Favorable Long Term Follow-up in Two Trials with Patients Receiving Autologous CAR-T cells and Allogeneic
CAR-T cells
Potential benefits of Sleeping Beauty approach include reduced costs, complexity, and improved tolerability
BOSTON, Aug. 04, 2016 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company
focused on new immunotherapies, today announced the publication of data highlighting the benefits of using the non-viral
Sleeping Beauty (SB) system to genetically modify T-cells to express a chimeric antigen receptor (CAR) for use against
leukemias and lymphomas. The article, titled “Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells,” was
published in the Journal of Clinical Investigation (doi:10.1172/JCI86721), and is available online here.
In the paper, 26 patients with multiply relapsed B-lineage acute lymphoblastic leukemia (ALL, n=17) or B-cell
non-Hodgkin lymphoma, (NHL, n=9) were enrolled in two investigator-initiated clinical trials at the University of Texas MD Anderson
Cancer Center infusing SB-modified T cells after autologous (n=7) or allogeneic (n=19) hematopoietic stem-cell transplantation
(HSCT).
- Autologous CAR-T: Seven patients with advanced NHL were treated with autologous HSCT followed by administration of
patient-derived CAR T cells. Six of the seven patients remain in complete remission (CR) and the 30-month progression-free
survival (PFS) and overall survival (OS) rates were 83.3% and 100%, respectively.
- Allogeneic CAR-T: Nineteen patients (ALL n=17, NHL n=2) received donor-derived CAR T cells. The patients had
advanced disease at the time of HSCT and CAR T cells were administered without additional lymphodepletion. Eleven of 19 patients
remain in remission with 1-year PFS and OS rates of 53% and 63%, respectively.
- HLA partially-matched allogeneic CAR-T: When the subset of allogeneic recipients of HSCT receiving haplo-identical
CAR T cells were examined, eight patients had 1-year PFS and OS rates of 75% and 100%, respectively.
SB-mediated gene transfer and stimulation resulted in large ex vivo expansion of T cells while
retaining CAR expression and without integration hotspots. Autologous and allogeneic T cells survived after infusion an average of
201 and 51 days, respectively. No unexpected acute infusion or delayed toxicities were noted in the autologous or allogeneic
recipients. Mild elevations in cytokines were observed without cytokine storm.
Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM,
states: “By following these patients over an extended duration, as we do in these studies, we can better understand the added
benefit of CAR-T over HSCT alone. Although the primary objective of these trials was not to establish efficacy, the recipients’
outcomes are encouraging with apparent doubling of survivals compared to historical controls. We are encouraged by these clinical
data and look forward to results from our Phase 1 study infusing our next generation CD19-specific CAR T cells in patients with
advanced lymphoid malignancies.”
Supported by results from two Phase I clinical studies conducted by investigators at MD Anderson Cancer Center,
the publication describes how the use of the SB transposon/transposase platform could reduce the costs and complexity associated
with recombinant viral vector-based immunotherapy. Additionally, by infusing a CD19-specific CAR T cells to target minimal residual
disease after autologous and allogeneic HSCT, the SB system may improve tolerability by avoiding cytokine storm.
“The use of the non-viral Sleeping Beauty platform provides us with leverage to both decrease the cost
of modifying T cells and reduce the T-cell manufacturing steps requiring GMP,” said Laurence Cooper, M.D., Ph.D., Chief Executive
Officer of ZIOPHARM. “As we continue to advance Sleeping Beauty engineered designs, ZIOPHARM benefits from both viral
and non-viral approaches within CAR-T, while focusing efforts on non-viral gene delivery for TCR given its unique ability to enable
personalized therapies for patients with solid tumors.”
About ZIOPHARM Oncology, Inc.:
ZIOPHARM Oncology is a Boston, Massachusetts-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 immuno-oncology programs, in collaboration with Intrexon Corporation (NYSE:XON) 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. The Company is advancing programs in multiple stages of development together with Intrexon Corporation's
RheoSwitch Therapeutic System® technology, a switch to turn on and off, and precisely modulate, gene expression in order to improve
therapeutic index. The Company's pipeline includes a number of cell-based therapeutics in both clinical and preclinical testing
which are focused on hematologic and solid tumor malignancies.
Forward-Looking Safe-Harbor Statement:
This press release contains certain forward-looking information about ZIOPHARM Oncology, Inc. that is intended
to be covered by the safe harbor for "forward-looking statements" provided by the Private Securities Litigation Reform Act of 1995,
as amended. Forward-looking statements are statements that are not historical facts, and in some cases can be identified by terms
such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited
to, statements regarding the Company's plans and expectations regarding its securities offerings, fundraising activities and
financial strategy, the progress, timing and results of preclinical and clinical trials involving the Company's drug candidates,
and the progress of the Company's research and development programs. All of such statements are subject to certain risks and
uncertainties, many of which are difficult to predict and generally beyond the control of the Company, that could cause actual
results to differ materially from those expressed in, or implied by, the forward-looking statements. These risks and uncertainties
include, but are not limited to: our ability to finance our operations and business initiatives and obtain funding for such
activities, whether chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-hIL-12, TCR and NK cell-based therapies, or any of
our other therapeutic candidates will advance further in the pre-clinical or clinical trials process and whether and when, if at
all, they will receive final approval from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies and for
which indications; whether chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-hIL-12, TCR and NK cell-based therapies, and
our other therapeutic products will be successfully marketed if approved; the strength and enforceability of our intellectual
property rights; competition from other pharmaceutical and biotechnology companies; and the other risk factors contained in our
periodic and interim SEC reports filed from time to time with the Securities and Exchange Commission, including but not limited to,
our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, and our Quarterly Report for the quarter ended March
31, 2016. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date
hereof, and we do not undertake any obligation to revise and disseminate forward-looking statements to reflect events or
circumstances after the date hereof, or to reflect the occurrence of or non-occurrence of any events.
Trademarks
RheoSwitch Therapeutic System® (RTS®) technology is a registered trademark of
Intrexon Corporation.
Contact: Lori Ann Occhiogrosso ZIOPHARM Oncology, Inc. 617-259-1987 locchiogrosso@ziopharm.com David Pitts Argot Partners 212-600-1902 david@argotpartners.com
