The primary objective of the study is to determine the effect of seralutinib on improving exercise capacity in subjects with WHO Group 1 PAH who are FC II or III. The secondary objective for this trial is to determine time to clinical worsening.

Inclusion Criteria:

1. Adult subjects aged 18 to 75 years.

2. Body mass index (BMI) ≥ 15 kg/m^2 and ≤ 40 kg/m^2.

3. Diagnosis of PAH classified by one of the following:

   1. Idiopathic PAH (IPAH) or heritable PAH (HPAH).
   2. PAH associated with connective tissue disease (CTD-APAH); PAH associated with anorexigen or PAH associated with methamphetamine use.
   3. Congenital heart disease with simple systemic to pulmonary shunt at least 1 year after surgical repair.

4. 6MWDs ≥ 150 meters and ≤ 475 meters during Screening prior to randomization.

5. WHO FC II or III.

6. US Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 2 Risk Score ≥ 5 OR NT-proBNP ≥ 300 ng/L OR PVR ≥ 800 dyne s/cm^5.

7. Cardiac catheterization within the screening period, or a standard of care right heart catheterization (RHC) (with pressure wave forms available for review) up to 48 weeks prior to Screening.

   1. Mean pulmonary arterial pressure (mPAP) > 20 mmHg (at rest), AND
   2. Pulmonary vascular resistance (PVR) ≥ 400 dyne·s/cm^5, AND
   3. Pulmonary capillary wedge pressure (PCWP) or left ventricle end-diastolic pressure (LVEDP) ≤ 15 mmHg.

8. Treatment with at least one allowed background PAH disease-specific medication prior to Screening.

   1. Subjects receiving treatment with endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, guanylate cyclase stimulators, and/or prostacyclin analogues or prostacyclin receptor agonists are eligible only if on a stable dose for at least 12 weeks prior to and throughout Screening.
   2. Subjects receiving treatment with sotatercept are eligible only if on a stable dose of sotatercept for at least 24 weeks prior to and throughout Screening, with a RHC performed during Screening (or within 2 weeks prior to Screening).

9. Pulmonary function tests (PFTs) at Screening or completed no more than 12 weeks prior to Screening.

10. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and on Day 1 before first administration of Investigational Product (IP).

11. WOCBP who are not abstinent and intend to be sexually active with a non-sterilized male partner must be willing to use a highly effective method of contraception from consent through 30 days following the last administration of IP.

12. Male subjects: Non-sterilized male subjects who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom from consent through 90 days after the last dose of IP.

Exclusion Criteria:

1. Evidence of chronic thromboembolic disease or acute pulmonary embolism.

2. Uncontrolled systemic hypertension as evidenced by systolic blood pressure > 160 mm Hg or diastolic blood pressure > 100 mm Hg.

3. Systolic blood pressure < 90 mm Hg during Screening.

4. WHO Pulmonary Hypertension Group 2 - 5.

5. Human immunodeficiency virus (HIV)-associated PAH, schistosomiasis associated PAH, PAH associated with portal hypertension, or pulmonary veno-occlusive disease (PVOD).

6. Recent history of left-sided heart disease and/or clinically significant cardiac disease within 48 weeks of Screening.

7. Left ventricular ejection fraction (LVEF) ≤ 50% within 24 weeks of Screening.

8. Hemodynamically significant valvular heart disease or uncontrolled symptomatic coronary disease.

9. History of atrial septostomy.

10. Uncontrolled atrial fibrillation or paroxysmal atrial fibrillation.

11. Untreated severe obstructive sleep apnea.

12. Hepatic dysfunction defined as Child-Pugh Class A or higher, or as evidenced by one of the following at Screening: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN.

13. Severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or IP administration (eg, history of intracranial hemorrhage, recurrent syncope).

14. Any musculoskeletal disease, injury, or any other disease that limits evaluation of 6MWT.

15. Initiation of an exercise program for cardiopulmonary rehabilitation within 12 weeks prior to Screening or planned during the study.

16. Pregnant or nursing or intends to become pregnant during the duration of the study.

17. Body weight < 37 kg at Screening.

18. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m^2 Hemoglobin (Hgb) concentration < 8.5 g/dL at Screening.

19. Evidence of active or latent Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C, or tuberculosis (TB) infection at Screening.

20. Prior/concurrent treatment with tyrosine kinase inhibitors or activin signaling inhibitors:

    1. Tyrosine kinase inhibitors, other than Janus kinase inhibitors approved for systemic autoimmune rheumatic diseases, within 12 weeks prior to Screening.
    2. Activin signaling inhibitors within 5 half-lives prior to Screening.

21. Requirement of IV inotropes (ie, levosimendan, dopamine, dobutamine, milrinone, norepinephrine) or IV diuretics for more than 24 hours within 4 weeks prior to Screening.

22. Subjects currently receiving oral anticoagulants (ie, warfarin/other vitamin K antagonists or direct-acting oral anticoagulants [DOACs]) if any of the following criteria are met:

    a. History within 24 weeks of Screening of: i. Syncope, or ii. Symptomatic bleeding in a critical area or organ iii. Intramuscular with compartment syndrome, or iv. Bleeding causing a fall in hemoglobin levels of 1.24 mmol/L (20 g/L or greater) or more, or v. Bleeding leading to a transfusion of 2 U or more of whole blood or red blood cells.

    b. History of central nervous system pathology.

    c. History of clinically significant (massive) hemoptysis.

    d. If on warfarin/other vitamin K antagonist, uncontrolled International normalized ratio (eg, INR > 3) as assessed.

    e. Platelet count < 150 x 10^9/L at Screening.

    f. Concomitant use of antiplatelet agents.

    g. CTD-APAH

    h. Concomitant use of sotatercept.

23. Prior participation in seralutinib studies and/or prior treatment with seralutinib.

24. Currently participating in or has participated in a study of an investigational agent or has used an investigational device for the treatment of PAH within 12 weeks or 5 half-lives of the investigational agent, whichever is longer, prior to Screening.

25. Current use of inhaled tobacco- or nicotine-containing products (including e-vapor products) and/or inhaled marijuana.

26. Current alcohol use disorder based on the opinion of the Investigator, and/or a positive test for drugs of abuse.

27. Subjects with a history of severe milk protein allergy or known intolerance to lactose.

28. QT interval corrected for heart rate using Fridericia's formula (QTcF) of > 500 msec.

29. Have any other condition or reason that, in the opinion of the Investigator or in the opinion of the Sponsor's Medical Monitor (MM) (or designee) in consultation with the Investigator, would prohibit the subject from participating in the study.