What's Happening?
Precision BioSciences, Inc. announced new and updated Phase 1 clinical data from its ELIMINATE-B study of PBGENE-HBV, an in vivo gene editing therapy designed to eliminate the root cause of chronic hepatitis B (HBV), covalently closed circular DNA (cccDNA).
The data, presented at The Liver Meeting® 2026, demonstrated complete and durable pregenomic RNA (pgRNA) loss to undetectable levels in 100% of evaluable patients at the 0.4 mg/kg dose, which is the expected go-forward dose. Liver biopsies from patients treated at this dose showed approximately 1-log and 1.5-log reductions in cccDNA. Additionally, all evaluable patients experienced reductions in hepatitis B surface antigen (HBsAg), with maximal reductions approaching 94%. The therapy exhibited a well-characterized and manageable safety profile across 59 administrations in 25 patients, with no dose-limiting toxicities. These findings support the advancement of PBGENE-HBV to a global Phase 2 study.
Why It's Important?
Chronic hepatitis B affects millions globally and currently has no cure, as existing treatments do not eliminate cccDNA, the persistent viral reservoir. PBGENE-HBV's ability to achieve complete and durable pgRNA loss and significant cccDNA reduction represents a potential breakthrough towards a viral cure. This could free patients from lifelong daily medication and significantly reduce the risk of liver cancer and cirrhosis. The consistent efficacy and manageable safety profile observed in the Phase 1 study are crucial for advancing this gene editing therapy, offering hope for a transformative treatment option for a disease with a high unmet medical need.
What's Next?
Based on the Phase 1 ELIMINATE-B findings, Precision BioSciences has selected 0.4 mg/kg as the go-forward dose for PBGENE-HBV and is initiating a global ELIMINATE-B2 Phase 2 study. This Phase 2 study will evaluate PBGENE-HBV as both a monotherapy and in combination with an antisense oligonucleotide (ASO) to assess its potential for viral and functional cures. The company expects to initiate dosing in the ELIMINATE-B2 study in the first quarter of 2027, with initial open-label data anticipated in the second half of 2027. The FDA has already granted Fast Track designation to PBGENE-HBV, which could expedite its development and review process.
Beyond the Headlines
This development highlights the immense potential of gene editing technologies, specifically ARCUS® platform, in addressing chronic infectious diseases. By directly targeting and eliminating cccDNA, PBGENE-HBV represents a fundamental shift from managing symptoms to seeking a definitive cure. The ability to achieve sustained undetectable HBV DNA, which is a validated FDA endpoint for chronic hepatitis B, could set a new standard for treatment. This approach could also pave the way for similar gene editing strategies for other persistent viral infections, demonstrating the broader impact of this technology beyond HBV. The ongoing Phase 2 study will be critical in confirming the long-term efficacy and safety, and ultimately, the curative potential of this innovative therapy.
