Precision BioSciences is advancing PBGENE-HBV, a novel gene editing therapy, through the ELIMINATE-B Phase 1 trial, showing encouraging initial safety and antiviral activity against chronic Hepatitis B. The trial, designed with multiple ascending dose levels, aims to evaluate the safety and efficacy of PBGENE-HBV in HBeAg-negative chronic Hepatitis B patients.
The initial results from the first cohort (n=3) receiving the lowest dose (0.2 mg/kg) indicate that PBGENE-HBV, which utilizes an ARCUS-encoding mRNA encapsulated in a lipid nanoparticle (LNP), was safe and well-tolerated. Importantly, no Grade ≥2 treatment-related adverse events or serious adverse events were observed across the three participants after the first dose.
Antiviral Activity
Beyond safety, PBGENE-HBV exhibited substantial antiviral activity, demonstrated by a reduction in Hepatitis B surface antigen (HBsAg) in two of the three participants after the initial dose. The ELIMINATE-B protocol involves three dose administrations at each level, aiming to maximize viral editing and achieve undetectable HBsAg levels. Precision BioSciences plans to complete subsequent administrations in all cohort 1 patients, building on the established safety profile and early antiviral activity.
Global Trial Expansion
The ELIMINATE-B study is actively enrolling HBeAg-negative chronic Hepatitis B patients across multiple global sites, including Moldova, Hong Kong, and New Zealand. The company plans to expand the trial to include sites in the U.S. and U.K., broadening the study to a genetically diverse patient population. Clinical data is expected to be shared throughout 2025.
Targeting the Root Cause of Hepatitis B
PBGENE-HBV is designed to eliminate covalently closed circular DNA (cccDNA) and inactivate integrated HBV DNA, addressing the root cause of chronic Hepatitis B. This approach differs from current treatments that primarily focus on viral suppression without eradicating cccDNA, often requiring lifelong administration.
Dr. Cassie Gorsuch, Chief Scientific Officer at Precision BioSciences, noted that preclinical studies of PBGENE-HBV demonstrated consistent safety and HBsAg reductions, aligning with the early data observed in the first cohort of patients. "The safety and early reduction of HBsAg suggests that PBGENE-HBV is doing what no previous treatment has been able to accomplish, eliminating the source of viral replication in cccDNA and inactivating integrated disease."
ARCUS Platform
PBGENE-HBV leverages Precision BioSciences' ARCUS gene editing platform, delivering an ARCUS nuclease-encoding mRNA to the liver via lipid nanoparticles. The ARCUS nuclease specifically targets and cuts a highly conserved sequence in the hepatitis B viral genome, designed to eliminate cccDNA and inactivate integrated HBV genomes.
Market Opportunity
Hepatitis B remains a significant global health challenge, with approximately 300 million people worldwide affected by chronic infection. Current treatments can suppress the virus but rarely lead to a functional cure, highlighting the need for innovative therapeutic strategies like PBGENE-HBV.
Precision BioSciences anticipates a U.S. IND filing in 2025 as part of its global Phase 1 regulatory strategy for PBGENE-HBV.
