GS-4997 in Adults With Pulmonary Arterial Hypertension

Inclusion Criteria:

- Diagnosis of idiopathic pulmonary arterial hypertension (IPAH), heritable pulmonary
arterial hypertension (HPAH), drug- and toxin-induced PAH, or PAH associated with
connective tissue disease, HIV infection, or congenital heart defects (repaired
greater than 1 year prior to Screening)

- Meet all of the following hemodynamic criteria by means of a screening right heart
catheterization (RHC) completed prior to randomization:

- Mean pulmonary artery pressure (mPAP) of ≥ 25 mm Hg

- Pulmonary vascular resistance (PVR) ≥ 400 dyne•sec/cm^5

- Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic
pressure (LVEDP) of ≤ 12 mm Hg if PVR ≥ 400 and < 500 dynes•sec/cm^5, or
PCWP/LVEDP ≤ 15 mm Hg if PVR ≥ 500 dynes•sec/cm^5

- Be able to walk a distance of at least 100 m

- Have World Health Organization (WHO) Functional Class II or III symptoms

- Meet the following criteria determined by pulmonary function tests completed no more
than 24 weeks prior to screening, performed with or without bronchodilation:

- Forced expiratory volume in one second (FEV1) ≥ 55% of predicted normal

- FEV1:forced vital capacity (FVC) ratio ≥ 0.60

- Receiving treatment with one or more drugs approved for PAH for ≥ 12 consecutive
weeks and at stable dose for ≥ 8 consecutive weeks

Exclusion Criteria:

- Diagnosis of PAH associated with significant venous or capillary involvement (PCWP >
15 mm Hg), pulmonary capillary hemangiomatosis, portal hypertension, or unrepaired
congenital heart defects

- Pulmonary hypertension (PH) belonging to groups 2 to 5 of the 2013 NICE
classification

- Left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic,
valvular or constrictive heart disease

- Uncontrolled hypertension (≥ 180/110 mm Hg) at Screening

- End stage renal disease (receiving peritoneal dialysis, hemodialysis, or status after
renal transplantation)

- Severe liver disease (Child-Pugh Class C, with or without cirrhosis)

Individuals may be rescreened one additional time with prior notification to and approval
by the sponsor.