ZIOPHARM Reports Fourth-Quarter 2015 Financial Results and Provides Update on Recent Activities BOSTON, MA

ZIOPHARM Reports Fourth-Quarter 2015 Financial Results and

Provides Update on Recent Activities

BOSTON, MA February 24, 2016 ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) today announced financial results for the fourth quarter ended

December 31, 2015, and provided an update on the company s recent activities.

We look forward to a number of important milestones

throughout 2016 across our gene and cell therapy platforms, said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. For our lead gene therapy, Ad-RTS-IL-12 + veledimex, this includes data presentations in the first half

of the year from our Phase 1 brain cancer trial, our Phase 1/2 breast cancer trial and from a translational, preclinical study demonstrating powerful antitumor effects when combining with checkpoint inhibitors. Through the balance of 2016, we expect

to initiate or continue prosecuting up to six proof-of-concept generating studies across multiple platforms, including viral and non-viral delivery of DNA, CAR-T and NK-cell therapies based upon autologous and allogeneic, or off-the-shelf,

strategies. These studies will help inform potential registration pathways and validate technologies that will enable us to achieve our game-changing goals, including delivering therapies for urgent unmet needs, such as progressive brain cancer, and

developing personalized TCR-based cell therapies for solid tumors.

To accelerate the success of our exciting clinical program, we are

building out our clinical and regulatory infrastructure by hiring additional personnel in these important areas of our company, said Caesar J. Belbel, Executive Vice President, Chief Operating Officer and Chief Legal Officer of ZIOPHARM.

Through the highly efficient management of our cash, the addition of these resources in support of our aggressive clinical strategy has had a minimal impact on the projection of our financial resources, which we anticipate will be sufficient

to fund our currently planned operations into the fourth quarter of 2017.

Ad-RTS-IL-12 + veledimex

Ad-RTS-hIL-12 + veledimex

is a gene therapy candidate for the controlled expression of interleukin 12 (IL-12), a critical protein for stimulating an anti-cancer T-cell immune response, using the RheoSwitch Therapeutic

System (RTS ) gene switch. ZIOPHARM is currently enrolling patients in two studies of Ad-RTS-hIL-12 + veledimex: a Phase 1b/2 study

for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy and a multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain

Adoptive Cell Therapies

ZIOPHARM is developing

various immuno-oncology programs, including chimeric antigen receptor T-cell (CAR-T), T-cell receptor (TCR) and natural killer (NK) adoptive cell-based therapies. These programs are being advanced in collaboration with Intrexon and the MD Anderson

Cancer Center and the biopharmaceutical business of Merck KGaA, Darmstadt, Germany (CAR-T only).

The Sleeping Beauty transposon-transposase is a unique non-viral system for introducing genes encoding CARs and TCRs into lymphocytes

and is exclusively licensed by Intrexon through MD Anderson and accessed as part of ZIOPHARM s collaboration with Intrexon. This non-viral approach has several potential advantages over viral delivery systems, including a lower cost of

generating genetically modified T cells as well as the ability to generate T cells with minimal ex vivo processing and can serve as a conduit to targeting solid tumor neoantigens using TCRs.

As previously announced,

ZIOPHARM anticipates launching clinical studies in three new programs in 2016:

Fourth-Quarter 2015 Financial Results

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-based therapies for the treatment of cancer. The Company s synthetic 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 kill

switch and 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:

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-IL-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 CAR-T approaches, Ad-RTS-IL-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. 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.

RheoSwitch Therapeutic System (RTS )

technology is a registered trademark of Intrexon Corporation.

ZIOPHARM Oncology, Inc.

Condensed Statements of Operations

(in thousands except share and per share data)

ZIOPHARM Oncology, Inc.

Lori Ann Occhiogrosso

ZIOPHARM Oncology, Inc.