treat the disease.
Approximately 70% of patients with Duchenne are treated with corticosteroids to manage the inflammatory component of the disease.
−Removed: EMFLAZA (deflazacort) is an FDA-approved corticosteroid marketed by PTC Therapeutics, Inc.
−Removed: and prednisone is also FDA-approved and is marketed by multiple companies.
−Removed: In October 2023, the FDA granted AGAMREE (vamorolone) approval in Duchenne patients 2 years and older and Catalyst Pharmaceuticals, Inc.
−Removed: is commercializing this product in the US following its North America exclusive license deal with Santhera.
+Added: Deflazacort and prednisone are FDA-approved corticosteroids and are marketed by multiple companies.
+Added: In October 2023, the FDA granted AGAMREE (vamorolone) approval in Duchenne patients aged 2 years and older, and Catalyst Pharmaceuticals, Inc.
+Added: has commercialized this product in the United States following its North America exclusive license deal with Santhera.
In addition, there are four exon skipping drugs which are marketed under an accelerated approval pathway from the FDA:
−Removed: EXONDYS 51 (eteplirsen), AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), which are naked PMOs approved for the treatment of Duchenne patients amenable to Exon 51, Exon 45 and Exon 53 skipping, respectively, and are marketed by Sarepta Therapeutics, Inc., and VILTEPSO (vitolarsen), a naked PMO approved for the treatment of Duchenne patients amenable to Exon 53 skipping, which is marketed by Nippon Shinyaku Co.
+Added: EXONDYS 51 (eteplirsen), AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen), which are naked phosphorodiamidate morpholino oligomers (PMOs) approved for the treatment of Duchenne patients amenable to Exon 51, Exon 45 and Exon 53 skipping, respectively, and are marketed by Sarepta Therapeutics, Inc., and VILTEPSO (vitolarsen), a naked PMO approved for the treatment of Duchenne patients amenable to Exon 53 skipping, which is marketed by Nippon Shinyaku Co.
In May 2024, Nippon Shinyaku Co.
−Removed: announced that no statistical significance was observed between the treatment group and the placebo group in NILTEPSO’s confirmatory study.
−Removed: This result may affect VILTEPSO’s accelerated FDA approval.
+Added: announced that no statistical significance was observed between the treatment group and the placebo group in VILTEPSO’s confirmatory study.
+Added: In November 2025, Sarepta announced that AMONDYS 45 and VYONDYS 53 missed their primary endpoint in the confirmatory study.
+Added: These results may affect these three drugs’ accelerated FDA approval.
In June 2022, PTC Therapeutics presented new topline results with Translarna (ataluren), for patients with nonsense mutation Duchenne, a subset of the disease that impacts between 10% and 15% of patients.
1 unchanged sentence
Translarna has been conditionally approved in the European Union and Brazil for ambulatory patients aged 2 years and older with Duchenne resulting from a nonsense mutation in the dystrophin gene.
−Removed: However, in January and June 2024, the Committee for Medicinal Products for Human Use (CHMP) of the EMA delivered negative opinions on the re-examination procedure for the conditional marketing authorization of Translarna.
−Removed: This may result in the withdrawal of Translarna from the EMA markets.
+Added: However, in March 2025, the European Commission adopted the negative opinions issued by the Committee for Medicinal Products for Human Use of the EMA for the renewal of conditional marketing authorization of Translarna.
+Added: While this action effectively removes Translarna’s marketing authorization in the European Economic Area, individual countries within the EU can leverage existing legislation to allow continued use of Translarna.
+Added: In February 2026, PTC Therapeutics withdrew its application to the FDA for Translarna in nonsense mutation Duchenne after receiving feedback on its filing.
In June 2023, the FDA approved Sarepta’s Biologics License Application seeking accelerated approval of their microdystrophin gene therapy, Elevidys (delandistrogene moxeparvovec), for the treatment of ambulant individuals with Duchenne between the ages of four to five years.
In June 2024, the FDA granted Elevidys full approval for the treatment of ambulatory individuals aged 4 years and older, and accelerated approval for the treatment of non-ambulatory individuals aged 4 years and older.
−Removed: Other companies focused on developing genetic based therapies for Duchenne that target dystrophin mechanisms include Solid Biosciences Inc., Genethon, PepGen, Dyne Therapeutics, Avidity Biosciences, REGENXBIO, WaveLife Sciences, and Entrada Therapeutics.
−Removed: In June 2024, Pfizer announced its gene therapy Phase 3 trial failed to meet the primary and key secondary endpoints and is no longer under development.
+Added: However, in November 2025, the FDA revised the Elevidys indication to limit to ambulatory individuals 4 years or older and added black box warnings about risks of acute and fatal liver injuries.
+Added: Other companies focused on developing genetic based therapies for Duchenne that target dystrophin mechanisms include Solid Biosciences Inc., Genethon, Dyne Therapeutics, Avidity Biosciences, REGENXBIO, Wave Life Sciences, and Entrada Therapeutics.
+Added: In September 2025, Avidity Biosciences announced positive topline and functional Phase 1/2 data for del-zota, demonstrating a statistically significant increase in dystrophin in individuals with Duchenne amenable to exon 44 skipping.
+Added: In December 2025, Dyne announced top line Phase 1/2 data for zeleciment rostudirsen (z-rostudirsen) demonstrating a statistically significant increase in dystrophin in individuals with Duchenne amenable to exon 51 skipping.
Gene editing treatments that are in preclinical development are also being pursued by Vertex and Sarepta Therapeutics.
We are also aware of several companies targeting non-dystrophin mechanisms for the treatment of Duchenne.
−Removed: In June 2022, Italfarmaco announced positive topline data from its completed Phase 3 trial with Givinostat, a histone deacetylase (HDAC) inhibitor, in boys with Duchenne.
−Removed: In March 2024, the FDA approved Duvyzat (givinostat) for the treatment of Duchene in patients aged six years and older.
+Added: In March 2024, the FDA approved Duvyzat (givinostat) for the treatment of Duchenne muscular dystrophy in patients aged
+Added: six years and older.
+Added: The European Commission granted Duvyzat a conditional approval in June 2025.
Moreover, in June 2021, Italfarmaco released top line Phase 2 data for givinostat in Becker.
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The future of this program in Becker is uncertain.
−Removed: Current pharmaceutical treatment is intended to improve diastolic filling in both oHCM and nHCM and reduce LVOT in oHCM patients only.
−Removed: The goal of current therapies is to achieve meaningful symptom relief.
−Removed: Non-vasodilating beta blockers and non-dihydropyridine calcium channel blockers are the first-line therapies for symptomatic oHCM and nHCM patients.
+Added: In June 2025, Capricor Therapeutics, Inc.
+Added: announced that the FDA has granted ODD to Deramiocel, the company’s lead cell therapy candidate, for the potential treatment of Becker, and this candidate is currently under regulatory review.
+Added: Satellos Bioscience, Inc.
+Added: is developing an orally administered small molecule drug designed to address deficits in muscle repair and regeneration and announced functional data from a Phase 1b trial in adult patients with Duchenne in May 2025.
+Added: Current first-line pharmaceutical treatment for patients with oHCM and nHCM consists of non-vasodilating beta blockers and non-dihydropyridine calcium channel blockers.
Commonly prescribed beta-blockers are atenolol, propranolol, and metoprolol.
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For oHCM patients who remain symptomatic, a sodium channel blocker with negative ionotropic drug properties may also be added, typically disopyramide (either Pfizer’s Norpace, marketed by Pfizer, or a generic form marketed by several companies) and/or Camzyos (mavacamten), a cardiac myosin inhibitor (CMI), may also be added.
−Removed: In the field of emerging treatments for HCM, competitors include Bristol-Myers Squibb (BMS), Cytokinetics, Imbria Pharmaceuticals, and Celltrion.
−Removed: BMS markets Camzyos (mavacamten), a CMI intended for the treatment of
−Removed: adults with symptomatic NYHA class II-III oHCM.
+Added: In the field of emerging treatments for HCM, competitors include Bristol-Myers Squibb (BMS), Cytokinetics, Imbria Pharmaceuticals, Lexicon Pharmaceuticals, and Celltrion, and Braveheart Bio.
+Added: BMS markets Camzyos (mavacamten), a CMI intended for the treatment of adults with symptomatic NYHA class II-III oHCM.
To date, Camzyos (mavacamten) has secured marketing approvals in the US, Europe, and other countries across five continents.
−Removed: Cytokinetics is also developing a CMI, aficamten (CK-274), for which positive Phase 3 oHCM results were announced in 2023.
−Removed: In December 2024, the FDA accepted the aficamten New Drug Application (NDA) with a Prescription Drug Free User Act (PDUFA) target action date set for September 26, 2025.
−Removed: In June 2023, Cytokinetics initiated another Phase 3 active-comparator clinical trial of aficamten compared to metoprolol in symptomatic oHCM patients.
+Added: In December 2025, Cytokinetics received FDA approval and a positive opinion recommending marketing authorization from the Committee for Medicinal Products for Human Use (CHMP) of the EMA for the treatment of oHCM in NYHA II-III for its CMI aficamten, marketed as Myqorzo, beginning in the first quarter of 2026.
In the second quarter of 2024, BMS and Cytokinetics initiated a study of mavacamten and aficamten, respectively, in pediatric population with symptomatic oHCM.
−Removed: BMS and Cytokinetics are also exploring their respective CMIs in ongoing Phase 3 nHCM clinical trials, and BMS is also developing a next generation CMI, MYK-224, for which a Phase 2 oHCM clinical trial is currently ongoing.
−Removed: Non-cardiac myosin targeting drugs in development include IMB-101 (Imbria Pharmaceuticals), a partial fatty acid oxidation (pFOX) inhibitor, CT-G20 (Celltrion), an anti-arrhythmic cibenzoline succinate, and trientine dihydrochloride (Univar Solutions), a selective copper II chelator.
−Removed: In November 2023, Imbria announced Phase 2 nHCM topline results of IMB-101;
−Removed: full results were published in March 2024.
−Removed: In the third quarter of 2024, Lexicon Pharmaceuticals initiated a Phase 3 trial of sotagliflozin, an SGLT1 and SGLT2 inhibitor, in patients with symptomatic obstructive and non-obstructive HCM.
+Added: In April 2025, BMS reported that its Phase 3 study of mavacamten in nHCM failed to meet its dual primary endpoints.
+Added: Cytokinetics is exploring Myqorzo in an ongoing Phase 3 nHCM clinical trial.
+Added: Lexicon Pharmaceuticals is currently conducting a Phase 3 study of Sotagliflozin, an SGLT 1/2 inhibitor, for the treatment of oHCM and nHCM.
+Added: Braveheart Bio is planning to initiate a global Phase 3 clinical trial in oHCM in 2026.
+Added: Other drugs in development that do not target cardiac myosin include Imbria Pharmaceuticals’ ninerafaxstat (IMB-101), a partial fatty acid oxidation (pFOX) inhibitor, Celltrion’s CT-G20, an anti-arrhythmic cibenzoline succinate, and Univar Solutions’ trientine dihydrochloride, a selective copper II chelator.
+Added: In November 2023, Imbria announced Phase 2 nHCM topline results of ninerafaxstat with full results published in March 2024, and in the second quarter of 2025, initiated a Phase 2b nHCM trial of ninerafaxstat.
+Added: In the third quarter of 2024, Lexicon Pharmaceuticals initiated a Phase 3 trial of sotagliflozin, an SGLT1 and SGLT2 inhibitor, in patients with symptomatic oHCM and nHCM.
We have limited knowledge of CT-G20’s Phase 1 oHCM trial status, while the trientine Phase 2 oHCM clinical trial is ongoing.
A myosin binding protein C3-targeting gene therapy candidate, TN-201, is being developed by Tenaya Therapeutics for genetic HCM.
−Removed: TN-201 is currently in a Phase 1b/2 study for which interim results were recently announced in December 2024.
+Added: TN-201 is currently in a Phase 1b/2 study for which interim results were announced in December 2024 with additional results presented at the 2025 American College of Cardiology Scientific Sessions.
We are aware of several preclinical HCM programs including:
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Our commercial success depends in part on our ability to obtain and maintain proprietary or intellectual property protection for our drug candidates, technology and know-how, to operate without infringing the proprietary or intellectual property rights of others and to prevent others from infringing our proprietary or intellectual property rights.
−Removed: We expect that we will seek to protect our proprietary and intellectual property position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements and drug candidates that are important to the development and implementation of our business.
+Added: We plan to protect our proprietary and intellectual property position by, among other methods, pursuing and obtaining patent protection in the United States and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements and drug candidates that are important to the development and implementation of our business.
We also rely on trade secrets, know-how, trademarks, continuing technological innovation and licensing opportunities to develop and maintain our proprietary and intellectual property position.
We currently, and expect that we will continue to, own or in-license patents and patent applications related to our key drug candidates.
−Removed: We own patents and patent applications that cover compositions of matter, methods of treating diseases such as Duchenne, Becker, LGMD and muscle spasticity disorders and combination therapies.
+Added: We own patents and patent applications that cover compositions of matter, methods of treating diseases such as Duchenne, Becker, LGMD, muscle spasticity disorders, cardiac diseases such as HCM and HFpEF, and combination therapies.
As of February 19, 2026, we own a patent portfolio consisting of 23 patent families.
We own 9 issued U.S.
−Removed: patents, 5 issued European patents, 5 issued Japanese patents, 2 issued Indian patents, 2 issued South African patents, 2 issued Singaporean patents, 2 issued Hong Kong patents, 2 issued Mexican patents, 16 pending non-provisional U.S.
+Added: patents, 5 issued European patents, 3 issued Chinese patents, 8 issued Japanese patents, 3 issued Australian patents, 2 issued Eurasian patents, 1 issued Korean patent, 2 issued Indian patents, 2 issued South African patents, 2 issued Singaporean patents, 2 issued Hong Kong patents, 2 issued Mexican patents, 1 issued Macao patent, 14 pending non-provisional U.S.
patent applications, 7 pending PCT applications and 62 pending foreign applications filed in 15 different countries and regions including Europe, Australia, Brazil, Canada, China, Eurasia, Israel, India, Japan, South Korea, Mexico, New Zealand, Singapore, South Africa, and Hong Kong.
−Removed: We own two issued U.S., one European, one South African, one Hong Kong, one Singaporean, one Mexican, and one Japanese patent that covers compositions of matter of sevasemten and methods of treatment using sevasemten that are expected to expire in 2039, excluding any patent term extensions.
−Removed: We own one PCT patent application and one U.S.
−Removed: non-provisional application that covers composition of matter of EDG-7500 and methods of treatment using EDG-7500.
+Added: We own two issued U.S., one European, one South African, one Hong Kong, one Singaporean, one Mexican, one Eurasian, one Chinese, one Australian, and one Japanese patent that covers compositions of matter of sevasemten and methods of treatment using sevasemten that are expected to expire in 2039, excluding any patent term extensions.
+Added: We own one issued U.S.
+Added: patent that covers composition of matter of EDG-7500 and methods of treatment using EDG-7500, which is expected to expire in 2043, excluding any patent term extensions.
+Added: We own one issued U.S.
+Added: patent that covers composition of matter of EDG-15400 and methods of treatment using EDG-15400, which is expected to expire in 2044, excluding any patent term extensions.
For our drug candidates, we generally pursue multilayered patent protection covering compositions of matter, methods of use and methods of manufacture.
−Removed: We also intend to pursue patent
−Removed: protection, if available, with respect to biomarkers that may be useful in selecting a patient population for use of our drug candidates.
+Added: We also intend to pursue patent protection, if available, with respect to biomarkers that may be useful in selecting a patient population for use of our drug candidates.
We intend to strengthen the patent protection of our drug candidates and technologies through additional patent application filings.
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Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the clinical trial is unlikely to meet its stated objectives.
−Removed: Some trials also include oversight by an independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, which may review data and endpoints at designated check points, make recommendations and/or halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.
+Added: Some trials also include oversight by an independent group of qualified experts organized by the clinical trial
+Added: sponsor, known as a data safety monitoring board, which may review data and endpoints at designated check points, make recommendations and/or halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.
There are also requirements governing the reporting of ongoing clinical studies and clinical trial results to public registries.
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The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the manufacturer must develop methods for testing the identity, strength, quality, and purity of the final drug.
−Removed: In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
+Added: In addition, appropriate packaging must be
+Added: selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
While the IND is active and before approval, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important increased incidence of a serious suspected adverse reaction compared to that listed in the protocol or investigator brochure.
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A Complete Response Letter usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, such as an additional pivotal Phase 3 clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies, or manufacturing.
−Removed: If a Complete Response Letter is issued, the sponsor must resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application.
+Added: If a Complete Response Letter is issued, the sponsor must resubmit the NDA, addressing all of the deficiencies identified in the letter, or
+Added: withdraw the application.
Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.
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Any product submitted to the FDA for approval, including a product with a fast-track designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval.
−Removed: A product is eligible for priority review if it has the potential to provide safe and effective therapy
−Removed: where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis, or prevention of a disease compared to marketed products.
+Added: A product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis, or prevention of a disease compared to marketed products.
The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review in an effort to facilitate the review.
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A sponsor may seek FDA designation of a product candidate as a “breakthrough therapy” if the product is intended, alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
−Removed: The designation includes all of the fast-track program features, as well as more intensive FDA interaction and guidance.
+Added: The designation
+Added: includes all of the fast-track program features, as well as more intensive FDA interaction and guidance.
The breakthrough therapy designation is a distinct status from both accelerated approval and priority review, which can also be granted to the same drug if relevant criteria are met.
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If a product that has received ODD and subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same biologic for the same indication for seven years from the approval of the NDA, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.
−Removed: Orphan drug exclusivity does not prevent the
−Removed: FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.
+Added: Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.
Among the other benefits of ODD are tax credits for certain research and a waiver of the NDA application user fee.
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This landmark Supreme Court decision may invite various stakeholders to bring lawsuits against the FDA to challenge longstanding decisions and policies, including FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for drug approvals, which could lead to uncertainties in the industry.
−Removed: Further, changes in the leadership of the FDA and other federal agencies under the new Trump administration may lead to new policies and changes in the regulations that may impact our clinical development and timelines.
+Added: changes in the leadership of the FDA and other federal agencies under the current administration have led to new policies and changes in the regulations that may impact our clinical development and timelines.
Post-Approval Requirements
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Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising, and potential civil and criminal penalties.
−Removed: Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA.
+Added: Physicians may prescribe, in their independent professional medical judgment, legally available products for uses that are not described in the
+Added: product’s labeling and that differ from those tested by us and approved by the FDA.
Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances.
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However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.
−Removed: The FDCA also
−Removed: provides three years of marketing exclusivity for a NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.
+Added: The FDCA also provides three years of marketing exclusivity for a NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug.
This three-year exclusivity covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the original active agent.
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Such laws include, without limitation, U.S.
−Removed: federal anti-kickback, anti-self-referral, false claims, transparency, including the federal Physician Payments Sunshine Act, consumer fraud, pricing reporting, data privacy, data protection, and security laws and regulations, including the Health Insurance Portability and Accountability Act of 1996 (HIPAA), as well as similar foreign laws in the jurisdictions outside the U.S.
+Added: federal anti-kickback, anti-self-referral, false claims, transparency, including the federal Physician Payments Sunshine Act, consumer fraud, pricing reporting, data privacy, data protection, and security laws
+Added: and regulations, including the Health Insurance Portability and Accountability Act of 1996 (HIPAA), as well as similar foreign laws in the jurisdictions outside the U.S.
Similar state and local laws and regulations may also restrict business practices in the pharmaceutical industry, such as state anti-kickback and false claims laws, which may apply to business practices, including but not limited to, research, distribution, sales, and marketing arrangements and claims involving healthcare items or services reimbursed by nongovernmental third-party payors, including private insurers, or by patients themselves;
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Significant uncertainty exists as to the coverage and reimbursement status of any newly approved product.
−Removed: Decisions regarding the extent of
−Removed: coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.
+Added: Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis.
One third-party payor’s decision to cover a particular product does not ensure that other payors will also provide coverage for the product.
9 unchanged sentences
A member state may approve a specific price for the medicinal product, or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.
−Removed: Pharmaceutical products may face competition from lower-priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products.
+Added: Pharmaceutical products may face competition from lower-
+Added: priced products in foreign countries that have placed price controls on pharmaceutical products and may also compete with imported foreign products.
Furthermore, there is no assurance that a product will be considered medically reasonable and necessary for a specific indication, that it will be considered cost-effective by third-party payors, that an adequate level of reimbursement will be established even if coverage is available, or that the third-party payors’ reimbursement policies will not adversely affect the ability for manufacturers to sell products profitably.
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Accordingly, the ACA remains in effect in its current form.
−Removed: It is unclear how future litigation or healthcare measures promulgated by the Biden administration will impact our business, financial condition and results of operations.
+Added: It is unclear how future litigation or healthcare measures promulgated by the current administration will impact our business, financial condition and results of operations.
Complying with any new legislation or changes in healthcare regulation could be time-intensive and expensive, resulting in a material adverse effect on our business.
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CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027.
−Removed: For 2028, up to an additional 15 drugs, which may be covered under either Medicare Part B or Part D, will be selected, and for 2029 and subsequent years, up to 20 additional Part B or Part D drugs will be selected.
+Added: For 2028, up to an additional 15
+Added: drugs, which may be covered under either Medicare Part B or Part D, will be selected, and for 2029 and subsequent years, up to 20 additional Part B or Part D drugs will be selected.
Various industry stakeholders have initiated lawsuits against the federal government asserting that the price negotiation provisions of the Inflation Reduction Act are unconstitutional.
−Removed: The impact of these judicial challenges and future regulations, healthcare measures and agency rules by the Trump administration on us and the pharmaceutical industry as a whole is currently unknown.
+Added: Further, the current administration has issued executive orders focused on decreasing prescription drug prices, including directing the Secretary of the U.S.
+Added: Department of Health and Human Services (HHS) to establish a mechanism through which American patients can buy drugs directly from manufacturers who sell at a most-favored-nation price and directing the U.S.
+Added: Trade Representative and Secretary of Commerce to take action to ensure foreign countries are not engaged in practices that purposefully and unfairly undercut market prices and drive price hikes in the U.S.
+Added: In November 2025, CMS announced a voluntary initiative called the GENEROUS Model (GENErating cost Reductions fOr U.S.
+Added: Medicaid Model) to introduce the option of most-favored-nation pricing to the Medicaid program, whereby a drug manufacturer may voluntarily offer supplemental rebates to participating state Medicaid programs for a manufacturer’s covered outpatient drugs.
+Added: Government agreements with pharmaceutical companies and other measures that use most-favored-nation pricing targets for prescription drugs or that increase generic and biosimilar drug entry sooner than expected can have a material adverse effect on our industry, ability to set adequate pricing for new drugs to recover R&D costs, ability to attract potential investors and potential buyers in the future, or the pricing of our approved product in the U.S.
+Added: and in foreign countries.
+Added: The impact of judicial challenges and future regulations, healthcare measures and agency rules by the current administration on us and the pharmaceutical industry as a whole is currently unknown.
The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our product candidates if approved.
5 unchanged sentences
We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate, if approved, is prescribed or used.
−Removed: It is possible that additional governmental action may be taken to address the COVID-19 pandemic.
Furthermore, there has been increased interest by third party payors and governmental authorities in reference to pricing systems and publication of discounts and list prices.
9 unchanged sentences
The National Competent Authority (NCA), and one or more Ethics Committees (ECs).
−Removed: Under the current regime all suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial have to be reported to the NCA and ECs of the Member State where they occurred.
+Added: Under the current regime all
+Added: suspected unexpected serious adverse reactions to the investigated drug that occur during the clinical trial have to be reported to the NCA and ECs of the Member State where they occurred.
The EU clinical trials legislation currently is undergoing a transition process mainly aimed at harmonizing and streamlining clinical-trial authorization, simplifying adverse-event reporting procedures, improving the supervision of clinical trials and increasing their transparency.
14 unchanged sentences
If the Member States Concerned raise no objections, based on a potential serious risk to public health, to the assessment, SOPC, labeling or packaging proposed by the RMS, the product is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).
−Removed: Under the above-described procedures, before granting the MA, EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria
−Removed: concerning its quality, safety and efficacy.
+Added: Under the above-described procedures, before granting the MA, EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.
Similar to the U.S.
20 unchanged sentences
Our website address is www.edgewisetx.com.
−Removed: We may use our website, press releases, public conference calls and public webcasts as means of disclosing material nonpublic information and for complying with our disclosure obligations under Regulation FD.
Information contained on, or that can be accessed through, our website or any website is not incorporated by reference into this Form 10-K and should not be considered to be part of this Form 10-K unless expressly noted.
10 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.