Key Inclusion Criteria:  Participant has provided informed consent prior to initiation of any study specific activities or procedures. In Japan, if a participant is younger than 20 years at the time of signing the informed consent, the informed consent must be obtained from both the participant and their legal representative. Men and women aged ≥ 18 to < 80 years at screening visit (≥ 19 to < 80 in South Korea). Diagnosis of UC established ≥ 3 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. If a histopathology report is not available at screening, then additional biopsies may be taken during the screening period for local histopathology analysis to corroborate. Moderately to severely active UC as defined by a modified Mayo score of 5 to 9, with a centrally read rectosigmoidoscopy endoscopic subscore ≥ 2 and no subscore < 1 prior to day 1.  Has documentation of:  A surveillance colonoscopy (performed according to local standard) within 12 months of day 1 visit for participants with pancolitis of > 8 years duration, or participants with left-sided colitis of > 12 years duration, or participants with primary sclerosing cholangitis. For all other participants, up-to-date colorectal cancer surveillance (performed according to local standard). Participants who do not have a colonoscopy report available in source documentation will have a colonoscopy instead of rectosigmoidoscopy performed as the screening endoscopy for the study, at the discretion of the investigator.  Participants must have demonstrated inadequate response, loss of response, or intolerance to at least 1 conventional therapy, biologic therapy, or targeted small molecule therapy (ie, Janus kinase [JAK]-inhibitor), as follows:  Conventional therapy failed participants:  Corticosteroids (corticosteroid-refractory colitis, defined as signs and/or symptoms of active UC despite oral prednisone [or equivalent] at doses of at least 30 mg/day for a minimum of 2 weeks; or corticosteroid-dependent colitis, defined as: an inability to reduce corticosteroids below the equivalent of prednisone 10 mg/day within 3 months of starting corticosteroids without a return of signs and/or symptoms of active UC; or a relapse within 3 months of completing a course of corticosteroids). History of intolerance of corticosteroids (including, but not limited to, Cushing's syndrome, osteopenia/ osteoporosis, hyperglycemia, or neuropsychiatric side-effects, including insomnia, associated with corticosteroid treatment). Immunomodulators: signs and/or symptoms of persistently active disease despite at least 3 months treatment with one of the following at locally approved doses: oral azathioprine (eg, ≥ 1.5 mg/kg/day) or 6-mercaptopurine (eg, ≥ 0.75 mg/kg/day), or oral azathioprine or 6-mercatopurine within a therapeutic range as judged by thioguanine metabolite testing, or a combination of a thiopurine and allopurinol within a therapeutic range as judged by thioguanine metabolite testing. History of intolerance to at least 1 immunomodulator (including but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, and lymphopenia) and have neither failed nor demonstrated an intolerance to a biological medication (anti-tumor necrosis factor [TNF] antibody, anti-integrin antibody, or interleukin [IL]-12/23 antagonists) that is indicated for the treatment of UC.  Biologic or targeted small molecule therapy failed participants: those who demonstrated inadequate response or loss of response or intolerance to biologic therapy for UC (eg, anti-TNF antibodies or IL-12/23 antagonists, anti-integrin antibodies) or targeted small molecules (eg, JAK inhibitors). The therapy used to qualify the participant for entry into this category must be approved for the treatment of UC in the country of use, at the time of use. Participants must fulfil one of the following criteria:  Inadequate response: signs and symptoms of persistently active disease despite induction treatment at the approved induction dosing that was indicated in the product label at the time of use. Loss of response: recurrence of signs and symptoms of active disease during approved maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not quality as having failed or being intolerant to UC biological therapy or JAK inhibitor). Intolerance: history of intolerance to infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, tofacitinib or other approved biologicals or JAK inhibitors (including but not limited to infusion-related event, demyelination, congestive heart failure, or any other drug-related adverse event that led to a reduction in dose or discontinuation of the medication).  If receiving any of the following therapies, participants must have stable dosage for the specified duration:  5-aminosalicylates (ASAs), stable dosage for ≥ 2 weeks prior to screening endoscopy. Oral corticosteroids: prednisone ≤ 20 mg/day or its equivalent, stable dose for ≥ 2 weeks prior to screening endoscopy. Budesonide: extended release tablets 9 mg/day [budensonide MMX], stable dose for ≥ 2 weeks prior to screening endoscopy. Conventional immunomodulators: azathioprine, 6-mercaptopurine, methotrexate, stable dosage for ≥ 12 weeks prior to screening endoscopy.  Key Exclusion Criteria:  Diagnosis of Crohn's disease, inflammatory bowel disease unclassified (indeterminate colitis), microscopic colitis, ischemic colitis, or clinical findings suggestive of Crohn's disease. Evidence of toxic megacolon, fulminant colitis, intra-abdominal abscess, or stricture/stenosis within the small bowel or colon. Participant has had extensive surgery for UC (for example, subtotal colectomy), or is likely to require surgery for the treatment of UC during the study. Currently receiving or had treatment within 12 months prior to screening with T cell depleting agents (eg, antithymocyte globulin, Campath).  Participant has received any of the following prescribed medication or therapy within the specified time period:  Anti TNF antibodies (eg, infliximab, adalimumab, golimumab) < 8 weeks prior to screening rectosigmoidoscopy. Anti integrin antibodies (eg, vedolizumab) < 8 weeks prior to screening rectosigmoidoscopy. IL 12/23 antagonist (eg, ustekinumab) < 8 weeks prior to screening rectosigmoidoscopy. JAK inhibitors (eg, tofacitinib) < 4 weeks prior to screening rectosigmoidoscopy. Any other commercially approved biologic agent or targeted small molecule < 8 weeks prior to screening rectosigmoidoscopy or < 5 half lives prior to screening rectosigmoidoscopy, whichever is longer Immunomodulatory medications, including oral cyclosporine, intravenous cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, thalidomide < 4 weeks prior to screening rectosigmoidoscopy. Any investigational biologic therapy within 8 weeks prior to screening rectosigmoidoscopy or < 5 half-lives prior to screening rectosigmoidoscopy, whichever is longer. Has used apheresis (eg, Adacolumnâ apheresis) < 2 weeks prior to screening rectosigmoidoscopy.