LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis

Inclusion Criteria:

• Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior torandomization, which includes endoscopic evidence of UC

• Have moderately to severely active UC defined by a Modified Mayo Score (mMS) of 5 to 9 with an Endoscopic Score (ES)≥2 confirmed by central reader and rectal bleeding (RB)≥1

• Have evidence of UC extending proximal to the rectum

• Have documented evidence of having had a surveillance colonoscopy within 1 year, oraccording to local guidelines, to evaluate for polyps, dysplasia, or malignancy,prior to randomization, if the participant has a history of UC symptoms for morethan 8 years

• Have an inadequate response to, loss of response to, or intolerance to at least oneconventional medication (including corticosteroids) or one advanced therapy (including biologics, Janus Kinase (JAK) inhibitors, or sphingosine-1-phosphate (S1P) immunomodulators). Participants with inadequate response to vedolizumab areexcluded

• Must meet contraception requirements

Exclusion Criteria:

• Have a current diagnosis of

• Crohn's disease

• Inflammatory Bowel Disease (IBD unclassified) (formerly known as indeterminatecolitis), or

• primary sclerosing cholangitis

• Have an inherited immunodeficiency syndrome or known monogenic cause of UC-likecolonic inflammation

• Have had or will need bowel resection or intestinal or intra-abdominal surgery

• Have evidence of toxic megacolon, intra-abdominal abscess, or stricture or stenosiswithin small bowel or colon that cannot be traversed by a colonoscope or that aresymptomatic

• Have any prior or current evidence of cancer gastrointestinal (GI) tract, orspecified lesions with increased risk of GI malignancies

• Have a diagnosis or history of malignant disease within 5 years prior torandomization