ZIOPHARM Reports First-Quarter 2016 Financial Results and Provides Update on Recent Activities BOSTON, MA

ZIOPHARM Reports First-Quarter 2016 Financial Results and

Provides Update on Recent Activities

BOSTON, MA May 10, 2016 ZIOPHARM Oncology, Inc. (Nasdaq: ZIOP) today announced financial results for the first quarter ended

March 31, 2016, and provided an update on the Company s recent activities.

We have solid momentum in each of our cell and gene therapy

programs, with the potential to move our lead gene therapy, Ad-RTS-IL-12 + veledimex, into a pivotal study next year, said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM. Ad-RTS-IL-12 + veledimex continues to yield

encouraging results as we recruit additional patients into an ongoing dose-escalation study in recurrent glioblastoma, and we look forward to presenting this data to the American Society of Clinical Oncology (ASCO) at its annual meeting in June of

this year. Given the dire outcomes in this patient population, a potential therapeutic benefit may be quickly assessed and, if these results remain durable, our goal would be to move into a registration study, following discussions with

Dr. Cooper added: As this promising program moves forward, we continue to test the potential of our cell therapy platform

and technologies in collaboration with leading partners in industry and academia. This includes clinical-stage platforms unique to ZIOPHARM, such as the non-viral Sleeping Beauty (SB) system, that are fundamental to making immune cell therapy

a cost-effective, widely-available treatment modality. These technologies are particularly important in leveraging T-cell receptors (TCRs) to target neoantigens in solid tumors which requires individualizing this immunotherapy, an approach that is

possible with our customizable, easy-to-manufacture non-viral gene transfer system. We expect to initiate or continue prosecuting up to six clinical trials across multiple platforms in 2016 and look forward to sharing data and outcomes from these

trials throughout the year.

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

lymphocytes and is exclusively licensed by Intrexon Corporation (NYSE: XON) through MD Anderson and accessed as part of ZIOPHARM s collaboration with Intrexon. This non-viral approach has several potential advantages over viral-based 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.

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 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 multi-center Phase 1 study in patients with recurrent or progressive glioblastoma multiforme (GBM), an aggressive form of brain cancer, and

a Phase 1b/2 study for the treatment of patients with locally advanced or metastatic breast cancer following standard chemotherapy.

Adoptive Cell Therapies

ZIOPHARM is developing

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

biopharmaceutical business of Merck KGaA, Darmstadt, Germany (CAR-T only).

ZIOPHARM expects the following

milestones to occur in 2016:

The Company is also evaluating additional potential preclinical candidates and

continuing discovery efforts aimed at identifying other potential product candidates under its Exclusive Channel Agreement with Intrexon. In addition, the Company may seek to enhance its pipeline in immuno-oncology through focused strategic

transactions, which may include acquisitions, partnerships and in-licensing activities.

First-Quarter 2016 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- 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.

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-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 chimeric antigen receptor T cell (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, 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.

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.