SEC Filing | Alaunos

ZIOPHARM Oncology, Inc.

/s/ Kevin G. Lafond

Date: June 9, 2016

Name: Kevin G. Lafond

Title: Vice President Finance, Chief Accounting Officer

and Treasurer

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8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(d) OF THE

SECURITIES EXCHANGE ACT OF 1934

Date of report (Date of earliest event reported): June 9, 2016

ZIOPHARM Oncology, Inc.

(Exact Name of Registrant as Specified in Charter)

Delaware

001-33038

84-1475642

(State or Other Jurisdiction

of Incorporation)

(Commission

File Number)

(IRS Employer

Identification No.)

One First Avenue, Parris Building 34, Navy Yard Plaza

Boston, Massachusetts

02129

(Address of Principal Executive Offices)

(Zip Code)

(617) 259-1970

(Registrant’s Telephone Number, including Area Code)

Not applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

¨	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425).

¨	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12).

¨	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)).

¨	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)).

Item 7.01 Regulation FD Disclosure

On June 9, 2016, ZIOPHARM Oncology, Inc., or the Company, will present the attached presentation at the Jefferies 2016 Healthcare Conference in New York, New York.

A copy of the above referenced presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K. This information, including the information contained in the presentation furnished as Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not incorporated by reference into any of the Company’s filings, whether made before or after the date hereof, regardless of any general incorporation language in any such filing.

Item 9.01 Financial Statements and Exhibits

(d)

Exhibits


Exhibit No.		Description

99.1		Presentation of the Company dated June 9, 2016

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

INDEX OF EXHIBITS


Exhibit No.		Description

99.1		Presentation of the Company dated June 9, 2016

EX-99.1

ZIOPHARM Oncology Jefferies 2016 Healthcare Conference June 2016 Exhibit 99.1

This presentation 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 on Form 10-Q 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. Forward-looking statements 2

Laurence Cooper, MD, PhD Named CEO in May 2015 Developed Sleeping Beauty technology in-licensed by ZIOP/XON in Jan 2015 Previously, Professor of Pediatric Oncology at MD Anderson Cancer Center (MDACC) where he led the bone marrow transplant program and developed significant expertise in immunotherapy Well capitalized with cash and equivalents of $124.8M at Q1 16, providing resources to fund operations into Q4 2017 Partnerships to implement multiple immunotherapies

Technologies CARs, TCRs, Cytokines, RTS, non-viral gene transfer, T cells, NK cells Combinations Cytokine & CAR, Cytokine & Checkpoint Inhibitor Implementing manufacturing processes for both autologous and allogeneic settings Targeting hematologic malignancies and solid tumors Continued optimization of manufacturing process to improve performance Leveraging manufacturing through the MDACC and CMOs Shorten manufacturing time to produce T or NK cells NK cells Patient-derived (autologous) Match one donor with multiple recipients. Generate large numbers of T or NK cells with retained capacity to proliferate. NK cells Off-the-shelf (allogeneic) Molecular Therapy (2016); doi:10.1038/mt.2016.106 Bio-engineering and bio-processing to execute tumor cells Molecular Therapy (2016); doi:10.1038/mt.2016.106.

Ad-RTS-IL-12 NK Cells Primary NK cells Combination with Ad-RTS-IL-12 Genetically-engineered TCR Sleeping Beauty TCR Sleeping Beauty TCR and cytokine Other Regulatory T Cells Modified Bacteria (microbiome) GBM Breast Cancer Pediatric GBM + Checkpoint Leukemia/Lymphoma Undisclosed Undisclosed Undisclosed Undisclosed AML Brain Cancer TBD TBD TBD GvHD GvHD CAR CD19 1st Generation CD19 2nd Generation CD19 3rd Generation with cytokine Myeloid malignancies target Merck Target 1 Merck Target 2 Off-the-shelf myeloid malignancies target Target 2016 Target 2017 Addressing unmet medical needs: pipeline Phase 2 Preclinical Phase 1

Controlled intra-tumor delivery of IL-12 Ad-RTS-IL-12 + veledimex IL-12 Pro-inflammatory cytokine can reverse immune escape mechanisms and improve the function of tumor-fighting T cells Ad-RTS-IL-12 + veledimex (V, oral ligand) explores local treatment strategy under the control of the RheoSwitch Therapeutic System® (RTS®) gene switch to modulate the IL-12 therapeutic window Expression of functional IL-12 in human subjects by direct intratumoral injection of Ad-RTS-hIL-12 + veledimex generates downstream IFN-γ and elevation of IL-10 and IP-10 We have previously demonstrated that intratumoral administration of Ad-RTS-IL-12 results in targeted tumor cytotoxicity and the induction of systemic T cell memory As of May 31st, we have safely treated 60 patients Ad injected intratumorally Oral ligand activates gene switch Localized production of IL-12 T-cell activation to tumor-associated antigens Influx of CD8+ T cells and reduction in CD4+ Tregs

A study of Ad-RTS-hIL-12 with veledimex in subjects with glioblastoma or malignant glioma GBM affects approximately 74,000 people worldwide each year Recurrent GBM has one of the lowest 3-year survival rates: 3%, among all cancers. For multiple recurrence, median overall survival (OS) is of 6 to 7 months OS in patients that have failed temozolomide and bevacizumab, or equivalent salvage chemotherapy, is approximately 3-5 months Clinicaltrials.gov: NCT02026271.

RTS® switch responds to the dose of veledimex in patients with recurrent GBM

Early data suggests benefit with a favorable trend in overall survival Too early to determine pseudoprogression versus progression All pseudoprogression / progression are assumed to trigger PD for PFS analysis Clinical benefit including long term survival and tumor regression, can occur after initial disease progression or after the appearance of new lesions in iRANO* Median OS has not been reached; median follow-up is 6.2 months with 10 out of 11 alive Data as of May 2016 *Okada, H., M. Weller, et al. (2015). "Immunotherapy response assessment in neuro-oncology: a report of the RANO working group." Lancet 16: 534-542.

Safety summary from GBM study to date (N = 11) Overall Ad-RTS-hIL12 + veledimex was well tolerated Neurotoxicities were manageable and reversible All serious adverse events (SAEs) and Grade 3 related toxicities were found to be rapidly reversible upon discontinuation of veledimex Common related adverse events (most Grade 1 and 2) include headache, fever, nausea / vomiting, WBC /leukocyte count decreased, platelet count decreased, and LFTs increased Four subjects had related SAEs One had a headache, nausea, vomiting, leukopenia, neutropenia, thrombocytopenia One had aseptic meningitis One had mild cytokine release syndrome One had platelet count decreased and ALT increased Enrollment and dose escalation ongoing

A study of Ad-RTS-hIL-12 with veledimex in subjects with breast cancer Phase 1b/2 study to examine the safety, tolerability and preliminary efficacy of one cycle of Ad-RTS-hIL-12 with veledimex following achievement of stable disease (SD) or partial response (PR) on standard first or second-line chemotherapy in breast cancer subjects Patient accrual: 9 subjects have been enrolled (8 HER2neg disease and 1 HER2+ disease) Biomarker analyses underway “On-target toxicities” as expected and promptly reversible upon stopping veledimex Data as of May 2016 Immunotherapy phase of treatment A single cycle of Ad-RTS-hIL-12 + veledimex goal of maintaining or improving pre-study response 1O : Safety and tolerability 2O : ORR, disease control and biomarkers Locally advanced or metastatic breast cancer of all subtypes up to 20% (8 subjects) with HER2+ breast cancer Response (PR or SD) to first- or second-line standard therapy Suspend chemotherapy phase of treatment (HER2 therapy permitted) Clinicaltrials.gov: NCT02423902.

Pediatric program Target refractory brain tumors in children Pre-clinical data at Society for Neuro Oncology Annual Meeting (November 2016) Combination program Combining Ad-RTS-hIL-12 with immune checkpoint inhibitors American Society of Cell and Gene Therapy oral presentation May 2016 Survival of mice treated with adenovirus-delivered IL-12 and anti-PD-1 therapy was superior to either treatment alone, with a combination demonstrating 100% survival Initiate combination study of Ad-RTS-hIL-12 with anti PD-1 Next steps for Ad-RTS-IL-12

Targeting tumor antigens with CARs and TCRs

Sleeping Beauty: First-in-human study using non-viral gene transfer Long-term follow-up data from 1st generation Sleeping Beauty platform in two trials infusing CAR+ T cells after hematopoietic stem-cell transplantation (HSCT) Showed favorable PFS and OS trends in both autologous and allogeneic cohorts Non-viral Sleeping Beauty T-cell survival compared favorably versus viral approaches 2nd generation Sleeping Beauty trial underway Sleeping Beauty T Cell survival averaged 201 days; max 360 days Sleeping Beauty T Cell survival averaged 51 days; max 180 days Historical Controls Sleeping Beauty Accepted for publication JCI

Improving CAR+ T cells by co-signaling through IL-15 receptor

Improving CAR+ T cells by co-signaling through IL-15 receptor T-cell survival Tumor only CAR CAR & mIL15

American Society of Cell and Gene Therapy oral presentation (May 2016) Fundamental to advancing SB platform, and any modified cell-based therapy, into a broadly deployed treatment option is a streamlined, simplified, and shortened manufacturing process, with a reduction in the associated cost Decreasing the time the SB-modified CD19-specfic T cells were in culture to 14 days improved the anti-tumor effect, providing support for ZIOPHARM's efforts to address the challenges of cost and time of bioprocessing cell therapies Reducing manufacturing time to generate CAR+ T cells using the Sleeping Beauty (SB) system

CAR+ T-cell platform to target myeloid malignancies Immunotherapy of tumors with unmet needs outside of the crowded viral CAR T treatment landscape for CD19+ malignancies Rapidly advancing a CAR T target for myeloid malignancies: Encouraging pre-clinical data including CAR expression, cytotoxicity, and IFN-g production Clinical trial is planned for 2016 In vivo model for myeloid malignancies CAR-T target Saline Untransduced T cells Targeted CAR T Cells Non-targeted CAR T Cells CAR expression Cytotoxicity IFNγ production

Exclusive agreement to develop and commercialize CAR-T cancer therapies 2 novel CAR T targets nominated Merck KGaA, Darmstadt, Germany to lead IND filing and pre-IND interactions, clinical development and commercialization Intrexon and ZIOPHARM retain ability to explore targets independently, granting Merck KGaA opt-in rights during clinical development Economics divided evenly between ZIOPHARM and Intrexon $413 million per product in milestones Tiered royalties up to lower-double digits on net sales Intrexon/Merck KGaA, Darmstadt, Germany in CAR-T

Ad-RTS-IL-12 NK Cells Primary NK cells Combination with Ad-RTS-IL-12 Genetically-engineered TCR Sleeping Beauty TCR Sleeping Beauty TCR and cytokine Other Regulatory T Cells Modified Bacteria (microbiome) CAR CD19 1st Generation CD19 2nd Generation CD19 3rd Generation with cytokine Myeloid malignancies target Merck Target 1 Merck Target 2 Off-the-shelf myeloid malignancies target Target 2016 Target 2017 Addressing unmet medical needs: pipeline Phase 2 Preclinical Phase 1 GBM Breast Cancer Pediatric GBM + Checkpoint Leukemia/Lymphoma Undisclosed Undisclosed Undisclosed Undisclosed AML Brain Cancer TBD TBD TBD GvHD GvHD

Non-viral Sleeping Beauty Viral delivery Target tumor antigens via multiple TCRs Limited appeal for targeting multiple intracellular antigens via TCRs Cost-effective approach High cost approach Rapid manufacture Labor intensive, slow manufacture Express multiple genes by combining DNA plasmids Packaging limits the cargo load Customizable, able to swap in different receptors Challenging to customize Sleeping Beauty (SB): Non-viral approach key for targeting intracellular antigens by TCRs

Targeting intracellular antigens: The key to implementing T-cell therapy for solid tumors

Targeting “shared” intracellular tumor antigens using a library of TCRs

“Clinical evidence supports the hypothesis that immunogenic products of somatic mutations unique to each patient’s cancer—so-called neoantigens—are the relevant targets for successful immunotherapies” “Success for cell-based immunotherapies may come from the arduous task of targeting the unique set of mutations that cause each patient’s cancer” “Presently, use of the Sleeping Beauty (SB) transposon / transposase system has advanced farthest in clinical development" Nat Med. 2016 Jan 6;22(1):26-36 Science. 2015 Apr 3;348(6230):62-8 Science. 2015 Apr 3;348(6230):69-74 Targeting “private” intracellular tumor antigens (neoantigens)

Tumor antigen is not known before the patient arrives Tumor and normal cells are interrogated to determine the neoantigen TCRs against known tumor antigen are prepared in real time TCR expressed in autologous T cells using SB platform Targeting neoantigens deploying personalized TCR-modified T cells

Neoantigen-specific TCRs expressed using SB system to target solid tumors Molecular Therapy 05 March 2016.

Natural killer (NK) cells Target tumors such as AML so do not require CAR Killing is independent of a specific (known) target antigen Do not have T-cell receptor (TCR), so do not require genetic editing to eliminate TCR May be used as an off-the-shelf therapeutic Cytokines, e.g., IL-12 are “fuel” for NK cells Build on promising proof-of-principle trials ongoing at MDACC infusing autologous and allogeneic NK cells Manufactured using designer feeder cells to generate large numbers Launching Phase 1 trials of off-the-shelf NK cells for AML and brain tumors in 2016 & 2017 Natural Killer Cells: Beyond CAR+ T cells

Regulatory T cells and manipulating the microbiome for graft-versus-host-disease (GvHD) Regulatory T cells Genetic modification L. lactis IL - 2 Genetic modification Donor Anti - inflammatory Gut health Sensors Regulatory T cells Prevention and/or treatment Recipient Acute GVHD Chronic GVHD

Multiple immunotherapies and combination immunotherapies are needed and being administered We stand alone in our ability to control the delivery of IL-12 We stand alone in being able to harness non-viral DNA as a method to genetically control T cells We are launching multiple immunotherapy trials Trial initiated with 2nd generation CD19 CAR-T utilizing non-viral Sleeping Beauty platform Three new trials in 2016: Combination immunotherapy, viral CAR-T, and NK cells We are combining different elements of the immune system (e.g., Ad-RTS-IL-12 and CPI) We have an ecosystem to efficiently develop and test new ideas in the clinic We have an expanding and unique platform to control the immune system

ZIOPHARM Oncology Jefferies 2016 Healthcare Conference June 2016