A Dose-escalation Study in Subjects With Pulmonary Arterial Hypertension (PAH)

Inclusion Criteria

- Subjects must be between 18-75 years of age (inclusive), at the time of signing the
informed consent.

- Documented diagnosis of PAH, defined as mPAP > 25 millimeter of mercury (mmHg) and
pulmonary wedge pressure (PWP) <= 15.

- Idiopathic PAH (IPAH), Hereditary PAH (HPAH), or PAH associated with collagen vascular
disease, or appetite suppressant use.

- World Health Organization (WHO) functional class I, II, or III, stable for at least 8
weeks prior to enrollment.

- Hemodynamically stable on background therapy with no evidence of uncontrolled right
heart failure (historic data), as determined by the investigator.

- Six minute walk (6MW) distance, as performed at screening or within 6 months prior to
screening, of >= 100 meters (m) and <= 500 m.

- Mean BP of >60 mmHg.

- Receiving stable doses of one or more medications that are approved for treatment of
PAH, including endothelin receptor antagonists, phosphodiesterase 5 inhibitors, and/or
prostanoids/prostacyclin receptor agonists, for a minimum of 12 consecutive weeks
before enrollment.

- Diuretic dose stable for 8 weeks.

- Body weight <= 100 kg and body mass index (BMI) within the range 18-35 kg per m square
(kg/m^2) (inclusive).

- Male and/or female (following confirmation of negative pregnancy test for Women of
Childbearing Potential [WOCBP]). Women who are pregnant or breastfeeding are excluded.

- Capable of giving signed informed consent.

Exclusion Criteria

- History of systemic hypotension, defined as systolic BP <90 mmHg and/or diastolic BP
<50 mmHg.

- Hospitalization for PAH associated deterioration in the previous 6 months.

- Any additional medical condition, serious intercurrent illness, or other extenuating
circumstance that, in the opinion of the Investigator, may significantly interfere
with study compliance, including all prescribed evaluations and follow-up activities.
Concurrent disease or condition that may interfere with study participation or safety
include bleeding disorders, arrhythmia, organ transplant, organ failure, current
neoplasm, poorly controlled diabetes mellitus, and serious neurological disorders.

- Complex repaired and unrepaired congenital heart disease.

- Subjects with Eisenmenger physiology.

- Alanine transferase (ALT) >2x upper limit of normal (ULN).

- Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35 percent).

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome or asymptomatic gallstones).

- Estimated glomerular-filtration-rate (eGFR) <45 milliliter per minute per 1.73 meter
square (mL/min/1.73m^2).

- QTc >480 millisecond (msec) or QTc > 500 msec in subjects with bundle branch block.

- Any bleeding concerns as evidenced by International normalized ratio (INR) >1.5 (in
subjects not receiving anticoagulation therapy) or platelet count <80,000.

- Hemoglobin (Hb) <10 gram per deciliter (g/dL).

- Sensitivity to any of the study treatments, or components thereof, or drug or other
allergy that, in the opinion of the investigator or Medical Monitor, contraindicates
participation in the study.

- Any use of an Angiotensin-converting enzyme (ACE) inhibitor or Angiotensin receptor
blocker or renin inhibitors within 14 days prior to dosing. Therapy can be stopped to
enable inclusion if deemed safe by the subject's treating physician.

- Use of any investigational product (IP) or device within 30 days prior to dosing, or
known requirement for any investigational agent prior to completion of all scheduled
study assessments.

- Positive human immunodeficiency virus (HIV) antibody test.

- Presence of Hepatitis B surface antigen (HBsAg) at screening.

- Positive Hepatitis C antibody test result at screening or within 3 months prior to
starting study treatment.

- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3
months prior to first dose of study treatment.

- Participation in the study would result in loss of blood or blood products in excess
of 300mL within 65 days.

- Exposure to more than 4 new chemical entities within 12 months prior to the first
dosing day.

- A known or suspected history of alcohol or drug abuse within the 2 years prior to
screening.

- Unable to refrain from smoking during the in-house treatment period.