First Patient Dosed in Phase 2a Sibofimloc Trial for Crohn's disease

ENTEROME announced the first patient has been dosed in a Phase 2a clinical trial of sibofimloc (EB8018/TAK-018) in patients with Crohn's disease. Sibofimloc is advancing through clinical development under a 2018 global licensing, co-development and co-commercialization partnership with Takeda Pharmaceutical Company.

Sibofimloc is a first-in-class, orally administered small molecule specifically designed to reduce the inflammatory cascade underlying Crohn's disease and remain gut-restricted, to minimize absorption into the bloodstream.

Sibofimloc binds FimH, a novel microbiome-derived therapeutic target validated by Enterome, to selectively disarm virulent bacteria in the gut that can cause intestinal inflammation without disrupting the local microbiome. It acts by inhibiting FimH-mediated inflammation induced by the interaction of pathogenic pro-inflammatory bacteria expressing FimH to human TLR4 receptors in the gut wall, thereby reducing the production of inflammatory cytokines including TNF alpha.

Sibofimloc was found to be well tolerated in healthy volunteers and in patients with Crohn's disease in Phase 1 studies, which also generated first indications of target engagement.

Based on these data, sibofimloc has been advanced into a randomized, double-blind, placebo-controlled, multicenter, Phase 2a study to evaluate its safety, tolerability and proof of concept for the prevention of recurrence of intestinal inflammation in up to 96 postoperative participants with Crohn's disease.

The primary endpoint of the study is the percentage of participants with endoscopic recurrence of Crohn's disease as assessed by Rutgeerts grading scale at week 26. The trial will take place in the US and Europe and results are expected in 2022.

"We are delighted with the progress being made with sibofimloc. The clinical and translational data have been encouraging for what could be a truly novel approach to treating inflammation in Crohn's disease patients. We look forward to advancing patient enrollment into the trial as quickly as possible," Vijay Yajnik, Global Clinical Lead, Microbiome and Senior Medical Director, GI Therapeutic Area Unit at Takeda, said.

"Sibofimloc blocks a virulence factor on pathogenic gut bacteria that Enterome has validated by the application of our metagenomic technologies and that is currently not targeted by any available therapiesm: Jan Fagerberg, Chief Medical Officer of Enterome, said. We believe that its novel anti-inflammatory mechanism of action could also be applicable in other serious inflammatory bowel diseases (IBD) and in different therapeutic settings of IBD, such as chronic active disease. The progress we are making in collaboration with Takeda is very exciting and we hope this new trial will demonstrate the clinical potential of sibofimloc."