– Controlled IL-12 gene therapy turns cold tumors
hot –– MRI indicates decreasing size of brain tumor lesions in
several patients –– Median overall survival for patients with
recurrent glioblastoma (rGBM) maintained at 12.5 months in 20mg
cohort with longer follow-up –– Company conference call today at
10:15AM ET with Drs. Chiocca, Goldman –
ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company
developing new gene and cell-based immunotherapies for cancer,
today announced positive data updates supporting survival benefit
and the underlying immune system mechanism for Ad-RTS-hIL-12 plus
veledimex, the Company’s controlled human interleukin-12 (hIL-12)
gene therapy candidate for brain cancer, at the 22nd Annual Meeting
and Education Day of the Society for Neuro-Oncology (SNO). This
gene therapy has demonstrated a targeted, anti-tumor immune
response for the treatment of recurrent glioblastoma (rGBM).
New data presented shows median overall survival
(mOS) of 12.5 months has been sustained for patients treated with
Ad-RTS-hIL-12 plus 20mg of veledimex (n=15) at a longer mean
follow-up time of 11.1 months as of October 18, 2017. This mOS of
12.5 months continues to compare favorably to the 5 to 8 months
survival established in historical controls for patients with rGBM.
Furthermore, the four patients with rGBM who received low-dose
steroids maintained 100 percent survival at a mean follow-up time
of 11.1 months. An anti-tumor effect was also evident with
centralized review of magnetic resonance imaging (MRI) showing
decreasing size of brain tumor lesions in several patients.
Additionally, data linking the intra-tumor
production of hIL-12 to patients’ overall survival was presented by
Francois Lebel, M.D., Chief Medical Officer of ZIOPHARM during an
oral poster session, “A Phase 1 Study of Ad-RTS-hIL-12 plus
Veledimex in Adult Recurrent Glioblastoma.” Highlights of this
presentation include:
- Immunohistochemistry analyses from three of three patient
biopsies after completion of veledimex demonstrated that IL-12
activates and sustains an immune response within rGBM;
- All three biopsies of rGBM lesions demonstrated evidence of an
anti-tumor response with extensive infiltration of CD8+ T cells
within the rGBM;
- Biopsies all showed sustained (greater than 4 months)
production of interferon-gamma, a cytokine crucial to arming an
immune response in the tumor microenvironment;
- Ratio of circulating killer CD8+ T cells to suppressor FOXP3+ T
cells correlates with survival;
- Interferon-gamma was undetectable in the blood at the time of
biopsies providing further evidence of an on-target response;
- Expression levels of both PD-1 and PD-L1 were upregulated in
all the biopsies, which suggests added potential efficacy for
combining Ad-RTS-hIL-12 plus veledimex with an immune checkpoint
inhibitor;
- Ad-RTS-hIL-12 plus veledimex continues to be safe and well
tolerated, as adverse events (AE) were predictable and reversible,
neurologic AEs were relatively mild and transient, and there were
no drug-related deaths.
“These new mechanistic data, especially taken
together with the promising extension of patients’ median overall
survival, provide additional validation that controlling IL-12 can
engage the body’s own immune system safely to generate a T-cell
response against rGBM. We are excited to see increasing evidence of
a targeted, local immune response making brain tumors hot and
illustrating how this immunotherapy contributes to patients’
survival,” said Dr. Antonio Chiocca, M.D., Ph.D., lead author of
this presentation and the 2017 President of the Society for
Neuro-Oncology, Professor of Neurosurgery at Harvard Medical
School, Surgical Director of the Center for Neuro-oncology at
Dana-Farber Cancer Institute, and Chairman of Neurosurgery and
Co-Director of the Institute for the Neurosciences at Brigham and
Women's Hospital.
Additional SNO presentations
included:
- “A Phase 1 Study of Ad-RTS-hIL-12 plus Veledimex in Pediatric
Brain Tumors,” was presented in a poster by Stewart Goldman, M.D.,
Division Head Hematology-Oncology, Neuro-Oncology & Stem Cell
Transplantation at Ann & Robert H. Lurie Children's Hospital in
Chicago. The Company previously announced that the first patient
was dosed in this open-label study designed to assess the safety
and tolerability of a single intratumoral injection of
Ad-RTS-hIL-12 plus veledimex in children.
- “Controlled Expression of IL-12 Improves Survival in Glioma by
Activating the Immune Response in Mice and Humans,” was presented
during an oral session by John A. Barrett, Ph.D., Vice President of
R&D/Translational Medicine at ZIOPHARM.
- Dr. Barrett delivered a second oral presentation, “Controlled
Expression of IL-12 Improves Survival in Glioma by Activating the
Immune Response in Mice and Humans.”
A copy of all four SNO presentations is
available in the Presentations and Publications section of the
Company's website, www.ziopharm.com.
“The established safety profile and tolerability
of intra-tumor administration of Ad-RTS-hIL-12 plus oral veledimex,
the durability of the overall survival results, and now the
powerful evidence of sustained immune activation all support our
goal of delivering a new treatment option to patients with
recurrent glioblastoma,” said Dr. Lebel. “We continue to work with
regulators and thought leaders to initiate a pivotal study of
Ad-RTS-hIL-12 plus veledimex in this setting before year end. In
addition, the immunohistochemistry analyses revealing extensive and
persistent immune cell infiltration within brain tumors and
upregulation of immune checkpoint biomarkers support our initiation
of a study of Ad-RTS-hIL-12 plus veledimex combined with an
anti-PD-1 drug this year.”
Conference Call and Webcast
In connection with this announcement, ZIOPHARM
will host a conference call and webcast slide presentation
featuring Drs. Chiocca and Goldman today, Nov. 20, at 10:15 a.m.
ET. The call can be accessed by dialing 1-844-309-0618 (U.S. and
Canada) or 1-661-378-9465 (international). The conference ID number
is 8089664. To access the accompanying slides and live webcast, or
the subsequent archived recording, visit the "Investors &
Media" section of the ZIOPHARM website at www.ziopharm.com. The
webcast will be recorded and available for replay on the Company's
website for two weeks.
About Ad-RTS-hIL-12 plus Veledimex:
ZIOPHARM is advancing Ad-RTS-hIL-12 plus
veledimex as a gene therapy for glioblastoma. Ad-RTS-hIL-12 is an
adenoviral vector administered via a single injection into the
tumor and engineered to express hIL-12, a powerful cytokine that
has demonstrated the potential to stimulate a targeted, anti-tumor
immune response. The expression of hIL-12 is controlled and
modulated with the RheoSwitch Therapeutic System® (RTS®) by the
small molecule veledimex, an activator ligand which has been shown
to cross the blood-brain barrier. The Company completed enrollment
in a multi-center, Phase 1 dose escalation trial designed to
evaluate Ad-RTS-hIL-12 in patients with recurrent or progressive
Grade III or IV glioma. The trial evaluated three veledimex dosing
cohorts (20mg, n = 15; 30mg, n = 4; and 40mg, n = 6). Patients
undergoing resection were injected intratumorally with Ad 2 x 1011
viral particles and received daily oral activator veledimex for 15
doses. The majority of patients in the 20mg cohort had 2 or more
recurrences prior to entry in the study, indicating very advanced
disease. ZIOPHARM anticipates initiation of a pivotal registration
trial for Ad-RTS-hIL-12 plus veledimex for the treatment of rGBM by
the end of 2017. The Company has also initiated a Phase 1 study to
evaluate the stereotactic administration of Ad-RTS-hIL-12 plus
veledimex in adult patients with rGBM, as well as a trial to
evaluate the gene therapy as a treatment for pediatric brain
tumors. In addition, ZIOPHARM plans to initiate enrollment of adult
patients with rGBM who will receive a single dose of Ad-RTS-hIL-12
plus veledimex in combination with a checkpoint inhibitor targeting
programmed cell death protein 1 (PD-1) by the end of 2017.
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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