The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of HJB647 at two different doses in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

This is a multi-center, randomized, participant- and investigator- blinded, placebo- controlled crossover study to investigate the safety, tolerability, and pharmacokinetics of HJB647 in participants with chronic stable heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF).

The study will consist of approximately 12 participants randomly assigned in a 1:1:1 ratio to one of three 3-day treatment sequences comprised of two doses of HJB647 and placebo. Dosing of the HJB647 and placebo is planned for 3 consecutive days. Participants will be domiciled during study drug administration period for close monitoring with a follow-up in-clinic visit on Day 7. A safety call will be performed on Day 33.

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

• Men and women aged 18 years or older
• Stable NYHA functional class II-III
• LVEF <50%
• NT-proBNP ≥600 pg/ml if in sinus rhythm or ≥900 pg/ml if in atrial fibrillation at screening
• On stable standard of care therapy with sacubitril/valsartan with a dose of at least 49/51 mg BID for at least 4 weeks before screening.

Exclusion Criteria:

Participants will be deemed ineligible for inclusion if they meet any of the following exclusion criteria:

• Acute decompensated heart failure within 3 months prior to screening
• SBP <105 mmHg at screening or baseline.
• Acute coronary syndrome, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, PCI, or carotid angioplasty within the 6 months prior to screening
• Hemodynamically significant mitral and/or aortic valve disease, or any prior valve replacement, except mitral regurgitation secondary to LV dilation at screening
• eGFR <30 ml/min/1.73m2 at screening, as measured by the CKD-EPI formula
• BMI >40 kg/m2
• Strong CYP3A4 inhibitors or inducers, sGC activators (vericiguat), PDE5 inhibitors, and nitroglycerin products
• Women of childbearing potential

Further eligibility criteria might apply in alignment with the trial protocol.