UC is a lifelong relapsing, remitting disease that affects approximately 900,000 people in the United States, 1.5 million people in Europe, and over 3 million people worldwide. Of these UC patients, approximately 45% to 55% have moderate to severe disease.

The pathogenesis of UC is believed to be multifactorial and includes contributions from genetic predisposition, breakdown of mucosal immune homeostasis, microbial dysbiosis and environmental factors. UC symptoms can vary in severity and generally start gradually. These may include bloody diarrhea, rectal bleeding, fecal incontinence, and lower abdominal pain. More severe complications of UC include toxic megacolon, which may result in colonic perforation and sepsis, requiring hospitalization. Although UC primarily impacts the colon, UC is also associated with manifestations in other organs, including joints, eyes and skin.

A UC diagnosis is confirmed through an endoscopy and mucosal biopsy for histopathology. To assess the severity of UC, physicians employ laboratory assessments including complete blood count and C-reactive protein, or CRP, count. UC is characterized as mild (rectal bleeding and fewer than four bowel movements a day), moderate (rectal bleeding and more than four bowel movements a day), severe (bleeding from the rectum, more than four bowel movements a day and the symptoms of systemic illness, e.g., fever, elevated heart rate, and low blood cell counts), or fulminant (more than ten bowel movements a day, continuous bleeding and a vastly enlarged colon or megacolon). UC severity may also be classified based on the parts of the colon affected by the disease.

The current standard of care for patients with moderate to severe UC who do not achieve remission on 5-ASA drugs or corticosteroids is to step up therapy to biologic drugs (particularly anti-TNFα agents or α4β7 integrin inhibitors) and JAK inhibitors. Up to 50% of patients treated with anti-TNFα agents do not respond to initial treatment, and another 30% to 40% of patients may lose response over time or become intolerant to anti-TNFs. While the treatment landscape of moderate to severe UC is expanding, existing treatment options, including novel oral molecules, are limited in terms of initial patient response, diminishing efficacy, tolerability, adverse events, systemic exposure, speed of action, route of administration or cost.

It’s important not to confuse an inflammatory bowel disease (IBD) like Ulcerative Colitis (UC) with irritable bowel syndrome (IBS). IBS is a disorder that affects the muscle contractions of the bowel and is not characterized by intestinal inflammation, nor is it a chronic disease.