Single-Ascending Dose Study of JK07 in Subjects With HFpEF

Inclusion Criteria: 1. Stable New Yok Heart Association (NYHA) Class II or III HF diagnosis, evident at least 6 months prior to enrollment as confirmed by medical history. 2. Documented prior objective evidence of heart failure as shown by 1 or more of the following criteria: 1. Previous hospitalization for heart failure with documented radiographic evidence of pulmonary congestion. 2. Elevated left ventricular (LV) end-diastolic pressure or pulmonary capillary wedge pressure at rest (≥15 mm Hg) or with exercise (≥25 mm Hg). 3. Elevated level of NT-proBNP (\>400 pg/mL) or brain natriuretic peptide (BNP) (\>200 pg/mL). 4. Echocardiographic evidence of medial E/e' ratio ≥ 15 or Left Atrial Volume (LAV) \>58 mL in male patients or \>52 mL in female patients. 3. Adequate acoustic windows on screening resting TTE 4. Documented structural abnormality consistent with HFpEF confirmed at the screening visit by clearly interpretable echocardiography assessment. 5. Meets 1 or more of the following criteria at the initial screening measurement: 1. A hs-cTnI \>99th percentile 2. NT-proBNP \>300 pg/mL (if not in atrial fibrillation or atrial flutter) or \>600 pg/mL (if in atrial fibrillation or atrial flutter), or if the screened participant is either of African descent or has a body mass index ≥30.0 kg/m2, a screening NT-proBNP \>240 pg/mL (if not in atrial fibrillation or atrial flutter) or \>480 pg/mL (if in atrial fibrillation or atrial flutter). 6. Body mass index (BMI) ≥18 kg/m2 and ≤45 kg/m2 7. Screening hemoglobin ≥9.0 g/dL, platelets ≥100x109 /mL, absolute neutrophil count (ANC) ≥1500/mL. 8. Sexually mature biological male subjects must agree to use a medically accepted method of contraception throughout the study and be willing and able to continue contraception until the end of the study (6-month time point). 9. Biological females of childbearing potential must present with a negative blood pregnancy test, must not be lactating, and must agree to employ adequate birth control measures for the duration of the study and be willing and able to continue contraception until the end of the study (6-month time point). 10. Subject is capable of giving signed informed consent. 11. Subject is willing and able to comply with the requirements of the protocol. Exclusion Criteria: Cardiac-Related 1. Participating in any other study and have received any other investigational drug within 30 days prior to screening or 5-half-lives, whichever is longer, 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. Has a prior diagnosis of hypertrophic cardiomyopathy or a known infiltrative or storage disorder causing HFpEF and/or cardiac hypertrophy, such as amyloidosis, Fabry disease, or Noonan syndrome with LV hypertrophy or a positive serum immunofixation result. 4. Has a history of syncope within the last 6 months or sustained ventricular tachycardia with exercise within the past 6 months. 5. Has persistent or permanent atrial fibrillation and is not therapeutically anticoagulated for at least the 4 weeks prior to the initial screening visit or is not adequately rate controlled within 6 months prior to informed consent according to investigator discretion. 6. Has known moderate or severe aortic valve stenosis, hemodynamically significant mitral stenosis, or severe mitral or tricuspid regurgitation at informed consent. 7. Has severe chronic obstructive pulmonary disease, or other severe pulmonary disease, requiring home oxygen, chronic nebulizer therapy, chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months of informed consent. 8. Diagnosed with medically documented acute coronary syndrome within 3 months of screening or a medically documented acute myocardial infarction within 6 months of screening. 9. Cardiac surgery, coronary artery revascularization, percutaneous coronary intervention, or valvuloplasty within 3 months prior to screening. 10. Any subject who has received an indication for coronary revascularization within 3 months prior to screening. 11. Any of the following confirmed by duplicate seated determinations on at least 3 consecutive readings (in clinic/office) following informed consent and prior to randomization: 1. Systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) \>100 mmHg 2. Sustained SBP \<90 mmHg and/or DBP \<40 mmHg and/or symptomatic hypotension 3. Sustained resting heart rate (HR) \<50 or ≥100 bpm or \>110 bpm if chronic AF at Screening (Visit 1) or prior to randomization for \>15 minutes in two episodes separated by one hour of observation 12. Cerebrovascular accident or hospitalizations for cardiovascular (CV) causes other than routine percutaneous procedures (such as device, battery, generator changes or pacemaker lead insertion/replacement), including HF, chest pain, stroke, transient ischemic attack, or arrhythmias within 3 months prior to screening. 13. Symptomatic carotid stenosis or transient ischemic attack or stroke within 60 days prior to informed consent. 14. Has a history of resuscitated sudden cardiac arrest or a known history of appropriate implantable cardioverter-defibrillator (ICD) discharge for life-threatening ventricular arrhythmia. (Note: history of anti-tachycardia pacing (ATP) is allowed.) 15. Subjects 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. 16. History or evidence of clinically significant arrhythmias 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 during screening and/or prior to randomization. Non-Cardiac Co-Morbidity 17. Clinically significant renal dysfunction as measured by the estimated glomerular filtration rate of \<45 mL/min/1.73m2 as calculated by local laboratory standards (Cockcroft-Gault equation for estimation of creatinine clearance \[CrCl\] \[Cockcroft and Gault 1976\]) at screening, or a clinically significant change in renal function between screening and baseline. 18. Clinically significant liver dysfunction as measured by: alanine aminotransferase (ALT) \>2.0 × the upper limit of normal (ULN), alkaline phosphatase \> 2.0 × ULN, aspartate aminotransferase (AST) \>2.0 × ULN, or gamma glutamyl transferase (GGT) \>2.0 × ULN or serum bilirubin ≥ 1.5 × ULN at screening, or a clinically significant change in liver function between screening and baseline. 19. Subjects with alteration of the coagulation panel (international normalized ratio \[INR\]) and/or prothrombin time (PT) ≥1.5 × the ULN; activated partial thromboplastin time (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. 20. Any subject who by Investigator's judgement, has a significant hematuria or proteinuria at screening. 21. Concurrent treatment with Class Ia or III antiarrhythmic drugs if the dosage has been adjusted within 2 months prior to informed consent. 22. Positive screening for human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C virus antibodies. 23. 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). 24. 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. 25. 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). All subjects are to undergo cancer screening following study enrollment in accordance with American Cancer Society Guidelines (See Appendix 1). 26. Pregnant or lactating at screening. 27. Subjects with clinically significant or poorly controlled disease including, but not limited to, endocrine (including diabetes and thyroid) disease, pulmonary (requires home oxygen, inhalants, steroids \>10 mg prednisone equivalent or 2x baseline physiologic steroid replacement, primary pulmonary hypertension, history of pulmonary emboli), neurological or psychiatric (even mild), GI, hematological, urological, immunological, ophthalmic, or orthopedic diseases as determined by the Investigator. 28. Any major surgical procedure within 1 month prior to screening or planned surgical procedure during the study period. 29. 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. 30. Subjects with orthopedic impairment which would prohibit credible or adequate assessment of 6MWT.