EnteroBiotix Limited has announced positive results from its Phase 1b IMPuLCE study evaluating EBX-102 in patients with liver cirrhosis. The study demonstrated proof-of-principle across multiple microbiome assessments, inflammatory biomarkers, and clinical assessments, supporting its continued development as a microbial therapy for individuals with liver disease. The randomized, double-blind, placebo-controlled study evaluated the safety, tolerability, and translational biomarker effects of two different doses of EBX-102 across ten sites in the United Kingdom, with participants followed up for 12 weeks after dosing.
Safety and Tolerability
EBX-102 was well-tolerated with an acceptable safety profile. The most common adverse events were gastrointestinal, mainly mild and self-limiting. No serious treatment-emergent adverse events were reported during the study.
Microbiome and Metabolite Shifts
Participants receiving the higher dose of EBX-102 showed significant shifts in stool bacterial microbiome composition compared to placebo, as assessed by 16SrRNA sequencing. Furthermore, statistically significant changes to stool bacterial metabolites were observed in participants receiving EBX-102. Shotgun sequencing is ongoing and will provide additional insights into engraftment.
Ammonia Excretion
Venous ammonia concentrations remained stable in all study participants. There was a statistically significant increase in stool ammonia concentrations in the treatment groups but not the placebo group, suggesting a shift towards enhanced ammonia excretion through the stool rather than absorption into the bloodstream.
Inflammatory Biomarkers
A reduction in plasma lipopolysaccharide-binding protein (LBP) was observed in the drug cohorts but not in the placebo. This may indicate successful modulation of the gut microbiota towards a more beneficial ecology, improved gut barrier integrity, and a reduced inflammatory response.
Gut-Brain-Axis Effects
An improvement in hospital anxiety and depression scores were observed in the treatment groups but not in the placebo group, with a stronger trend at the higher dose, indicating potential gut-brain-axis effects.
Expert Commentary
Professor Ewan Forrest, Chief Investigator of the IMPuLCE study and Honorary Professor at the University of Glasgow, commented, "These exciting data demonstrate that EBX-102 is well tolerated in patients with chronic liver disease, showing promising biological effects that strongly support further clinical development. The observed improvement in mental health scores is particularly intriguing, and we look forward to continuing to explore the potential of EBX-102 in future liver disease trials."
About EBX-102
EBX-102 is an encapsulated full-spectrum microbiome therapeutic with differentiated characteristics, such as consistency, high-bacterial diversity, and stability. EnteroBiotix has platform manufacturing technologies and a well-developed analytical toolkit that enable the scalable manufacture of EBX-102. The Company controls the supply chain for its products through sophisticated MHRA-licensed manufacturing infrastructure together with its Number 2® brand, which ensures the safety, security, quality, and sufficiency of supply of microbiota obtained from healthy human donors.
