– Data to be Presented at the 2016 ASCO Annual Meeting –
– Company to Discuss Results with Regulators after Additional Follow Up –
BOSTON, May 18, 2016 (GLOBE NEWSWIRE) -- ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP) today announced that interim
results from the Company’s ongoing Phase 1, multi-center dose-escalation study of the gene therapy candidate Ad-RTS-hIL-12 +
orally-administered veledimex in patients with recurrent or progressive glioblastoma will be presented at the American Society of
Clinical Oncology (ASCO) Annual Meeting held June 3-7, 2016, at McCormick Place in Chicago, Illinois. Ad-RTS-hIL-12 + veledimex is
a novel viral gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a pro-inflammatory cytokine critical
for stimulating anti-cancer immune responses.
Glioblastoma is an aggressive primary brain tumor affecting approximately 74,000 people worldwide each
year.i, ii Recurrent glioblastoma is an aggressive cancer with one of the lowest 3-year survival rates,
at 3%, among all cancers.iii For patients who have experienced multiple recurrences the prognosis is particularly
poor, with a median overall survival (OS) of 6-7 months, while OS in patients that have failed temozolomide and bevacizumab, or
equivalent salvage chemotherapy, is approximately 3-5 months.iv, v
The primary objective of the study is to determine the safety and tolerability of a single intratumoral
Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 +
veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response.
Eleven patients with recurrent high-grade gliomas (one with grade III and ten with grade IV) have been treated to date with
Ad-RTS-hIL-12 through direct injection into their brain tumors, including seven patients in the first dose cohort (veledimex dosed
at 20 mg) and four in the ongoing second dose cohort (veledimex dosed at 40 mg). Veledimex was taken orally to activate the
production of IL-12 from the tumor site and stimulate an immune response.
Patients enrolled in this multi-center study have all failed standard therapy, with nine of eleven patients
failing additional salvage treatments, for a mean of 2.7 prior lines of therapy in cohort one and 2.0 prior lines in cohort two. No
enrollment restrictions were placed on tumor size or location within the supratentorial space. Overall median follow-up for
patients enrolled in the trial is 6.2 months with 10 of 11 alive. In the fully-enrolled cohort one, 6 of 7 (86%) patients remain
alive with a median follow up of 6.8 months. Enrollment in cohort two is ongoing. Even at its lowest dose, the presence of IL-12 in
the bloodstream could be detected, demonstrating that veledimex is bioavailable and crosses the blood brain barrier at sufficient
levels to turn on the RheoSwitch (RTS®) and generate IL-12, which could be measured in the blood stream. Furthermore,
for those patients that experienced adverse events associated with the treatment, discontinuing veledimex reversed these adverse
events.
“Early results observed in the limited number of patients who have been treated with Ad-RTS-hIL-12 + veledimex
are very encouraging for a Phase 1 study,” said Ennio Antonio Chiocca, M.D., Ph.D., Harvey W. Cushing Professor of Neurosurgery,
Department of Surgery, Harvard Medical School, Surgical Director, Center for Neuro-oncology, Dana-Farber Cancer Institute,
Chairman, Neurosurgery, Brigham And Women's Hospital and Co-Director, Institute for the Neurosciences, Brigham And Women's
Hospital. “Virus-based gene therapy used to stimulate an immunological response in the brain is at the frontier of innovation in
treatment, with Ad-RTS-hIL-12 offering perhaps the most controllable approach within this field. In this study, we see encouraging
signs of immune activation following the administration of Ad-RTS-hIL-12 + veledimex.”
Overall Ad-RTS-hIL-12 + veledimex was well tolerated. All serious adverse events and Grade 3 related toxicities
were rapidly reversible upon discontinuation of veledimex. The most common related adverse events included headache,
nausea/vomiting, fever, white blood cell/leukocyte count decrease, platelet count decrease and liver function test increase. Four
subjects had related serious adverse events.
“Because the brain is a segregated and fragile environment, the ability to turn an immune response on and off is
critical to balancing efficacy and tolerability,” said Francois Lebel, M.D., Executive Vice President, Research and Development,
Chief Medical Officer at ZIOPHARM. “As we continue to follow patients with extremely guarded prognoses in this multi-center trial,
we hope that these promising early trends in survival are maintained. Our goal, once we reach an optimal dose, will be to promptly
initiate registration trial discussions with regulators."
Dr. Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM, added: "Basing our approach on the
genetic engineering of adenovirus offers a simpler strategy than replicating viral-therapy options, one that can be rapidly
controlled via a drug activating a gene switch, and one that does not rely on intratumoral catheterization. We look forward to
testing Ad-RTS-hIL-12 + veledimex not just on its own, but in combination with other immuno-oncology approaches, including
checkpoint inhibitors and natural killer cells, in clinical trials that we plan to start this year and next. Our data suggest that
patients can take a drug by mouth to activate the immune response in their tumors with exciting results.”
Ad-RTS-hIL-12 + veledimex has been granted Orphan Drug Designation by the U.S. Food and Drug Administration for
the treatment of patients with malignant glioma.
ASCO Presentation Details
Title: Effect of controlled intratumoral viral delivery of Ad-RTS-hIL-12 + oral veledimex in subjects with
recurrent or progressive glioma
Poster Session: Central Nervous System Tumors
Date and Time: Saturday, June 4, 2016 1:00 PM – 4:30 PM CT
Abstract Number: 2052
Poster: #239
Location: Hall A
In addition to the GBM study, a study design for the Company’s Phase 1b/2 clinical trial of Ad-RTS-hIL-12 +
veledimex in locally advanced or metastatic breast cancer will be outlined at the ASCO annual meeting. The study, which is being
conducted at the Memorial Sloan Kettering Cancer Center in New York, is designed to examine the safety, tolerability and efficacy
of Ad-RTS-hIL-12 immunotherapy given following standard of care chemotherapy in up to 40 women with locally advanced or metastatic
breast cancer of all subtypes. The Company expects that outcome data from this study will be presented at a scientific meeting in
the second half of the year.
Title: Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive
locally advanced or metastatic breast cancer
Poster Session: Developmental Therapeutics—Immunotherapy
Date and Time: Sunday, June 5, 2016 8:00 AM – 11:30 AM CT
Abstract Number: TPS3097
Poster: #418a
Location: Hall A
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 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: 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.
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i. Mrugala MM. Advances and challenges in the treatment of glioblastoma: a clinician's perspective. Discov Med.
2013;15:221-230.
http://www.discoverymedicine.com/Maciej-M-Mrugala/2013/04/25/advances-and-challenges-in-the-treatment-of-glioblastoma-a-clinicians-perspective/.
Accessed March 24, 2015.
ii. McCubrey JA, LaHair MM, Franklin RA. OSU–0312 in the treatment of glioblastoma. Mol Pharmacol.
2006;70:437-439.
iii. International Agency for Research on Cancer. World Cancer Report. 2003. http://www.iarc.fr/en/publications/pdfs-online/wcr/2003/WorldCancerReport.pdf.
iv. Omuro, A. Glioblastoma and Other Malignant Gliomas. A Clinical Review JAMA. 2013 Nov
6;310(17):1842-50.
v. Iwamoto et al. Patterns or relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 2009;
73(15):1200-1206
Contact: Lori Ann Occhiogrosso ZIOPHARM Oncology, Inc. 617-259-1987 locchiogrosso@ziopharm.com David Pitts Argot Partners 212-600-1902 david@argotpartners.com
