The purpose of the study is to evaluate the safety, tolerability, and clinical efficacy of PN-943 450 mg twice daily [BID] and PN-943 150 mg BID, compared with placebo BID, in subjects with moderate to severe active Ulcerative Colitis (UC).

The study consists of a 12-week double-blind, placebo-controlled treatment period. Participants will be randomized in a 1:1:1 ratio to PN-943 450 mg BID, PN-943 150 mg BID, or matching placebo BID.

Participants who successfully complete the double-blind period may be eligible for an extended treatment period of 40 weeks duration.

Key Inclusion Criteria:

1. Male and female subjects age 18 (or the minimum country specific age of consent if >18) to 75 years.
2. Subject understands the study procedures and agrees to participate in the study by giving written informed consent.
3. Diagnosis of UC supported by appropriate documentation of biopsy results consistent with UC.
4. Moderate to severe active UC.
5. Demonstrated inadequate response, loss of response, or intolerance of at least 1 of oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, or a biologic (excluding vedolizumab).

Key Exclusion Criteria:

1. Subject with a current diagnosis of Crohn's disease (CD), indeterminate colitis (IC), microscopic colitis, ischemic colitis, radiation colitis.
2. History of colonic dysplasia other than completely removed low-grade dysplastic lesion.
3. History of active bacterial, viral, fungal or mycobacterial infection requiring hospitalization or IV antibiotic/anti-infective treatment within 4 weeks of screening or oral antibiotics/anti-infectives within 2 weeks of screening.
4. Prior treatment with vedolizumab, natalizumab, or any agent targeting the α4β7 or β1 integrin or planned during the study.
5. Positive stool test for C. difficile.
6. Chronic recurrent or serious infection.
7. Known primary or secondary immunodeficiency.
8. Pregnant or lactating female or considering becoming pregnant during the study or within 30 days after the last dose of study medication.
9. History of any major neurological disorders.