Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Key Inclusion Criteria:

• Age 18 and greater, body weight ≥ 45kg
• Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs)
• Diagnosed with oHCM consistent with current American College of CardiologyFoundation/American Heart Association and European Society of Cardiology guidelinesand satisfy both criteria:
• Has documented left ventricular ejection fraction (LVEF) ≥55%
• NYHA Class II or III
• Has documented oxygen saturation at rest ≥90% at Screening
• Is able to perform an upright CPET and has a respiratory exchange ratio (RER) ≥1.0 atScreening per central reading

Key Exclusion Criteria:

• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM,such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6months prior to Screening
• History of resuscitated sudden cardiac arrest (at any time) or known history ofappropriate implantable cardioverter defibrillator (ICD) discharge forlife-threatening ventricular arrhythmia within 6 months prior to Screening
• Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present atScreening
• Persistent or permanent atrial fibrillation not on anticoagulation for at least 4weeks prior to Screening and/or not adequately rate controlled within 6 months priorto Screening
• Treatment (within 14 days prior to Screening) or planned treatment during the studywith disopyramide or ranolazine
• Treatment (within 14 days prior to Screening) or planned treatment during the studywith a combination of β-blockers and calcium channel blockers
• LVOT gradient with Valsalva maneuver <30 mmHg at Screening
• Has been successfully treated with invasive septal reduction (surgical myectomy orpercutaneous alcohol septal ablation [ASA]) within 6 months prior to Screening orplans to have either of these treatments during the study
• ICD placement within 2 months prior to Screening or planned ICD placement during thestudy
• Has a history or evidence of any other clinically significant disorder, condition, ordisease that, in the opinion of the investigator, would pose a risk to participantsafety or interfere with the study evaluation, procedures, or completion
• Prior treatment with cardiotoxic agents such as doxorubicin or similar