On, Gilead Sciences and genome-editing company Precision BioSciences announced that they have entered into a collaboration to develop therapies targeting the in-vivo elimination of hepatitis B virus (HBV) with Precision’s proprietary genome editing platform, ARCUS.
Under the terms of the agreement, Precision will be primarily responsible for the development, formulation, and preclinical evaluation of the investigational nucleases, and Gilead will be responsible for the clinical development and commercialization of potential therapies. Gilead will fully fund the research and development. Precision is eligible to receive milestone payments of up to an aggregate of $445 million and tiered royalties that go up to the mid-teens for commercial products developed through the collaboration.
ARCUS is a next-generation genome editing platform derived from a homing endonuclease, a natural genome-editing enzyme. Precision states that the backbone of the ARCUS technology is the ARC nuclease, a fully synthetic enzyme similar to a homing endonuclease but significantly improved to be the starting point for the genome-editing platform. The ARC nuclease is small, has incomparable specificity, and can be customized to recognize a DNA sequence within any target gene. ARC nucleases are created using a set of proprietary in-silico and lab-based techniques to ensure maximum gene-editing efficiency with minimum off-target activity. According to Precision, ARC nucleases can be optimized to control potency and specificity based on the analysis of cutting activity in a relevant model organism.
“An estimated 257 million people are living with HBV infection around the world. Current HBV treatments suppress HBV viral replication but do not completely clear the virus,” Gilead Sciences said in a company press release. “The presence of covalently closed circular DNA (cccDNA) enables HBV replication if treatment is stopped. Preliminary studies at Gilead using ARCUS nucleases to target HBV cccDNA in vitro have demonstrated significant activity against cccDNA and integrated HBV DNA in human hepatocytes.”
“Gilead’s cure-based approach to hepatitis B is comprehensive and exciting,” commented Derek Jantz, chief scientific officer, Precision Biosciences, in the release. “Precision is pleased that initial studies with our ARCUS platform have established an important role for genome editing in their HBV program. This is an excellent application for our technology, which has made notable progress toward therapeutic in-vivo editing in relevant models over the last year.”