CY 6031 Study Will Evaluate the Effects of Treatment With Aficamten (CK-3773274) Over a 24-week Period on Cardiopulmonary Exercise Capacity and Health Status in Patients With Symptomatic oHCM

Key Inclusion Criteria:

- Males and females between 18 and 85 years of age, inclusive, at screening.

- Body mass index <35 kg/m2.

- Diagnosed with HCM per the following criteria:

- Has LV hypertrophy and non-dilated LV chamber in the absence of other cardiac
disease and

- Has an end-diastolic LV wall thickness as measured by the echocardiography core
laboratory of:

- ≥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

- Has resting LVOT-G ≥30 mmHg and post-Valsalva LVOT G ≥50 mmHg during screening as
determined by the echocardiography core laboratory.

- LVEF ≥60% at screening as determined by the echocardiography core laboratory.

- NYHA Functional Class II or III at screening.

- Hemoglobin ≥10g/dL at screening.

- Respiratory exchange ratio (RER) ≥1.05 and pVO2 ≤90% predicted on the screening CPET
per the core laboratory.

- Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on
stable doses for >6 weeks prior to randomization and anticipate remaining on the same
medication regimen during the trial. Patients treated with disopyramide must also be
concomitantly treated with a beta blocker and/or calcium channel blocker.

Key Exclusion Criteria:

- Known or suspected infiltrative, genetic or storage disorder causing cardiac
hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).

- Significant valvular heart disease (per investigator judgment).

- Moderate-severe valvular aortic stenosis.

- Moderate-severe mitral regurgitation not due to systolic anterior motion of the
mitral valve.

- History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any time
during their clinical course.

- Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations).

- Has been treated with septal reduction therapy (surgical myectomy or percutaneous
alcohol septal ablation) or has plans for either treatment during the trial period.

- Documented paroxysmal atrial fibrillation during the screening period.

- Paroxysmal or permanent atrial fibrillation is only excluded IF:

- rhythm restoring treatment (eg, direct-current cardioversion, atrial fibrillation
ablation procedure, or antiarrhythmic therapy) has been required ≤6 months prior
to screening.

- rate control and anticoagulation have not been achieved for at least 6 months
prior to screening.

- History of syncope or sustained ventricular tachyarrhythmia with exercise within 6
months prior to screening.

- Has received prior treatment with CK-3773274 or mavacamten.