Shares of Ziopharm, Intrexon Quiet Following Presentation Showing HIL-12 is Fully Functional in Study Assay

ZIOPHARM Oncology, Inc. ZIOP, a biopharmaceutical company focused on the discovery and development of new cancer therapies, and Intrexon Corporation XON, a leader in synthetic biology, today announced the presentation of a preclinical study demonstrating the potential for using Intrexon's regulated gene expression system, the RheoSwitch Therapeutic System^® (RTS^®), in human mesenchymal stem cells (hMSCs). The study, "Regulated Immunomodulators Expression Using the RheoSwitch Therapeutic System^® (RTS^®) Platform in Human Mesenchymal Stem Cells," will be presented at the 2013 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which is taking place October 19-23, 2013 in Boston. hMSCs possess an inherent ability to traffic to tumors and sites of inflammation, making them an attractive possibility as a cellular vehicle delivery system, while the RTS^® platform is a novel regulated gene expression system which, when activated by an orally available activator ligand (AL), veledimex, can be used to express one or more anti-cancer effectors. Together, these technologies offer the potential to optimize the delivery, dose and schedule of one or more immunotherapies to achieve maximum therapeutic efficacy and tolerability. "In the lab and clinic, the RTS^® gene switch has been effectively combined with various methods of delivery, including dendritic cells, as well as viral and DNA plasmid vectors, to optimize our regulated therapeutic gene expression systems," said Jonathan Lewis, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. "Mesenchymal stem cells, which naturally seek out cancer cells, offer an exciting new method for delivering gene systems to cancer cells. Together, these technologies give us unprecedented control over the delivery and expression of one or more anti-cancer effectors." "The therapeutic use of hMSCs is a field of study with rapidly growing importance in a number of disease areas," said Samuel Broder, M.D., Senior Vice President of Intrexon's Health Sector and former Director of the National Cancer Institute. "For a cancer-directed gene expression system that relies on a cellular host, it may be the ideal delivery mechanism. This study brings to life the possibility of a self-guided cellular factory that can express multiple anti-cancer effectors, on demand, directly at the tumor site." For the study, ZIOPHARM and Intrexon evaluated RTS^® regulated expression of three immunomodulators, human IL-12, human IFNα, and a CTLA4 decoy, in single, dual or triple combinations, from adenovirally transduced hMSC.  In a single immunomodulator system, sustained cell levels of IL-12 expression were observed up to 53 days following transduction when maintained in the presence of veledimex.  Furthermore, cycling of in vitro exposure periods between veledimex and excipient demonstrated the ability for on/off/on and off/on/off kinetics of IL-12 expression by transduced hMSCs. For the multi-effector systems, hIL-12 and hIFNα were found to be fully biofunctional in their respective cell based functional assays: hIL-12 increased IFNγ secretion from NK92 cells and hIFNα enhanced STAT1 reporter activity. Further, the CTLA4 decoy demonstrated ability to inhibit protein interaction in a cross-competitive assay. Taken together, these in vitro studies highlight the potential use of MSCs for tumor-targeted delivery of single or multiple RTS^® regulated cancer immunotherapies. The use of these novel regulated immunotherapeutic approaches could potentially be translated into an effective clinical regimen for a variety of cancers. The study was conducted jointly between ZIOPHARM and Intrexon Corporation as part of an Exclusive Channel Collaboration to research, develop and commercialize novel in vivo DNA- and cell-based oncology therapeutics using different approaches, all regulated by Intrexon's proprietary RheoSwitch Therapeutic System^® (RTS^®) platform.  A copy of this poster presentation, by Chan et. al (abstract # C234), can be found on ZIOPHARM's website.