Sangamo Presents Oncology Genome Editing Capabilities at Keystone Symposium on Emerging Cellular Therapies

RICHMOND, Calif., Feb. 13, 2018 /PRNewswire/ -- Sangamo Therapeutics (Nasdaq: SGMO) yesterday presented preclinical data demonstrating the Company's engineering capabilities in T cell genome editing using zinc finger nucleases (ZFNs). Sangamo Scientist Sumiti Jain, Ph.D. delivered the presentation, "Dual Knock-Out of Endogenous T-Cell Receptor and Human Leukocyte Antigen and Site-Specific Insertion of a CD19-CAR: Implications for Allogeneic T Cell Therapy," at the Keystone Symposium on Emerging Cellular Therapies: T Cells and Beyond.

Sangamo's T cell engineering capabilities have advanced rapidly in the last two years with recent improvements to the architecture of zinc finger nucleases (ZFNs). These novel architectural enhancements have resulted in a 300-fold increase in potential design options for a given genetic sequence, yielding higher on-target modification activity, with editing efficiencies now reaching as high as 99.5%, and off-target cleavage consistently below the level of detection.

"For T cell editing applications in oncology, the improvements to our ZFN platform technology across the dimensions of precision, efficiency and specificity open a wealth of potential product opportunities in autologous and allogeneic cellular therapies," said Dr. Sandy Macrae, CEO of Sangamo.

At the Keystone Symposium, Dr. Jain's presentation highlighted Sangamo's ability to accomplish highly efficient "multiplex" genome editing of T cells. Efficient multiplex editing, the ability to make multiple genetic changes in a single step, is critical for the development of next-generation cellular immunotherapies to treat liquid and solid tumors in cancer, as well as in other areas such as autoimmune disorders and infectious diseases. Multiplex editing enables simultaneous "knock out" of certain genes to prevent the body from rejecting the treatment and "knock in" of new genes to equip the modified T cells with targeted antitumor functions.

"With more than a decade of experience in ex vivo genome editing, we have developed a deep understanding of T cell immunology that enables us to optimize the T cell editing process," said Dr. Gary Lee, Senior Director of Genome Editing at Sangamo. "The improved ZFN platform provides an extremely potent editing platform that allows us to use significantly reduced doses of mRNA and AAV. As a result, the gene editing process is highly efficient and well tolerated during ex vivo cell expansion, and, we believe, is the 'manufacturing ready' profile needed for clinical product development."

At the Keystone Symposium, Jain presented work leading to a T cell with four edits achieved in a single step:

    --  Elimination of endogenous T cell receptor (TCR) expression by knock-out
        of the TCR alpha constant locus (TRAC) with greater than 97% efficiency
    --  Elimination of (human leukocyte antigen) HLA Class I proteins by
        knock-out of b(2)-microglobulin (B2M) with greater than 91% efficiency
    --  Targeted integration into either the TRAC or B2M locus with double
        knock-out of TCR and HLA Class I:
        --  91% efficiency with green fluorescent protein (GFP)
        --  77% efficiency with CD19 chimeric antigen receptor (CAR)
    --  Four simultaneous edits including triple knockout of TCR (93%), B2M
        (96%), CISH, a checkpoint gene (93%), and targeted insertion of GFP
        (91%) resulting in 76% of all cells with all four edits

Sangamo's strategy in oncology is to advance the T cell editing platform in collaboration with partners that have synergistic technologies and with the appropriate development and commercialization expertise.

Dr. Jain's slides are available on the Presentations + Publications page of the technology section of Sangamo's website.

About Sangamo's Zinc Finger Nucleases
Sangamo's proprietary genome editing technology is based on a naturally occurring class of proteins called zinc finger DNA-binding proteins (ZFPs) which recognize and bind to specific sequences of DNA. Sangamo can engineer these naturally occurring ZFPs to bind to virtually any chosen DNA sequence. By combining ZFPs with nucleases (DNA cutting enzymes) to create zinc finger nucleases (ZFNs), Sangamo can harness the powerful targeting capabilities of zinc fingers to edit the human genome, specifically knocking out a DNA sequence or adding a new gene in a precise location.

In 2017, Sangamo scientists have reported on recent advancements in design and engineering which have enhanced the profile of ZFNs across three important criteria for the development of therapeutic genome editing: Precision, Efficiency and Specificity. With thousands of zinc finger modules in the Sangamo library and an array of linkers attaching the zinc fingers and the FOK1 nuclease domain, Sangamo is able to assemble highly specific ZFN pairs for virtually any chosen target site. For any given 20-base pair window in the genome, Sangamo has on average 450 functionally distinct ZFN modules to evaluate. Sangamo believes that the very high design density of the Company's ZFN library has operational advantages in choosing a final ZFN pair with an optimal profile to advance into potential clinical development.

About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic therapies that transform patients' lives using the Company's industry leading platform technologies in genome editing, gene therapy, gene regulation and cell therapy. For more information about Sangamo, visit

Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to Sangamo's expectations for cellular immuno-oncology treatments, the clinical and therapeutic potential of Sangamo's ZFN gene editing platform, Sangamo's strategy to advance its T cell editing platform in collaboration with partners, and other statements that are not historical facts. These forward-looking statements are based on Sangamo's current plans, objectives, estimates, expectations and intentions and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with: gene therapy product candidate development and the inherent uncertainty of clinical success, including the risks that Sangamo and/or its collaborators may encounter unanticipated toxicity or adverse events or fail to demonstrate efficacy in clinical development; the initiation, enrollment and completion of the stages of its clinical trials; technological challenges; technological developments by its competitors and others in the gene therapy and/or cellular immuno-oncology treatment fields; Sangamo's dependence on collaborations to further the development of its technology platforms, including Sangamo's potential inability to successfully enter into new collaborations with third parties on acceptable terms, or at all, in order to advance its T cell editing platform. A more detailed discussion of these and other risks and uncertainties may be found under the caption "Risk Factors" and elsewhere in Sangamo's SEC filings and reports, including Sangamo's Quarterly Report on Form 10-Q for the quarter ended September 30, 2017 and future filings and reports by Sangamo. Sangamo assumes no obligation to update the forward-looking information contained in this press release.

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