– Clinical data show continued survival benefit,
tumor response, and multi-year persistence of Sleeping
Beauty-modified CD19-specific CAR+ T cells –– Point-of-care
CD19-specific CAR+ T cells co-expressing mbIL15 with control switch
show sustained persistence, anti-tumor effect in preclinical models
without the need for culturing –– Point-of-care clinical trial
planned for 2018 –
ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company
developing new gene and cell-based immunotherapies for cancer,
today announced data supporting its non-viral approach to rapid
manufacture of chimeric antigen receptor (CAR)-modified T cells to
treat patients with cancers were presented at the 59th American
Society of Hematology (ASH) Annual Meeting and Exposition in
Atlanta.
ZIOPHARM is advancing its non-viral Sleeping
Beauty (SB) platform towards point-of-care (P-O-C) for very rapid
manufacturing of genetically modified CAR+ T cells. Data presented
from first- and second-generation SB clinical trials demonstrate
safety, tolerability, disease response, long-term survival, and
persistence of infused CD19-specific CAR+ T cells. Preclinical
studies showed that P-O-C CAR+ T cells co-expressing membrane-bound
interleukin-15 (mbIL15) and a control switch manufactured within
two days do not require activation or propagation in tissue culture
to achieve anti-tumor effects and prolonged T-cell survival.
Building on these data, the Company plans to initiate its first
P-O-C clinical trial in 2018.
“Together, these results underpin the
paradigm-shifting potential of our P-O-C platform by demonstrating
the persistence of our Sleeping Beauty-modified T cells,
optimization of the CAR, and pro-survival effect resulting from
mbIL15 expression. This reinforces our plans to deliver genetically
modified products in less than two days,” said Laurence Cooper,
M.D., Ph.D., Chief Executive Officer of ZIOPHARM Oncology. “The
need for a non-viral approach for commercialization of cell therapy
is becoming increasingly evident as the challenges of lengthier,
more complex, and more expensive viral-based approaches are scaled
up. We look forward to advancing Sleeping Beauty and our P-O-C
approach with the goal of producing genetically modified T cells to
fight cancers at a fraction of current costs and manufacturing
time.”
These ASH presentations are based on clinical
trials and research being conducted in collaboration with The
University of Texas MD Anderson Cancer Center and Intrexon
Corporation (NYSE:XON). The three posters and slides for one oral
presentation are available in the Presentations and Publications
section of the Company's website, www.ziopharm.com.
Poster Presentation: “Long Term Follow
up after Adoptive Transfer of CD19-Specific CAR+ T Cells
Genetically Modified Via Non-Viral Sleeping Beauty System Following
Hematopoietic Stem-Cell Transplantation (HSCT)”
Partow Kebriaei, M.D., Professor, Department of
Stem Cell Transplantation & Cellular Therapy, The University of
Texas MD Anderson Cancer Center, presented updated results,
building upon findings previously published in the Journal of
Clinical Investigation. Two trials demonstrated that
first-generation SB-modified CD19-specific CAR+ T cells appear to
provide long-term cancer control when infused after hematopoietic
stem-cell transplantation (HSCT) for patients with advanced CD19+
malignancies and could be detected years after administration in
some recipients. All seven patients with advanced CD19+
non-Hodgkin’s lymphoma (NHL) that received autologous T cells were
alive at a median survival of 40 months since infusion, with
progression-free survival (PFS) reported at 86% and overall
survival (OS) at 100%. For 19 patients with advanced CD19+ acute
lymphoblastic leukemia (ALL) and NHL infused with allogeneic T
cells following HSCT, nine patients were alive with a median
survival of 31 months. The PFS rate and OS rates are 32% and 49%,
respectively. Of the subset of eight patients who received
donor-derived T cells after haploidentical HSCT, PFS and OS rates
are 50% and 63%, respectively. Persistence of circulating
SB-modified CAR+ T cells was demonstrated at two years in an
autologous and allogeneic patient and for four years in two
autologous patients.
Oral Presentation: “Shortening the Time
to Manufacture CAR+ T Cells with Sleeping Beauty System Supports
T-Cell Engraftment and Anti-Tumor Effects in Patients with
Refractory CD19+ Tumors”
Dr. Kebriaei presented interim data from an
ongoing second-generation trial demonstrating that the manufacture
of SB-modified T cells could be shortened from four weeks to two
weeks and that autologous T cells infused after lymphodepleting
chemotherapy could be detected, and exhibited anti-tumor effects
and an encouraging safety profile in patients with
relapsed/refractory CD19+ malignancies. Complete responses at one
month were reported in four of eight patients with either ALL
(n=5), chronic lymphocytic leukemia (n=1), or diffuse large B-cell
lymphoma (n=2), with two morphologic complete responses at three
months. Follow up blood tests demonstrated sustained persistence of
infused T cells and targeting of malignant and normal B cells.
There were no dose limiting toxicities with only grade 1 or 2
adverse events being reported. T-cell dose escalation
continues.
Poster Presentation, “CD19-Specific
Chimeric Antigen Receptor-Modified T Cells with Safety Switch
Produced Under ‘Point-Of-Care’ Using the Sleeping Beauty System for
the Very Rapid Manufacture and Treatment of B-Cell
Malignancies”
Rutul Shah, interim Head of Operations, Intrexon
Human Therapeutics, presented preclinical findings showing T cells
expressing CD19-specific CAR, mbIL15, and control (safety) switch
were generated under P-O-C using the SB system. These T cells were
manufactured in less than two days and did not require ex vivo
activation or propagation and demonstrated potent anti-tumor effect
and sustained CAR+ T-cell persistence in mice. These data support
clinical evaluation of genetically modified T cells very rapidly
manufactured using the SB system.
Poster Presentation, “Autologous T Cells
Modified to Co-express CD33-Specific Chimeric Antigen Receptor and
a Kill Switch for Treatment of CD33+ Acute Myeloid
Leukemia”
Tim Chan, PhD, Senior Director, Intrexon Human
Therapeutics, presented preclinical data supporting an ongoing
Phase 1 study of CD33-specific CAR+ T-cell therapy for the
treatment of relapsed or refractory acute myeloid leukemia. In
vitro analyses demonstrated that CAR+ T cells exhibited redirected
specificity for CD33. Co-expression of a kill switch was shown to
eliminate CAR+ T cells by cetuximab-mediated antibody-dependent
cellular cytotoxicity both in vitro and in vivo.
About ZIOPHARM Oncology,
Inc.
ZIOPHARM Oncology is a Boston,
Massachusetts-based biotechnology company employing innovative gene
expression, control and cell technologies to deliver safe,
effective and scalable cell- and viral-based therapies for the
treatment of cancer and graft-versus-host-disease. 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® (RTS®) 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 progress and timing of the
development 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: the Company's ability to finance its
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 other product candidates will advance further in the preclinical
research or clinical trial 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 the
Company's other therapeutic products it develops will be
successfully marketed if approved; the strength and enforceability
of the Company's intellectual property rights; competition from
other pharmaceutical and biotechnology companies; as well as other
risk factors contained in the Company's periodic and interim
reports filed from time to time with the Securities and Exchange
Commission, including but not limited to, the risks and
uncertainties set forth in the "Risk Factors" section of the
Company's Quarterly Report on Form 10-Q for the quarter ended
September 30, 2017 and subsequent reports that the Company may file
with the Securities and Exchange Commission. Readers are cautioned
not to place undue reliance on these forward-looking statements
that speak only as of the date hereof, and the Company does 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® and RTS® are
registered trademarks of Intrexon Corporation.
Contact:David ConnollyZIOPHARM
Oncology617-502-1881dconnolly@ziopharm.com
David PittsArgot
Partners212-600-1902david@argotpartners.com
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