A Study to Assess Safety & Effectiveness of Tovinontrine in Chronic Heart Failure With Reduced Ejection Fraction (Cycle-1-REF)

Inclusion Criteria:

• Is an adult male or female patient ≥18 years of age

• Has evidence in the medical history supporting a diagnosis of clinical HF syndrome,NYHA functional class II to III, with the duration of at least 6 months prior to thetime of Screening. The HF syndrome is defined by documentation of 1 or more of thefollowing:

• At least 1 of the typical symptoms due to HF such as dyspnea and/or fatiguelimiting exercise capacity;

• At least 1 of the typical signs of HF such as peripheral edema, elevatedjugular venous pressure, pulmonary crackles; or

• Hospitalization, emergency department visit, or outpatient visit for HFrequiring intravenous (IV) or subcutaneous (SQ) diuresis within the past 12months.

• Has ejection fraction (EF) ≤ 40% by transthoracic echocardiogram (TTE) performed andinterpreted locally at the time of Screening;

• Has NT-proBNP level ≥ 600 pg/mL at the time of Screening. Patients with atrialfibrillation or flutter at the time of Screening are required to have an NT-proBNPlevel of ≥ 1000 pg/mL at the time of Screening;

• Is on stable optimized doses of guideline-directed HF therapy, per Investigator'sclinical judgement, for a minimum of 4 weeks prior to the time of Screening andduring Screening, with no planned changes after randomization.

• Has had no addition of new guideline-directed HF therapy within the 3 months priorto the time of Screening or during the Screening Period;

Exclusion Criteria:

• Has a documented EF >40% by TTE within 6 months of the time of Screening or duringthe Screening Period;

• Has evidence of recent HF exacerbation defined by hospitalization or requirement forIV or SQ diuretics within 60 days of the time of Screening or during the ScreeningPeriod;

• Has a requirement for routine, scheduled outpatient IV infusions for HF (ie,inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration;

• Has elective interventions (eg, percutaneous coronary intervention, deviceimplantations, percutaneous structural heart disease interventions, cardiac andnon-cardiac surgery) planned to occur during involvement in this study;

• Has acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid orother major cardiovascular surgery, or carotid angioplasty within 60 days of thetime of Screening or during the Screening Period;

• Has had a prior or planned orthotopic heart transplantation;

• Has presence of or plan for mechanical circulatory support;

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