ZIOPHARM ONCOLOGY INC - FORM 8-K - EX-99.1

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8-K - FORM 8-K - ZIOPHARM ONCOLOGY INC	d545839d8k.htm

Better Cancer Medicine

Deutsche Bank 38

Annual Healthcare Conference

Jonathan Lewis, MD, PhD

Chief Executive Officer

Exhibit 99.1

May 29, 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 March 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.

May 29, 2013

DNA Therapeutics

Using the power of DNA to treat

and prevent cancer

May 29, 2013

May 29, 2013

•

Paradigm-shifting, synthetic biology technology for precise, controlled

delivery of therapeutic proteins in vivo

•

Engineered

approach to product design allows us to rapidly develop new

genetically-based treatments for cancer with multiple effectors

•

Focused, disciplined and iterative approach to development decreases risk

through:

–

Early “go/no go”

decisions

–

Fast proof-of-concept and preclinical validation

–

Creating a virtuous circle of product development and improvement

–

Minimizing expense

•

Lead candidate, Ad-RTS-IL-12 in Phase 2 clinical trials for melanoma and

breast cancer

DNA-Based Therapeutics

May 29, 2013

Cells

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

toxin

Systemic

decoy

Intracellular

decoy

Metabolic

Enzyme

Protein

Ligand

RNA

Molecular and Cellular Oncology DNA-Coded Toolset

May 29, 2013

A Platform System for Rapidly Developing

Controllable DNA Therapies

Inventoried DNA modules

Monogenic

Multigenic

Viral delivery vector

RheoSwitch

Therapeutic System

3’

Target Gene(s)

for Expression

Intramuscular Cell Plasmid

REG

May 29, 2013

Using Natural Cell Biology to Regulate Proteins

Target Cell

Controlled

Therapeutic

proteins

Adaptable

Precision

mRNA

Oral ligand activates

DNA, protein

production begins

Translation

May 29, 2013

Ad IL-12

Melanoma

Breast

GBM

DC IL-12

Melanoma

GBM

Cell signal targeting

Multigenic platforms

Immunotherapy Programs

Palifosfamide

(SCLC)

Science-Driven Oncology Portfolio

IND

Compound

Pre Clinical

Phase 1

Phase 2

IL-12 Program

Ad-RTS-IL-12

DC-RTS-IL-12

May 29, 2013

May 29, 2013

Ad-RTS-IL-12

•

Interleukin-12 (IL-12) is

a potent, naturally

occurring anti-cancer

protein central to

initiation and regulation

of cellular anti-cancer

immune responses

•

Regulated intratumoral

expression of IL-12

promotes activation of

TIL’s to drive a cytotoxic

immune response

against distant tumors

May 29, 2013

Increases CD8

TILs in the 4T1 Syngeneic Mouse Model

Vehicle

INXN-1001

150

mg/m

Ad-RTS-mIL-12

1x10

May 29, 2013

Systemic Tumor Response in B16 Melanoma Model

Group

untreated;

Group

food

~675

mg/m

/day;

Group

Ad-RTS-mIL-12

1x10

Days 12 & 19; Group 4 AL + Ad-RTS-mIL-12. Arrows = administration of Ad-RTS-mIL-12

Treated

Tumor

the

Right

Flank

Untreated

Tumor

the

Left

Flank

May 29, 2013

A Phase I/II, Open Label Study of Ad-RTS-hIL-12 + AL in

Subjects with Unresectable Stage III or IV Melanoma

•

3 + 3, single-arm design

•

Primary endpoint –

Safety and tolerability of intratumoral injections of

1012 vp

Ad-RTS-hIL-12 in combination with escalating doses of

INXN-1001

•

Secondary endpoint –

Inform the selection of a dose of INXN-1001

•

Phase I dose escalation complete

•

Phase II ongoing (preliminary data 1H 2014)

5mg

(INXN-1001)

20mg

(INXN-1001)

100mg

(INXN-1001)

160mg

(INXN-1001)

160mg

(INXN-1001)

12 subjects in Phase I (dose escalation)

Up to 15 subjects in Phase 2 (expansion)

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

C1D1

C1D16

C2D1

May 29, 2013

•

Clinical activity at 100 mg and 160 mg doses coincided with the highest

serum levels of IL-12 and IFN-

Summary of Immunological and Clinical Activity

–

Prominent inflammatory responses in injected and non-injected

lesions

–

Decrease in size of injected and non-injected lesions

•

Clinical activity at higher dose cohorts (5 of 7, 71%)

–

4-fold median increases from baseline at peak levels compared with

lower dose cohorts

•

Dose-dependent increase in serum levels of IL-12 and IFN-

•

Flow cytometric analyses of PBMCs revealed

–

7-fold and 4-fold median increase from baseline at peak levels in

absolute CD3+ and CD8+ T cell values, respectively, compared with

lower dose cohorts

May 29, 2013

Summary of Safety

May 29, 2013

•

Controlled expression of IL-12 limits systemic toxicity while inducing

biological and clinical activity in a dose-dependent fashion

–

Toxicity reversible on stopping oral activator ligand

•

The

most

common

TEAEs

( 20%

subjects):

•

Chills and Pyrexia (73% each), Nausea (67%), Fatigue (60%),

Vomiting (33%), Anorexia (27%), Arthralgia and Diarrhea (20%

each)

•

Toxicity profile is consistent with the MOA of the drug

•

No DLT identified

•

One

unrelated

death

secondary

septicemia

•

Preclinical

–

Intratumoral administration of Ad-RTS-mIL-12 (Ad) in 4T1 BALB/c

mouse breast carcinoma model: dose-related decrease in tumor growth

rate. (AACR 2013)

–

Therapeutic strategy appears to be well tolerated

•

Phase 2

–

Multi-center, randomized, open-label

–

Ad-RTS IL-12 in combination w/palifosfamide

–

Non-resectable, recurrent or metastatic breast cancer

–

Enrolling up to 68 patients

–

Early data expected year end 2013

Advanced Breast Cancer

May 29, 2013

Dose-dependent Anti-Tumor Activity of in

Murine 4T1 (Breast Cancer) Model

Time (Days)

Vehicle Control

Ad-RTS-mIL12 (AD)

INXN-1001 (AL) 15 mg/m2

AD + AL 15 mg/m2

AD + AL 30 mg/m2

AD + AL 75 mg/m2

AD + AL 150

mg/m2 IPM 40

mg/m2

IPM 80 mg/m2

IPM 120 mg/m2

AD + AL 30 mg/m2 + IPM 40mg/m2

AD + AL 30 mg/m2 + IPM 120

mg/m2

Tumor Size Quadruple

Start of Treatment

May 29, 2013

Glioblastoma Multiforme: Promising 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

GL261

Orthotopic

Syngeneic

Mouse

Glioma

Model

100

No Treatment

DC-no vector

DC-RTS-IL12 (MOI 10000)

Ad-RTS-IL12 (5x10

)

AL chow

Ad-RTS-IL12 (5x10

) + AL

DC-RTS-IL12 (MOI 10000) + AL

Time (Days)

May 29, 2013

May 29, 2013

Preclinical and

Discovery

Programs

A Platform System for Rapidly Developing

Controllable DNA Therapies

Inventoried DNA modules

Monogenic

Multigenic

Viral delivery vector

RheoSwitch

Therapeutic System®

3’

REG

Target Gene(s)

for Expression

Intramuscular Cell Plasmid

May 29, 2013

Using Natural Cell Biology to Regulate Proteins

May 29, 2013

Precision

Oral ligand activates

DNA, protein

production begins

Controlled

Therapeutic

proteins

Adaptable

Translation

mRNA

Target Cell

IP1:

LacZ

IP1:

LacZ

rLUC

Stuffer

SP-RTS

IP2:

fLuc

IP2:

fLuc

rLUC

Stuffer

SP-RTS

IP3:

SEAP

IP3:

SEAP

rLUC

Stuffer

SP-RTS

IP4:

GUS

IP4:

GUS

rLUC

Stuffer

SP-RTS

IP4:

GUS

IP4:

GUS

rLUC

SP-RTS

IP1:

LacZ

IP1:

LacZ

IP2:

fLuc

IP2:

fLuc

IP3:

SEAP

IP3:

SEAP

#: Not significantly different than

background (p>0.05)

*: Not significantly different than

the control (p>0.05)

Next Generation: Multigenic Approach

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

LacZ/rLUC Uninduced

SEAP/rLUC Uninduced

LacZ/rLUC Induced

SEAP/rLUC Induced

fLUC/rLUC Uninduced

GUS/rLUC Uninduced

fLUC/rLUC Induced

GUS/rLUC Induced

Conclusion:

4 Inducible gene programs can be placed in parallel on the

same vector without affecting gene program performance

May 29, 2013

Small Molecule

Programs

May 29, 2013

Small Molecule Programs

Palifosfamide

Bi-functional DNA alkylating agent that has activity in multiple tumors by evading

typical resistance pathways, less toxic and ease of administration

Phase

soft

tissue

sarcoma

program

terminated,

ongoing

adaptive

Phase

small

cell lung

Indibulin

Novel oral tubulin binding agent; expected low toxicity, neurotoxicity not seen

Ongoing Phase 1/2 study in metastatic breast cancer

Darinaparsin

Novel

mitochondrial-

and

hedgehog-targeted

agent

(organic

arsenic);

oral

and

Ongoing studies in partnership with Solasia

May 29, 2013

Expected Milestones

Program

Milestone

Timing

2013

IL-12

Melanoma preliminary Phase 2 data

Breast cancer preliminary Phase 2 data

GBM preclinical proof of concept

Multigenic platforms

Preclinical data

Immunotherapy

Programs

Preclinical data

2014

Palifosfamide

Interim SCLC data (MATISSE)

IL-12

GBM Phase 1 / 2 study initiation

Melanoma Phase 2 data

Breast Phase 2 data

May 29, 2013

•

Primary shares outstanding: approximately 82.9M

•

Cash: approximately $55.7M @ 3/31/13

•

Current cash resources expected to support operations

into 1Q 2014

Financial Highlights

May 29, 2013

•

Paradigm-shifting, synthetic biology technology for precise,

controlled delivery of therapeutic proteins in vivo

•

Engineered approach to product design allows us to rapidly develop

new genetically-based treatments for cancer with multiple effectors

•

Focused, disciplined and iterative approach to development

•

Lead therapeutic Ad-RTS-IL-12 in Phase 2 melanoma and breast

cancer for early validation of target and platform

•

“Next-wave”

of therapeutic approaches in research pipeline

(antibody technology, protein-protein technology, immunotoxins,

etc.)

•

Well capitalized through data inflection points

Conclusion

May 29, 2013

Better Cancer Medicine

Deutsche Bank 38

Annual Healthcare Conference

Jonathan Lewis, MD, PhD

Chief Executive Officer

May 29, 2013

ZIOPHARM ONCOLOGY INC - FORM 8-K - EX-99.1 - May 29, 2013

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