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

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8-K - FORM 8-K - ZIOPHARM ONCOLOGY INC	d502146d8k.htm

Better Cancer Medicine

Barclays Global Healthcare Conference

Jonathan Lewis, MD, PhD

Chief Executive Officer

Exhibit 99.1

March 13, 2013

Forward-Looking Statements

This presentation contains certain forward-looking statements about ZIOPHARM Oncology that are 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; our expectations regarding approval for our products by the U.S. Food and Drug Administration or equivalent foreign

regulatory agencies; estimates regarding the market potential for our products; 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 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 therapeutic product 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 our therapeutic products; 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

Form

10-K

for

the

fiscal

year

ended

December

31,

2011,

and

our

Quarterly

Report

Form

10-Q for

the fiscal quarter ended September 30, 2012. 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.

March 13, 2013

Small

Molecules

Synthetic

Biology

Better Cancer Medicine

Diverse Portfolio of Therapeutics Addressing

Unmet Medical Needs in Cancer

Paradigm Shifting Approaches

to Impact and Cure Cancer

March 13, 2013

Data-Driven Oncology Portfolio

March 13, 2013

Palifosfamide

Soft Tissue Sarcoma

Small Cell Lung Cancer

Oral Formulation

Ad-RTS-IL-12

Melanoma

Breast (+palifosfamide)

Other Candidates

Indibulin

Breast Cancer

Darinaparsin

PTCL

Compound

Preclinical

Phase 1

Phase 2

Phase 3

•

Palifosfamide

–

Two Phase 3 programs

•

Metastatic soft tissue sarcoma

•

Small cell lung cancer

–

Potential in multiple tumor types

–

Exceptional intellectual property profile (t0 2029)

•

Synthetic Biology

–

Two Phase 2 programs

•

Melanoma

•

Breast cancer

–

Exploring multiple opportunities for new-paradigm treatment modality

–

Controlled switch for in vivo protein production

Near-Term Value Drivers

March 13, 2013

Major Clinical Milestones Over Next 18 Months

Q1-13

Q2-13

Q3-13

Q4-13

Q1-14

Q2-14

Possible NDA Submission

TOP LINE DATA

Possible ASCO Late-breaking

Interim Analysis

Palifosfamide

IL-12 DNA

Possible Phase 1 Melanoma ASCO Presentation

March 13, 2013

MATISSE

PHASE 2 MELANOMA

PHASE 2 BREAST CANCER (COMBO)

PICASSO

Palifosfamide

March 13, 2013

Broad Application

Effect in solid tumors and hematological malignancies

Safety, Efficacy and

Accessibility

Potent bi-functional DNA alkylating agent that has

activity in multiple tumors by evading typical

resistance pathways (in class with bendamustine,

cyclophosphamide, and ifosfamide), with low toxicity

and ease of administration

Addressing Unmet Needs

Orphan Drug status established for STS in U.S. and

Europe

Exceptional Intellectual

Property Profile

U.S. pharmaceutical composition patent rights

extending to 2029; other pending applications WW

A Potent Bi-Functional DNA Alkylating Agent

March 13, 2013

Soft Tissue Sarcoma

•

High unmet medical need; no first-line drug approved in ~30 years

•

First-line metastatic, non-GIST STS:

–

Approximately 9,000 in U.S.

–

Approximately 14,000 in Europe

•

Market in transformation

March 13, 2013

–

April 2012 FDA full approval of Votrient

for second-line

therapy (PFS endpoint); August 2012 European full approval

remainder of world Company estimated from epidemiology (SEER, NCCN).

IntrinsiQ: # new patient prescriptions written for first-line, non-GIST STS over 12 months.

Votrient

ODAC

March

20,

2012

Phase 3 Design (PICASSO 3)

447 subjects; first-line metastatic STS

Regimen:

Palifosfamide + doxorubicin vs. placebo + doxorubicin

Primary Endpoint:

PFS for full approval

Powering:

Powered for both PFS and OS

PFS Analysis:

Independent blinded radiologic review; Efficacy analysis by IDMC

IDMC following pre-determined number of PFS events

Results:

Pivotal topline PFS data, OS futility analysis (OS remains blinded)

to be announced week of March 25, 2013

March 13, 2013

•

PFS primary endpoint in Phase 3 registration trials and

now supportive for certain indications:

–

In 2011, 4 oncology products approved based on PFS as primary

trial endpoint

–

In 2012, 7 oncology products approved based on PFS as primary

trial

endpoint,

including

pazopanib

(Votrient

)

receiving

full

approval for STS

Regulatory Strategy: Evolving Landscape of

PFS as Primary Endpoint

March 13, 2013

Multicenter, Randomized, Stratified, Balanced

Phase 2 Data (PICASSO)

Source: Best of ASCO 2010 (PFS Data), internal analysis (OS Data)

* Expected 2-yr survival is 25% based on evaluation of randomized data

** Control arm confirmed by EORTC ifosfamide vs doxorubicin study, ESMO 2012

March 13, 2013

Phase 3: Correctly Modeled and Powered for PFS & OS

PFS: median

7.8 mos.

4.4 mos.

PFS: hazard ratio

0.43

OS: hazard

ratio (with crossover)

0.78

2-yr survival (with crossover)*

40%

30%

Safety

•

Similarity between arms

•

encephalopathy, hemorrhagic cystitis, Fanconi's Syndrome

Grade 3+ events

•

Neutropenia and elevated creatinine (

similar between arms

)

Pali+Dox

Dox**

Arm

EORTC 62012 Randomized Phase 3 Trial (ESMO)

PICASSO

EORTC

Appropriate Risk/Benefit Ratio Is Critical

March 13, 2013

Pali+Dox

Dox

Ifos+Dox

Dox

PFS: median

7.8 mos.

4.4 mos.

7.4 mos.

4.6 mos.

PFS: hazard ratio

0.43

0.74

OS: hazard

ratio (with

crossover

)

0.78

2yr. N/A (mOS: 0.83)

2-yr survival

40%

30%

31%

28%

Safety

•

Similarity between arms

•

encephalopathy, hemorrhagic

cystitis, Fanconi's Syndrome

•

Dropouts for toxicity

17.6% (I+D) vs.

2.6% (D) (including toxic death)

Grade 3+ events

•

Neutropenia and elevated creatinine

(similar between arms)

•

Febrile Neutropenia

45.9% (I+D) vs.

13.6% (D)

Small Cell Lung Cancer

•

High unmet medical need; no innovation in decades

•

Worldwide

market

opportunity:

250,000+patients

–

30,000-35,000 patients in the U.S.

•

Rationale: ifosfamide only first-line therapy to show benefit added to

SOC

(platinum

plus

etoposide)

excessive

toxicity

•

Palifosfamide added to SOC demonstrating early success in highly

refractory

patients

combination

well

tolerated

SEER, Globocan.

March 13, 2013

Hoosier Oncology Group - Einhorn et. al.

MATISSE Adaptive Trial Design

Single pre-planned

evaluation by the IDMC

•

125

Events

Continue trial with decreased sample size

Complete trial as planned

Continue trial with increased

event size

March 13, 2013

Optimize chances of success

Stop trial for efficacy/futility

Complete trial as planned or resize/

repower study

•

MATISSE

trial

enrollment

ahead

projection

•

Successful IDMC safety review of initial 20 patients

•

Interim analysis of 125 events expected end of 2013

MATISSE Trial Progress

March 13, 2013

•

Recent,

U.S.

orphan

drug

launches

oncology

priced

$9K

$23K

per cycle range

–

Examples

products:

Adcetris

™

Caprelsa

Zelboraf

Market Potential

Scenarios

U.S.

Only

Peak

Gross

Revenues

$Million

Palifosfamide Price Per Patient Per Year

Patients

Treated

$ 54,000

$ 72,000

$ 90,000

Soft Tissue

Sarcoma

4,000

$ 216

$ 288

$ 360

4,500

$ 243

$ 324

$ 405

5,000

$ 270

$ 360

$ 450

Small Cell

Lung Cancer

8,000

$ 432

$576

$ 720

10,000

$ 540

$ 720

$ 900

12,000

$ 648

$ 864

$ 1,o80

SCLC

March 13, 2013

>$1

total

global

market

potential

for

palifosfamide

STS

and

Synthetic Biology

March 13, 2013

•

Revolutionary technology for precise, controlled delivery of DNA

expressing therapeutic proteins in vivo

•

Lead Ad-RTS-IL-12 candidate in melanoma, breast cancer

•

Next generation of therapeutic approaches in research pipeline

–

Modular inducible cancer immunotherapy (MICI)

–

Antibody therapy

–

Multigenic approaches

Synthetic Biology

March 13, 2013

Using Natural Cell Biology to Produce Proteins:

Adenoviral Approach

Oral ligand activates DNA

transcription, protein

production begins

Target Cell

March 13, 2013

mRNA

Translation

Therapeutic

proteins

Adaptable

Controlled

Precision

Phase 1/2 Ad-RTS-IL-12 Candidate

•

Ad-RTS-IL-12 Phase 1b in metastatic melanoma

–

Biologically effective dose was determined

–

Clinical activity observed in 71% of patients (n=7),

two highest dose cohorts

–

No dose-limiting toxicity reported to date

•

Ad-RTS-IL-12 Phase 2 in metastatic melanoma

–

Multi-center, single-arm, open-label expansion stage

study

–

Enrolling up to 15 patients

Baseline

Necrosis prior

to cycle 2

March 13, 2013

Design

Randomized, open-label study of Ad-RTS-IL-12 monotherapy

combination with palifosfamide in patients with

recurrent/metastatic breast cancer and accessible lesions

Up to 68 subjects

Population

Recurrent/metastatic breast cancer

Primary Endpoint

16-week PFS rate

Select Secondary

Endpoints

•

Objective response rate by modified RECIST v1.1

•

Duration of response

•

Evaluate pharmacodynamic tumor markers

Outcome

•

Changing regulatory landscape of breast cancer

•

Acceptance of pCR (pathologic CR) as a validated

endpoint for accelerated approval in neoadjuvant setting

•

Potential rapid positioning of this combination from

refractory to neoadjuvant setting

Phase 2 Breast Cancer

Ad-RTS-IL-12 + palifosfamide

March 13, 2013

Using Synthetic and Natural Cell Biology to Produce Proteins:

Intramuscular Plasmid DNA

EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics 2012 (animal model).

Therapeutic

Proteins

Engineered DNA Transgene

Plasmids

Orally Activated

Sustained protein production and therapeutic anti-tumor efficacy drawing

from only a single intramuscular administration of plasmid DNA.

March 13, 2013

Next Generation: Multigenic Approach

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

0.0

1.0

2.0

3.0

4.0

5.0

6.0

7.0

8.0

LacZ/rLUC Uninduced

fLUC/rLUC Uninduced

SEAP/rLUC Uninduced

GUS/rLUC Uninduced

LacZ/rLUC Induced

fLUC/rLUC Induced

SEAP/rLUC Induced

GUS/rLUC Induced

Conclusion:

4 Inducible gene programs can

be placed in parallel on the

same vector without affecting gene program performance

#: Not significantly different than

background (p>0.05)

*: Not significantly different than

the control (p>0.05)

March 13, 2013

•

Primary shares outstanding: approximately 83.2M

•

Cash: approximately $95.3M @ 9/30/12

•

Current cash resources expected to support operations

into 2H 2013

Financial Highlights

March 13, 2013

Major Clinical Milestones Over Next 18 Months

Q1-13

Q2-13

Q3-13

Q4-13

Q1-14

Q2-14

Possible NDA Submission

TOP LINE DATA

Possible ASCO Late-breaking

Interim Analysis

Palifosfamide

IL-12 DNA

Possible Phase 1 Melanoma ASCO Presentation

March 13, 2013

PHASE 2 BREAST CANCER (COMBO)

MATISSE

PICASSO

PHASE 2 MELANOMA

Better Cancer Medicine

Barclays Global Healthcare Conference

Jonathan Lewis, MD, PhD

Chief Executive Officer

March 13, 2013

ZIOPHARM ONCOLOGY INC - FORM 8-K - EX-99.1 - March 13, 2013

Attached files

ZIOPHARM ONCOLOGY INC Reports