Inclusion Criteria:

• Between 18-85 years of age
• Body mass index < 40 kg/m2
• Diagnosed with nHCM and has a screening echocardiogram with the following:
  • End-diastolic left ventricular (LV) wall thickness:
    • ≥ 15 mm in one or more myocardial segments OR
    • ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM AND
    • Resting LVOT-G < 30 mmHg AND Valsalva LVOT-G < 50 mmHg AND
    • LVEF ≥ 60%
  • Participants with a history of intracavitary obstruction are eligible
• NYHA class II or III
• Respiratory exchange ratio of ≥ 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) ≤ 90% for age and sex
• KCCQ-CSS score of ≥ 30 and ≤ 85
• NT-proBNP of:
  • NT-pro BNP ≥ 300 pg/mL or NT-proBNP ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR
  • For Black participants, an NT-pro BNP ≥ 225 pg/mL or NT-proBNP ≥ 675 pg/mL if in atrial fibrillation or atrial flutter

Exclusion Criteria:

• Significant valvular heart disease (per Investigator judgment)
• Moderate or severe valvular aortic stenosis or fixed subaortic obstruction
• Moderate or severe mitral regurgitation
• Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)
• Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of myocardial infarction.
• History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy -Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)
• Documented room air oxygen saturation reading < 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension
• History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 3 months prior to screening
• History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control)
• Screening diastolic blood pressure ≥ 100 mmHg -Received prior treatment with aficamten
• Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening)
• Undergone septal reduction therapy < 6 months prior to screening
• Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period
• Paroxysmal or permanent atrial fibrillation is excluded only if:
  • rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to screening
  • rate control and anticoagulation have not been achieved for at least 3 months prior to screening.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 4/26/2024. Questions regarding updates should be directed to the study team contact