A Trial to Investigate PALI-2108 Versus Placebo in Participants With Moderately to Severely Active Ulcerative Colitis

Key Inclusion Criteria: * Documented clinical diagnosis of UC for ≥ 3 months prior to Screening. The diagnosis of UC must be confirmed by endoscopic and histologic evidence. * If a histopathology report is not available in the source records, a biopsy for a local histopathology evaluation (to obtain a report) can be obtained during the screening endoscopy procedure. * Moderately to severely active UC, defined as: * mMS of 5 to 9 (inclusive), AND * ES ≥ 2, AND * RB ≥ 1. * Participants must satisfy at least one of the criteria listed under item a OR at least one of the criteria listed under item b: a. History of inadequate response or loss of response, or intolerance to at least one prior UC therapy, defined as: i. Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide ≥ 9 mg/day for ≥ 2 weeks. ii. Corticosteroid dependence: unable to taper \< 10 mg/day prednisone equivalent within 3 months, or relapse within 3 months of discontinuation. iii. Immunosuppressants: azathioprine ≥ 2 mg/kg/day, 6-mercaptopurine (6-MP) ≥ 1.0 mg/kg/day (or therapeutic 6-thioguanine nucleotide \[6-TGN\] level) for ≥ 12 weeks, or methotrexate ≥ 15 mg/week subcutaneous or intramuscular. iv. Approved advanced therapies at the approved labelled dose: 1. Anti-tumor necrosis factor (TNF), anti-integrin (vedolizumab), or anti-IL-12/23 for at least 8 weeks; anti-IL 23 for at least 12 weeks. 2. Janus kinase (JAK) inhibitor for at least 8 weeks; sphingosine-1-phosphate receptor (S1PR) modulator for at least 12 weeks. Note: Demonstration of intolerance requires no minimum dose nor duration of use. b. Currently receiving one or more of the following treatments: i. Stable oral prednisone at ≤ 20 mg/day (or equivalent) or budesonide ≤ 9 mg for ≥ 2 weeks prior to randomization. ii. Stable dose of thiopurine (azathioprine or 6-MP) for ≥ 4 weeks prior to randomization, and have started the treatment ≥ 12 weeks prior to randomization. iii. Stable dose of oral aminosalicylates for ≥ 2 weeks prior to randomization. Key Exclusion Criteria:• Diagnosis of Crohn's disease or IBD-Unclassified (IBD-U; indeterminate colitis) or a history of ischemic colitis or radiation colitis. * UC limited to rectum (\< 15 cm from anal verge). * Any prior history of suicidal behavior (actual, interrupted, aborted attempt, or preparatory acts). * Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation type 4 or 5, or any active suicidal ideation with some intent to act. * Severe depression at Screening based on a validated scale threshold (e.g., Patient Health Questionnaire-9 \[PHQ-9\] ≥ 20, or PHQ-9 item 9 \> 0) at Screening. * Failure or intolerance of \> 3 classes of approved advanced therapies or \> 4 approved individual advanced therapies.