Intrexon, ZIOPHARM and Merck KGaA, Darmstadt, Germany Advancing Next-Generation Non-Viral CAR-T Platform Empowered by Membrane-Bound IL-15 Under RheoSwitch Therapeutic System(R) Control

Two CAR Targets Selected Enable Range of Potential Therapeutic Candidates for Both Solid and Liquid Tumors

GERMANTOWN, MD and BOSTON, MA, USA I April 03, 2017 I Intrexon Corporation (NYSE:XON), a leader in the engineering and industrialization of biology to improve the quality of life and health of the planet, ZIOPHARM Oncology (NASDAQ:ZIOP), a biopharmaceutical company focused on new immunotherapies, and Merck KGaA, Darmstadt, Germany, a leading science and technology company, today announced an update on the development of next-generation chimeric antigen receptor T cell (CAR-T) therapy for cancer as part of their strategic collaboration and license agreement.

Intrexon and ZIOPHARM Oncology, in an exclusive partnership with Merck KGaA, Darmstadt, Germany, are advancing a unique approach to develop therapeutic candidates for two CAR-T targets expressed on a wide range of tumor types, including hematologic malignancies and solid tumors.

The distinctive methodology centers on two technologies: the proprietary RheoSwitch Therapeutic System® (RTS®) platform to regulate expression of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty non-viral gene integration.

"Sleeping Beauty and the RTS® approach are a powerful combination to improve the manufacturing process and instill control over CAR-modified T cells co-expressing cytokines such as membrane-bound IL-15. The collaboration with Intrexon and Merck KGaA, Darmstadt, Germany, has been a catalyst to progress these next-generation gene therapy technologies. We are excited by the progress and look forward to advancing this innovative approach toward the clinic in mid-2018," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM.

The interleukin-15 (IL-15) cytokine is increasingly recognized as a key driver of therapeutic effect in CAR-T therapy, including in a recent Journal of Clinical Oncology publication which correlated lymphoma remissions with elevated IL-15 levels. Through the RTS® gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus providing a new paradigm in T-cell therapy.

Additionally, the non-viral Sleeping Beauty transposon-transposase is an exceptional system for introducing genes encoding CARs and TCRs into T cells that holds multiple advantages over viral-based delivery systems. It simplifies genetic modification, and when coupled with reduced ex vivo processing, offers a pathway to shortened manufacturing and personalized T-cell therapies.

About Intrexon Corporation
Intrexon Corporation (NYSE: XON) is Powering the Bioindustrial Revolution with Better DNA to create biologically-based products that improve the quality of life and the health of the planet.  The Company's integrated technology suite provides its partners across diverse markets with industrial-scale design and development of complex biological systems delivering unprecedented control, quality, function, and performance of living cells.  We call our synthetic biology approach Better DNA®, and we invite you to discover more at or follow us on Twitter at @Intrexon, on Facebook, and LinkedIn.

About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a Boston, Massachusetts-based biotechnology company employing novel gene expression, control and cell technologies to deliver safe, effective and scalable cell- and viral-based therapies for the treatment of cancer and graft-versus-host-disease. The Company's immuno-oncology programs, in collaboration with Intrexon Corporation (NYSE:XON) and the MD Anderson Cancer Center, include chimeric antigen receptor T cell (CAR-T) and other adoptive cell-based approaches that use non-viral gene transfer methods for broad scalability. The Company is advancing programs in multiple stages of development together with Intrexon Corporation's RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve therapeutic index. The Company's pipeline includes a number of cell-based therapeutics in both clinical and preclinical testing which are focused on hematologic and solid tumor malignancies.


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