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

Phase 1b/2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of HS235 Added to Background Treatment in Adults With PAH

Phase 1b/2 Study of HS235 Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of the Activin Signaling Inhibitor HS235 Added to Background Treatment in Adults with Pulmonary Arterial Hypertension (PAH)

A Phase 1b/2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study Assessing the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of the Activin Signaling Inhibitor HS235 Added to Background Treatment in Adults with Pulmonary Arterial Hypertension (PAH)

Inclusion Criteria:

Participants are eligible to be included in the study only if they meet all of the following criteria:

1. Male and female participants, 18 years of age and older.

2. Body Mass Index (BMI) 18.5 and 40 kg/m2 and body weight at or below 120 kg.

3. Baseline RHC performed during the Screening Period documenting:

   1. A minimum PVR of ≥ 5 Wood units (WU) or ≥ 400 dyn·sec·cm-5 and,
   2. A pulmonary artery wedge pressure (PAWP) of ≤ 15 mm Hg.

4. Diagnosis of WHO pulmonary arterial hypertension (PAH) Group 1.

5. Symptomatic PAH classified as WHO Functional class II to IV.

6. On stable doses of at least 2 approved background PAH therapies and diuretics.

7. 6-Minute Walk Distance (6MWD) ≥ 150 m and ≤ 500 m repeated twice during screening.

8. Ability to adhere to study visit schedule and understand and comply with all protocol requirements.

Exclusion Criteria:

1. PH WHO Groups 2, 3, 4 or 5.
2. Hospitalization for any worsening medical condition or major surgery within 4 weeks prior to screening.
3. Any symptomatic coronary disease events.
4. History of heart transplant or on heart transplant list.
5. Uncontrolled systemic hypertension.
6. History of restrictive, constrictive or congestive cardiomyopathy.
7. History of significant mitral regurgitation or aortic regurgitation valvular disease.
8. Untreated or poorly controlled moderate or severe obstructive sleep apnea.
9. A diagnosis of worse than moderate COPD or worse than mild ILD.
10. Cerebrovascular event within 90 days prior to screening
11. A pneumonectomy or lobectomy
12. Having received an activin signaling inhibitor such as sotatercept at any time prior to screening
13. A Hgb > sex-specific ULN
14. Platelets count < 100,000/mm3
15. Severe (stage ≥4) renal failure with eGFR < 30 mL/min/m2
16. Abnormally elevated liver function enzymes (ALT or AST > 3X ULN, or total bilirubin > 1.5X ULN).