Exhibit 99.1
Exhibit 99.1
The Future of Cancer Therapy
BIO CEO & Investor Conference
February 2014
www.ziopharm.com
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 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.
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ZIOPHARM Today
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
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Why Focus on DNA-Based Medicine?
DNA synthesis 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
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Intrexon Collaboration: Leveraging Our Assets
ZIOP: translational medicine and oncology drug development XON: synthetic biology platform enabling DNA delivery and control
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 cancers
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We Have the Tools to Treat Cancer Better
Effectors
mAb scFv Protein Metabolic Intracellular RNA
toxin Ligand Enzyme decoy
Cells T Cell B Cell Macrophage NK cell Treg Other immune Epithelial Endothelial
cells
Immune Cells Non-immune Cells
Direct tumor lysis Pro-apoptosis
Anti-tumor Complement ADCC Necrosis
cytotoxicity Anti-angiogenesis
Innate immunity stimulation Growth inhibition
function Adaptive immunity stimulation Anti-tumor metabolism
Immune evasion inhibition EMT blockade
Tumor
and microenvironment
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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
Gene Expression
High Potency
Monogenic/Multigenic
RheoSwitch®
Dose-control
Orally activated biologic on/off switch
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IL-12 Production is Modulated by Veledimex (Activator Ligand) in HT 1080 Cells
ON
59
49
39
29
19 OFF
OFF
9
-1
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)
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Veledimex Tightly and Precisely Controls the Expression of IL-12ß mRNA in the Tumor
ON
1000000
100000
10000
1000
100
10
OFF OFF
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0.1
Baseline Maximum D1-D7 7 Days Post-treatment
100 mg 160 mg
Veledimex Dose n=7
Tumor mRNA (mRNA/1e6 vp)
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Cytotoxic T Cells & Memory T Cells (TILs) Significantly Increase in Tumors Following Ad-RTS-IL-12 Treatment
Off
On
CD8+
CD45RO+
Images were obtained using an Aperio ScanScope XT whole-slide imager and digitized at 20x.
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Systemic Immune Activity: patterns of anti-tumor response
%Change from baseline lesion size
50
25
0 -25 -50 -75
Patient#
1 2 3
Peak Serum IL-12 Concentration
12000
11137 ± 3530
10000
8000
6000
rIL-12 = recombinant IL-12
hIL-12 = Ad RTS IL-12
4000
2000
27 ± 14
0
rIL-12* hIL-12
Concentration of IL-12 (pg/mL)
*Atkins, MB et al Clin Cancer Res 1997;3:409-417
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Clinical Observations to Date
We can control gene 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 dosing stopped
“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
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Glioblastoma Multiforme: IL-12 Preclinical Activity
Kaplan Meier Survival in GL261 Orthotopic Syngeneic Mouse Glioma Model
100
80
Percent survival
60
40
20
0
0 10 20 30 40 50 60 70 80
Time (Days)
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
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Significant Market Potential for Ad-RTS-IL-12
Incidence
Breast Cancer
234,580
Glioma
18,000
Melanoma
76,690
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IL-12 Program Plans
Melanoma Phase 2 combination study with SOC
FPI 1H 2014
Preliminary data YE 2014
Breast Cancer Phase 2 combination study with SOC
FPI 1H 2014
Preliminary data 1H 2015
GBM Phase 1 dose-escalation study
FPI 1H 2014
Preliminary data YE 2014
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A Growing Oncology Portfolio
Compound Pre Clinical Phase 1 Phase 2
Ad-RTS-IL-12 IND
Melanoma
Breast
GBM
Cell-based programs
Cell signal targeting
Multigenic platforms
Immunotherapy programs
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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
in® and Erbitux®
Embedded cellular bioreactors to deliver multiple proteins systemically using RheoSwitch® platform
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Upcoming Milestones
Program Milestone Timing
IL-12 Phase 2 breast cancer study data 2014
Phase 2 advanced melanoma study data 2014
Initiate Phase 1/2 glioblastoma multiforme study 1H 2014
Initiate Phase 2 melanoma combo study 1H 2014
Initiate Phase 2 breast cancer combo study 1H 2014
New Indications Report discovery and preclinical data 2014
Submit INDs for monogenic/multigenic studies 2H 2014 and
beyond
Publications and Across programs 2014
Presentations
Corporate Partnering opportunities Ongoing
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Financial Highlights
Approx. 100 million shares outstanding (pro forma) Approx. $77.4 million in cash and investments (pro forma)
No debt
Development partner/top shareholder: Intrexon Corp. (NYSE: XON)
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ZIOPHARM Oncology
Phase 2 program advancing in breast cancer and melanoma
Glioblastoma results due in 2014
Preparing INDs for new studies in 2014 and 2015
Exploring multigenic combination therapies to improve standards of care
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The Future of Cancer Therapy
NASDAQ: ZIOP
www.ziopharm.com