INTRODUCTION
autoimmune disorder, ulcerative colitis, UC, PD, IBD
MUCOSAL INFLAMMATION, AUTOIMMUNE DISORDER, ULCERATIVE COLITIS, INFLAMMATORY BOWEL DISEASE
As a major subtype of inflammatory bowel disease (IBD), ulcerative colitis (UC) is a chronic, debilitating, and progressive autoimmune disorder characterized by relapsing and remitting mucosal inflammation which extends from the rectum up to proximal segments of the colon.Nearly half of patients with UC require hospitalization at some point, and of these 50% have a 5‐year risk of re‐hospitalization.Inflammasomes are multimeric protein complexes that are formed in various immune and non‐immune cells in response to signals from pathogens, and are a key component of the innate immune response.Selnoflast (RO7486967) is a selective and reversible small molecule NLRP3 inflammasome inhibitor. In vitro pharmacological studies revealed that selnoflast is a potent inhibitor of IL‐1β release in activated human monocyte‐derived macrophages. Selnoflast has no inhibitory activity on two other inflammasomes, the Nucleotide‐binding Oligomerization Domain (NOD)‐like receptor (NLR) family CARD domain containing 4 (NLRC4) or absent in melanoma‐2 (AIM2) (unpublished results). Selnoflast has been studied in one completed Phase 1, randomized, double‐blind, placebo‐controlled Entry‐Into‐Human study (NCT04086602), which evaluated the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) after single and multiple ascending doses administered orally in 64 healthy subjects.Here, we report the findings from a randomized, placebo‐controlled, investigator‐ and patient‐blinded Phase 1b study designed to evaluate the safety, tolerability, PK, and PD of selnoflast in patients with moderate to severe active UC.