Abstract Text: Celiac disease (CeD) is a chronic inflammatory disorder triggered and maintained by ingestion of gluten and which has no approved pharmacologic treatment. KAN-101 is an investigational therapy composed of a liver-targeting glycosylation signature conjugated to a gliadin-derived peptide designed to induce tolerance as a therapeutic approach to the treatment of CeD. The Assessment of KAN-101 in CeD (ACeD) study evaluated safety and tolerability of KAN-101 and immune biomarker responses following a 3-day oral 9 gram gluten challenge (GC) in CeD patients who received multiple doses of KAN-101 at 0.15, 0.3, or 0.6 mg/kg or placebo (NCT04248855). No serious adverse events or dose-limiting toxicities were observed in the study. Adverse events observed during the study were mild to moderate in severity, resolved within hours of onset, and were consistent with symptoms experienced by CeD patients upon ingestion of gluten. Blood biomarker data demonstrated antigen-specific tolerance to gliadin, induction of gliadin-specific T cell anergy and control of the broader immune response to gluten, indicating bystander suppression activity. KAN-101 also modulated a key disease biomarker, GC IL-2, which has been reported to be associated with symptomatic responses in CeD patients. Cytokine responses following KAN-101 administration demonstrate a shift from activating (IL-2) to regulatory (IL-10) upon repeat exposure of liver-targeted antigen. In conclusion, the ACeD Ph1 clinical trial demonstrated that KAN-101 was safe and tolerated in CeD patients, induced immunological tolerance to gliadin and modulated a biomarker of clinical efficacy. KAN-101 is currently being tested in Ph2 studies in CeD patients.
