PRIMEx - A Study of 2 Doses of Oral CXA-10 in Pulmonary Arterial Hypertension (PAH)

This is a multicenter double-blind, placebo-controlled study to evaluate the safety, efficacy
and pharmacokinetics of 2 doses of CXA-10 on stable background therapy in 96 subjects 18 to
80 years of age with PAH.

The study will be performed in approximately 45 study centers across the United States of
America and Europe. The recruitment period is anticipated to be approximately 12 months.
Approximately 115 subjects will be enrolled to ensure at least 96 subjects complete the
study.

Study participation for each subject will last approximately 5 months. The study will consist
of a screening period (within 30 days prior to dosing), 90 day (approximately 3 months)
treatment period and approximately 14 days follow-up period after the end of treatment visit.

Inclusion Criteria:

- Males and females between 18 to 80 years of age inclusive at Screening

- Weight ≥40 kg

- Must have a diagnosis of WHO Group 1 PH

- Have a World Health Organization (WHO) Classification of Functional Status Class II or
III of patients with PH

- Must meet hemodynamic criteria by means of a right heart catheterization

- Meet pulmonary function test parameters

- A 6 MWD test of ≥125m and ≤550m at the visit

- Subjects must have a resting arterial oxygen saturation (SaO2) ≥90%, with or without
supplemental oxygen, as measured by pulse oximetry at Screening

- Subjects enrolled in a prescribed exercise program for pulmonary rehabilitation must
be in a stable program for 3 months prior to Screening (Visit 1) and must agree to
maintain their current level of rehabilitation throughout the study. If subjects are
not enrolled in a prescribed exercise training program for pulmonary rehabilitation,
they cannot enroll during the Screening/Baseline Period or throughout the study

- If receiving simvastatin-containing products: dose should not exceed 20 mg/day

- Subjects must be receiving no more than two of the following previously approved PAH
therapies: phosphodiesterase type 5 (PDE-5) inhibitors, endothelin receptor antagonist
(ERA), soluble guanylate cyclase (sGC) stimulator, prostanoids, prostacyclin receptor
agonists and must be on stable doses (≥3 months) at Screening (Visit 1)

Exclusion Criteria:

- Contraindications for CMRI imaging

- WHO Groups 2, 3, 4 and 5 Pulmonary Hypertension

- Unrepaired congenital heart defects and significant congenital heart defects (i.e.,
atrial septal defects, ventricular septal defects, and patent ductus arteriosus)
repaired less than 1 year prior to Screening (Visit 1) (Group 1 classification of
Pulmonary Hypertension)

- QTcF > 500 msec

- Acute myocardial infarction or acute coronary syndrome within the last 90 days

- Cerebrovascular accident/transient ischemic attack (CVA/TIA) within the last 90 days

- Hospitalization for left heart failure within the last 90 days

- Clinically significant aortic or mitral valve disease defined as greater than mild
regurgitation or mild stenosis; pericardial constriction; restrictive or constrictive
cardiomyopathy; left ventricular dysfunction (LVEF < 50%); left ventricular outflow
obstruction; symptomatic coronary artery disease; autonomic hypotension; or fluid
depletion

- Atrial fibrillation and life-threatening cardiac arrhythmias

- Personal or family history of congenital prolonged QTc syndrome or sudden or sudden
unexpected death due to a cardiac reason

- Clinically significant anemia

- Severe hepatic impairment or active chronic hepatitis

- Receiving intravenous inotropes within 2 weeks prior to Screening

- History of angina pectoris or other condition that was treated with long or short
acting nitrates <12 weeks of Screening

- Subject has taken immunosuppressant therapy < 12 weeks prior to Screening

- Recent (within 1 year) history of abusing alcohol or illicit drugs.

- History of any primary malignancy, with no evidence of disease for at least 5 years

- Treatment with any investigational drug or device within 30 days or 5 half-lives