Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13)

Inclusion Criteria:

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 ofscreening documenting a minimum PVR of ≥ 4 Wood units and pulmonary capillary wedgepressure (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 1year 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 Therapiesfor Pulmonary Hypertension (COMPERA) 2.0 risk score ≥2 (intermediate to-low-risk orabove)

5. Diagnosis of PAH within 12 months of screening and on stable doses of a double ortriple 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 investigatorprior to starting study drug administration; she must agree to ongoing urine orserum pregnancy testing during the course of the study and until 8 weeks afterthe last dose of the study drug

• If sexually active with a male partner, have used highly effectivecontraception without interruption, for at least 28 days prior to starting theinvestigational product AND agreed to use the same highly effectivecontraception in combination with a barrier method during the study (includingdose interruptions) and for 16 weeks (112 days) after discontinuation of studytreatment

• Refrain from breastfeeding a child or donating blood, eggs, or ovum for theduration of the study and for at least 16 weeks (112 days) after the last doseof study treatment

8. Male participants must meet the following criteria:

• Agree to use a condom, defined as a male latex condom or nonlatex condom NOTmade out of natural (animal) membrane (e.g., polyurethane), during sexualcontact with a pregnant female or a female of childbearing potential whileparticipating in the study, during dose interruptions, and for at least 16weeks (112 days) following investigational product discontinuation, even if hehas undergone a successful vasectomy

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

9. Ability to adhere to study visit schedule and understand and comply with allprotocol requirements

10. Ability to understand and provide written informed consent

Exclusion Criteria:

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 pulmonarycapillary hemangiomatosis

3. Hemoglobin at screening above gender-specific upper limit of normal (ULN), per locallaboratory 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 aftera 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 MDRDequation)

• Serum alanine aminotransferase, aspartate aminotransferase, and total bilirubinlevels > 3 × ULN

• Platelet count < 50,000/mm3 (< 50.0 × 109 /L)

8. Currently enrolled in or have completed any other investigational product studywithin 30 days for small molecule drugs or within 5 half-lives for investigationalbiologics 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 1year 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 daysprior to the Screening Visit or planned initiation during the study (participantswho are stable in the maintenance phase of a program and who will continue for theduration 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 theScreening 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 myocardialinfarction, percutaneous coronary intervention, coronary artery bypass graftsurgery, or cardiac anginal chest pain) in the past 6 months prior to the ScreeningVisit

22. Cerebrovascular accident within 3 months prior to the Screening Visit

23. Acutely decompensated heart failure within 30 days prior to the Screening Visit, asper investigator assessment

24. Significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitationvalvular disease

25. Received intravenous inotropes (e.g., dobutamine, dopamine, norepinephrine, andvasopressin) within 30 days prior to the Screening Visit

26. Has an active malignancy with the exception of fully excised or treated basal cellcarcinoma, cervical carcinoma in-situ, or prostate cancer that is not currently orexpected, during the study, to be treated with radiation therapy, chemotherapy,and/or surgical intervention, or hormonal treatment