∙ Participants must meet the following criteria to be enrolled in this proof-of-concept study:

• Age 18 to 85 years

• Clinical diagnosis of HFpEF:

• • Left ventricular ejection fraction ≥50%, with no history of LVEF below 45% in more than two consecutive measurements under stable conditions

• Demonstrated Cpc-PH by all of the following:

‣ Baseline RHC performed within 28 days of randomization documenting a minimum PVR of ≥320 dyn•sec/cm5 (4 wood units)

⁃ Mean pulmonary arterial pressure (mPAP) of \>20 mmHg

⁃ Pulmonary capillary wedge pressure (PCWP) \>15 mmHg but \< 30 mmHg

• New York Heart Association FC of II or III

• Six-minute Walk Distance ≥100 m repeated twice during Screening and both values within 15% of each other, calculated from the highest value

• Chronic medication for HF or for any underlying condition, administered at a stable (per investigator) dose for ≥30 days prior to Visit 1. Diuretics and/or anticoagulants are excepted from this rule but should not be newly started or stopped within 30 days of Visit 1, and a prescribed dose change should not occur within 7 days of Visit 1. Anticoagulation may be suspended for RHC if necessary.

• Women of childbearing potential must:

‣ Have 2 negative urine or serum pregnancy tests as verified by the investigator during the Screening Period; must agree to ongoing pregnancy testing during the course of the study and until 8 weeks after the last dose of the study drug

⁃ If sexually active with a male partner: use highly effective contraception without interruption for at least 28 days prior to starting the investigational product AND agree to use the same highly effective contraception in combination with a barrier method during the study (including dose interruptions), and for 16 weeks (112 days) after discontinuation of study treatment

⁃ Refrain from breastfeeding a child or donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study drug

• Male participants must:

‣ Agree to use a condom, defined as a male latex condom or non latex condom NOT made out of natural (animal) membrane (e.g., polyurethane), during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions, and for at least 16 weeks (112 days) following investigational product discontinuation, even if he has undergone a successful vasectomy

⁃ Refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study drug

• Ability to adhere to the study visit schedule and understand and comply with all protocol requirements

⁃ Agreement to not participate in any other trials of investigational drugs/devices while enrolled in the A011-16 study

⁃ Ability to understand and provide documented consent for participation