Full Press Release Details
Jefferies Immuno-Oncology Summit
Forward-looking statements
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. 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.
Partnerships to implement multiple immunotherapies
Clinical Collaborators
Rapid Clinical Development
DNA Engine & Research (via Intrexon)
Biopharmaceutical PBL and IL-12 business of Merck KGaA, (via
Intrexon) Darmstadt, Germany
Laurence Cooper, MD, PhD
Named CEO in May 2015
Developed Sleeping Beauty
technology in-licensed
ZIOP/XON in Jan 2015
Previously professor
pediatric oncology at MD
Anderson Cancer Center:
expertise in immunotherapy,
Technologies to execute tumor cells
Safe targets Reduce burden on
manufacturing Infuse T cells that maintain their replicative potential
Co-infuse T cells with multiple specificities
Combine introduced immuno-receptor with cytokine Add conditional and induced expression Combine genetic insertion with genetic editing
Combine cell therapy with other immunotherapies
Target driver mutations expressed
exclusively within a patient s tumor
Overcome the time to generate the T-cell products Overcome cost
Platforms to products
Patient-derived platforms
Myeloid T cell malignancies
Beauty T cell I Neo-antigen 1 T cell 2
Neo-antigen 2 T cell 3 Neo-antigen 3
Understanding targets and delivering immunotherapies
Off-the-shelf platforms Allogeneic (off-the-shelf)
Myeloid malignancies
NK cell Adenovirus Antigens need
Bio-engineering and bio-processing
manufacturing processes for both autologous and allogeneic settings RTS and switches will address off-target effects, especially in solid tumors Continued optimization of manufacturing process to improve performance
Shortened manufacturing of CAR T cells shows superior in vivo activity
Leveraging manufacturing through
Patient-derived (autologous)
Shorten manufacturing time to produce T or NK cells
Off-the-shelf (allogeneic)
cells Infusions cells
Match one donor with multiple recipients. Generate large numbers of T or NK cells with retained capacity to proliferate.
Addressing unmet medical needs: pipeline
Preclinical Phase I Phase II
CD19 3rd Generation with cytokine
Myeloid malignancies target Undisclosed
Merck Target 1 Undisclosed
Merck Target 2 Undisclosed
Off-the-shelf myeloid malignancies target Undisclosed
Primary NK cells AML
Combination with Ad-RTS-IL-12 Brain Cancer
Genetically-engineered TBD
Sleeping Beauty TCR TBD
Sleeping Beauty TCR and cytokine TBD
Modified Bacteria (microbiome) GvHD
Ad-RTS-IL-12 + veledimex
Ad-RTS-hiL-12 Oral Activator Distant Tumors Cytotoxic Response Lymphatics IL-12 IFNg APC CD8+ CD4+
Combination therapy with checkpoint inhibitors
Pre-clinical data demonstrates improved
anti-tumor response in mice with glioma
*As of Dec 15, 2015 Updated data at ASGCT 2016
Early brain tumor data encouraging (N=7)*
Patients enrolled at multiple centers Biomarkers supportive of activity Neurotoxicity minimal and manageable
On-target toxicities as expected and promptly reversible upon stopping veledimex
Early breast cancer data encouraging (N=6)*
patient achieved 12 week PFS endpoint
Patient accrual accelerating with 5 patients enrolled during 4th
quarter Looking for confirmation of increased memory T cells as seen in previous trials
toxicities as expected and promptly reversible upon stopping veledimex
Updated data for both studies at
T cells genetically modified with tumor-specific CAR or TCRs
Effector Effector functions functions
Transposon DNA plasmid IR/DR IR/DR CAR hEF1
Transposase DNA plasmid (or in vitro transcribed mRNA) CMVIE SB11 Transposase Co-delivery into cells by nucleofection
Transposase Transposon CAR Nucleus Cytoplasm The Sleeping Beauty transposon-transposase system represents a unique
non-viral system for introducing genes encoding T-cell receptors and chimeric antigen receptors into lymphocytes that can be of great value in the development of personalized immunotherapies for patients with cancer.
Steven A. Rosenberg M.D., Ph.D. December 2015
Advantages of Sleeping Beauty non-viral platform:
Provides conduit to targeting solid tumor neo-antigens using T-
Lowers the cost of generating genetically modified T cells
Has the potential to generate T cells with minimal ex vivo
Sleeping Beauty: First-in-human study
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
Recipient 49% 3-year PFS reported for patients with advanced DLBL
Recipient Donor Allogeneic HSCT 20 to 34% 1-year Os reported for patients with advanced ALL
Autologous HSCT & CD19-specific CAR+T cells 83% 3-year PFS for patients with DLBL SB-modified CAR+T cells Allogeneic HSCT & CD19-specific CAR+T cells 63% 1-year Os for patients