Treatment of Ulcerative Colitis

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 UC patients fail to reach remission with anti-TNFα antibodies, and another 30% to 40% of patients may lose response over time or become intolerant to anti-TNFs. Patients who lose response to anti-TNFα antibody drugs are generally switched to another anti-TNFα agent. Although this is successful in 40% to 60% of patents, there remains a lack of treatment options for patients who lose response to multiple anti-TNFα therapies. While the benefits often far outweigh the risks of biologics for patients suffering from IBD, non-adherence to the treatment regimen is common (reported to be 30% to 40%) due to injection or infusion site issues, side effects, allergic reactions, and the increased risk of infections and lymphoma. Response to treatment is defined as more than 30% improvement in the 3-Component Adapted Mayo score. It is estimated that less than 50% of UC patients treated with anti-TNFα therapies will achieve clinical remission (complete resolution of all symptoms), and many of these patients will lose response over time. Patients who do not respond well to therapy may require surgery to remove the diseased portion of the colon. Because uncontrolled UC increases the risk of colon cancer, some long-term UC patients have colectomies as a preventative measure or when routine colon biopsies show signs of colon cancer.

Cyclosporine & Ulcerative Colitis

Cyclosporine, a calcineurin inhibitor, is a potent immunosuppressant that has been widely used for over 40 years to prevent organ transplant rejection as well as for various inflammatory disorders. Cyclosporine has been used to rapidly induce remission in difficult to treat UC cases, but requires strict monitoring for toxicity. Current IV and oral cyclosporine formulations have unfavorable physiochemical properties that limit the drug’s utility as an effective treatment for UC. Systemic delivery is associated with significant side effects and current oral formulations do not allow for local delivery of cyclosporine to the colon.
An orally administered cyclosporine product with targeted delivery to the colon could be an attractive alternative for UC patients who no longer respond to 5-ASAs and/or corticosteroids or who have an inadequate clinical response to conventional or biologic therapies. We believe that our lead product candidate, ST-0529 could provide an effective treatment for both induction and maintenance therapy for patients with moderate to severe UC with a safety and efficacy profile supportive of long-term dosing.

ST-0529 is currently in clinical research and is not approved as safe and effective for use by the FDA, or any Regulatory agency.