Precision BioSciences has announced that it has received Clinical Trial Application (CTA) approval in Moldova for PBGENE-HBV, its lead candidate for chronic hepatitis B virus (HBV) infection. This marks the initiation of the Phase 1 clinical program for PBGENE-HBV, a first-in-human study evaluating the safety and efficacy of an in vivo gene editing therapy designed to target and eliminate the root cause of chronic HBV. The company is moving towards dosing patients.
Targeting cccDNA for Functional Cure
PBGENE-HBV leverages Precision BioSciences' ARCUS gene editing platform to target covalently closed circular DNA (cccDNA), the key source of replicating HBV, and inactivate integrated HBV DNA in hepatocytes. The ARCUS nuclease-encoding mRNA is delivered to the liver via lipid nanoparticles, where it cuts a highly conserved sequence in the HBV viral genome. This approach aims to achieve a functional cure for chronic hepatitis B, a condition affecting nearly 300 million people globally.
Clinical and Regulatory Strategy
"At Precision, we remain laser-focused on execution, and our first CTA approval for PBGENE-HBV represents another significant milestone as we complete our transition to a clinical stage in vivo gene editing company," said Michael Amoroso, Chief Executive Officer of Precision BioSciences. The company is actively screening and preparing to dose patients at its clinical site in Moldova. Precision BioSciences is also pursuing additional CTA and IND approvals globally, supported by a regulatory package highlighting the safety and antiviral effects of PBGENE-HBV in preclinical models, including non-human primates.
Unmet Need in Chronic Hepatitis B
Hepatitis B remains a significant global health challenge, with current treatments primarily focused on viral suppression rather than eradication. Existing therapies, such as nucleos(t)ide analogs, require lifelong administration and offer only a 1-3% chance of functional cure. An estimated 15% to 40% of patients with chronic HBV infection may develop serious complications, including cirrhosis, liver failure, or hepatocellular carcinoma.
PBGENE-HBV: A Novel Approach
PBGENE-HBV stands out as the first clinical-stage approach designed to directly target and eliminate cccDNA. "PBGENE-HBV is the first and only clinical stage approach to directly target and eliminate cccDNA, giving it the potential to achieve a functional cure," added Dr. Murray Abramson, Senior Vice President, Head of Clinical Development of Precision BioSciences. The company plans to share additional information about its Phase 1 program, including the final preclinical safety package, at the upcoming AASLD meeting in November.
