Precision Signs Another Collab for ARCUS Genome Editing Platform

In two separate announcements, Durham, N.C.-based Precision BioSciences announced a license and collaboration deal with Philadelphia-based iECURE and described its clinical development plans.

Precision BioSciences focuses on developing allogeneic CAR T therapies and in vivo gene correction treatment using its ARCUS genome-editing platform. iECURE focuses on mutation-agnostic in vivo gene editing. The two companies inked a deal under which iECURE will advance Precision’s PBGENE-PCSK candidate into Phase I trials. It also gets access to Precision’s PCSK9-directed ARCUS nuclease for more gene-editing therapies, initially focused on liver diseases.

They expect to file an Investigational New Drug (IND) as early as 2022 for the PBGENE-PCSK9 candidate for familial hypercholesterolemia (FH). Precision will hold the rights to the compound. In return, Precision granted iECURE a license to use its PCSK9-directed ARCUS nuclease for gene transport into the well-characterized PCSK9 locus for other pre-specified rare genetic diseases. Precision picks up an equity stake in iECURE with potential milestone and royalty payments.

“We founded iECURE with the aim of focusing on genetic diseases with significant unmet need that we could target in a mutation-agnostic manner,” said Joseph Truitt, chief executive officer of iECURE. “After evaluating different gene-editing technologies and platforms, we believe gene editing with ARCUS, including use of the uniquely designed ARCUS nuclease as a gene insertion tool targeting the PCSK9 gene will help us rapidly advance several candidates to the clinic with the potential to deliver on the promise of highly efficient, specific, and safe gene insertion.”

In a separate statement, Derek Jantz, chief scientific officer and co-founder of Precision, noted, “Today, we are excited to share additional data highlighting the precision and versatility of our ARCUS platform, which is designed to enable safe, specific and efficient gene editing. Since ARCUS can be delivered via AAV or LNP, it has potential utility in treating diseases in the liver as well as many genetic diseases that affect tissues beyond the liver.”

He went on to say, “In addition, the unique enzymology of ARCUS enables it to make complex gene insertion and gene repair edits more efficiently than other editing platforms. We believe these unique attributes of ARCUS support its differentiation for in vivo use and its potential to treat a broader range of genetic diseases than other editing technologies.”

In addition to the programs with iECURE, Precision has initiated IND-enabling procedures with plans to submit an IND for PBGENE-PH1 for primary hyperoxaluria type 1 (PH1) in 2023 and PBGENE-HBV for chronic hepatitis B virus (HBV) with an IND/CTA in 2024.

The featured preclinical data included the company’s argument that ARCUS is a better gene insertion and editing tool than CRISPR-based approaches for the PCSK9 locus. The company said in non-human primates, ARCUS was more efficient than CRISPR at inserting a Factor IX transgene into the PCSK9 locus, in studies for hemophilia B.

“ARCUS has demonstrated highly efficient gene insertion with a PCSK9-directed nuclease that will be foundational to iECURE in addressing rare genetic diseases, as well as long-term durability reflecting its curative potential with a single administration,” said James M. Wilson, M.D., Ph.D., Precision’s co-founder.

The company also presented preclinical data for its ARCUS for chronic HBV, mitochondrial genome editing, FH, PH1, and Duchenne Muscular Dystrophy (DMD)(PBGENE-DMD).

Precision and Eli Lilly entered a partnership in November 2020 to use ARCUS genome editing for up to six potential in vivo targets for genetic disorders, with the first three for DMD, a liver-directed target (PBGENE-LLY2) and a CNS-directed target, PBGENE-LLY3.

Jantz said, “Lilly will help us research ARCUS-mediated editing in muscle and CNS. Even as we aggressively invest in wholly-owned programs, we will continue to leverage collaborations that enable us to explore novel applications of ARCUS and reach patients quicker.”