Precision BioSciences provides updates on its therapeutic approach to cure hepatitis B

– ARCUS Genome Editing Achieved Substantial Reductions in both cccDNA and Hepatitis B Surface Antigen (HBsAg), 85% and 77% respectively, in HBV-infected Primary Human Hepatocytes (PHH)

– Significant Decrease in HBsAg and High On-target Editing Achieved in Novel Mouse and Non-human Primate Models Following Lipid Nanoparticle (LNP) Delivery of ARCUS mRNA

– Circulating HBsAg Surface Antigen was Durably Decreased by 96% in Mice

– Data Published also Presented at the 2022 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting

– Precision to Continue Developing PBGENE-HBV Product Candidate Using LNP Delivery and Expects to Submit an IND/CTA in 2024

DURHAM, N.C., May 18, 2022– Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage gene editing company developing ARCUS-based ex vivo allogeneic CAR T and in vivo gene editing therapies, today announced preclinical research from its ongoing in vivo gene editing program targeting hepatitis B virus (HBV) has been published online in Molecular Therapy. Data from this study, “Targeting the Hepatitis B cccDNA with a Sequence-Specific ARCUS Nuclease to Eliminate Hepatitis B Virus In Vivo,” support the Company’s continued development of its PBGENE-HBV candidate as a promising gene editing approach that aims to eliminate virus persistence by targeting covalently closed circular DNA (cccDNA) in patients with chronic hepatitis B. This study was conducted in collaboration with Gilead Sciences and Acuitas Therapeutics and was also presented this week during the Gene Editing in Cancer and Complex Diseases oral session at the ASGCT Annual Meeting.

“We’re very excited to see this study published in Molecular Therapy and to showcase the compelling reductions in cccDNA and surface antigen obtained with our ARCUS gene editing platform in two novel animal models of HBV infection. Our data suggest that LNP-delivered ARCUS mRNA is worth further exploration as a possible functional cure for chronic hepatitis B,” said Derek Jantz, Chief Scientific Officer and Co-founder of Precision BioSciences.

Precision’s gene editing program for chronic hepatitis B is designed to apply ARCUS to knock out persistent cccDNA and inactivate integrated hepatitis B genomes, potentially achieving durable HBsAg loss and functional cure. In this preclinical study, ARCUS efficiently targeted and degraded HBV cccDNA by 85% and reduced expression of HBsAg by 77% in HBV-infected PHH. Importantly, the optimized specificity of the ARCUS nuclease completely prevented detectable chromosomal translocations in the PHH model.

To evaluate ARCUS in vivo, novel mouse and non-human primate models were developed that utilized an episomal adeno-associated virus (AAV) containing a portion of the HBV genome to serve as a surrogate for cccDNA. After administration of LNP containing ARCUS mRNA, high on-target editing and a robust decrease in the cccDNA surrogate was observed in both episomal models, along with a durable 96% reduction of HBsAg in mice.

“The real challenge with HBV is that it persists in chronically infected hepatocytes as an extrachromosomal genome called cccDNA. Unless we can eliminate cccDNA, there’s always the potential that the virus can reactivate,” continued Cassandra Gorsuch, Ph.D., Head of Gene Therapy at Precision BioSciences and lead author of the paper. “Current standard-of-care treatments for chronic hepatitis B work by lowering or suppressing the amount of HBV found in infected cells in the body but have no direct impact on the presence of cccDNA, and therefore rarely clear the virus fully, necessitating life-long therapy.”

Precision’s in vivo development pipeline currently comprises six novel product candidates for genetic diseases. Three of these product candidates are wholly owned — PBGENE-HBV for chronic hepatitis B, PBGENE-PH1 for primary hyperoxaluria type 1 and PBGENE-PCSK9 for familial hypercholesteremia — and Precision expects to advance them to IND or CTA over the next three years.

About Precision BioSciences, Inc.

Precision BioSciences, Inc. is a clinical stage biotechnology company dedicated to improving life (DTIL) with its novel and proprietary ARCUS genome editing platform. ARCUS is a highly precise and versatile genome editing platform that was designed with therapeutic safety, delivery and control in mind. Using ARCUS, the Company’s pipeline consists of multiple ex vivo “off-the-shelf” CAR T immunotherapy clinical candidates and several in vivo gene editing candidates designed to cure genetic and infectious diseases where no adequate treatments exist. For more information about Precision BioSciences, please visit www.precisionbiosciences.com.