 Better Cancer Medicine Deutsche Bank 38 th Annual Healthcare Conference Jonathan Lewis, MD, PhD Chief Executive Officer Exhibit 99.1 May 29, 2013 |
 Forward-Looking Statements This presentation contains certain forward-looking information about ZIOPHARM Oncology 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. Words such as “expect(s),” “feel(s),” “believe(s),” “will,” “may,” “anticipate(s)” and similar expressions are intended to identify forward-looking statements. These statements include, but are not limited to, statements regarding our ability to successfully develop and commercialize our therapeutic products; our ability to expand our long-term business opportunities; financial projections and estimates and their underlying assumptions; and future performance. 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 or projected by, the forward-looking information and statements. These risks and uncertainties include, but are not limited to: whether any of our therapeutic candidates will advance further in the 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 any of our therapeutic candidates will be successfully marketed if approved; whether our DNA-based biotherapeutics discovery and development efforts will be successful; our ability to achieve the results contemplated by our collaboration agreements; the strength and enforceability of our intellectual property rights; competition from pharmaceutical and biotechnology companies; the development of and our ability to take advantage of the market for DNA-based biotherapeutics; our ability to raise additional capital to fund our operations on terms acceptable to us; general economic conditions; and the other risk factors contained in our periodic and interim reports filed with the SEC including, but not limited to, our Annual Report on Form 10-K for the fiscal year ended December 31, 2012, and our Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2013. Our audience is 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. May 29, 2013 |
 DNA Therapeutics Using the power of DNA to treat and prevent cancer May 29, 2013 |
 May 29, 2013 • Paradigm-shifting, synthetic biology technology for precise, controlled delivery of therapeutic proteins in vivo • Engineered approach to product design allows us to rapidly develop new genetically-based treatments for cancer with multiple effectors • Focused, disciplined and iterative approach to development decreases risk through: – Early “go/no go” decisions – Fast proof-of-concept and preclinical validation – Creating a virtuous circle of product development and improvement – Minimizing expense • Lead candidate, Ad-RTS-IL-12 in Phase 2 clinical trials for melanoma and breast cancer DNA-Based Therapeutics |
 May 29, 2013 Cells DC T Cell B Cell Macrophage NK cell Treg Other immune cells Direct tumor lysis ADCC Complement cytotoxicity Innate immunity stimulation Adaptive immunity stimulation Immune evasion inhibition Pro-apoptosis Necrosis Anti-angiogenesis Growth inhibition Anti-tumor metabolism EMT blockade Anti-tumor function MSC Epithelial Endothelial Fibroblast and ECM Tumor cell Tumor and microenvironment Effectors Immune cells Non-immune Cytokines mAb scFv scFv toxin Systemic decoy Intracellular decoy Metabolic Enzyme Protein Ligand RNA Molecular and Cellular Oncology DNA-Coded Toolset |
 May 29, 2013 A Platform System for Rapidly Developing Controllable DNA Therapies Inventoried DNA modules Monogenic Multigenic Viral delivery vector RheoSwitch Therapeutic System ® 3’ Target Gene(s) for Expression Intramuscular Cell Plasmid REG |
 May 29, 2013 Using Natural Cell Biology to Regulate Proteins Target Cell Controlled Therapeutic proteins Adaptable Precision mRNA Oral ligand activates DNA, protein production begins Translation |
 May 29, 2013 Ad IL-12 Melanoma Breast GBM DC IL-12 Melanoma GBM Cell signal targeting Multigenic platforms Immunotherapy Programs Palifosfamide (SCLC) Science-Driven Oncology Portfolio IND Compound Pre Clinical Phase 1 Phase 2 |
 IL-12 Program Ad-RTS-IL-12 DC-RTS-IL-12 May 29, 2013 |
 May 29, 2013 Ad-RTS-IL-12 • Interleukin-12 (IL-12) is a potent, naturally occurring anti-cancer protein central to initiation and regulation of cellular anti-cancer immune responses • Regulated intratumoral expression of IL-12 promotes activation of TIL’s to drive a cytotoxic immune response against distant tumors |
 May 29, 2013 Increases CD8 + TILs in the 4T1 Syngeneic Mouse Model Vehicle INXN-1001 150 mg/m 2 + Ad-RTS-mIL-12 1x10 10 vp |
 May 29, 2013 Systemic Tumor Response in B16 Melanoma Model Group 1 untreated; Group 2 AL in food ~675 mg/m 2 /day; Group 3 Ad-RTS-mIL-12 1x10 10 vp Days 12 & 19; Group 4 AL + Ad-RTS-mIL-12. Arrows = administration of Ad-RTS-mIL-12 Treated Tumor on the Right Flank Untreated Tumor on the Left Flank |
 May 29, 2013 A Phase I/II, Open Label Study of Ad-RTS-hIL-12 + AL in Subjects with Unresectable Stage III or IV Melanoma • 3 + 3, single-arm design • Primary endpoint – Safety and tolerability of intratumoral injections of 1012 vp Ad-RTS-hIL-12 in combination with escalating doses of INXN-1001 • Secondary endpoint – Inform the selection of a dose of INXN-1001 • Phase I dose escalation complete • Phase II ongoing (preliminary data 1H 2014) 5mg (INXN-1001) 20mg (INXN-1001) 100mg (INXN-1001) 160mg (INXN-1001) 160mg (INXN-1001) 12 subjects in Phase I (dose escalation) Up to 15 subjects in Phase 2 (expansion) |
 Prominent Inflammatory Response Correlates with High levels of IFN- • Initial increase in lesion size due to inflammatory response seen at Cycle 1 Day 16 • Lesion was undetectable at Cycle 2 Day 1 • Subject ultimately progressed and was taken off study C1D1 C1D1 C1D16 C1D16 C2D1 C2D1 May 29, 2013 |
 • Clinical activity at 100 mg and 160 mg doses coincided with the highest serum levels of IL-12 and IFN- Summary of Immunological and Clinical Activity – Prominent inflammatory responses in injected and non-injected lesions – Decrease in size of injected and non-injected lesions • Clinical activity at higher dose cohorts (5 of 7, 71%) – 4-fold median increases from baseline at peak levels compared with lower dose cohorts • Dose-dependent increase in serum levels of IL-12 and IFN- • Flow cytometric analyses of PBMCs revealed – 7-fold and 4-fold median increase from baseline at peak levels in absolute CD3+ and CD8+ T cell values, respectively, compared with lower dose cohorts May 29, 2013 |
 Summary of Safety May 29, 2013 • Controlled expression of IL-12 limits systemic toxicity while inducing biological and clinical activity in a dose-dependent fashion – Toxicity reversible on stopping oral activator ligand • The most common related TEAEs ( 20% of subjects): • Chills and Pyrexia (73% each), Nausea (67%), Fatigue (60%), Vomiting (33%), Anorexia (27%), Arthralgia and Diarrhea (20% each) • Toxicity profile is consistent with the MOA of the drug • No DLT identified • One unrelated death secondary to septicemia |
 • Preclinical – Intratumoral administration of Ad-RTS-mIL-12 (Ad) in 4T1 BALB/c mouse breast carcinoma model: dose-related decrease in tumor growth rate. (AACR 2013) – Therapeutic strategy appears to be well tolerated • Phase 2 – Multi-center, randomized, open-label – Ad-RTS IL-12 in combination w/palifosfamide – Non-resectable, recurrent or metastatic breast cancer – Enrolling up to 68 patients – Early data expected year end 2013 Advanced Breast Cancer May 29, 2013 |
 Dose-dependent Anti-Tumor Activity of in Murine 4T1 (Breast Cancer) Model 4 2 0 6 8 10 12 14 16 5 10 15 Time (Days) 20 25 30 0 Vehicle Control Ad-RTS-mIL12 (AD) INXN-1001 (AL) 15 mg/m2 AD + AL 15 mg/m2 AD + AL 30 mg/m2 AD + AL 75 mg/m2 AD + AL 150 mg/m2 IPM 40 mg/m2 IPM 80 mg/m2 IPM 120 mg/m2 AD + AL 30 mg/m2 + IPM 40mg/m2 AD + AL 30 mg/m2 + IPM 120 mg/m2 Tumor Size Quadruple Start of Treatment May 29, 2013 |
 Glioblastoma Multiforme: Promising Preclinical Activity 100 % survival observed with Ad-RTS-IL-12 + AL or DC-RTS-IL-12 + AL INXN-1001 dosing Day 4 to EOS at ~ 675 mg/m²/day in chow; DC –RTS-IL12 or Ad-RTS-IL12 on Day 5 Kaplan Meier Survival in GL261 Orthotopic Syngeneic Mouse Glioma Model 0 10 20 30 40 50 60 70 80 0 20 40 60 80 100 No Treatment DC-no vector DC-RTS-IL12 (MOI 10000) Ad-RTS-IL12 (5x10 9 ) AL chow Ad-RTS-IL12 (5x10 9 ) + AL DC-RTS-IL12 (MOI 10000) + AL Time (Days) May 29, 2013 |
 May 29, 2013 Preclinical and Discovery Programs |
 A Platform System for Rapidly Developing Controllable DNA Therapies Inventoried DNA modules Monogenic Multigenic Viral delivery vector RheoSwitch Therapeutic System® 3’ REG Target Gene(s) for Expression Intramuscular Cell Plasmid May 29, 2013 |
 Using Natural Cell Biology to Regulate Proteins May 29, 2013 Precision Oral ligand activates DNA, protein production begins Controlled Therapeutic proteins Adaptable Translation mRNA Target Cell |
 IP1: LacZ IP1: LacZ rLUC rLUC Stuffer Stuffer Stuffer Stuffer Stuffer Stuffer SP-RTS SP-RTS IP2: fLuc IP2: fLuc rLUC rLUC Stuffer Stuffer Stuffer Stuffer Stuffer Stuffer SP-RTS SP-RTS IP3: SEAP IP3: SEAP rLUC rLUC Stuffer Stuffer Stuffer Stuffer Stuffer Stuffer SP-RTS SP-RTS IP4: GUS IP4: GUS rLUC rLUC Stuffer Stuffer Stuffer Stuffer Stuffer Stuffer SP-RTS SP-RTS IP4: GUS IP4: GUS rLUC rLUC SP-RTS SP-RTS IP1: LacZ IP1: LacZ IP2: fLuc IP2: fLuc IP3: SEAP IP3: SEAP #: Not significantly different than background (p>0.05) *: Not significantly different than the control (p>0.05) Next Generation: Multigenic Approach 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 LacZ/rLUC Uninduced SEAP/rLUC Uninduced LacZ/rLUC Induced SEAP/rLUC Induced fLUC/rLUC Uninduced GUS/rLUC Uninduced fLUC/rLUC Induced GUS/rLUC Induced Conclusion: 4 Inducible gene programs can be placed in parallel on the same vector without affecting gene program performance May 29, 2013 |
 Small Molecule Programs May 29, 2013 |
 Small Molecule Programs Palifosfamide Bi-functional DNA alkylating agent that has activity in multiple tumors by evading typical resistance pathways, less toxic and ease of administration Phase 3 soft tissue sarcoma program terminated, ongoing adaptive Phase 3 in small cell lung Indibulin Novel oral tubulin binding agent; expected low toxicity, neurotoxicity not seen Ongoing Phase 1/2 study in metastatic breast cancer Darinaparsin Novel mitochondrial- and hedgehog-targeted agent (organic arsenic); oral and IV Ongoing studies in partnership with Solasia May 29, 2013 |
 Expected Milestones Program Milestone Timing 2013 IL-12 Melanoma preliminary Phase 2 data 4Q Breast cancer preliminary Phase 2 data 4Q GBM preclinical proof of concept 4Q Multigenic platforms Preclinical data 4Q Immunotherapy Programs Preclinical data 4Q 2014 Palifosfamide Interim SCLC data (MATISSE) 1H IL-12 GBM Phase 1 / 2 study initiation 1H Melanoma Phase 2 data 1H Breast Phase 2 data 2H May 29, 2013 |
 • Primary shares outstanding: approximately 82.9M • Cash: approximately $55.7M @ 3/31/13 • Current cash resources expected to support operations into 1Q 2014 Financial Highlights May 29, 2013 |
 • Paradigm-shifting, synthetic biology technology for precise, controlled delivery of therapeutic proteins in vivo • Engineered approach to product design allows us to rapidly develop new genetically-based treatments for cancer with multiple effectors • Focused, disciplined and iterative approach to development • Lead therapeutic Ad-RTS-IL-12 in Phase 2 melanoma and breast cancer for early validation of target and platform • “Next-wave” of therapeutic approaches in research pipeline (antibody technology, protein-protein technology, immunotoxins, etc.) • Well capitalized through data inflection points Conclusion May 29, 2013 |
 Better Cancer Medicine Deutsche Bank 38 Annual Healthcare Conference Jonathan Lewis, MD, PhD Chief Executive Officer th May 29, 2013 |