Intrexon is joining forces with Ziopharm Oncology in a collaboration that will concentrate on the treatment and prevention of graft-versus-host disease (GvHD).

GvHD is a major complication of allogeneic hematopoietic stem-cell transplantation (HSCT), which significantly impairs the quality of life and survival of many recipients.

Intrexon and Ziopharm’s focus will be to address 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., CEO of Ziopharm, in a press statement.

The two firms will embark on 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 gene control approaches such as its RheoSwitch® platform. The second endeavor 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.

The partners envision expanding on the benefits of IL-2 immunotherapy using Intrexon's technologies to generate clinical-grade Tregs that can precisely deliver IL-2.

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 increase the number of patients eligible to receive allogeneic HSCT, as well as the number of effective donor/recipient combinations.

In January 2011, Intrexon paid $11.63 million for a 5% stake in Ziopharm Oncology as part of a global collaboration through which Ziopharm gained rights to use its partner’s UltraVector® transgene engineering platform for the development of DNA-based anticancer drugs.

Further signaling the two companies’ future collaborative efforts, Ziopharm Oncology restructured in March 2013 “to align staffing to current objectives and to marshal its resources toward achieving success with its synthetic biology programs,” following its decision to terminate development of its palifosfamide (ZIO-201) for first-line metastatic soft tissue sarcoma.

At that time, Ziopharm said it would instead immediately place its exclusive strategic focus on its synthetic biology programs, which are those that are being developed in partnership with Intrexon. The lead therapeutic candidate, Ad-RTS IL-12, is now being tested in two Phase II studies—one for advanced melanoma, and the other for nonresectable recurrent or metastatic breast cancer in combination with palifosfamide.

Commenting on the current collaborative agreement, Samuel Broder, M.D., senior vice president and head of Intrexon's Health Sector, said in a statement, “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 includes equal sharing of operating profits.

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