Gilead Sciences will use Precision BioScience’s ARCUS genome editing platform to develop therapies targeting the in vivo elimination of hepatitis B virus (HBV) under a collaboration that could generate more than $445 million for Precision, the companies said.
The companies cited preliminary studies at Gilead using ARCUS nucleases to target HBV covalently closed circular DNA (cccDNA) in vitro, which they said have shown “significant” activity against cccDNA and integrated HBV DNA in human hepatocytes.
The ARCUS platform is derived from a natural genome-editing enzyme called homing endonucleases—site-specific DNA-cutting enzymes encoded in the genomes of many eukaryotic species. According to Precision, homing endonucleases have the unusual ability to precisely recognize long DNA sequences (12–40 base pairs) that are typically rare enough to occur only once in a complex genome. These nondestructive enzymes trigger gene conversion events that modify the genome in a very precise way, most frequently by the insertion of a new DNA sequence, the company said.
ARCUS technology is based on the ARC nuclease, a fully synthetic enzyme similar to a homing endonuclease but significantly improved. ARC nucleases are small, possess unparalleled specificity, and can be customized to recognize a DNA sequence within any target gene, according to Precision.
ARC nucleases are created using proprietary in silico and lab-based techniques designed to ensure maximum gene editing efficiency with minimum off-target activity. The nucleases can be optimized to control potency and specificity based on the analysis of cutting activity in a relevant model organism, Precision adds.
Precision reasons—and Gilead apparently agrees—that the ability to target a single DNA break in a complex genome and achieve gene modification without random off-targeting makes homing endonucleases ideal as starting material for a therapeutic-grade genome editing technology.
“We look forward to exploring this technology as an important component of our HBV cure research efforts,” John McHutchison, M.D., Gilead CSO and head of research and development, said in a statement.
Added Precision CSO Derek Jantz, “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.”
Top-Ranked Private Gene Editing Company
Two weeks ago, Precision topped GEN’s list of private gene editing companies among the Top 10 Companies Leveraging Gene Editing, based on the company’s total capital raised of $135.65 million. Most of that capital, $110 million, was raised through a Series B round led by ArrowMark Partners, the third-largest financing among private biopharmas that garnered venture capital during the first half of 2018.
While current HBV treatments—including Gilead’s Hepsera® (adefovir dipivoxil), Vemlidy® (tenofovir alafenamide), and Viread (tenofovir)—are designed to suppress HBV viral replication, they do not completely clear the virus, since the presence of covalently closed circular DNA (cccDNA) enables HBV replication if treatment is stopped.
During the first half of this year, Vemlidy sales more than quadrupled to $134 million from $33 million in January–June 2017. However, Viread sales plummeted 68%, to $179 million from $560 million a year ago.
Gilead does not break out Hepsera sales, but includes the treatment in its “Other” category, which includes the Pseudomonas aeruginosa (Pa) treatment Cayston® (aztreonam for inhalation solution), and the hepatitis C treatment Sovaldi® (sofosbuvir). Sales of Gilead’s “Other” drugs fell to $221 million from $730 million in the first half of 2017.
Precision has agreed to primarily oversee the development, formulation, and preclinical evaluation of the investigational nucleases, while Gilead will be responsible for the clinical development and commercialization of potential therapies, the companies said. Gilead has agreed to fully fund the research and development.
Gilead also agreed to pay Precision up to $445 million tied to achieving milestones, as well as tiered royalties that go up to the mid-teens on sales of commercial products developed through the collaboration.