Enterome highlights Microbiome publication describing sibofimloc’s novel mechanism of action for the treatment of Crohn’s disease

Enterome highlights Microbiome publication describing sibofimloc’s novel mechanism of action for the treatment of Crohn’s disease

• The mechanism of action of the investigational medicine sibofimloc positions it as a potential novel and important treatment option for Crohn’s disease
• Oral sibofimloc is a first-in-class gut-restricted small molecule FimH-blocker designed to treat the underlying cause of Crohn’s disease and maintain patients in a non-inflammatory disease state 
• Sibofimloc is advancing through clinical development under a global licensing, co-development and co-commercialization partnership between Takeda and Enterome

Paris, France – September 16, 2021

Enterome SA, a clinical stage biopharmaceutical company developing novel drugs based on its unique ability to decode molecular interactions in the gut microbiome impacting human health, announces the publication of a new paper describing the novel mechanism of action of its investigational medicine sibofimloc (also called TAK-018) for the treatment of Crohn’s disease (CD) in the high impact peer-reviewed journal Microbiome. Sibofimloc is currently in Phase 2a clinical trial and is being developed under a global licensing, co-development and co-commercialization agreement with Takeda Pharmaceutical Company Limited (“Takeda”).

Sibofimloc is a first-in-class, orally administered, gut-restricted small molecule FimH-blocker designed to treat the underlying cause of CD and maintain patients in a non-inflammatory disease state.

In the paper, the authors showed that blocking the adhesion of overabundant FimH-expressing bacteria to the gut wall is a promising therapeutic mechanism that effectively disarms these virulent bacteria without killing them. This mechanism represents a highly selective strategy to suppress the potentially critical trigger of intestinal inflammation in CD patients without disturbing the overall composition of the gut microbiota.

Sibofimloc was shown to selectively bind and aggregate FimH-expressing bacteria in 65%-85% of ileal biopsies from CD patients. Aggregation of bacteria to sibofimloc led to a strong decrease in inflammation and a general improvement of gut integrity. Furthermore, when used at therapeutically relevant doses, sibofimloc preserved normal gut tissue integrity.

Dr Vijay Yajnik, Senior Medical Director of the Gastroenterology Therapeutic Area Unit at Takeda, said: “Current therapies for the treatment of Crohn’s disease target the patient’s immune system, but there still remains a significant unmet medical need to develop new therapies targeting novel pathways including the gut microbiome. The published research on sibofimloc shows a very promising finding that it exerts its local anti-inflammatory action by blocking pathogenic bacteria without disrupting the commensal gut microbiome.”

Dr Christophe Bonny, Chief Scientific Officer at Enterome, said: “It is a great achievement for the Enterome team that we have been able to publish such promising data. Sibofimloc’s innovative mechanism of action targets the virulence factor FimH expressed on pathogenic gut bacteria from the Enterobacteriaceae family. This target has been validated by the application of Enterome’s unique and proprietary technologies. Sibofimloc, which is currently the only drug candidate targeting the underlying cause of the disease, is in a Phase 2 trial in post-operative Crohn’s disease and a data readout is expected in H1 2023. 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 as a maintenance therapy with an attractive safety profile.”

The Phase 1b trial evaluating sibofimloc in active CD patients was well tolerated, demonstrated minimal systemic exposure and decreased several inflammatory biomarkers.

Reference

Chevalier*, Laveissière*, et al. Blockage of bacterial FimH prevents mucosal inflammation associated with Crohn’s disease. Microbiome (2021) DOI: 10.1186/s40168-021-01135-5 Link