Gene-editing therapy shows first elimination of hepatitis B viral reservoir

Precision BioSciences Reports First Evidence of cccDNA Elimination in Hepatitis B Patients

Precision BioSciences announced on Wednesday that its gene-editing therapy PBGENE-HBV is the first treatment to demonstrate direct elimination of cccDNA — the persistent viral reservoir responsible for chronic hepatitis B — in liver biopsies from patients enrolled in the Phase 1 ELIMINATE-B trial.

The data, presented as a late-breaking poster at the European Association for the Study of the Liver (EASL) Annual Congress 2026 in Barcelona, showed a 1-log (10-fold) reduction in cccDNA-derived transcripts following treatment, with additional edits inactivating viral polymerase in the remaining cccDNA molecules. All six patients with detectable pregenomic RNA (pgRNA) at baseline achieved complete pgRNA loss in blood, and all 15 evaluated patients experienced substantial declines in hepatitis B surface antigen across dose levels.stocktitan

A Potential Path Toward Functional Cure

cccDNA has long been considered the central obstacle to curing hepatitis B because it serves as the sole template for viral replication. Current nucleoside analog therapies suppress circulating virus but do not eliminate this reservoir, requiring lifelong treatment for an estimated 296 million people living with chronic infection worldwide. PBGENE-HBV, which uses Precision’s proprietary ARCUS gene-editing platform delivered via lipid nanoparticles, is designed to cut and destroy cccDNA directly in infected liver cells.precisionbiosciences

The biopsy findings also showed that after three doses of PBGENE-HBV, approximately 80% of remaining cccDNA had been edited, further supporting cumulative antiviral activity with repeat dosing.stocktitan

Safety and Next Steps

Across 38 doses administered to 16 patients in five cohorts, no dose-limiting toxicities were observed. The most common adverse events were transient infusion-related reactions and reversible liver enzyme elevations. One patient at the highest dose level of 0.8 mg/kg experienced serious hypotension-related events, prompting a mitigation protocol that has since prevented recurrence of severe events.streetinsider

The company held an investor webcast on May 27 to discuss the findings with hepatitis B experts. Precision plans to enroll additional patients, collect further biopsy data, and advance toward Part 2 of the ELIMINATE-B trial, with the next update expected by year-end 2026. The FDA has granted PBGENE-HBV Fast Track designation and indicated that sustained loss of HBV DNA could serve as an approvable endpoint.stocktitan