Alaunos Therapeutics, Inc. · NASDAQ:TCRT
Alaunos Therapeutics — ZIOPHARM Oncology — Investor Presentation (June 2015)
33 slides from Alaunos Therapeutics's investor presentation, Jun 18, 2015
Slide 1: The Future of Cancer Therapy
June 2015 www.ziopharm.com The Future of Cancer Therapy Exhibit 99.1
Slide 2: 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 n
Slide 3: Financial Highlights
Financial Highlights NASDAQ symbol “ZIOP” Approximately 128.2 million shares outstanding Cash and cash equivalents of approximately $129.7 million Cash resources sufficient to fund our operations into 2Q 2017 Excludes 2Q payment of $57.5 million from Intrexon related to the biopharmaceutical busines
Slide 4: Intrexon and ZIOPHARM Collaboration with the Biopharmaceutical Business of Merck KGaA
Intrexon and ZIOPHARM Collaboration with the Biopharmaceutical Business of Merck KGaA Highlights Significant Value of CAR-T Platform Exclusive strategic collaboration and license agreement to develop and commercialize CAR-T cancer therapies Exclusive access to CAR T suite of technologies, including
Slide 5: Key Investment Highlights
Key Investment Highlights Robust synthetic immunology pipeline targeting hematologic malignancies and solid tumors Non-viral and viral CAR-T, TCR, and NK-cell therapies IL-12 gene therapy: adenoviral vector for IL-12 expression controlled via oral activator Differentiated technology platforms In viv
Slide 6: Milestones 2015 / 2016
Milestones 2015 / 2016 Intra-tumoral IL-12 RheoSwitch ® Phase 1/2 Breast Cancer with SOC initiated Q2 2015 Phase 1 GBM initiated Q2 2015 – potential early data Q4 2015 CAR-T Initiate Phase 1 next-generation CD19 CAR trials Potential early data on Phase 1 CARs studies in Q4 2015 Initiate novel CAR fo
Slide 7: Overall strategy and differentiation
Overall strategy and differentiation
Slide 8: Robust Pipeline In Synthetic Immunology
Pre Clinical Phase 1 Phase 2 Robust Pipeline In Synthetic Immunology Compound Ad-RTS-IL-12 gene Rx IND Breast GBM Adoptive Cell Therapies B-cell Malignancies Myeloid Malignancies RTS-controlled T cell Solid Tumors Universal Donor
Slide 9: IL-12 Gene Therapy
IL-12 Gene Therapy Adenoviral vector engineered to express IL-12 utilizing RheoSwitch Therapeutic System® 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-i
Slide 10: Ad-RTS-IL-12 — Oral Veledimex
Ad-RTS-IL-12 — Oral Veledimex Precisely Controls Expression of IL-12 ( in vivo control) Improved persistence and survival in tumor microenvironment Limits on-target, off-tumor toxicities
Slide 11: Phase 1b/2 Study of IL-12 Gene Therapy in Locally Advanced/Metastatic Breast Cancer
Phase 1b/2 Study of IL-12 Gene Therapy in Locally Advanced/Metastatic Breast Cancer Immunotherapy phase of treatment A single cycle of Ad-RTS-hIL-12 + veledimex goal of maintaining or improving pre- study response O : Safety and tolerability O : ORR, disease control and biomarkers Immunotherapy phas
Slide 12: Phase 1 Study of IL-12 Gene Therapy in Recurrent or Progressive Glioblastoma/Gr.III Malignant Glioma
Phase 1 Study of IL-12 Gene Therapy in Recurrent or Progressive Glioblastoma/Gr.III Malignant Glioma A single cycle of Ad-RTS-hIL-12 + escalating veledimex O : Safety and tolerability O : Determine MTD and immune response, including ORR, PFS and OS A single cycle of Ad-RTS-hIL-12 + escalating veledi
Slide 13: Cell Therapy: Portfolio of Effector Cells
Cell Therapy Portfolio of Effector Cells 1. Chimeric Antigen Receptor (CAR+) T cells: Target cell surface tumor-associated antigens (TAAs) independent of HLA “Public” antigens 2. T Cell Receptor (TCR + ) cells: Target intracellular TAAs dependent on HLA “Private” antigens 3. Natural Killer (NK) cell
Slide 14: Improving the Therapeutic Potential of CAR-T
Improving the Therapeutic Potential of CAR-T Understanding of the effector cell biology Co-stimulation with cytokine Signals 1 & 2 Signal 3
Slide 15: Advantages of Non-Viral Gene Integration
Advantages of Non-Viral Gene Integration Sleeping Beauty transposon/transposase system Fast, efficient and nimble gene transfer method Improves cost, time, and complexity compared to viral-based integration
Slide 16: Management of Potential Toxicity through Inducible Immunoreceptor Expression
Inducible CAR + T Cell Inducible TCR + T Cell CAR + T Cell TCR + T Cell Next Generation Management of Potential Toxicity through Inducible Immunoreceptor Expression ( in vivo control) Many attractive target antigens are also expressed on normal cells Veledimex
Slide 17: Building the Next-Generation of Inducible Cytokines
Next Generation Building the Next-Generation of Inducible Cytokines ( in vivo control) Therapeutic potential of effector cells depends on recognition of tumor cells and recycling effector function in tumor microenvironment. Veledimex
Slide 18: IL-12 Cell Therapy
IL-12 Cell Therapy Zhang, Rosenberg et al., Feb 2015, Clinical Cancer Research Tumor Infiltrating Lymphocytes Genetically Engineered with an Inducible Gene Encoding Interleukin-12 for the Immunotherapy of Metastatic Melanoma • TIL plus IL-12 can mediate objective responses in up to 70% of patients w
Slide 19: Next-generation CAR+ T cells
Next-generation CAR + T cells Bioprocessing Close system Ex vivo cytokines Cryopreservation CAR design Humanization Stalk Endodomains Cytokine IL-12 Others Time in culture 0-30 days
Slide 20: New CD-19 CAR Design Using Sleeping Beauty
New CD-19 CAR Design Using Sleeping Beauty Prior Sleeping Beauty CAR Design Modified-1 Sleeping Beauty CAR Design T cell infusion (day 1) Next-generation design demonstrates superior in vivo activity in pre-clinical models Established Disease Model Minimal Residual Disease Model T cell infusion (day
Slide 21: Cytokine Signaling Enhances CARs
Cytokine Signaling Enhances CARs Persisting T-cell Subsets ( in vitro ): Established Disease Model CD95 Expression: + + + + Memory Subset: SCM CM EM EMRA
Slide 22: CD19-specific CAR+ T cells
CD19-specific CAR + T cells Template for CAR + T cells Safety • Nearing completion Efficacy • New CAR Efficacy POC OTS • Generate in advance of need
Slide 23: Dual CMC Distribution Approaches for Cell Therapies
Dual CMC Distribution Approaches for Cell Therapies Registration Trials & Global Distribution with Multiple Pharma Partners Centralized Point-of-care (POC) Genetically modified T cells One patient Multiple Patients Autologous T cells Allogeneic T cells Real time In advance of need
Slide 24: Steps Toward Point-of-Care Distribution
Self Months Months Weeks Weeks Days Days Hours Hours T-cell manufacturing time T-cell acquisition Genetic modification Infusion Steps Toward Point-of-Care Distribution
Slide 25: Off-the-Shelf (OTS) Solution
Off-the-Shelf (OTS) Solution
Slide 26: Ongoing Phase 1 Safety Study: First Generation Proof of Concept
Safely infuse patients No immediate or late toxicity No excess GVHD Outpatient infusions 50% of patients with aggressive disease remain in remission after transplant & CAR + T cells Safely re-infuse CAR + T cells from patient-specific cryopreserved banks (n=3 re-treated) CAR + T cells apparently eff
Slide 27: ZIOPHARM Oncology TCRs
a. ZIOPHARM Oncology TCRs : In vitro testing > Mouse data Human data Code-of-conduct Printed DNA
Slide 28: Drive Pipeline Forward To Create Value
Drive Pipeline Forward To Create Value How Are We Differentiated Translation of immunology to immunotherapies T cells NK cells Non-viral gene transfer (personalized therapies) CAR TCR Cytokine Cellular engineering Expression Control Personalized and orally controlled cytokine transcription CAR + T c
Slide 29: Differentiated Technology Platforms
Technology Intrexon / ZIOPHARM / MD Anderson Differentiated Technology Platforms Lower cost, controllable toxicity, autologous and allogeneic RheoSwitch Therapeutic System® Most advanced family of ligands and switches available for dynamic range, safety, and temporal control (on-off-on etc.) Non-Vir
Slide 30: Personalized Therapy for Disease and Patient
Personalized Therapy for Disease and Patient Infuse T cells with more than one specificity Personalized for the disease Intra-tumor Inter-tumor Heterogeneity of tumor-associated antigen (TAA) Infuse T cells with one or more specificity Personalized for the patient “N=1” trial paradigm
Slide 31: The New Industrialization of T cells
Power-Law Curve The New Industrialization of T cells
Slide 32: The N=1 approach has been shown for non-genetically modified T cells
The N=1 approach has been shown for non-genetically modified T cells
Slide 33: The Future of Cancer Therapy
www.ziopharm.com The Future of Cancer Therapy
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