EnteroBiotix Reports Positive Ph1b Results for EBX-102 in Liver Cirrhosis

EBX-102 has shown potential across various evaluations, including microbiome assessments, inflammatory biomarkers, and clinical assessments, supporting its ongoing development as the first microbial therapy for liver disease patients.

EnteroBiotix Limited, located in Glasgow, Scotland, announced positive findings from its Phase 1b IMPuLCE study on November 11, 2024. The biotechnology company, focused on creating full-spectrum microbiome therapeutics, evaluated EBX-102 in liver cirrhosis patients. This first-in-human trial was a randomized, double-blind, placebo-controlled study involving adult participants with stable liver cirrhosis. Conducted across ten sites in the United Kingdom, the trial aimed to assess the safety, tolerability, and translational biomarker effects of two different doses of EBX-102. Participants were monitored for 12 weeks after receiving the dosage.

Dr James McIlroy, CEO of EnteroBiotix, expressed gratitude to the participants and investigators for their contributions to the study, which enabled the development of EBX-102. He highlighted the importance of the data collected, which supports further research, noting that the results showed multiple microbiome and systemic measurements indicative of mechanistic proof-of-principle. Dr McIlroy emphasized the significant unmet medical needs in advanced liver disease and the promising potential efficacy of EBX-102 for this population.

Key findings from the study include the following:

1. EBX-102 was well tolerated, with a satisfactory safety profile. The most common adverse events were gastrointestinal, mostly mild, and self-limiting. There were no reports of serious treatment-emergent adverse events.
2. Participants in Cohort 2, who received the higher dose of EBX-102, exhibited significant changes in stool bacterial microbiome composition compared to the placebo group, as assessed through 16SrRNA sequencing.
3. There were statistically significant changes in stool bacterial metabolites among participants receiving EBX-102. Ongoing shotgun sequencing will provide further insights into engraftment.
4. Venous ammonia concentrations remained stable across all study participants. However, there was a statistically significant increase in stool ammonia concentrations in the treatment groups, suggesting enhanced ammonia excretion through the stool rather than absorption into the bloodstream.
5. A reduction in plasma lipopolysaccharide-binding protein (LBP) was noted in the drug cohorts but not in the placebo group. This may indicate successful modulation of the gut microbiota towards a more beneficial ecology, improved gut barrier integrity, and a reduced inflammatory response.
6. Participants in the treatment groups showed an improvement in hospital anxiety and depression scores, with a more pronounced effect at the higher dose, suggesting potential gut-brain-axis effects.

Professor Ewan Forrest, Chief Investigator of the IMPuLCE study and Honorary Professor at the University of Glasgow’s School of Cardiovascular & Metabolic Health, remarked that the data demonstrate that EBX-102 is well tolerated in patients with chronic liver disease. The promising biological effects observed strongly support further clinical development. Professor Forrest found the improvement in mental health scores particularly intriguing and expressed eagerness to continue exploring EBX-102’s potential in future liver disease trials.

EBX-102 is an encapsulated full-spectrum microbiome therapeutic with characteristics such as consistency, high bacterial diversity, and stability. EnteroBiotix employs platform manufacturing technologies and a comprehensive analytical toolkit to enable the scalable production of EBX-102. The company ensures the safety, security, quality, and sufficiency of microbiota from healthy human donors through its sophisticated manufacturing infrastructure and Number 2® brand.

EnteroBiotix is dedicated to developing therapeutics for gastrointestinal and hepatic diseases. Its therapies contain diverse ecosystems of microorganisms, stabilized using proprietary technology, designed to enhance gut health by augmenting the gut microbiome. The company is currently enrolling patients in a Phase 2 double-blind, placebo-controlled, multi-center clinical study for irritable bowel syndrome (IBS) and is progressing a Phase 2a study with Imperial College for patients undergoing allo-HSCT.