Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004

This is a multi-center, Phase 2 Long-Term, Open Label Extension (OLE) Study to assess the safety and tolerability of pemziviptadil (PB1046) at an optimally titrated dose. This is a Long-Term, Open label Extension (OLE) Study for subjects with (PAH), having participated in double-blind Study PB1046-PT-CL-0004. The study will include adult subjects previously diagnosed with symptomatic PAH, who are receiving background clinician-directed therapy for PAH.

During this period, subjects will continue to be followed for safety and tolerability, as well as for periodic efficacy, quality of life data and immunogenicity. The study will continue per the schedule of events until such time when pemziviptadil (PB1046) is able to be self-administered, becomes commercially available to the subjects in a particular country or region, or the sponsor terminates the study due to lack of efficacy, safety or other reasons.

Subjects entering this study will enter from the double-blind Study PB1046-PT-CL-0004. The starting dose level of pemziviptadil (PB1046) for all subjects in this parent study was a sub-therapeutic or minimally effective dose (MED) of 0.2 mg/kg, administered by SC injection.

Subjects were randomized into the MED) Group or a dose-titration group. In the dose-titration group, individual subjects were titrated up to their maximum tolerated dose (MTD) in a blinded fashion, with the objective of titrating subjects up to a dose of at least 1.2 mg/kg or higher in the MTD Group, while subjects in the MED Group remained at the MED level of 0.2 mg/kg, and underwent "sham dose-titration" to maintain the blind.

Subjects entering the 0006 trial prior to implementation of this protocol amendment will remain blinded until such time that open label dosing will not unblind the 0004 study.

Eligibility Criteria:
Inclusion Criteria:

* Subjects must have completed Week 17 / End of Study of PB1046-PT-CL-0004;
* Willing and able to sign a written Informed Consent (IC) prior to all study-related procedures;
* Agrees to use a medically acceptable method of contraception (both male and female patients) throughout the entire study period and continuing for 30 days after their last dose of study drug. if the possibility of conception exists. Medically acceptable methods of contraception include the following: abstinence (not having sex), vasectomy (with confirmed negative sperm counts), condoms and partner using vaginal spermicide and/or cervical cap with spermicide or sponge; oral, implantable, or injectable contraceptives (starting ˃2 months before dosing), diaphragm with vaginal spermicide, intrauterine device, surgical sterilization (˃6 months after surgery). Female subjects ˂45 years of age of non-childbearing potential are defined as being surgically sterile by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Female subjects 45to-60 years of age, inclusive, who are post-menopausal for at least 1 year, and have a follicle-stimulating hormone (FSH) level confirmation indicating post-menopausal status, will be considered to be of non-childbearing potential. Female subjects \> 60 years of age are considered post-menopausal and of non-childbearing potential;
* Willing and able to understand and follow instructions, return to the study unit for specified study visits; and, be able to participate in the study through the Stable Dose Maintenance Period, at a minimum.

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;
* Pregnant or lactating female subjects;
* Significant liver dysfunction as measured by any one of the following during participation in PB1046-PT-CL-0004. (If exclusionary laboratory results become available after the subject has enrolled in PB1046-PT-CL-0006 they should be discontinued. a. alanine aminotransferase (ALT) \> 3.0 times upper limit of normal (ULN) or; b. aspartate aminotransferase (AST) \> 3.0 times ULN or; c. serum bilirubin ≥ 1.6 mg/dL.
* Recent 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;
* In the opinion of the principal investigator (PI), any major surgical procedure within 90 days, or a planned surgical procedure during the study period; which would impact participation in PB1046-PT-CL-0006.
* Other new medical or psychiatric conditions which, in the opinion of the Investigator, would place the subject at increased risk, would preclude obtaining voluntary consent, or would confound the objectives of the study;
* Known hypersensitivity to study drug or any of the excipients of the drug formulation.