Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction

Inclusion Criteria:

• Willing and able to provide signed informed consent form (ICF) prior to participationin any study-related procedures.

• Age ≥40 and ≤80 years.

• A known history of chronic ischemic or non-ischemic cardiomyopathy of at least 6months duration from the time of the initial diagnosis.

• Receiving heart failure (HF) treatment, including, but not limited to, angiotensinconverting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), and anevidence-based beta blocker for the treatment of HF. Subjects who cannot tolerate ACEIor ARB due to reduced renal function or hypotension are eligible. Subjects may bereceiving aldosterone antagonists, but this is not a requirement for the study.

• HF is considered to be stable in the judgment of the Investigator AND doses of HFtreatment have been stable for at least 1 month prior to the Screening Visit.

• In normal sinus rhythm (electrocardiogram documented) at Screening and Day 1 and nohistory of atrial fibrillation in the past 12 months

• No hospitalization related to HF within 1 month prior to the Screening Visit.

• Left Ventricular Ejection Fraction (LVEF) ≤ 40% by 2-D echocardiography at Screening.

• At least 3 viable segments (hyperenhancement ≤ 25%) by a qualifying delayedgadolinium-enhanced cardiac MRI examination at Screening (confirmed by independentcore lab).

• Women of childbearing potential must agree to use 1 of the following methods of birthcontrol from the date they sign the ICF until two months after the last dose of studymedication:

• Abstinence, maintenance of monogamous relationship with a male partner who hasbeen surgically sterilized by vasectomy, or barrier method AND either hormonalcontraception or an intrauterine device or system.

Exclusion Criteria:

• History of any concurrent medical condition which, in the opinion of the Investigator,significantly increased the potential risks associated with administration of studymedication or any other aspect of study participation.

• Any contraindication to MRI scanning.

• Left ventricular end diastolic dimension (LVEDD) indexed to Body Surface Area is > 45mm/m2.

• Coronary or peripheral revascularization procedures, valvular procedures, OR any majorsurgical procedure within 3 months prior to the Screening Visit.

• Acute coronary syndrome, stroke or transient ischemic attack (TIA) within 3 monthsprior to the Screening Visit.

• Obstructive or restrictive cardiomyopathy, infiltrative diseases of the myocardium (e.g., amyloid, sarcoid, etc.) myocarditis, or reductions in LV function thought to besecondary primarily to valvular heart disease, prior cardiac valve surgery or knownaortic stenosis.

• The presence or anticipated placement of any pacemaker, implantable cardioverterdefibrillator (ICD), or cardiac resynchronization therapy (CRT) devices during theensuing 6-week study period.

• Presence of second degree or advanced heart block.

• Uncontrolled hypertension defined as a systolic blood pressure > 160 mmHg or adiastolic blood pressure > 110 mmHg on at least two consecutive readings.

• Presence of any left ventricular thrombus, pericardial disease, uncorrected thyroiddisease or a dyskinetic left ventricular aneurysm.

• History of cancer that causes symptoms, disabilities, or is likely to lead tohospitalization or treatment in the next 12 months.

• Currently receiving treatment with chemotherapeutic agents or immunosuppressant agentsor has received prior radiation therapy to the chest.

• Liver enzymes (alanine aminotransferase [ALT] AND/OR aspartate. aminotransferase [AST]) elevation > 3 times the upper limit of normal (ULN).

• Total bilirubin > 1.5 times ULN in the absence of Gilbert's Syndrome.

• Bleeding diathesis or any known blood dyscrasia.

• Anemia, defined as hemoglobin < 9 g/dL or planned blood transfusions in the next 6weeks.

• Estimated glomerular filtration rate (eGFR) < 30 mL/min, using the Modification ofDiet in Renal Disease (MDRD) Study equation.

• History of hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV) infection,or diagnosis of immunodeficiency.

• Known active drug or alcohol abuse within 1 year of the Screening Visit. Alcohol abuseis defined as 15 or more drinks for men per week or 8 or more for women.

• Recipient of any investigational drugs, stem cell or gene therapies, or devices ORparticipation in another clinical trial, within 3 months prior to the Screening Visit.

• Female subjects who are pregnant, planning to become pregnant, or lactating.

• Requiring any change in doses of cardiovascular medication (including diuretics) inorder to control worsening of HF symptoms.

• Known allergy to gadolinium.

• Currently receiving treatment with therapeutic doses of anticoagulants. Antiplatelettherapy used to prevent cardiovascular disease (primary prevention) or to treatchronic disease (secondary prevention) is permitted.

• Currently receiving treatment with sacubitril/valsartan or trimetazidine.

• Hyponatremia defined as plasma Na+ level <125 mEq/L (UK only).