Have had an established diagnosis of ulcerative colitis (UC) for ≥3 months prior to randomization, 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, or according to local guidelines, to evaluate for polyps, dysplasia, or malignancy, prior to randomization, if the participant has a history of UC symptoms for more than 8 years
Have an inadequate response to, loss of response to, or intolerance to at least one conventional 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 are excluded
Must meet contraception requirements
You may not be if
Have a current diagnosis of
* Crohn's disease
* Inflammatory Bowel Disease (IBD unclassified) (formerly known as indeterminate colitis), or
* primary sclerosing cholangitis
Have an inherited immunodeficiency syndrome or known monogenic cause of UC-like colonic 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 stenosis within small bowel or colon that cannot be traversed by a colonoscope or that are symptomatic
Have any prior or current evidence of cancer gastrointestinal (GI) tract, or specified lesions with increased risk of GI malignancies
Have a diagnosis or history of malignant disease within 5 years prior to randomization
Clareo Health | LY4268989 in Adults With Moderately to Severely Active Ulcerative Colitis
