Study of JK07 in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF)

Inclusion Criteria

• Adults 18 and 80 years with stable NYHA Class II or III HF diagnosis (ischemic or non-ischemic confirmed by medical history) at least 6 months prior to enrollment as confirmed by medical history.
• Stable HF defined as no hospitalizations for cardiac-related issues within the previous 2 months prior to the screening visit or between screening and randomization, other than for routine percutaneous procedures such as device, battery, generator changes or pacemaker lead insertion/ replacement.
• Subjects with clearly interpretable echocardiographic images and with a screening LVEF ≤ 40% in the absence of ≥ Grade 3 valvular disease on 2D-TTE.
• Subjects must be taking clinician-directed appropriate pharmacological therapy for HF as per the 2017 ACC/AHA/HFSA treatment guidelines at stable doses and at investigator determined discretion (except for diuretics) for at least 2 months prior to informed consent.
• Subjects with implantable cardioverter-defibrillators (ICDs) are allowed at the discretion of the investigator, but only if both the following criteria are met: (a) paced beats cannot exceed 15% of beats as quantified by screening e-Patch, and (b) if a non-paced baseline ECG can be obtained on day 1 prior to study drug administration.
• Body mass index ≥18 kg/m2 and ≤45 kg/m2. 6. Screening hemoglobin ≥9.0 g/dL, platelets ≥100 K/mL, ANC ≥1500/mL. 7. Able and willing to use adequate contraception until the end of the study.
• Capable of providing informed consent and to comply with the protocol.

Exclusion Criteria

• Participating in any other study, have received any other investigational drug within 30 days prior to screening or 5-half-lives or any other investigational implanted device within 30 days prior to screening, or are taking part in a nonmedication study which, in the opinion of the Investigator, would interfere with study compliance or outcome assessments.
• Any past participation in a study that has investigated the NRG-1 pathway (e.g., Neucardin, Cimaglermin).
• Heart failure due to hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricula dysplasia (ARVD), stress-induced ("Takotsubo") cardiomyopathy, chemotherapy-induced cardiomyopathy, peripartum cardiomyopathy, infiltrative or inflammatory cardiomyopathies, and primary valvular disease.
• Medically documented acute coronary syndrome within 3 months of screening or a medically documented acute MI within 6 months of screening.
• Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or valvuloplasty within 3 months prior to screening.
• Any subject who has received an indication for coronary revascularization within 3 months prior to screening.
• Any major surgical procedure within 1 month prior to screening or planned surgical procedure during the study period.
• Sustained systolic blood pressure 100 beats per minute sustained for >15 minutes except in sustained atrial fibrillation when a heart rate of up to 110 beats per minute is acceptable.
• Cerebrovascular accident or hospitalizations for CV (cardiovascular) causes other than routine percutaneous procedures such as device, battery, generator changes or pacemaker lead insertion/ replacement or device generator changes, including HF, chest pain, stroke, transient ischemic attack, or arrhythmias within 3 months prior to randomization.
• At screening have an abnormal or clinically significant 12-lead ECG abnormality that, in the opinion of the Investigator, would affect efficacy or safety evaluation or place the subject at risk.
• History or evidence of clinically significant arrhythmia uncontrolled by drug therapy or use of an implantable defibrillator, long QT syndrome, or evidence of QT prolongation with QTcF >450 ms for males or QTcF >470 ms for females prior to randomization.
• Clinically significant renal dysfunction as measured by the estimated GFR 2.0 × ULN, alkaline phosphatase > 2.0 × ULN,