Precision Bio's PBGENE-HBV demonstrates direct cccDNA elimination in chronic hepatitis B trial

Precision BioSciences (Nasdaq: DTIL) reported data for its pipeline candidate PBGENE-HBV, demonstrating what the company described as the first clinical evidence of direct cccDNA elimination in liver biopsies from patients with chronic hepatitis B. The company presented the data via a late-breaking presentation at the European Association for the Study of the Liver Congress 2026. The Durham, North Carolina-based Precision Bio said the findings, drawn from 16 patients across five dosing cohorts, establish a biological basis for viral cure that no approved or development-stage therapy has previously demonstrated in human tissue.

The ELIMINATE-B trial is a multi-cohort, dose-escalation first-in-human study evaluating PBGENE-HBV — a lipid nanoparticle-delivered mRNA encoding an ARCUS nuclease designed to introduce targeted edits in HBV covalently closed circular DNA — in patients with chronic hepatitis B infection. As of the May 4, 2026 data cutoff, 38 doses had been administered across 16 patients, with 13 receiving repeat administrations and follow-up ranging from 1.5 to more than 12 months.

Liver biopsy analysis using long-read transcript sequencing demonstrated a 1-log, or 10-fold, reduction in cccDNA-derived transcripts after two administrations at the 0.4 mg/kg dose level, attributed to direct cccDNA elimination. In the less than 1% of cccDNA that remained following the primary elimination mechanism, secondary editing via indels was observed to inactivate viral replication by disrupting polymerase function. After three administrations, editing reached 80% of the residual cccDNA, suggesting a cumulative dose-response relationship.

On the biomarker side, durable loss of pregenomic RNA in blood was observed in 100% of patients with detectable pgRNA at baseline (n=6) across four distinct dosing cohorts. The company said complete loss of detectable blood pgRNA corresponded to undetectable pgRNA in post-treatment liver biopsy, supporting its use as a surrogate for hepatic cccDNA activity. Published data cited by Precision, from Terrault et al. in the Journal of Infectious Disease (2025), indicate that pgRNA loss is associated with an approximately 10-fold increased probability of cure following discontinuation of nucleoside analog therapy. Separately, 100% of patients (n=15) experienced HBsAg declines across all dose levels, with the first patient treated maintaining durable decline for more than one year after initial dosing.

On safety, no dose-limiting toxicities were observed. The most common adverse events were infusion-related reactions consistent with lipid nanoparticle administration, resolving within 24 hours. Grade 3 or higher reversible ALT/AST elevations were observed but described as asymptomatic, with no elevated bilirubin and no Hy's Law cases at any dose level. Grade 3 hypotension occurred during dose escalation, and one patient in the 0.8 mg/kg cohort experienced two serious adverse events following a second LNP administration, one of which was deemed treatment-related and mechanistically linked to hypotension. The company said the patient is ambulatory and stable. Mitigation measures — slower infusion rate and increased steroid premedication — have since been implemented, and no Grade 3 or higher hypotension or LNP-related liver enzyme elevations have been observed across the approximately 20% of doses administered under the revised protocol.

Competitive context

Chronic hepatitis B affects an estimated 250 to 300 million people globally, and while nucleoside analogs such as tenofovir and entecavir suppress viral replication effectively, they do not eliminate cccDNA and require indefinite administration. Functional cure rates with existing therapies remain below 10% in most treated populations. PBGENE-HBV's ARCUS platform is a compact, non-CRISPR meganuclease system, which the company contends may offer immunogenicity and payload-size advantages over Cas9-based approaches being explored by others in the field. The ELIMINATE-B data remain early-stage with a small patient cohort. Precision said it expects to provide additional updates on the ELIMINATE-B trial, including data from nucleoside analog withdrawal and expansion into Part 2, by the end of 2026.

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