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

1. 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.
2. 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.
3. Subjects with clearly interpretable echocardiographic images and with a screening LVEF ≤ 40% in the absence of ≥ Grade 3 valvular disease on 2D-TTE.
4. 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.
5. 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.

5. 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.

8. Capable of providing informed consent and to comply with the protocol.

Exclusion Criteria:

1. 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.
2. Any past participation in a study that has investigated the NRG-1 pathway (e.g., Neucardin, Cimaglermin).
3. 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.
4. Medically documented acute coronary syndrome within 3 months of screening or a medically documented acute MI within 6 months of screening.
5. Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or valvuloplasty within 3 months prior to screening.
6. Any subject who has received an indication for coronary revascularization within 3 months prior to screening.
7. Any major surgical procedure within 1 month prior to screening or planned surgical procedure during the study period.
8. Sustained systolic blood pressure \<90 mm Hg and/or diastolic blood pressure \<50 mm Hg.
9. Sustained resting heart rate >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.
10. 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.
11. 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.
12. 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.
13. Clinically significant renal dysfunction as measured by the estimated GFR \<45 mL/min/1.73m2 at screening, or a clinically significant change in renal function between screening and baseline.
14. Clinically significant liver dysfunction as measured by: ALT >2.0 × ULN, alkaline phosphatase > 2.0 × ULN, AST >2.0 × the ULN, or GGT >2.0 × the ULN or serum bilirubin ≥ 1.2 × the ULN at screening, or a clinically significant change in liver function between screening and baseline.
15. Subjects with alteration of the coagulation panel (INR) and/or PT ≥ 1.5 × the ULN; aPTT ≥ 1.5 × ULN, or serum albumin ≤ 3 gm/dL. For subjects on warfarin or other anticoagulants, an INR (or PT) considered by the Principal Investigator as therapeutically appropriate will be allowed.
16. Subjects with values of CPK and/or CK-MB >2.5 times normal institutional limits at screening.
17. Any subject who by Investigator's judgement, has a significant hematuria or proteinuria at screening.
18. Concurrent treatment with Class Ia or III antiarrhythmic drugs (the medication must have been discontinued more than 2 months before informed consent).
19. Positive screening for HIV antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies.
20. Known history of or active alcohol abuse (no more than 14 units/week for males or 7 units/week for females) or use of illicit drugs within 1 year prior to randomization (excluding recreational use of marijuana or cannabidiol [CBD]-based products.
21. Other medical or psychiatric condition that, in the opinion of the Investigator, would preclude obtaining voluntary consent/assent or would confound the secondary objectives of study.
22. A history of pathologically-confirmed malignancy of any type or any pathologically-confirmed pre-malignant condition (e.g. ductal carcinoma in situ, colonic polyp with premalignant diagnosis, or cervical atypia).
23. Pregnant or lactating female subjects at screening.
24. Subjects with clinically significant or poorly controlled disease including, but not limited to, endocrine (including diabetes and thyroid) disease, neurological or psychiatric (even mild), GI, hematological, urological, immunological, or ophthalmic diseases as determined by the Investigator.
25. Subjects who are not non-smokers or light smokers (no more than 5 cigarettes per day) and who cannot abstain from smoking from 2 weeks prior to the administration of IP through the end of the study.