A Study of HS235 for Treatment of Pulmonary Arterial Hypertension (PAH) in Adults

Prior treatment

• Hospitalization for any worsening medical condition or major surgery within 4 weeks prior to screening.
• Cerebrovascular event within 90 days prior to screening
• Having received an activin signaling inhibitor such as sotatercept at any time prior to screening

Other illness

• Any symptomatic coronary disease events.
• History of heart transplant or on heart transplant list.
• Uncontrolled systemic hypertension.
• History of restrictive, constrictive or congestive cardiomyopathy.
• History of significant mitral regurgitation or aortic regurgitation valvular disease.

Lab values

• A Hgb \> sex-specific ULN
• Platelets count \< 100,000/mm3
• Severe (stage ≥4) renal failure with eGFR \< 30 mL/min/m2
• Abnormally elevated liver function enzymes (ALT or AST \> 3X ULN, or total bilirubin \> 1.5X ULN).

Other

• PH WHO Groups 2, 3, 4 or 5.
• Untreated or poorly controlled moderate or severe obstructive sleep apnea.
• A diagnosis of worse than moderate COPD or worse than mild ILD.
• A pneumonectomy or lobectomy

• Participants are eligible to be included in the study only if they meet all of the following criteria:
• Male and female participants, 18 years of age and older.
• Body Mass Index (BMI) 18.5 and 40 kg/m2 and body weight at or below 120 kg.
• Baseline RHC performed during the Screening Period documenting:
  • A minimum PVR of ≥ 5 Wood units (WU) or ≥ 400 dyn·sec·cm-5 and,
  • A pulmonary artery wedge pressure (PAWP) of ≤ 15 mm Hg.
• Diagnosis of WHO pulmonary arterial hypertension (PAH) Group 1.
• Symptomatic PAH classified as WHO Functional class II to IV.
• On stable doses of at least 2 approved background PAH therapies and diuretics.
• 6-Minute Walk Distance (6MWD) ≥ 150 m and ≤ 500 m repeated twice during screening.
• Ability to adhere to study visit schedule and understand and comply with all protocol requirements.