ZIOPHARM Oncology Reports First Quarter 2017 Financial Results and Provides Update on Recent Activities Advancing Plans to Initiate Pivotal Study for Ad-RTS-hIL-12 + Veledimex for Treatment of Recurrent Brain Cancer - Co

ZIOPHARM Oncology Reports First Quarter 2017 Financial Results and Provides Update on Recent Activities

Advancing Plans to Initiate Pivotal Study for Ad-RTS-hIL-12 + Veledimex for Treatment of Recurrent Brain Cancer

Company to Host Conference Call Today at 4:30 p.m. ET -

BOSTON, May 1, 2017 ZIOPHARM Oncology,

Inc. (Nasdaq: ZIOP), a biopharmaceutical company focused on new immunotherapies, today announced its financial results for the first quarter ended March 31, 2017, and provided an update on the company s recent activities.

ZIOPHARM is making significant advances, including progress towards finalizing a registration path for Ad-RTS-hIL-12 + veledimex for recurrent glioblastoma and furthering development in our

point-of-care approach with T-cell CAR-based therapies, said Laurence Cooper, M.D.,

Ph.D., Chief Executive Officer of ZIOPHARM Oncology. ZIOPHARM is assessing several paths for the pivotal trial, including a single-arm study of Ad-RTS-hIL-12 + veledimex compared to historical controls. With a commercialization path in view, we are evaluating partnership opportunities for Ad-RTS-hIL-12 + veledimex to understand the breadth of options available to ZIOPHARM for bringing this important therapeutic candidate

The IL-12 data from the brain cancer trial firmly establishes that the RheoSwitch

Therapeutic System works as a switch in humans, added Dr. Cooper. By combining the most clinically advanced non-viral gene integration

platform, Sleeping Beauty, and transcriptional switch system, RheoSwitch, we will use our point-of-care approach to significantly shorten the time to manufacture

T cells and to tailor the expression of introduced genes after infusion using veledimex. This will address two major issues with CAR-based therapies, namely the cost of therapy and control of T cells to reduce

Ad-RTS-hIL-12 + veledimex

Ad-RTS-hIL-12 + veledimex is ZIOPHARM s gene therapy candidate for the controlled expression of

interleukin-12 (IL-12), a critical protein for stimulating an anti-cancer immune response, using a RheoSwitch Therapeutic System (RTS ) inducible gene-delivery system, or switch, that enables controlled in vivo expression of therapeutic proteins. ZIOPHARM is

currently conducting a multi-center Phase 1 study of Ad-RTS-hIL-12 + orally administered veledimex in patients with recurrent or progressive glioblastoma multiforme

(GBM), an aggressive form of brain cancer.

ZIOPHARM will be presenting updated results from its Phase 1, multicenter, dose-escalation study of Ad-RTS-hIL-12 + veledimex in patients with recurrent or progressive glioblastoma at the 2017 American Society of Clinical Oncology

(ASCO) Annual Meeting on June 5, 2017.

Our initial discussions with regulators have been encouraging, and we look forward to moving Ad-RTS-hIL-12 + veledimex into a pivotal study as quickly as possible this year. Details of the pivotal Phase 3 trial will be made

available following completion of discussions with regulators and clinical advisors, said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. We continue to see encouraging

outcomes in our Phase 1, multi-center study of Ad-RTS-hIL-12 + veledimex in patients with recurrent high-grade gliomas and plan

to share updated results from this study at ASCO.

The Company also expects to initiate Phase 1 studies of Ad-RTS-hIL-12 + veledimex in pediatric brain cancer, as well as in combination with an

anti-PD-1 checkpoint inhibitor in adult glioblastoma, as planned, in the first half of 2017.

Adoptive Cell Therapies

ZIOPHARM is developing

chimeric antigen receptor (CAR) T cell (CAR+ T), T-cell receptor (TCR) T cell (TCR+ T), and natural killer (NK) adoptive cell-based therapies. These

programs are being advanced in collaboration with Intrexon Corporation, MD Anderson Cancer Center, the National Cancer Institute and Merck Serono, the biopharmaceutical business of Merck KGaA (CAR+

Announced Advancement of Next-Generation Non-Viral CAR+ T Platform Empowered by Membrane-Bound IL-15 Under RTS Gene Switch Control. In April 2017,

ZIOPHARM and its partners, Intrexon and Merck KGaA, Darmstadt, Germany, announced the advancement of a unique approach to develop therapeutic candidates for two CAR+ T targets expressed on a wide range of tumor types, including hematologic

malignancies and solid tumors. The distinctive methodology centers on the proprietary RTS platform to regulate production of membrane-bound interleukin-15 (mbIL15) co-expressed with CARs and Sleeping Beauty, a non-viral genetic modification system to genetically modify clinical-grade T cells. The companies expect to advance this

innovative approach towards the clinic in 2018.

The IL-15 cytokine is increasingly recognized as a

key driver of therapeutic effect in CAR+ T therapy, including in a recent Journal of

Clinical Oncology publication which correlated lymphoma remissions in patients whose IL-15 levels were elevated after lymphodepleting chemotherapy. Through the

RTS gene switch, the expression of mbIL15 can be regulated to help CARs target cancers in a controlled manner, thus providing a new paradigm in T-cell

Announced Advances in Point-of-Care Approach

for Rapidly Producing CAR-Expressing T Cells Utilizing the Sleeping Beauty System. In January 2017, ZIOPHARM announced improved production times utilizing its non-viral

platform to engineer T cells in an ongoing Phase 1 study of second-generation Sleeping Beauty-modified CD19-specific CAR+ T cells. ZIOPHARM continues to refine its Sleeping Beauty

system to further reduce time to manufacture genetically modified T cells. Preclinical studies of third-generation Sleeping Beauty-modified CAR+ T cells co-expressing mbIL15 demonstrated

reduced time to administration (less than two days) through elimination of the need for in vitro T-cell activation and propagation. Plans to

progress this point-of-care approach with infusion of CAR+ T

cells in less than two days are underway. The combination of Sleeping Beauty and RTS-mbIL15, has the potential to solve the dual problems of cost and toxicities as genetically modified T cells can be rapidly produced for preclinical testing,

and the RTS is a clinically validated switch, which may be used with veledimex to control T-cell persistence via conditional expression of mbIL15. The Company expects to advance towards a Phase 1 study

evaluating the point-of-care in 2017.

Cooperative Research and Development Agreement (CRADA) With the National Cancer Institute Utilizing Sleeping Beauty System to Generate T Cells Targeting Neoantigens. In January 2017, ZIOPHARM and its partner, Intrexon,

announced the signing of a CRADA with the National Cancer Institute (NCI) for the development of adoptive cell transfer-based immunotherapies genetically modified using the Sleeping Beauty system to express TCRs targeting neoantigens for the

treatment of solid tumors. Research conducted under the CRADA will be at the direction of Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI s Center for Cancer Research. The Company anticipates that this program will

advance to Phase 1 during the second half of 2017.

Anticipated and Achieved 2017 Milestones

First-Quarter 2017 Financial Results

Conference Call and Slide Webcast

ZIOPHARM will host a conference call and webcast slide presentation today, Monday, May 1, 2017, at 4:30 p.m. ET. The call can be accessed by dialing (844)

309-0618 (U.S. and Canada) or (661) 378-9465 (international). The passcode for the conference call is 8375689. To access the slides and live audio 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 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 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 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 Company s plans and

expectations regarding its securities offerings, fundraising activities and financial strategy, 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: our ability to finance our 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 our other therapeutic candidates will advance further in the preclinical 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, 2016 and our Quarterly Report on Form

10-Q for the quarter ended March 31, 2017. 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 and RTS are registered trademarks of Intrexon Corporation.

Vice President, Corporate Communications

and Investor Relations

ZIOPHARM Oncology, Inc.

Statements of Operations

(in thousands except share and per share data)

ZIOPHARM Oncology, Inc.