Exacis Develops mRNA-Engineered iPSC-Derived NK Cells for Difficult-To-Treat Tumors

Exacis Biotherapeutics announced several steps in the preclinical development of its ExaNK™ engineered NK cell-therapy candidates.

ExaNK™ cells are generated from induced pluripotent stem cells (iPSCs) that are made using mRNA-based cell-reprogramming and gene-editing technologies. ExaNK™ cells are designed to resist rejection when administered to patients, with the goal of reducing or eliminating the need for costly and dangerous lymphodepletion, a procedure normally performed using cytotoxic chemotherapy, which carries risks of neurotoxicity and infection. These engineered iPSCs will form the basis for Exacis' tumor-targeted ExaCAR-NK™ cells as well as non-CAR-bearing ExaNK™ cells designed to improve the effect of monoclonal antibodies against both liquid and solid tumors.

Exacis produces rejection-resistant ExaNK™ cells by performing functional editing of key stealthing targets in its proprietary mRNA-reprogrammed iPSCs. These engineered iPSCs are then differentiated to the final NK-cell product using Exacis' proprietary high-yield differentiation process. The resulting ExaNK™ cells show higher tumor cell-killing activity and cytokine production in vitro than peripheral blood-derived NK cells, with no evidence of self-killing (i.e., "fratricide").

Exacis develops its off-the-shelf products using iPSCs to avoid the need for donors. This approach aims to lower the cost and increase the availability and consistency of engineered immuno-oncology cell therapies in comparison to currently approved products.

The discoveries announced were made in collaboration with Exacis' parent company, Factor Bioscience, and have been submitted for presentation at a major conference later this year. Exacis has also disclosed the details of these discoveries in a provisional patent application filed earlier this month.

"These results illustrate the sound scientific basis for Exacis' approach to the development of next-generation engineered NK-cell therapies," said Matt Angel, PhD, CEO of Factor Bioscience and Chair of Exacis' Scientific Advisory Board. "Combining cell reprogramming with gene editing allows the production of a near-unlimited supply of genetically uniform engineered cells, while using mRNA for both the cell-reprogramming and gene-editing steps uniquely enables the generation of footprint-free cells with no risk of vector integration."

"We continue to be encouraged by the rapid progress we are making towards developing accessible, next-generation engineered cell therapies that will improve patient experiences and outcomes. This first opportunity to expand our substantial intellectual property portfolio marks a key milestone for the company," said Gregory Fiore MD, CEO and President of Exacis Biotherapeutics.

Next steps for Exacis include scaling the iPSC expansion and differentiation processes to prepare for IND-enabling studies to be conducted later this year.