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Cancer Res. 2015 Sep 1;75(17):3505 18. PMID: 26330164 Extensive Data Outreach 27 CRI CIMT EATI AACR Immunotherapy Conference September 16 19, NY, NY SITC November 4 8, National Harbor , MD SNO November 19 23, San Antonio, TX CAR T Summit November 12 13, Boston, MA ASH December 5 8, Orlando FL SABCS December 9 12, San Antonio TX Additional papers With More to Come for 2015 28 ZIOPHARM Oncology Pipeline Solid Tumors 2016+ Heme 2015+ Virotherapy Multi center trials 2015+ Multi Modal 2016+ Expanded Indications 2016+ Single Agent 2015+ CAR Cytokine 2016+ Adoptive Cell Therapy TCR 2016+ CAR 2015+ NK cells 2016+ T cells 2015+ Allogeneic 2016+ Autologous 2015+ Wells Fargo Healthcare Conference SEPTEMBER 2015
Cancer Gene Ther. 2015 Mar;22(2):64 6. PMID: 25675874 Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19 specific chimeric antigen receptor. Cancer Gene Ther. 2015 Mar;22(2):95 100. PMID: 25591810 Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity.
PLoS One. 2015 Jun 1;10(6):e0128151 PMID: 26030772 Genetic Engineering of T Cells to Target HERV K, an Ancient Retrovirus on Melanoma. Clin Cancer Res. 2015 Mar 31. [Epub ahead of print] PMID: 25829402 Moving from tinkering in the garage to assembly line production: the manufacture of genetically modified T cells expressing chimeric antigen receptors (CARs) comes on line.
New CAR designs for patients with hematologic malignancies and solid tumors 2. Combining CAR with cytokines IL 12 IL 15 TCR based T cell therapy NK cell immunotherapy Next generation Adoptive Cell based Clinical Trials 19 How do we achieve on target anti cancer activity? The Promise and Challenges of DNA based Immuno Oncology Avoid 20 Strategies to widen therapeutic index to Target Solid Tumors 21 Off the shelf T Cells 22 Elimination of Endogenous TCR 23 Fitting Together the Pieces of the Puzzle NK cells T cells TCRs CARs Virotherapy Cytokines Remote Controlled 24 Clinical Programs Ziopharm 2015 Ad RTS IL12 Multicenter CARs MDACC 25 Clinical Programs Ziopharm 2016+ Ad RTS IL12 CARs and interleukin Multicenter NK cells TCRs CARs Multicenter MDACC MDACC Multicenter 26 Abstracts European Hematology Association (June 2015) Donor derived, CD19 directed, CAR modified T cells infused after allogeneic hematopoietic stem cell transplantation as pre emptive donor lymphocyte infusion in patients with CD19+ malignances CRI CIMT EATI AACR ( September 2015) Demonstration of systemic antitumor immunity via intratumoral regulated expression of IL 12 in advanced breast cancer and melanoma patients Demonstration of systemic antitumor immunity via intratumoral regulated expression of IL 12 as a gene therapy approach to treatment of cancer Bio engineered Dectin 1 CAR+ T cells to control invasive fungal infection Ex vivo generation of clinical grade T cells by using activating and propagating feeder cells to cross link T cell receptor Designing CARs for personalized immunotherapy: rapid assembly of CARs from principal components using EZ CAR platform Transcriptional and epigenetic signatures of ex vivo propagated three distinct TCR V 1, TCR V 2 and TCR V 3 cell subtypes with broad specificity for malignancies Papers Sleeping Beauty Transposition of Chimeric Antigen Receptors Targeting Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1) into Diverse Memory T Cell Populations.
Among 8 patients who received haplo HCST and CAR, 100% of remain alive and 75% remain in remission Rate of CMV reactivation after CAR + T cell administration was 24% vs. 41% previously reported for our patients without infusion Trial at MDACC, Updated from EHA 2015; Will be submitted for publication 16 Persistence of Infused CAR + T Cells Trial at MDACC, Updated from EHA 2015; Will be submitted for publication 17 Improving Therapeutic Potential of CAR + T Cells Signals 1 2 Signal 3 18 1.
J Oncol Pharm Practice, 2014, 20:257 Population 19 patients with advanced CD19 + ALL (n=17) or NHL (n=2) Safety 3 patients developed GVHD which is lower than the expected range after allogeneic HSCT alone Efficacy 58% of patients (n=11/19) remain in complete remission (CR) and 10/19 remain alive and in CR (1 death in CR) following CAR + T cell infusion with a median follow up of 6.5 months post transplant among survivors.
Several subjects then restarted on veledimex Ad RTS IL 12 Gene Therapy Clinical Response To Date 8 Early Response Data Expected in 4Q 2015 Phase 1 Study of IL 12 Gene Therapy in Recurrent or Progressive Glioblastoma/Grade III Malignant Glioma A Multi Center Gene Therapy Study A single cycle of Ad RTS hIL 12 + escalating veledimex 1O : Safety and tolerability 2O : Determine MTD and immune response, including ORR, PFS and OS N = 72 Recurrent or progressive glioblastoma or Grade III malignant glioma Stratified according to clinical indication for tumor resection: Resection plus injection vs. stereotactic injection alone 9 Immunotherapy phase of treatment A single cycle of Ad RTS hIL 12 + veledimex goal of maintaining or improving pre study response 1 O : Safety and tolerability 2 O : ORR, disease control and biomarkers N = 40 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) Phase 1b/2 Study of IL 12 Gene Therapy in Locally Advanced/Metastatic Breast Cancer Early Response Data Expected in 4Q 2015 10 11 Pipeline Demonstrated the ability of Veledimex to cross blood brain barrier in animal models (AACR 2014) Proof of concept in humans being explored in ongoing multi center gene therapy trial Combination therapies Veledimex for activation of genetically modified T cells in brain 12 CAR + T cells Target cell surface tumor associated antigens (TAAs) independent of HLA Public cell surface antigens TCR + T cells Target intracellular TAAs dependent on HLA Private intra cellular antigens NK cells Target tumor with loss of HLA No antigens Cell Therapy 13 Sleeping Beauty (SB) Non viral Gene Integration Step 1 (safety) Step 2 (efficacy) Step 3 (scale) 14 Pre emptive donor lymphocyte Infusion with CD19 directed CAR + T cells infused after autologous hematopoietic stem cell transplantation (HSCT) Population 7 patients with advanced non Hodgkin lymphoma (NHL) Safety Patients have not demonstrated any acute or late toxicity to CAR + T cell infusions Efficacy 100% of patients remain alive following a single CAR + T cell infusion with a median follow up of 24 months 86% of patients (n=6) remain alive and in complete remission (CR) Trial at MDACC; Will be submitted for publication 15 Pre emptive donor lymphocyte infusion with CD19 directed, CAR + T cells infused after allogeneic HSCT *Wilhelm et al.
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. 3 NASDAQ: ZIOP Robust synthetic immunology pipeline Virotherapy adoptive cell therapy Multiple partnerships Differentiated technology platforms Gene switch, non viral integration and viral based delivery Multiple trial launches in 2015/2016 Well capitalized Cash and equivalents of $176.1 million (Pro forma) Sufficient to fund our planned operations into Q1 2018 Highlights 4 Delivering on the Premise and Promise of Gene and Immune based Therapies Fully Aligned with research and development (Intrexon) Big pharma partnership (CARs) Bio processing for next generation products Aligned with academic centers for manufacturing of cells for investigator initiated trials Contract manufacturing for ZIOP sponsored trials in place Established suite of correlative studies Undertaking multi center gene therapy trials Multi faceted approach to gene therapy (non viral and viral) Ability to manipulate the immune response in situ (generate immune response within patient) Ability to provide an immune response (infuse immune cells) Ability to manipulate virus after infusion Ability to manipulate immune cells after infusion Immune cells targeting tumor through CAR, TCR, and NK Infuse patient derived immune cells Infuse 3 rd party (allogeneic) immune cells Virotherapy RTS Gene Switches Viral Non viral Gene Integration Cell Therapy CAR T, TCR and NK Cells Autologous and Allogeneic Our Approach 5 IL 12 Virotherapy Adenoviral vector engineered to express IL 12 utilizing RheoSwitch Therapeutic System (RTS ) gene switch Injected intra tumor with IL 12 expression controlled via administration of oral activator ligand veledimex Regulated intra tumoral expression of IL 12 promotes activation of tumor infiltrating lymphocytes to drive cytotoxic immune response against distant tumors 6 Improved persistence and survival in tumor microenvironment Limits on target, off tumor toxicities Administer virus locally to achieve systemic anti tumor effects (Breast) Administer virus locally to achieve local anti tumor effects (GBM) RTS Gene Switch Technology 7 Expression of functional IL 12 in human subjects by direct intra tumoral injection of Ad RTS hIL 12 + oral veledimex generates downstream IFNg production and rapid systemic elevation of IL 10 and IP 10 Documented systemic immune activation and clinical effect in advanced, heavily pretreated melanoma and breast cancer patients Adverse event profile, including cytokine release syndrome, of Ad RTS hIL 12 + veledimex is predictable, controllable, and fully and rapidly reversible on stopping veledimex .
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, 2014, and our Quarterly Report on Form 10Q for the quarter ended June 30, 2015.
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.
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.
Wells Fargo Healthcare Conference SEPTEMBER 2015 Exhibit 99.1 2 Forward looking Statements 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.