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| 8-K - FORM 8-K - ZIOPHARM ONCOLOGY INC | d606430d8k.htm |
 BioCentury Newsmakers
Jonathan Lewis, MD, PhD
Chief Executive Officer
The Future of Cancer Therapy
Exhibit 99.1
September 2013 |
 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 June 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 o or non-occurrence of any events.
2
September 2013 |
 1.
Clinical stage synthetic biology cancer company
2.
We believe we are the farthest advanced at regulating gene function
in
vivo
in
humans,
regulating
gene
expression,
and
titrating
levels
of expression
3.
Lead clinical program is Ad-RTS-IL-12
4.
We have multiple novel programs driving towards IND, and expect
at least 8 INDs through 2015
5.
These are built on a similar platform to Ad-RTS-IL-12, and in place
of IL-12 will include different genes of interest for immunotherapy,
cell signal targeting and novel multigenic approaches
6.
Data will be presented near-term at AACR/NCI/EORTC, SABCS,
and additional scientific meetings and publications
ZIOP
3
September 2013 |
 DNA-Based Medicine Enables
•
Therapies with desired biofunction to be
purpose-built •
The concentration/dose of biologic therapy to be
precisely controlled
•
Improvement
in
therapeutic
index,
because
potent
biologic modifiers can be turned on and off and targeted
to specific tissues and cells
•
Pursuit of combination biologic therapy in an
economically
feasible
manner
4
September 2013 |
 •
Powerful, scalable technology platform
•
Potential for innovation in cancer-drug development:
•
ZIOP collaboration with Intrexon enables:
–
better control of therapeutic index/frequency
–
multigenic approaches
–
pipeline expansion with multiple INDs
–
attractive partnership opportunities
Strategic focus on synthetic biology
Foundation in Place for Significant Growth
New cancer
treatment
paradigm
Tumor
targeting
Statistical
modeling
Precision
engineering
5
September 2013 |
 •
Clinical stage synthetic biology platform (DNA and cell-based
therapy) driving development
•
Our advantage is that we are the farthest advanced at precisely
regulating gene function in vivo in humans
•
Multiple value-creating milestones in 2013/14
–
Pre-clinical/clinical data
–
Scientific publications and presentations
•
Ad-IL-12 advancing through Phase 2 POC studies
•
Poised to deliver multiple new INDs in 2014/15/16
–
New IND submissions will expand into new genes of
interest, and cancer indications
On Track to Execute
6
September 2013 |
 Cells
DC
T Cell
B Cell
Macrophage
NK cell
Treg
Other 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
Anti-tumor function
MSC
Epithelial
Endothelial
Fibroblast and ECM
Tumor cell
Tumor and microenvironment
Effectors
Immune cells
Non-immune
Cytokines
mAb
scFv
scFv
toxin
Systemic
decoy
Intracellular
decoy
Metabolic
Enzyme
Protein
Ligand
RNA
Molecular and Cellular Oncology DNA-Coded Toolset
7
September 2013 |
 Intrexon Collaboration: Fueling the IND Engine
Genetic control of cells
Controlled delivery of therapeutic proteins
cancer drug
translational and
development expertise
Promising portfolio of cancer therapeutics
gene engineering and
cell control technology
8
September 2013 |
 Upcoming Milestones
Program
Milestone
Timing
2013-2014
IL-12
Phase 2 breast cancer study data
2H 2013/2014
Phase 2 advanced melanoma study data
2H 2013/2014
Initiate Phase 1/2 glioblastoma multiforme study
Initiate Phase 2 melanoma combo study
Initiate Phase 2 breast cancer combo study
1H 2014
1H 2014
1H 2014
Synthetic Biology
Report discovery and preclinical data
2H 2013/1H 2014
Submit new INDs for monogenic/multigenic studies
2H 2014
Small Molecule Program
Report interim SCLC data (MATISSE)
1H 2014
Publications and Presentations
AACR-NCI-EORTC; SABCS; Scientific Publications
2H 2013
Corporate
Seek partnering opportunities
Pursue new cancer targets
Divest non-strategic assets
Ongoing
9
September 2013 |
 The
Potential of DNA-Based Therapeutics •
Improve
treatment of all cancers, starting with breast
cancer, melanoma, and GBM
•
Treat
currently incurable cancers
•
Generate
a
multi-billion-dollar opportunity
10
September 2013 |
 A
Growing Oncology Portfolio IND
Compound
Pre
Clinical
Phase 1
Phase 2
Ad-RTS-IL-12
Melanoma
Breast
GBM
Cell-based programs
Cell signal targeting
Multigenic
platforms
Immunotherapy Programs
11
September 2013 |
 Multiple Opportunities for External Partnering
Aggressive IND Strategy Supporting Future Growth
12
September 2013 |
 DNA-Based Therapeutics
Controlled Delivery of Therapeutic Proteins with RheoSwitch®:
This is the most advanced clinical method to turn genes on and off
Dose-control
Orally activated
biologic on/off switch
Local
High Potency
Monogenic/Multigenic
Gene Expression
RheoSwitch®
13
September 2013 |
 Initial
Target:
Interleukin-12,
A
Potent
Cancer
Therapeutic
•
Cytokine with anti-tumor effects
•
Potent Stimulation of T-cells and
gamma interferon
•
Narrow therapeutic index/ toxicity has limited IL-12
utility
Improved therapeutic index may be possible
using RheoSwitch
®
technology
14
September 2013 |
 IL-12 Production is Modulated by Activator
Ligand in HT 1080 Cells
On
Off
On
AL=75nM
15
September 2013 |
 Regulated expression of IL-12 in the tumor by switch control
Subjects
received
intratumoral
injection
of
1x10
12
viral
particles
(INXN-2001)
on
Day
1
of
each
cycle
and INXN-1001 (subject 107, 100 mg; subject 111, 160 mg) on Days 1-7 of
each cycle. Genomic DNA
and
total
RNA
were
extracted
and
analyzed
as
described.
1
Livak KJ and TD Schmittgen. 2001. Methods
25(4):402-8.
ASCO 2013
Off
Off
Off
Off
On
16
September 2013
5604
5.4
5778
0.5
0
1000
2000
3000
4000
5000
6000
7000
Screening
C1D2
C1D15
Screening
C1D2
C1D15
Subject 107 (100 mg)
Subject 111 (160 mg)
IL-12
Fold Change Relative to Screening Visit
On
1
1
1 |
 Cytotoxic T Cells & Memory T Cells Increase in Tumor
following Treatment with Ad-RTS-hIL-12
Images were obtained using an Aperio ScanScope XT whole-slide imager and
digitized at 20x. ASCO 2013
Screening
C1D15
Subject
111
(160 mg)
17
September 2013 |
 Prominent Inflammatory Response Correlates
with
High
levels
of
IFN-
•
Initial increase in lesion size due to
inflammatory response seen at Cycle 1
Day 16
•
Lesion was undetectable at Cycle 2 Day 1
•
Subject ultimately progressed and was
taken off study
C2D1
18
September 2013
C1D1
C1D16 |
 Dose-dependent Anti-Tumor Activity of Ad-RTS-mIL-12 +
Activator Ligand (AL) in Murine 4T1 Breast Cancer Model
0
2
4
6
8
10
12
14
16
0
4
8
12
16
20
24
28
32
Time (Days)
Vehicle
Ad-RTS-mIL-12
INXN
-1001 (AL) 15 mg/m2
Ad-RTS-mIL-12 + AL 15 mg/m2
Ad-RTS-mIL-12 + AL 30 mg/m2
Ad-RTS-mIL-12 + AL 75 mg/m2
Ad-RTS-mIL-12 + AL 150 mg/m2
Tumor
volume
reached
100
–
200
mm
3
19
September 2013 |
 Glioblastoma
Multiforme:
IL-12
Preclinical
Activity
100% survival observed with Ad-RTS-IL-12 + AL or
DC-RTS-IL-12 + AL INXN-1001 dosing Day 4 to EOS at ~ 675
mg/m²/day in chow; DC –RTS-IL12 or Ad-RTS-IL12 on Day 5
Kaplan Meier Survival
in GL261 Orthotopic Syngeneic Mouse Glioma Model
0
10
20
30
40
50
60
70
80
0
20
40
60
80
100
No Treatment
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)
20
September 2013 |
 Highlights of IL-12 Program
•
Currently demonstrating safety and efficacy in Phase 2 POC
studies
•
Preparing for combination studies in melanoma, breast cancer
•
Expanding clinical program to GBM
IL-12 program reaching key milestones in 2013/2014
21
September 2013 |
 Incidence
Melanoma
76,690
Breast Cancer
234,580
Glioblastoma
18,000
Significant Market Potential for IL-12
Source: American Cancer Society 2013/Schwartzbaum 2006
22
September 2013 |
 1.
Clinical stage synthetic biology cancer company
2.
We believe we are the farthest advanced at regulating gene function
in
vivo
in
humans,
regulating
gene
expression,
and
titrating
levels
of expression
3.
Lead clinical program is Ad-RTS-IL-12
4.
We have multiple novel programs driving towards IND, and expect
at least 8 INDs through 2015
5.
These are built on a similar platform to Ad-RTS-IL-12, and in place
of IL-12 will include different genes of interest for immunotherapy,
cell signal targeting and novel multigenic approaches
6.
Data will be presented near-term at AACR/NCI/EORTC, SABCS,
and additional scientific meetings and publications
ZIOP
23
September 2013 |
 BioCentury Newsmakers
Jonathan Lewis, MD, PhD
Chief Executive Officer
The Future of Cancer Therapy
September 2013 |