Rodolphe Clerval

– Abstract –

Mining the gut microbiome: a new source of targets and small molecules for treating chronical disorders

Gut microbiome plays a crucial role in the building-up of our immunity system at birth. It is a life-long personal and natural protection but increasing evidence suggests that dysregulated immune responses against commensal microbes in the gut are strongly involved in Inflammatory Bowel Diseases, Oncology, Metabolic disorders, Depression, Allergies amongst numerous diseases.

Our target and drug discovery platform is based on full sequencing and mapping of total fecal bacterial gene content that leads to the characterization of the gut metagenome associated with a disease phenotype. This technology enables the identification of genes and pathways of interest associated with the development of diseases. The metagenomics dataset generated is then associated with a high throughput screening platform that allows the discovery of news drugs and targets.

Two lead programs were discovered through this platform  :

  • EB8018 is an oral and non-systemic small molecule drug candidate that is designed to block FimH, a key virulence factor expressed by pro-inflammatory Enterobacteria. EB8018 prevents colonization of gut wall, mucosal inflammatory cytokine production and entry of such bacteria into the gut wall.
  • E0510 : this program aims to discover novel bacterial-derived cancer antigens that are expressed in human gut microbiome. The first preclinical candidate (E02401) has demonstrated strong potency to induce T-cell activation against solid tumors.

Enterome has entered clinical development stage, with EB8018 being currently evaluated in Crohn’s patients and E02401 will be tested in cancer patients in 2018.