A Study to Evaluate the Efficacy, Safety, and Tolerability of MYK-224 in Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Inclusion Criteria: * Has adequate acoustic windows, to enable accurate TTEs as determined by the echocardiography core laboratory. * Men or women diagnosed with oHCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines, satisfying both of the following criteria: * Has unexplained left ventricular (LV) hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness ≥ 15 millimeter (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy or with a known disease-causing mutation), as determined by core laboratory interpretation. AND \-- Has a LVOT peak gradient during screening as assessed by echocardiography of ≥ 50 millimeters of mercury (mm Hg) at rest, or ≥ 30 mm Hg at rest and ≥ 50 mm Hg with Valsalva maneuver (confirmed by echocardiography core laboratory interpretation). * Has resting LVEF ≥ 60% at the Screening visit as determined by echocardiography core laboratory. * New York Heart Association (NYHA) functional class II or III symptoms at screening. * Has a valid measurement of LVOT post-exercise peak gradient at screening as determined by echocardiography core laboratory. Exclusion Criteria: * Presence of any medical condition that precludes exercise stress testing. * History of syncope or sustained ventricular tachyarrhythmia within 6 months prior to screening. * Known infiltrative or storage disorder causing cardiac hypertrophy that mimics HCM, such as Fabry disease, amyloidosis, or Noonan syndrome with left ventricular hypertrophy. * Prior treatment with mavacamten or aficamten. An exception may be made in cases where myosin inhibitor use was not within 4 months of the Screening visit, and with the agreement of both the Investigator and the Medical Monitor. * 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 (Note: Individuals with an unsuccessful myectomy or percutaneous ASA procedure performed \> 6 months prior to Screening may be enrolled if study eligibility criteria for LVOT gradient criteria are met). * Implantable cardioverter-defibrillator (ICD) placement or pulse generator change within 2 months prior to screening or planned new ICD placement during the study (pulse generator changes, if needed during the study are allowed). * Has a history of resuscitated sudden cardiac arrest (any time) or known history of appropriate implantable cardioverter-defibrillator (ICD discharge for life-threatening ventricular arrhythmia within 6 months prior to screening. * Has paroxysmal, atrial fibrillation with atrial fibrillation present per the Investigator's evaluation of the participant's ECG at the time of Screening. * Has 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 (Note: Participants with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed). * Has QT interval with Fridericia correction (QTcF) \> 500 msec when QRS interval \< 120 msec or QTcF \> 520 msec when QRS ≥ 120 msec if participant has left bundle branch block or any other 12-lead ECG abnormality considered by the investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type II). * Has known moderate or severe (per investigator's judgment) aortic valve stenosis at screening. * History of LV systolic dysfunction (LVEF \< 45%) at any time during their clinical course. * Clinically significant pulmonary disease associated with exertional dyspnea. * Has known significant unrevascularized obstructive coronary artery disease (\>70% stenosis in one or more main epicardial coronary arteries) or history of myocardial infarction Note: participants with prior coronary artery bypass grafting (CABG) or percutaneous coronary interventions (PCIs) are allowed if the procedure was performed at least 12 weeks prior to screening * Prior treatment with cardiotoxic agents such as anthracyclines (eg, doxorubicin) or similar Other protocol-defined criteria apply.