University of Kansas Medical Center

Eligible participants must meet all of the following criteria to be enrolled in the study: 1. Age ≥ 18 years 2. Documented diagnostic right heart catheterization (RHC) within 12 months of screening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) of ≤ 15 mmHg, with the diagnosis of WHO PAH Group 1 in any of the following subtypes: - Idiopathic PAH - Heritable PAH - Drug/toxin-induced PAH - PAH associated with connective tissue disease - PAH associated with simple, congenital systemic to pulmonary shunts at least 1 year following repair 3. Symptomatic PAH classified as WHO FC II or III 4. Either Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 6 or Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk or above) 5. Diagnosis of PAH within 12 months of screening and on stable doses of a double or triple combination of background PAH therapies and diuretics (if any) for at least 90 days prior to screening 6. Six-minute walk distance ≥ 150 m repeated twice at screening at least 4 hours apart, but no longer than 1 week apart, and both values are within 15% of each other (calculated from the highest value) 7. Females of childbearing potential must meet the following criteria: - Have 2 negative urine or serum pregnancy tests as verified by the investigator prior to starting study drug administration; she must agree to ongoing urine or serum 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, have used highly effective contraception without interruption, for at least 28 days prior to starting the investigational product AND agreed 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 treatment 8. Male participants must meet the following criteria: - Agree to use a condom, defined as a male latex condom or nonlatex 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 treatment 9. Ability to adhere to study visit schedule and understand and comply with all protocol requirements 10. Ability to understand and provide written informed consent

Participants will be excluded from the study if any of the following criteria are met: 1. Diagnosis of pulmonary hypertension (PH) WHO Groups 2, 3, 4, or 5 2. Diagnosis of the following PAH Group 1 subtypes: human immunodeficiency virus (HIV)-associated PAH and PAH associated with portal hypertension, schistosomiasis-associated PAH, pulmonary veno occlusive disease, and pulmonary capillary hemangiomatosis 3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per local laboratory test 4. Uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 180 mmHg or sitting diastolic BP > 110 mmHg during the Screening Visit after a period of rest 5. Baseline systolic BP < 90 mmHg at screening 6. Pregnant or breastfeeding women 7. Any of the following clinical laboratory values at the Screening Visit: - Estimated glomerular filtration rate < 30 mL/min/1.73 m2 (as defined by MDRD equation) - Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels > 3 × ULN - Platelet count < 50,000/mm3 (< 50.0 × 109 /L) 8. Currently enrolled in or have completed any other investigational product study within 30 days for small molecule drugs or within 5 half-lives for investigational biologics prior to the date of documented informed consent 9. Known allergic reaction to sotatercept (ACE-011), its excipients, or luspatercept 10. History of pneumonectomy 11. Pulmonary function test values of forced vital capacity < 60% predicted within 1 year prior to the Screening Visit 12. Stopped receiving any PH chronic general supportive therapy (e.g., diuretics, oxygen, anticoagulants, and digoxin) within 60 days prior to the Screening Visit 13. Initiation of an exercise program for cardiopulmonary rehabilitation within 90 days prior to the Screening Visit or planned initiation during the study (participants who are stable in the maintenance phase of a program and who will continue for the duration of the study are eligible) 14. Untreated more than mild obstructive sleep apnea 15. History of known pericardial constriction 16. History of restrictive or congestive cardiomyopathy 17. History of atrial septostomy within 180 days prior to the Screening Visit 18. Electrocardiogram with Fridericia's corrected QT interval > 500 ms during the Screening Period 19. Personal or family history of long QT syndrome or sudden cardiac death 20. Left ventricular ejection fraction < 50% on historical echocardiogram (ECHO) within 1 year prior to the Screening Visit 21. Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) in the past 6 months prior to the Screening Visit 22. Cerebrovascular accident within 3 months prior to the Screening Visit 23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, as per investigator assessment 24. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease 25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, and vasopressin) within 30 days prior to the Screening Visit 26. Has an active malignancy with the exception of fully excised or treated basal cell carcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently or expected, during the study, to be treated with radiation therapy, chemotherapy, and/or surgical intervention, or hormonal treatment