On May 25, 2021 Exacis Biotherapeutics Inc., a development-stage immuno-oncology company working to democratize access to the most advanced and effective cancer treatments, reported that key data related to its engineered iPSC-derived NK-cell platform at the American Society of Gene & Cell Therapy 24th Annual Meeting (Press release, Exacis Biotherapeutics, MAY 25, 2021, View Source [SID1234580591]). These data include the successful generation of functional NK cells from iPSCs engineered to contain a biallelic knockout of a key MHC class I gene. Exacis’ cell engineering strategy is designed to allow its ExaNK cells to evade surveillance by the patient’s immune system, thus rendering the cells rejection resistant, or "stealth", to enable increased persistence in patients without genotoxic pre-conditioning.

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"These results demonstrate the precision and efficiency of two key components of our platform, the mRNA-mediated cell reprogramming and the mRNA gene editing technologies, including mRNA vectorization of our proprietary, targeted gene editing endonuclease," said James Pan, PhD, Head of Discovery and Development at Exacis. "Our virus-free and DNA-free approach to cell engineering allows us to develop engineered cell therapies with no risk of vector integration and the associated long term safety issues."

"The results we are seeing in the lab continue to reinforce our hypothesis that highly effective cell therapy products can be produced using methods to greatly reduce safety risks and streamline manufacturing. We continue to take steps toward our goal of expanding patient access to these life saving cell therapy products," stated Gregory Fiore MD, President and CEO of Exacis Biotherapeutics.

Presentation Highlights:

Digital Presentation: "High-Efficiency Generation of Biallelic Gene Knockout iPSC Lines Using mRNA Gene Editing"

Abstract Number: 768

Allogeneic cell therapies derived from gene-edited iPSCs are being developed to address challenges associated with donor-derived allogeneic cell therapies, including host immune rejection of allogeneic cells. While these challenges can theoretically be addressed through genetic engineering, performing the required biallelic editing of defined loci remains technically challenging with current gene-editing approaches. We demonstrate efficient and precise targeting of defined loci in iPSCs using a novel, mRNA-encoded gene-editing endonuclease. We show generation of iPSC lines containing biallelic knockouts of a key MHC class I gene with 50% efficiency using mRNA reprogrammed iPSCs and a novel mRNA encoded gene editing protein. Absence of off-target editing was confirmed by whole-genome sequencing of one of the engineered iPSC lines. The high efficiency and specificity of this process enabled the selection of an iPS cell line containing only the desired edits without the extensive screening often required with other gene-editing approaches. When differentiated into NK cells, the engineered cells showed enhanced tumor cell engagement and cytokine production in comparison to peripheral blood derived control NK cells. The engineered cells are being further developed as a rejection resistant cell

therapy platform onto which additional components, including chimeric antigen receptors (CARs) and activity-enhancing cytokines, can be added.