MD Anderson, Intrexon and ZIOPHARM connect on immunotherapy

Biotech companies Intrexon and ZIOPHARM Oncology have licensed unique MD Anderson immunotherapy technology, creating an alliance to hone a new way of customizing immune system attack cells to find and kill cancer cells.

In an agreement signed Jan. 13, the two publicly traded companies each agreed to pay MD Anderson $50 million in company stock — a total of $100 million — to license technology developed in the lab of Laurence Cooper, M.D., Ph.D., professor of Pediatrics, including a new method for genetically engineering immune T cells to target cancer.

Cooper and colleagues worked with Perry Hackett, Ph.D., professor of Biological Sciences at the University of Minnesota, to develop a DNA plasmid-based gene transfer system called Sleeping Beauty to modify T cells, creating a chimeric antigen receptor (CAR) on them that recognizes and binds to a specific cell-surface protein on targeted malignant cells.

Their gene transfer system is the only one that doesn’t rely on viral delivery of the desired gene to the T cell’s genome and is typically simpler and cheaper to use than viral approaches, Cooper says.

Cooper’s group has built on this approach to deliver patient-derived CAR T cells in clinical trials and is developing ways to generate T cell products for universal, off-the-shelf application.

“Genetically engineering our patients’ immune system T cells to efficiently attack and destroy cancer cells represents one of the most exciting approaches with curative potential in oncology today,” MD Anderson President Ron DePinho, M.D., said. “We believe coupling MD Anderson’s unique CAR T cell approach with the powerful technologies of ZIOPHARM and Intrexon will allow us to build T cells that hit cancer harder, with greater precision, under tighter control and with potentially fewer side effects for patients. This agreement ranks as one of MD Anderson’s most substantial collaborations and will provide significant resources to fuel its mission of Making Cancer History®.”

‘The most advanced set of technologies’

Intrexon and ZIOPHARM have combined to develop a tightly controlled system that injects a gene-expression package into tumors that expresses the anti-tumor cytokine interleukin-12 (IL-12), but only when patients take a pill that contains a ligand to activate the gene. When the patient stops taking the pill, IL-12 expression stops, allowing for specific dosing for a set time. Expression is controlled by Intrexon’s proprietary biologic switch known as the RheoSwitch Therapeutic System®.

The companies and MD Anderson expect the collaboration to yield next-generation therapies based on designer cytokines and CAR T cells under the control of RheoSwitch® to target blood and solid tumor cancers. They project five patient-derived CAR T cells to enter the clinic in 2015 with off-the-shelf programs starting in 2016.

“It is a shared vision to maximize the speed and breadth of multigenic innovation for patients through the use of nimble, nonviral DNA cell manufacturing strategies that can further overcome viral packaging constraints and economic limitations,” stated Gregory Frost, Ph.D., senior vice president and head of Intrexon’s Health Sector. “Collectively, this will assemble the most advanced set of technologies to empower the strongest adoptive cell therapy pipeline that can drive innovation through multiple horizons and patient populations.”

Moon Shots Program connection

Work continues in conjunction with MD Anderson’s Moon Shots Program, an ambitious initiative to accelerate the conversion of scientific discoveries into clinical advances and significantly reduce cancer deaths. Cooper leads the Applied Cellular Therapeutics platform for the moon shots, providing expertise and new cellular therapy capabilities for both blood and solid tumor cancers. Clinical trials using non-virally produced CAR T cells are either under way or planned for specific moon shots.

“The promise of controlled, cell-based immuno-oncology therapy is that we can achieve dramatic, long duration anti-cancer results while keeping patients out of intensive care during treatment. As importantly, we can reproduce these results in a globally scalable and economically viable way,” remarked Jonathan Lewis, M.D., Ph.D., and Chief Executive Officer of ZIOPHARM Oncology. “The MD Anderson Cancer Center has long been a leader in cancer therapy, in terms of innovation, patient care, and the highest quality research. As part of our commitment to this important partnership and the acceleration of translational medicine, ZIOPHARM will build a base of operations in Houston to join and collaborate with the academic and medical community around this world-class institution.”

Under the licensing agreement, the two companies also will provide $15 to $20 million annually for three years for MD Anderson research and clinical trials. They will enter into additional collaboration and technology transfer agreements to accelerate technology and clinical development.

“The human application of T cell therapies provides cancer patients with new hope, and the alignment of MD Anderson’s immunotherapy and translational programs with Intrexon and ZIOPHARM will help make that hope a reality,” Cooper said. “These two interconnected companies have first-in-class genetic tools and systems to reprogram cells and the management and regulatory expertise to undertake development of potent and focused cell-based immunotherapies.”

This agreement marks a significant financial milestone as well as a scientific one — it’s one of the most substantial collaborations in MD Anderson’s history.