A Study to Assess the Safety, Tolerability, and Hemodynamic Response of PB1046 in Subjects With PAH

Inclusion Criteria:

- Willing and able to provide written informed consent and follow all study-related
procedures;

- Confirmed diagnosis of Pulmonary Arterial Hypertension (WHO Group 1) and WHO
Functional Class II or III by clinical diagnostic criteria assessed by the
Investigator and have a permanently implanted pulmonary artery hemodynamic monitor
(IHM);

- Adult subjects ≥18 years of age willing and able to utilize contraception as needed
for 30 days after their last dose of study drug;

- Body mass index ≥ 18 kg/m2 and ≤ 47 kg/m2;

- Receipt of Investigator-directed stable (no change in dose or addition or removal of a
therapy) medical-therapy in accordance with local standard of care for the management
of PAH for 30 days prior to screening and between screening and first dose and are in
stable clinical condition;

- Screening hemoglobin ≥ 9.0 g/dL secondary to the volume of blood to be collected
during the study period;

- Willing and able to return to the study unit for specified study visits, or
accommodate home visits;

- Willing and able to transmit hemodynamics via IHM and monitor systemic blood pressure
while at home and record results.

Exclusion Criteria:

- Concomitant medical disorder, condition, or history, that in the opinion of the
Investigator would impair the subject's ability to participate in or complete the
requirements of the study;

- Concomitant medical disorder that is expected to limit the subject's life-expectancy
to ≤ 1 year;

- Pregnant or lactating female subjects;

- First positive result from serology testing at visit 1 (screening labs) for human
immunodeficiency virus, hepatitis B surface antigen, or hepatitis C virus prior to
first dose;

- Participation in another investigational study within 30 days prior to screening or
are taking part in a non-medication study which, in the opinion of the Investigator,
would interfere with the study compliance or outcome assessments;

- Use of bosentan therapy for PAH within 30 days prior to screening or during study
participation;

- Sustained systolic blood pressure (SBP) < 95 mmHg and/or diastolic blood pressure
(DBP) < 50 mmHg (confirmed by a duplicate seated reading) on at least 3 consecutive
readings (self-monitored or office) prior to first dose, or overt symptomatic
hypotension;

- Sustained resting heart rate >110 beats per minute (BPM) at screening (V1) or prior to
first dose (confirmed by duplicate assessments of office vital signs or consecutive
ECG assessments) on at least 3 consecutive readings prior to first dose;

- Clinically significant renal dysfunction as measured by the estimated glomerular
filtration rate (eGFR) of < 40 mL/min/1.73m2 as calculated by the MDRD equation: eGFR
= 175 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African
American) (conventional units);

- Clinically significant liver dysfunction as measured by any one of the following: a.
alanine aminotransferase (ALT) >3.0 time ULN or; b. aspartate aminotransferase (AST)
>3.0 time ULN or; c. serum bilirubin ≥ 1.6 mg/dL;

- Known history of substance abuse that in the opinion of the Investigator would impair
the subject's ability to participate in or complete the requirements of the study;

- Any major surgical procedure within 30 days prior to screening or planned surgical
procedure during the study period;

- In-patient hospitalization (defined as greater than 23 hours) within 30 days of
subject dosing;

- Enrollment within the past 3 months prior to screening or plans to enroll during the
study into a cardiopulmonary rehabilitation program;

- Other medical or psychiatric condition which, in the opinion of the Investigator,
would place the subject at increased risk or would preclude obtaining voluntary
consent or would confound the objectives of study;

- Known hypersensitivity to study drug or any of the excipients of the drug formulation.