Development of targeted therapeutic antibodies for the treatment of inflammatory bowel disease: A proof of concept

Direct, topical delivery of monoclonal antibodies to the gastrointestinal tract could improve treatment.

There is an urgent need to achieve higher rates of clinical response, remission and mucosal healing in inflammatory bowel disease (IBD). Several therapeutic monoclonal antibodies have revolutionized the treatment of Crohn’s disease and ulcerative colitis. Despite the potency of these agents towards well accepted targets of disease, they have afforded limited long-term efficacy in patients resulting in loss of response and chronic complication.

Here we hypothesize that improved efficacy can be achieved via direct, topical delivery of existing monoclonal antibody drugs using resistant and highly absorbable formulations. These drugs can be delivered to the site of disease at concentrations sufficient to drive improved efficacy, while avoiding the systemic toxicity normally associated with monoclonal antibodies. Furthermore, we believe an anatomically targeted delivery approach affords the opportunity to deliver combination therapies targeting multiple known drivers of disease, which has largely been avoided due to the potential for heightened systemic toxicity.

As a proof of concept, we conducted studies evaluating whether intracecally delivered monoclonal antibodies might penetrate disrupted mucosa and confer improved efficacy when compared with systemic administration. Taken together, these findings provide a proof of concept for direct topical delivery of therapeutic antibodies, and suggest the potential for improved efficacy in the treatment of IBD.