Full Press Release Details
The Future of Cancer Therapy
BIO CEO & Investor Conference
Forward-Looking Statements
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 September 30, 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.
Clinical-stage cancer
immunotherapy company
Focus on treatment through DNA expression and control Phase 1/2 program targeting
melanoma, breast cancer and glioma
Intrexon partnership enabling potential paradigm shift
New INDs through 2015 exploring multigenic approach to cancer treatment
Why Focus on DNA-Based Medicine?
and delivery enable:
creation of new therapies which target cancer cells precise control of biologic
concentration and dosing better therapeutic index through controlled protein delivery and cellular targeting economically feasible approach to combination biologic therapies
Intrexon Collaboration: Leveraging Our Assets
ZIOP: translational medicine and oncology drug development XON: synthetic biology platform enabling DNA delivery and
Exclusive channel partner agreement in all human cancer:
ZIOP responsible for product development and commercialization XON responsible for manufacturing, process-improvement
R&D, patents 50:50 revenue/net-profit split
Current targets: melanoma, breast cancer, glioma, other
We Have the Tools to Treat Cancer Better
mAb scFv Protein Metabolic Intracellular RNA
toxin Ligand Enzyme decoy
Cells T Cell B Cell Macrophage NK cell Treg Other immune Epithelial Endothelial
Immune Cells Non-immune Cells
Direct tumor lysis Pro-apoptosis
Anti-tumor Complement ADCC Necrosis
Innate immunity stimulation Growth inhibition
function Adaptive immunity stimulation Anti-tumor metabolism
Immune evasion inhibition EMT blockade
and microenvironment
The Power of Intrexon s RheoSwitch Technology
Controlled Expression and Delivery of Therapeutic Proteins with RheoSwitch :
This is the most advanced clinical method to turn genes on and off
Monogenic/Multigenic
Orally activated biologic on/off switch
IL-12 Production is Modulated by Veledimex (Activator Ligand) in HT 1080 Cells
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84 90
Time after viral transduction (hours)
mIL-12 expression(ng/ml medium/6hrs)
Veledimex Tightly and Precisely Controls the Expression of IL-12 mRNA in the Tumor
Baseline Maximum D1-D7 7 Days Post-treatment
Tumor mRNA (mRNA/1e6 vp)
Cytotoxic T Cells & Memory T Cells (TILs) Significantly Increase in Tumors Following Ad-RTS-IL-12 Treatment
Images were obtained using an Aperio ScanScope XT whole-slide imager and digitized at 20x.
Systemic Immune Activity: patterns of anti-tumor response
%Change from baseline lesion size
Peak Serum IL-12 Concentration
rIL-12 = recombinant IL-12
hIL-12 = Ad RTS IL-12
Concentration of IL-12 (pg/mL)
*Atkins, MB et al Clin Cancer Res 1997;3:409-417
Clinical Observations to Date
expression to achieve a desirable immune response
High expression of IL-12 mRNA in tumors, tightly controlled
by veledimex dose Increased tumor infiltrating lymphocytes observed in the tumor microenvironment, suggesting multiple favorable biologic effects of IL-12 expression
We have seen potent systemic biologic activity and reversible toxicity
Melanoma: potent biologic activity in injected and non-injected lesions
Breast: on-mechanism and on-target toxicity demonstrates powerful immune response controlled by dose-dependent expression of IL-12
Adverse events consistent with immunotherapy use and immune response; serious adverse events reversed after veledimex
This opens the possibility that, for the first time, we can achieve personalized
scheduling as a component of personalized cancer medicine.
Larry Norton, M.D., Deputy Physician-in-Chief
for Breast Cancer Programs, Memorial Sloan-Kettering Cancer Center
Glioblastoma Multiforme: IL-12 Preclinical Activity
Kaplan Meier Survival in GL261 Orthotopic Syngeneic Mouse Glioma Model
0 10 20 30 40 50 60 70 80
No Treatment DC-no vector
DC-RTS-IL12 (MOI 10000) Ad-RTS-IL12 (5x109) AL chow DC-RTS-IL12 (MOI 10000) + AL Ad-RTS-IL12 (5x109) + AL
Veledimex (AL) dosing Day 4 to EOS at ~ 675 mg/m2/day in chow; DC-RTS-IL-12 or Ad-RTS-IL-12 on Day 5
100% survival observed with Ad-RTS-IL-12 + AL or DC-RTS-IL-12 + veledimex
Significant Market Potential for Ad-RTS-IL-12
Melanoma Phase 2 combination
Preliminary data YE 2014
Breast Cancer Phase 2
combination study with SOC
Preliminary data 1H 2015
GBM Phase 1 dose-escalation study
Preliminary data YE 2014
A Growing Oncology Portfolio
Clinical Phase 1 Phase 2
Cell signal targeting
Multigenic platforms
Immunotherapy programs
Potential DNA Combination Therapies: Future INDs
Human mesenchymal stem cells genetically modified with genes that program the body to destroy cancer
Multigenic therapeutic antibodies such as single chain versions of Hercept
Embedded cellular bioreactors to deliver multiple proteins systemically using RheoSwitch platform
Program Milestone Timing