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 Cardiology
Foundation/American Heart Association and European Society of Cardiology guidelines
and 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 at
Screening per central reading

- LVOT gradient with Valsalva maneuver >=30 mmHg at Screening determined by
echocardiography core lab

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 6
months prior to Screening

- History of resuscitated sudden cardiac arrest (at any time) or known history of
appropriate implantable cardioverter defibrillator (ICD) discharge for
life-threatening ventricular arrhythmia within 6 months prior to Screening

- Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at
Screening

- Persistent or permanent atrial fibrillation not on anticoagulation for at least 4
weeks prior to Screening and/or not adequately rate controlled within 6 months prior
to Screening

- Treatment (within 14 days prior to Screening) or planned treatment during the study
with disopyramide or ranolazine

- Treatment (within 14 days prior to Screening) or planned treatment during the study
with 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 or
percutaneous alcohol septal ablation [ASA]) within 6 months prior to Screening or
plans to have either of these treatments during the study

- ICD placement within 6 months prior to Screening or planned ICD placement during the
study

- Has a history or evidence of any other clinically significant disorder, condition, or
disease that, in the opinion of the investigator, would pose a risk to participant
safety or interfere with the study evaluation, procedures, or completion

- Prior treatment with cardiotoxic agents such as doxorubicin or similar