EX-99.1 2 d658439dex991.htm EX-99.1 EX-99.1
www.ziopharm.com
J.P. Morgan 32nd Annual Healthcare Conference
January 2014
Jonathan Lewis, MD, PhD
Chief Executive Officer
The Future of Cancer Therapy
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, 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 of or non-occurrence of any events.
Forward-Looking Statements
1


Clinical-stage, synthetic-biology oncology company
Gene based therapies regulating protein expression and controlling cellular function
Clear leader in in vivo control of gene regulation and expression
Technology channel partner Intrexon Corp. (NYSE: XON)
Phase 2 program: Ad-RTS-IL-12
High intratumoral expression of IL-12
Targeting multiple cancers, including melanoma,
breast cancer and glioma
Multiple new clinical studies planned through 2015
Technology platform driving clinical program
Enabling multigenic approach to
immunotherapy and cancer therapy
Multiple INDs planned through 2015
ZIOPHARM Today
2


Synthetic DNA enables:
creation of new therapies with
targeted biofunction
precise
control
of
biologic
concentration and dosing
better therapeutic index
through controlled protein delivery
and cellular targeting
economically feasible approach
to combination biologic therapies
Why Focus on Synthetic
DNA-Based Medicine?
3
Synthetic DNA is DNA that is intelligently and intentionally
designed for a specific function.


Molecular and Cellular Oncology
DNA-Coded Toolset
4


Controlled Expression and Delivery of Therapeutic Proteins with RheoSwitch®: 
This is the most advanced clinical method to turn genes on and off
The Power of Intrexon’s RheoSwitch®
Technology
Local
High Potency
Monogenic/Multigenic
Dose-control
Orally activated biologic on/off switch
5


IL-12 Production is Modulated by Veledimex
(Activator Ligand) in HT 1080 Cells
6


Veledimex Tightly and Precisely Controls
the Expression of IL-12ß
mRNA in the Tumor
7


CD8+
CD45RO+
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.
8


Subjects with unresectable stage III/IV melanoma,
n=13 (Phase 1) + n= 8 (Phase 2, ongoing)
Intratumoral injection of Ad-RTS-hIL-12 on Day 1 of each cycle
Oral administration of veledimex to activate gene expression of hIL-12
Phase 1/2 Melanoma Study
9
Primary Objective 
Evaluate the safety and tolerability of intratumoral
injections of Ad-RTS-hIL-12 in combination with veledimex
Secondary Objective
Inform the selection of a veledimex dose and regimen
for further study in combination with Ad-RTS-hIL-12


Initial increase in lesion size due
to immune response seen
at Cycle 1 Day 16
Lesion was undetectable
at Cycle 2 Day 1
Subject ultimately progressed
and was taken off study
Prominent Tumor Infiltrating Lymphocyte
Response Correlates with Biologic Activity
C1D1
C1D16
C2D1
10


Kaplan Meier Survival in GL261 Orthotopic Syngeneic Mouse Glioma
Model
Glioblastoma Multiforme:
IL-12 Preclinical Activity
11
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


Tight control of expression and biologic activity
High expression of IL-12 mRNA in tumors, tightly controlled by veledimex dose
Increased tumor infiltrating lymphocytes (TILs)  observed in the
tumor
microenvironment, suggesting multiple favorable biologic effects of IL-12 expression
On-mechanism and on-target response and toxicity
Melanoma:
potent
biologic
activity
in
injected
and
non-injected
lesions
Breast:
on-mechanism
and
on-target
toxicity
demonstrates
powerful
manifestation
of
the
immune
system
controlled
by
dose-dependent
inducible
expression
of
IL-12
Adverse events consistent with immunotherapy use and immune response;
Serious adverse events reversed after veledimex dosing stopped
Optimization of dose and scheduling to refine response and tolerability is ongoing
“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
Clinical Conclusions to Date
12


Significant Market Potential for Ad-RTS-IL-12
13


GBM Phase 1
dose-escalation study
IL-12 Next Study Timelines
14
Melanoma Phase 2
combination study with SOC
Breast cancer Phase 2
combination study with SOC
FPI 1H 2014
Preliminary
data YE 2014
FPI 1H 2014
Preliminary
data YE 2014
FPI 1H 2014
Preliminary
data 1H 2015


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
15


We can intelligently and intentionally
construct multi-gene therapies
16


Human mesenchymal stem cells (hMSCs) genetically
modified with multigenic hIL-12, hIFNa, and CTLA4 decoy
Potential use of hMSCs for tumor-targeted delivery
of multiple RTS®
regulated cancer immunotherapies
Integration of modularized protein engineering technology
and the RTS®
platform to develop high-affinity
trastuzumab (Herceptin®) and cetuximab (Erbitux®)
single-chain variable fragment-Fc proteins for gene therapy
Potential use of inducible multigenic systems to treat
cancer using multigenic therapeutic antibodies
RTS®
regulated immunomodulatory proteins expressed
from  multigenic embedded cellular bioreactor (ECB)
using electroporation into skeletal muscle
Potential use of ECBs to deliver multiple proteins
systemically, under control of RTS®
platform
Combination Therapies Targeting Multiple
Cancers: Potential INDs
17


Upcoming Milestones
18
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
Presentations
Across programs
2014
Corporate
Seek partnering opportunities
Ongoing


Approx. 100 million shares outstanding (pro forma)
Approx. $77.4 million in cash and investments
(pro forma)
No debt
Channel partner/top shareholder
Intrexon Corp. (NYSE: XON)
Financial Highlights
19


Ad-RTS-IL-12 advancing through Phase 2 studies in breast cancer and melanoma
On-mechanism and on-target response and toxicity observed
Expanded data anticipated in late 2014 and in 2015
Pre-clinical/clinical data on glioblastoma in 2014
Poised to launch multiple new studies in 2014 and beyond
INDs targeting new gene expression patterns, new cell types and new indications
ZIOPHARM Oncology
20


www.ziopharm.com
NASDAQ: ZIOP
Jonathan Lewis, MD, PhD
Chief Executive Officer
The Future of Cancer Therapy