Efficacy and Safety of Seralutinib in Adult Subjects With PAH (PROSERA)

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.