ZIOPHARM Announces First Patient Enrolled in Phase I Study; Drug Uses Sleeping Beauty Platform


ZIOPHARM Oncology, Inc. recently announced that the first patient has been enrolled in a Phase I clinical study of its second-generation non-viral CD19-specific chimeric antigen receptor (CAR) modified T-cell therapy in patients with advance lymphoid malignancies. The CD19-specific T cells were modified using the Sleeping Beauty system to stably express the CAR in T cells.

The Sleeping Beauty transposon-transposase is a unique non-viral system for introducing genes encoding CARs and T-cell receptors (TCRs) into lymphocytes and is exclusively licensed by Intrexon Corporation through The University of Texas MD Anderson Cancer Center and accessed as part of ZIOPHARM’s collaboration. This non-viral approach may play an important role in immunotherapy and has several potential advantages over viral delivery systems, including: lower cost of generating genetically modified T cells,
generate T cells with minimal ex vivo processing, conduit to targeting solid tumor neo-antigens using TCRs, and pathway to overcome regulatory hurdles

“The survival benefit seen in early clinical results with our first generation CD19-specific CAR+ T cells were highly encouraging, and preclinical results to date suggest that our next-generation CAR structure may improve upon these outcomes,” said Laurence Cooper, MD, PhD, Chief Executive Officer of ZIOPHARM. “These studies continue to strengthen our understanding of the application and benefit of the Sleeping Beauty platform, the only efficient non-viral gene transfer system in clinical application. Sleeping Beauty offers the potential to significantly reduce the expense and simplify the implementation of genetically modified T cells, both of which are critical to the personalization and broad application of immunotherapies based on CARs and TCRs.”

In two prior trials the first-generation CD19-specific CAR+ T cells, patient-derived (autologous) or donor-derived (allogeneic) T cells were administered to recipients with advanced CD19-expressing leukemias and lymphomas after hematopoietic stem-cell transplantation (HSCT). Results demonstrated an apparent doubling of survivals compared to historical controls.

The second-generation Sleeping Beauty CAR+ T cells employ a revised CAR construct designed to improve persistence and anti-tumor response over the first generation therapy. Additionally, this investigational treatment is independent of HSCT. This trial is being conducted at MD Anderson.

ZIOPHARM Oncology is a Boston, MA-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. The company’s synthetic immuno-oncology programs, in collaboration with Intrexon Corporation 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. For more information, visit www.ziopharm.com.