Intrexon and ZIOPHARM to Develop Immunotherapies for Treatment of Graft-Versus-Host Disease

Intrexon Corporation XON, a leader in synthetic biology, announced today it has formed a new Exclusive Channel Collaboration (ECC) with ZIOPHARM Oncology, Inc. ZIOP, a biopharmaceutical company focused on new cancer immunotherapies, for the treatment and prevention of graft-versus-host disease (GvHD), a major complication of allogeneic hematopoietic stem-cell transplantation (HSCT) which significantly impairs the quality of life and survival of many recipients. The collaboration will focus on addressing the underlying pathologies of GvHD through engineered cell platforms to express and deliver interleukin-2 (IL-2), a cytokine critical for modulation of the immune system. "The combined expertise and the knowledge gained from our current research programs with Intrexon in adoptive T-cell therapies and cytokine modulation for treatment of cancer, position us well to develop and implement therapeutic approaches addressing an area of high unmet medical need for patients with GvHD," said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. Through the ECC, the companies plan to pursue engineered cell therapy strategies, used either separately or in combination, for targeted treatment of GvHD. The first approach is infusion of regulatory T cells (Tregs) conditionally expressing IL-2 utilizing Intrexon's proprietary gene control approaches such as its RheoSwitch® platform. The second is deployment of orally-delivered microbe-based ActoBiotics® therapeutics expressing IL-2 to modulate immune function. Allogeneic HSCT is used for the treatment of various diseases including hematological malignancies, immunological deficiencies as well as non-malignant conditions. Approximately 40 to 60% of HSCT recipients develop GvHD, either acute or chronic, when immune (graft) cells in a transplant patient recognize their engrafted host as foreign and attack the patient's (host) cells. Immunosuppressive agents and systemic steroids routinely used to treat GvHD have limited efficacy and toxicity, defining the need for safer, more effective therapies. Human studies have shown that administration of low-dose subcutaneous IL-2 in patients with steroid-refractory GvHD acts via Tregs to ameliorate its manifestations. The ECC intends to expand on the benefits of IL-2 immunotherapy under Intrexon's technologies to generate clinical-grade Tregs that can precisely deliver IL-2. In addition, the ActoBiotics® platform will be harnessed for its ability to target delivery of IL-2 to the digestive tract, a site which plays a significant role in the body's immune system. These new ways of treating and preventing GvHD have the potential to broaden the number of patients eligible to receive allogeneic HSCT and also increase the number of effective donor/recipient combinations. Samuel Broder, M.D., Senior Vice President and Head of Intrexon's Health Sector stated, "GvHD substantially impairs the quality of life and survival of transplant patients. We believe adoptive therapy with gene-modified T cells may offer an exciting alternative approach for restoring 'immune homeostasis' and countering the destructive pro-inflammatory mediators of GvHD. This ECC also includes access to the ActoBiotics® platform as an innovative approach to GvHD." Under the terms of the agreement, Intrexon will receive a technology access fee of $10 million in cash and reimbursement for all research and development costs. The agreement also provides for equal sharing of operating profits. Conference Call and Webcast September 28, 2015, at 5:00 PM ET ZIOPHARM and Intrexon will host a conference call and webcast slide presentation today, September 28, 2015, at 5:00 PM ET to discuss their GvHD exclusive channel collaboration. The call can be accessed by dialing (877) 751-7350 (U.S. and Canada) or (918) 559-5237 (international). The passcode for the conference call is 50985976. To access the slide and live audio webcast, or the subsequent archived recording, visit the "Investors & Media" section of the ZIOPHARM website at www.ziopharm.com. The webcast will be recorded and available for replay on the Company's website for two (2) weeks.