Treatment of Fungal-Associated Irritable Bowel Disease Using IL-1 Inhibitors

Background & Unmet Need

• Intestinal fungi play an important role in regulating mucosal immunity as a highly immunoreactive component of the microbiota
• Deep sequencing-based assays of the gut mycobiome have revealed consistent evidence for “fungal dysbiosis” as a hallmark of inflammatory bowel disease (IBD)
• Candida is the most prevalent fungal genus, and its relative abundance is consistently increased in several IBD cohorts based on fecal sequencing
• However, it is currently unknown whether fungi play an essential role in directing mucosal immunity or disease outcomes
• Unmet Need: Methods to probe the mycobiome at the fungal strain and patient-specific level to inform potential mycobiome-targeted therapies for IBD

Technology Overview

• The Technology: Method to identify and treat IBD patients harboring specific C. albicans strains with IL-1 inhibitors
• Using a proprietary platform that combines high-resolution sequencing, culturing, genomics, and in vitro and in vivo models, the inventors identified opportunistic C. albicans strains that dominate the colonic mucosa of ulcerative colitis (UC) patients
• The Discovery: C. albicans strains that secrete the toxin candidalysin drive intestinal inflammation through an IL-1β dependent manner
• PoC Data: IL-1R blockade using an anti-IL-1R antibody dramatically reduced neutrophil recruitment, inflammatory Th17 cell accumulation and colonic inflammation in C. albicans colonized mice

Technology Applications

• Method for identifying IBD patients who may benefit from anti-IL-1 or antifungal therapies
• Platform for further studying the impact of the mycobiota on immunity and disease pathogenesis

Technology Advantages

• Anti-IL-1 monoclonal antibodies are already approved for other indications
• Provides a precision medicine approach to identify IBD patients who are most likely to benefit from anti-IL-1 treatment