Attached files
| file | filename |
|---|---|
| 8-K - 8-K - ZIOPHARM ONCOLOGY INC | d701605d8k.htm |
 March
2014 The Future of Cancer Therapy
www.ziopharm.com
Exhibit 99.1 |
 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, 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.
Forward-Looking Statements
1 |
 Clinical-stage Immuno-Oncology company
Focus on treatment through DNA expression and cell 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
ZIOPHARM Today
2 |
 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
biologic therapies and Immuno-
Oncology
Why Focus on DNA-Based Medicine?
3 |
 ZIOP:
translational medicine and oncology drug development XON: synthetic biology platform
enabling DNA delivery and control
Exclusive channel partner agreement for the treatment of 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
Intrexon Collaboration: Leveraging Our Assets
Page 4 |
 We Have the
Tools to Treat Cancer Better 5
Cytokines
mAb
scFv
scFv
toxin
Systemic
decoy
Intracellular
decoy
Metabolic
Enzyme
RNA
Protein
Ligand
DC
T Cell
B Cell
Macrophage
NK cell
Treg
Other immune
cells
Immune Cells
Direct tumor lysis
ADCC
Complement cytotoxicity
Innate immunity stimulation
Adaptive immunity stimulation
Immune evasion inhibition
Pro-apoptosis
Necrosis
Anti-angiogenesis
Growth inhibition
Anti-tumor metabolism
EMT blockade
Non-immune Cells
Effectors
Cells
Anti-tumor
function
Tumor
and microenvironment
MSC
Epithelial
Endothelial
Tumor
Cell
Skeletal
Muscle |
 Controlled
Expression and Delivery of Therapeutic Proteins with Intrexon’s RheoSwitch®:
This is the most advanced clinical method to turn genes on and off
The Power of RheoSwitch®
Technology
High Potency
Monogenic/Multigenic
Dose-control
Orally activated biologic on/off switch
Gene Expression
RheoSwitch®
6 |
 Ad-RTS-IL-12: Solving the Problem of Serum
Concentration
Page 7
rIL-12 = recombinant
IL-12
hIL-12 = Ad-
RTS-
IL-12
*Atkins, MB et al Clin Cancer Res 1997;3:409-417
11137 ±
3530
27 ±
14
0
2000
4000
6000
8000
10000
12000
rIL-12*
hIL-12 |
 IL-12
Production is Modulated by Veledimex (Activator Ligand) in HT 1080 Cells
8
OFF
OFF
ON
-1
9
19
29
39
49
59
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
90
Time after viral transduction (hours) |
 Oral Veledimex
Tightly and Precisely Controls the Expression of IL-12ß mRNA in the Tumor
9
Veledimex Dose
n=7
OFF
OFF
ON
0.1
1
10
100
1000
10000
100000
1000000
Baseline
Maximum D1-D7
7 Days Post-treatment
100 mg
160 mg |
 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. 10
On
Off
CD8+
CD45RO+ |
 Systemic
Immune Activity: Patterns of Anti-Tumor Response
Patient#
1
3
2
Page 11
-75
-50
-25
0
25
50 |
 High
expression of IL-12 mRNA in tumors, tightly controlled by veledimex dose Clinical
Observations to Date 12
We can control gene expression to achieve a desirable immune response
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
Increased tumor infiltrating lymphocytes observed in the tumor
microenvironment,
suggesting
multiple
favorable
biologic
effects
of
IL-12
expression |
 Kaplan Meier
Survival in GL261 Orthotopic Syngeneic Mouse Glioma Model
Glioblastoma Multiforme:
IL-12 Preclinical Activity Measuring Survival
13
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 0
10
20
30
40
50
60
70
80
0
20
40
60
80
100
DC-no vector
DC-RTS-IL12 (MOI 10000)
Ad-RTS-IL12
(5x10
9
)
AL chow
Ad-RTS-IL12
(5x10
9
) + AL
DC-RTS-IL12 (MOI 10000) + AL
Time (Days)
No Treatment |
 Significant
Market Potential for Ad-RTS-IL-12 14
Melanoma
76,690
Breast Cancer
234,580
Incidence
Glioma
18,000 |
 A Growing
Oncology Portfolio 15
Compound
Pre Clinical
Phase 1
Phase 2
Ad-RTS-IL-12
IND
Melanoma
Breast
GBM
Cell-based programs
Immuno-Oncology
programs
Cell signal targeting
Multigenic platforms |
 Human
allogeneic mesenchymal stem cells genetically modified with genes that activate the
immune system to destroy cancer
Multigenic therapeutic antibodies such as single
chain versions of Herceptin®
and Erbitux®
Embedded cellular bioreactors to deliver multiple
proteins systemically using RheoSwitch®
platform
DNA Combination Therapies:
Potential Future INDs
16
*
AACR-NCI-EORTC 2013 |
 Upcoming
Clinical Milestones 17
Program
Milestone
Timing
Breast cancer
Initiate Phase 2 combination study with SOC
1H 2014
-
Report preliminary data
1H 2015
Report results from ongoing Phase 2 study
2014
Melanoma
Initiate Phase 2 combination study with SOC
1H 2014
-
Report preliminary data
YE 2014
Report results from ongoing Phase 2 advanced
melanoma study
2014
Glioblastoma
Initiate Phase 1/2 dose escalation study
1H 2014
-
Report preliminary data
YE 2014 |
 Approx. 100 million shares outstanding Approx. $68 million in cash and investments No debt
Development partner/top shareholder:
Intrexon Corp. (NYSE: XON)
Financial Highlights
18 |
 We
understand the biologic basis of cancer- and how to
engineer
new products
We have the ability to deliver DNA and stimulate a controlled
therapeutic
immune response
Clinical testing is validating our vision
Intrexon
partnership is enabling expansion of our pipeline
Big pharma
is very
interested
in our approach
We have the potential to radically change the economics
of
cancer treatment
Our financial success
will be driven by multiple products and
collaborations,
not one or two
Why Invest in ZIOPHARM?
Page 19 |
 NASDAQ:
ZIOP The Future of Cancer Therapy
www.ziopharm.com |