This study is to Evaluate safety, tolerability and efficacy of PN-943 treatment in subjects with moderate to severe active ulcerative colitis compared to placebo. Secondary: Evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and biomarker responses to PN-943 in subjects with moderate to severe active ulcerative colitis.

Eligible participants must be male or female subjects age 18 (or the minimum country specific age of consent if >18) to 75 years.

This is a two-part study: Part 1 is a randomized, double-blind, placebo-controlled, parallel design 12- week induction treatment period in patients with moderate to severe active UC, Part 2 is an extended treatment period of 40 weeks that will include subjects who successfully complete Part 1.

Must have a diagnosis of UC for ? 8 weeks prior to screening supported by appropriate documentation of biopsy results consistent with UC, in the opinion of the investigator; if UC has been present for > 10 years, a total colonoscopy with biopsy must have been performed within 2 years of screening to rule out dysplasia.

Must have demonstrated inadequate response, loss of response, or intolerance of at least 1 of the following treatments including oral aminosalicylates (5-ASAs), corticosteroids, immunomodulators, IL-12/23 antagonists, and/or TNF? antagonists.