Phase 1b Clinical Study in Patients With Active Ulcerative Colitis

Prior treatment

• Severe extensive colitis as evidenced by:
  • Likeliness to require hospitalization for medical care or surgical intervention of any kind for UC (e.g., colectomy) within 12 weeks after randomization
  • Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months prior to screening) of toxic megacolon, or bowel perforation
• History of or current evidence of colonic dysplasia; or recent history (within 2 years prior to randomization). Note: If adenomatous polyps present, must be completely removed per routine practice prior to the study participant's first dose of investigational product.

Other illness

• Diagnosis of Crohn's disease (CD) or indeterminate colitis, microscopic colitis, ischemic colitis, radiation colitis, acute diverticulitis, or the presence or history of a fistula consistent with CD based on medical history
• History of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy; or is planning to undergo bowel surgery during the course of the study.
• History of spontaneous gastrointestinal (GI) perforation (other than appendicitis or mechanical injury), or at significantly increased risk of GI perforation based on the Investigator's judgment

Lab values

• Has severe UC during as defined by ≥6 bloody stools per day AND at least 1 of the following during Screening:
  • Pulse \>90 bpm
  • Oral temperature of \>37.8 °C
  • Hemoglobin \<10.5 g/dL
  • CRP of \>30 mg/L
  • Erythrocyte sedimentation rate \>30 mm/h

• Diagnosis of UC with disease duration of at least 12 weeks prior to randomization
• Evidence of active UC at Screening, defined by all of the following:
  • MMS of 5 to 8, inclusive;
  • ES ≥ 2;
  • RBS of ≥ 1; and
  • Evidence of active UC extending ≥15 cm from the anal verge via colonoscopy (confirmed by central read)
• UCEIS score ≥ 4 with erosion/ulcer sub-score of ≥1 (confirmed by central read)
• An inadequate response to, loss of response to, or intolerance to at least 1 of the following conventional therapies as defined below:
  • Oral 5-ASA compounds
  • Glucocorticoids (topical or systemic)
  • Thiopurines
• If receiving oral 5-aminosalicylates (5-ASAs) or oral corticosteroids (≤20 mg prednisolone equivalent) for treatment of their UC, they must be on a stable dose for at least 28 days prior to randomization
• Previous exposure to a single biologic agent, JAK inhibitor, or S1P inhibitor is allowed (not required) if it was discontinued for reasons other than primary no response. Discontinuation must have been more than 8 weeks or 5 half-lives (whichever is longer) prior to first dose of study treatment.