Microbiome Theranostic for Sulfasalazine Treatment in Patients with IBD-Associated Spondyloarthritis

Background & Unmet Need

• Patients with Inflammatory Bowel Disease (IBD) frequently experience rheumatic manifestations of disease, most commonly spondyloarthritis (SpA)
• There is no widely accepted standard of care for IBD-associated spondyloarthritis (IBD-SpA)
• Sulfasalazine is one of the earliest medications to demonstrate efficacy for inducing IBD remission, but is only effective in reducing rheumatic symptoms in a subset of patients with IBD-SpA
• Sulfasalazine is a prodrug consisting of sulfapyridine (SP) and 5-aminosalicylate, linked by a diazo bond which is cleaved by colonic microbiota
• The antibacterial capability of SP to disrupt bacterial synthesis of folate has led to the hypothesis that the microbiome may play a role in the efficacy of SAS
• Unmet Need: Methods for determining which IBD-SpA patients will respond to Sulfasalazine to increase patient response rates to this therapy

Technology Overview

• The Technology: A theranostic for predicting and rescuing treatment response to Sulfasalazine in patients with IBD-SpA
• The Discovery: A small clinical trial identified enrichment of Faecalibacterium prausnitzii (F. prau) and other ‘folate trap’ bacteria as a biomarker for Sulfasalazine response in IBD-SpA patients
• Mechanistically, Sulfasalazine therapy enhances butyrate synthesis via F. prau, which limits colitis in responder microbiomes
• PoC Data: Relative abundance of F. prau alone and with additional taxa demonstrates strong ability to discriminate between Sulfasalazine responders and non-responders (AUC of ROC curve: 0.78, p<0.05 and 0.095, p<0.01, respectively)
• Administration of folate trap bacteria F. prau in non-responder mouse models of IBD rescues response to Sulfasalazine, marked by reduced weight loss and cecal lipocalin, a biomarker of intestinal inflammation

Technology Applications

• Method to predict response to Sulfasalazine in IBD-SpA patients by measuring relative abundance of folate-trap bacteria
• Method for treating IBD-SpA patients who lack a functional folate trap by administering Sulfasalazine in combination with one or more folate trap bacteria, such as F. prau

Technology Advantages

• Theranostic test measuring relative abundance of bacteria can be completed via standard PCR-based procedures and at low cost
• Sample collection for theranostic test is non-invasive and standard for IBD patients
• Can increase speed to correct treatment selection for IBD-SpA patients, which is essential due to the progressive nature of the disease