EBX-102 Shows Promise As First Microbiome Therapeutic for Cirrhosis

James McIlroy, MBChB

Credit: EnteroBiotix

EnteroBiotix Limited has announced positive results from its phase 1b Intestinal Microbiota Product in Liver Cirrhosis and Encephalopathy (IMPuLCE) study evaluating EBX-102 in patients with liver cirrhosis.^1.2

Findings from the first-in-human study of EBX-102 provide evidence for proof-of-principle across multiple microbiome assessments, inflammatory biomarkers, and clinical assessments, supporting its continued development as the first microbial therapy for patients with liver disease.¹

“In addition to safety and tolerability data supporting further studies, we observed multiple microbiome and systemic measurements supporting mechanistic proof-of-principle,” James McIlroy, MBChB, CEO of EnteroBiotix, said in a press release.¹ “There are very large unmet medical needs in the field of advanced liver disease, and it is greatly encouraging that EBX-102 has potential efficacy in this population.”

An encapsulated full-spectrum microbiome therapeutic, EBX-102 has differentiated characteristics, such as consistency, high-bacterial diversity, and stability. It is an orally administered capsule that contains diverse full-spectrum microbial ecosystems intended to restore microbial ecology and act in concert to target multiple key disease pathways.^1,2

The scalable manufacture of EBX-102 is made possible by platform manufacturing technologies and a well-developed analytical toolkit from EnteroBiotix, which 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 the supply of microbiota obtained from healthy human donors.¹

IMPuLCE was a randomized, double-blind, placebo-controlled phase 1b study of adult participants with stable liver cirrhosis. It was conducted across 10 sites in the United Kingdom and designed to evaluate the safety, tolerability, and translational biomarker effects of 2 different doses of EBX-102.¹

According to a press release from EnteroBiotix, EBX-102 was well tolerated with an acceptable safety profile. The most common adverse events were gastrointestinal, and mainly mild and self-limiting. Of note, no serious treatment-emergent adverse events were reported.¹

Results showed participants receiving the higher dose of EBX-102 in cohort 2 showed significant shifts in stool bacterial microbiome composition compared to placebo, assessed by 16SrRNA sequencing. Additionally, participants receiving EBX-102 showed statistically significant changes in stool bacterial metabolites, with ongoing shotgun sequencing is ongoing and will provide additional insights into engraftment.¹

Although venous ammonia concentrations remained stable in all study participants, investigators called attention to a statistically significant increase in stool ammonia concentrations in the EBX-102 treatment groups but not the placebo group, suggesting a shift towards enhanced ammonia excretion through the stool rather than absorption into the bloodstream.¹

Investigators also observed a reduction in plasma lipopolysaccharide-binding protein in the EBX-102 cohorts but not in the placebo, indicative of successful modulation of the gut microbiota towards a more beneficial ecology, improved gut barrier integrity, and reduced inflammatory response.¹

Of note, improvements 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.¹

“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,” Ewan Forrest, chief investigator of the IMPuLCE study and an honorary professor in the School of Cardiovascular and Metabolic Health at the University of Glasgow, said in a press release.¹ “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.”

References

1. ^{EnteroBiotix. EnteroBiotix Announces Positive Ph1b Clinical Results of EBX-102 in Liver Cirrhosis. November 11, 2024. Accessed November 11, 2024. https://www.enterobiotix.com/news/enterobiotix-positive-clinical-results-ebx-102-liver-cirrhosis}
2. ^{EnteroBiotix. EnteroBiotix Initiates Phase 2 study of microbiome drug EBX-102 in liver cirrhosis and hepatic encephalopathy. March 28, 2024. Accessed November 11, 2024. https://www.enterobiotix.com/news/phase-2-study-of-microbiome-drug-ebx-102}