Precision BioSciences Presents PBGENE-HBV Clinical Data at EASL 2026
Precision BioSciences announced the presentation of new and late-breaking clinical data from the ELIMINATE-B study evaluating PBGENE-HBV at the European Association for the Study of the Liver, or EASL, annual congress 2026. The late-breaking data, titled 'First evidence of elimination and inactivation of cccDNA in liver biopsies collected from patients with chronic hepatitis B treated with PBGENE-HBV' was presented. These data represent the first ever clinical evidence for a therapeutic agent's elimination and inactivation of cccDNA in liver biopsies collected from treated patients with chronic hepatitis B. These data provide compelling evidence supporting PBGENE-HBV's primary mechanism, direct antiviral targeting and elimination of cccDNA. To date, this has not been previously achievable with other commercial or development-stage modalities. As of the data cut off on May 4, 38 doses have been administered to 16 patients across five cohorts. Multiple datasets support cccDNA targeting, elimination and permanence of effect by PBGENE-HBV. Liver biopsy analysis using long-read transcript sequencing, which enables distinct characterization of PBGENE-HBV's effect on cccDNA versus integrated hepatitis DNA, demonstrated a 1-log reduction in cccDNA transcripts through its primary mechanism, cccDNA elimination, after only two dose administrations at the 0.4 mg/kg dose. These results represent the first evidence of cccDNA elimination by a direct targeting treatment modality. Following the elimination edits, further editing of the remaining less than1% of cccDNA occurred via the secondary mechanism of action, cccDNA indels. These indels permanently inactivate viral replication in the cccDNA by knocking out polymerase function. Both of these cccDNA editing outcomes result in viral destruction. Additional biopsy evidence of cumulative PBGENE-HBV effect after repeat dose administrations was also observed, with editing reaching 80% of the remaining cccDNA after three administrations. These data suggest additional PBGENE-HBV administrations drive cumulative editing and a greater benefit of permanent viral eradication. The new EASL data support pgRNA as the most relevant and specific serum biomarker as it comes exclusively from cccDNA and is the necessary precursor for HBV DNA viral production. Durable loss of blood pgRNA was demonstrated in 100% of patients treated with PBGENE-HBV who had detectable levels pre-treatment. These landmark results were achieved across four distinct dosing cohorts, providing a clear therapeutic window with multiple paths to be explored through ongoing clinical development. Complete loss of detectable blood pgRNA directly corresponded to undetectable pgRNA in post-treatment liver biopsy, further supporting pgRNA as the appropriate clinical biomarker for assessing PBGENE-HBV effect on cccDNA in the liver. Published literature has demonstrated that loss of pgRNA supports an approximately 10-fold increased probability of cure after discontinuation of nucleoside analog therapy. Overall, 100% of patients experienced substantial HBsAg declines demonstrating broad activity of PBGENE-HBV across all dose levels. Declines in HBsAg are consistent with PBGENE-HBV's elimination of cccDNA as validated in new biopsy data being presented at EASL 2026. Duration of response is ongoing and ranges across varying patient follow up from 1.5 to 12+ months across all patients who received repeat administrations, at data cutoff. These results were observed and consistent across a heterogeneous population spanning geographies, baseline HBsAg levels, and multiple HBV genotypes. In the first patient treated and PBGENE-HBV's longest clinical exposure to date, durable HBsAg decline for more than one year after initial dose supports the permanence of PBGENE-HBV gene editing elimination mechanism which is critical for complete viral cure. As of data cutoff, 38 doses have been administered across 16 patients in 5 cohorts for the safety analysis. No dose limiting toxicities were observed. The most common adverse events include infusion-related reactions consistent with LNP effects, with onset and resolution within 24 hours of infusion. While transient, greater than or equal to Grade 3 reversible ALT/AST lab abnormalities have been observed, they were asymptomatic with no elevated bilirubin, and no Hy's law in any patient at any dose level. Grade 3 hypotension was observed during dose escalation, and one patient in the highest dose cohort (0.8 mg/kg) experienced two SAEs after the second LNP administration. One of the events was deemed treatment related and mechanistically related to hypotension. The patient is ambulatory, home, and stable. The etiology of hypotension following subsequent doses of LNP is now understood and simple measures such as slower infusion rate and increased steroid doses have been implemented. Up to 20% of the doses delivered in the ELIMINATE-B trial have now been administered under the mitigation protocol and no greater than or equal to Grade 3 hypotension events or greater than or equal to Grade 3 LNP-related ALT/AST lab abnormalities have been observed since the implementation. These data will be reviewed in more detail during the investor webcast and posted on our website under the Investor Relations webpage here. The next steps for the ELIMINATE-B trial are to treat more patients under current cohorts in Part 1 of the trial increasing the size and strength of the data set. Precision expects to collect additional biopsy data to support the direct targeting and elimination of cccDNA. Precision is working with global investigators to create the future framework for nucleoside analog withdrawal and expansion into Part 2 of the ELIMINATE-B trial. The current and future dataset is expected to inform selection of the optimal dosing schedule for Part 2 expansion. Precision expects to provide additional updates on the ELIMINATE-B trial by the end of 2026.
