A Phase 2, Multicenter, Open-Label Study to Evaluate the Intermediate/Long Term Safety and Efficacy of AIR001 in Subjects With WHO Group 1 Pulmonary Arterial Hypertension

Inclusion Criteria:

1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any subject-mandated procedures.
2. Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Has completed the 16-week AIR001-CS05study as planned.
4. If on corticosteroids, has been receiving a stable dose of less than or equal to 20 mg/day of prednisone (or equivalent dose, if other corticosteroid) for at least 1 month (30 days) prior to the AIR001-CS05 study Baseline/Day 1 visit. If receiving treatment for Connective Tissue Disease (CTD) with any other drugs, doses should remain stable, if clinically feasible, for the duration of the AIR001-CS06 study.
5. Women of childbearing potential must be using at least one form of medically acceptable contraception (i.e. either oral, topical, implanted hormonal contraceptives, or an intrauterine device) or two barrier methods; have a negative pregnancy test at Screening and Baseline/Day 1 and agree to use reliable methods of contraception until at least 24-hours after the last dose of study drug. Women who are surgically sterile (i.e. hysterectomy, bilateral oophorectomy, or tubal ligation) or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Men who are not sterile (i.e. have not had a vasectomy) must also agree to use contraception until at least 24-hours after the last dose of study drug.

Exclusion Criteria:

1. Participation in a device or other interventional clinical studies (other than AIR001-CS05), within 1 month (30 days) of Baseline/Day 1 and/or during study participation.
2. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure > 160 mmHg or sitting diastolic blood pressure > 100 mmHg during Baseline/Day 1 visit.
3. Systolic blood pressure < 90 mmHg at Baseline/Day 1.
4. Diagnosis of Down syndrome.
5. Moderate to severe hepatic impairment classified as a Child-Pugh Class B or C at Baseline/Day 1.
6. Has chronic renal insufficiency as defined by serum creatinine > 2.5 mg/dL or has an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min at Baseline/Day 1, or requires dialytic support.
7. Has a hemoglobin (Hgb) concentration < 8.5 g/dL at Baseline/Day 1.

8. Personal or family history of the following:

   1. Congenital or acquired methemoglobinemia;
   2. RBC CYPB5 reductase deficiency.
9. History of glucose-6-phosphate dehydrogenase (G6PD) deficiency or any contraindication to receiving methylene blue.
10. For subjects with Human immunodeficiency virus (HIV) associated PAH, requirement for the use of inhaled pentamidine.
11. The use of oral or topical nitrates (nitroglycerin, glyceryl trinitrate (GTN), isosorbide dinitrate, and isosorbide mononitrate) within 1 month (30 days) prior to Baseline/Day 1 or throughout the AIR001-CS06 study until EOS or Termination visit. Note: Intravenous GTN in an emergency setting may be administered by starting with a low dose and titrating upward, while the subject is being monitored closely for changes in blood pressure and heart rate.
12. Known or suspected hypersensitivity or allergic reaction to sodium nitrite or sodium nitrate.
13. History of malignancy within 5-years prior to Baseline/Day 1 of the AIR001-CS05 study, with the exception of localized non-metastatic basal cell carcinoma of the skin and in situ carcinoma of the cervix.
14. Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
15. Has a psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs 1 month (30 days) prior to study Baseline/Day 1 of the AIR001-CS05 study and for the duration of the study.
16. Is currently pregnant or breastfeeding or intends to become pregnant during the duration of the study.
17. Investigators, study staff or their immediate families.