Enterome announced the successful completion of the first Phase 1 clinical study with its lead candidate EB8018, a small molecule designed to block FimH, as a potential new orally-administered treatment for Crohn's disease.
EB8018 was found to be well tolerated in healthy volunteers across a wide range of doses tested. The compound also demonstrated a pharmacokinetic (PK) profile consistent with it being a gut-restricted molecule that is soluble in the gut and thereby able to act on its target in the gut microbiome. EB8018 also exhibited minimal absorption into the blood potentially limiting interactions with other drugs that are absorbed into the blood stream. The results from the study will be presented at an upcoming medical congress.
Enterome is in the process of initiating a Phase 1b trial of EB8018 in patients with Crohn's Disease who have active inflammation of the gut. This study will investigate the safety, PK and preliminary signals of efficacy of EB8018. The results from these studies are expected to provide information that will support the design of a Phase 2 clinical proof-of-concept trial with EB8018 that is planned to start in 2018.
The Phase 1 study was designed to determine the safety and tolerability profile of single and multiple doses of EB8018 in healthy subjects. The study also assessed the pharmacokinetic profile of single and multiple doses of EB8018 and the effects of EB8018 on the healthy gut microbiome. In parallel with the Phase 1 study, Enterome is developing a potential non-invasive microbiome biomarker to identify patients that may benefit from treatment with EB8018.
"The outcome of the first-in-human trial with EB8018 is an encouraging step towards demonstrating its clinical potential in patients with active Crohn's Disease. EB8018 is a first-in-class, orally-administered investigational medicine that is targeted at disarming specific bacteria in the gut that cause inflammation, without disrupting the microbiome,” Jai Patel, Enterome's Chief Medical Officer, said. “It represents a novel, non-biologic, non-steroidal, non-immunomodulatory approach for the treatment of Crohn's Disease. We are now preparing to test EB8018 in Crohn's patients with a view to a larger scale clinical proof-of-concept trial next year."
Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract. Emerging evidence suggests that the microbiome plays an important role in triggering an abnormal mucosal immune response in patients with Crohn's disease.
Enterome is targeting the FimH adhesin, which is over-expressed on the surface of bacteria that bloom in patients with Crohn's Disease. Blocking the FimH adhesin has been shown to reduce or inhibit the local inflammation in the gut wall triggered by the microbiome. Research studies have demonstrated an imbalance of bacteria in the microbiomes of patients with Crohn's Disease, with a significant increase of pro-inflammatory bacteria, a reduction of anti-inflammatory bacteria as well as a reduction in the diversity of bacterial species. The pro-inflammatory bacteria trigger inflammation in the gut wall by inducing local production of cytokines by activating TLR-4 and subsequent invasion of the gut wall through CEACAM6 and GP-2 receptors, which are strongly upregulated in the ileocecal region of the gut wall in patients with Crohn's Disease.
EB8018 is an orally administered, gut-restricted small molecule drug with minimal absorption into the bloodstream. It is designed to preventing local cytokine production in the gut wall by selectively disarming the virulent FimH-expressing bacteria without disrupting the gut microbiome. It represents a novel, non-biologic, non-steroidal, non-antibiotic, non-immunomodulatory approach for the treatment of Crohn's disease. Enterome in-licensed EB8018 from Vertex Pharmaceuticals.