Alaunos Therapeutics (TCRT) 8-K Regulation FD Disclosure

June 2015

www.ziopharm.com

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,

2014

and

other

filings

with

the

SEC,

which

are

available

at

www.sec.gov.

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.

1

Forward-Looking Statements

Financial Highlights

NASDAQ symbol “ZIOP”

Approximately 128.2 million shares outstanding

Cash and cash equivalents of approximately $129.7 million

Cash resources sufficient to fund our operations into 2Q 2017

Excludes 2Q payment of $57.5 million from Intrexon related to the

biopharmaceutical business of Merck KGaA

agreement

No debt

* As of March 31, 2015

2

Intrexon

and ZIOPHARM Collaboration with the 

Biopharmaceutical Business of Merck KGaA

Highlights

Significant Value of CAR-T Platform

3

Exclusive strategic collaboration and license agreement to develop and commercialize

CAR-T cancer therapies

Exclusive access to CAR T suite of technologies, including MD Anderson technologies

Intrexon

and ZIOPHARM responsible for all platform and product developments until IND filing

Biopharmaceutical business of Merck KGaA

to nominate targets of interest, lead IND filing and pre-IND

interactions, clinical development and commercialization

Intrexon

and

ZIOPHARM

retain

ability

to

explore

targets

independently,

granting

Merck

KGaA

opt-in

rights

during clinical development

Up to $941M for two

targets recognizes value of CAR T programs and technology, de-

risks portfolio and adds significant global development expertise

Upfront, milestone and royalty payments divided evenly between ZIOPHARM and

Intrexon

Upfront payment of $115 million

For the first two targets, up to $826 million development, regulatory and commercial milestones ($413 million

per product)

Tiered royalties up to lower-double digits on net sales

Merck KGaA

may elect additional targets at additional cost

Key Investment Highlights

Robust synthetic immunology pipeline targeting hematologic

malignancies and solid tumors

Non-viral and viral CAR-T, TCR, and NK-cell therapies

IL-12 gene therapy: adenoviral vector for IL-12 expression controlled via oral activator

Differentiated technology platforms

In vivo control of gene expression by oral pill

Non-viral: faster and less complex

lower cost

Dual approach: Point-of-Care (autologous) & Off-the-Shelf (allogeneic)

Agreement with biopharmaceutical business of Merck KGaA: to

elect initial 2 CAR-T targets

Multiple trial launches in 2015/2016 with potential data in Q4 2015

Well capitalized

4

Milestones 2015 / 2016

Intra-tumoral IL-12 RheoSwitch

®

Phase 1/2 Breast Cancer with SOC

initiated Q2 2015

Phase 1 GBM initiated Q2 2015 –

potential early data Q4 2015

CAR-T

Initiate Phase 1 next-generation CD19 CAR trials

Potential early data on Phase 1 CARs studies in Q4 2015

Initiate novel CAR for myeloid malignancies in late 2015/early 2016

Other Leukemia and Solid Tumor CAR-T trials in 2016

Allogenic, Off-the-Shelf T-Cell Studies in 2016

5

Overall strategy and differentiation

6

Robust Pipeline In

Synthetic Immunology

Compound

Pre Clinical

Phase 1

Phase 2

Ad-RTS-IL-12 gene Rx

IND

Breast

GBM

Adoptive Cell Therapies

B-cell

Malignancies

Myeloid Malignancies

RTS-controlled

T cell

Solid Tumors

Universal Donor

7

IL-12 Gene Therapy

Adenoviral vector engineered

to express IL-12 utilizing

RheoSwitch Therapeutic

System® gene switch

Injected intra-tumor with IL-12

expression controlled via

administration of oral activator

ligand veledimex

Regulated intra-tumoral

expression of IL-12 promotes

activation of tumor-infiltrating

lymphocytes to drive cytotoxic

immune response against

distant tumors

8

Ad-RTS-IL-12 —

Oral Veledimex

Precisely Controls Expression of IL-12 (in vivo control)

9

Improved persistence and survival in tumor microenvironment

Limits on-target, off-tumor toxicities

Phase 1b/2 Study of IL-12 Gene Therapy in

Locally Advanced/Metastatic Breast Cancer

Immunotherapy phase of treatment

A single cycle of Ad-RTS-hIL-12 +

veledimex

goal of maintaining or improving pre-

study response

1

O

: Safety and tolerability

2

O

: ORR, disease control and biomarkers

Immunotherapy phase of treatment

A single cycle of Ad-RTS-hIL-12 +

veledimex

goal of maintaining or improving pre-

study response

1

O

: Safety and tolerability

2

O

: ORR, disease control and biomarkers

N = 40

locally advanced or metastatic

breast cancer of all subtypes

up to 20% (8 subjects) with

HER2+ breast cancer

Response (PR or SD) to first-

or second-line standard

therapy

N = 40

locally advanced or metastatic

breast cancer of all subtypes

up to 20% (8 subjects) with

HER2+ breast cancer

Response (PR or SD) to first-

or second-line standard

therapy

Suspend

chemotherapy

phase of treatment

(HER2 therapy

permitted)

Suspend

chemotherapy

phase of treatment

(HER2 therapy

permitted)

10

Phase 1 Study of IL-12 Gene Therapy in Recurrent

or Progressive Glioblastoma/Gr.III

Malignant Glioma

A single cycle of Ad-RTS-hIL-12 +

escalating veledimex

1

O

: Safety and tolerability

2

O

: Determine MTD and immune

response,

including

ORR,

PFS

and

OS

A single cycle of Ad-RTS-hIL-12 +

escalating veledimex

1

O

: Safety and tolerability

2

O

: Determine MTD and immune

response,

including

ORR,

PFS

and

OS

N = 72

Recurrent or progressive

glioblastoma or Grade III

malignant glioma

Stratified according to clinical

indication for tumor

resection: Resection plus

injection vs. stereotactic

injection alone

N = 72

Recurrent or progressive

glioblastoma or Grade III

malignant glioma

Stratified according to clinical

indication for tumor

resection: Resection plus

injection vs. stereotactic

injection alone

11

Cell Therapy

Portfolio of Effector Cells

1. Chimeric Antigen Receptor (CAR+) T cells:

Target cell surface tumor-associated antigens (TAAs) independent of HLA

“Public” antigens

2. T Cell Receptor (TCR

+

) cells:

Target intracellular TAAs dependent on HLA

“Private” antigens

3. Natural Killer (NK) cells:

Target tumor with loss of HLA

No “antigens”

12

Improving the Therapeutic Potential of

CAR-T

Understanding of the effector cell biology

Co-stimulation with cytokine

Signals 1 & 2

Signal 3

13

Advantages of

Non-Viral Gene Integration 

Sleeping Beauty transposon/transposase system

Fast, efficient and nimble gene transfer method

Improves

cost, time, and complexity compared to viral-based integration

14

Management of Potential Toxicity

through Inducible Immunoreceptor

Expression (in vivo control)

Many attractive target antigens are also expressed on normal cells

Inducible

CAR

+

T

Cell

Inducible

TCR

+

T

Cell

CAR

+

T

Cell

TCR

+

T

Cell

15

Veledimex

Next

Generation

Building the Next-Generation of

Inducible Cytokines (in vivo control)

Therapeutic potential of effector cells depends on recognition of tumor cells and

recycling effector function in tumor microenvironment. 

16

Veledimex

Next

Generation

IL-12 Cell Therapy

Zhang, Rosenberg et al., Feb 2015, Clinical Cancer Research

Tumor Infiltrating Lymphocytes Genetically Engineered with an Inducible Gene Encoding

Interleukin-12 for the Immunotherapy of Metastatic Melanoma

•

TIL plus IL-12 can mediate objective responses in up to 70% of

patients with metastatic melanoma

•

Enhances the activity of effector CD4+ and CD8+ T cells as well

as natural killer NK and NK T cells

•

Collapse of tumor stroma is triggered by IL-12 induction of Fas*

•

50 to 100 fold fewer cells compared to standard TIL protocols

and in the absence

of IL-2 co-administration

•

Transferred cells did not

persist long-term and

were associated with

severe dose-limiting

toxicity

* Kerkar, Rosenberg et al., Mol

Ther. 2013 Jul;21(7):1369-77

17

Next-generation CAR

+

T cells

Bioprocessing

Close system

Ex vivo cytokines

Cryopreservation

CAR design

Humanization

Stalk

Endodomains

Cytokine

IL-12

Others

Time in culture

0-30 days

18

New CD-19 CAR Design Using Sleeping

Beauty

Prior Sleeping Beauty CAR Design

Modified-1 Sleeping Beauty CAR Design

T cell infusion (day 1)

Next-generation design demonstrates

superior in vivo activity in pre-clinical models

Established Disease Model

Minimal Residual Disease Model

T cell infusion (day 6)

Prior Sleeping Beauty CAR Design

Modified-1 Sleeping Beauty CAR Design

19

Cytokine Signaling Enhances CARs

Persisting T-cell Subsets (in vitro):

Established Disease Model

20

CD95 Expression:     

+          +          +   

+

Memory Subset:      

SCM

CM           EM

EMRA

CD19-specific CAR

+

T cells

Template for CAR

+

T cells

Safety

•

Nearing completion

Efficacy

•

New CAR

Efficacy

POC

OTS

•

Generate in

advance of need

21

Dual CMC Distribution Approaches for

Cell Therapies

Registration Trials & Global Distribution

with Multiple Pharma Partners

Centralized

Point-of-care

(POC)

Genetically

modified T cells

One patient

Multiple Patients

Autologous T cells

Allogeneic T cells

Real time

In advance of need

22

Self

Months

Months

Weeks

Weeks

Days

Days

Hours

Hours

T-cell manufacturing time

T-cell

acquisition

Genetic

modification

Infusion

Steps Toward Point-of-Care Distribution

23

Off-the-Shelf (OTS) Solution

24

Safely infuse patients

No immediate or late toxicity

No excess GVHD

Outpatient infusions

50% of patients with aggressive

disease remain in remission after

transplant & CAR

+

T cells

Safely re-infuse CAR

+

T cells from

patient-specific cryopreserved

banks (n=3 re-treated)

CAR

+

T cells apparently effective in

the adjuvant disease setting

Approximately

28-day

CAR

+

T-cell

persistence

Ongoing Phase 1 Safety Study:

First Generation Proof of Concept

N = 16 pts treated, 8 remain in CR

with median 7.5 mo. follow-up

Kebriaei

et.

al,

EHA

2015

25

Future of T-cell therapy

26

Drive Pipeline Forward To Create Value

How Are We Differentiated

Translation of immunology to

immunotherapies

T cells

NK

cells

Non-viral gene transfer

(personalized therapies)

CAR

TCR

Cytokine

Cellular engineering

Expression Control

27

Personalized and orally controlled cytokine

transcription

CAR

+

T

cells

Ad-RTS-

IL-12

Differentiated Technology Platforms

Lower cost, controllable toxicity, autologous and allogeneic

28

Technology

Intrexon / ZIOPHARM

/ MD

Anderson

RheoSwitch

Therapeutic System®

Most advanced family

of ligands and switches available for dynamic

range, safety, and temporal control (on-off-on etc.)

Non-Viral

Integration Platform

First in-human

testing of Sleeping Beauty system in hematopoietic

cells

UltraVector®

Industrialized

assembly and screening of multigenic DNA modules for

synthetic biology

Adoptive Cell Therapy

Expertise in development and implementation of novel

immunotherapy trials

Laser-enabled Analysis and

Processing (LEAP®)

Computerized

image-based

selection

and

laser

processing

for

cell

identification and purification

AttSite® Recombinases

Stable,

targeted gene integration and expression with proprietary

serine recombinases

Personalized Therapy for Disease

and Patient

Infuse T cells with more than one specificity

Personalized for the disease

Intra-tumor

Inter-tumor

Heterogeneity of tumor-associated antigen (TAA)

Infuse T cells with one or more specificity

Personalized for the patient

“N=1” trial paradigm

29

Power-Law Curve

The New Industrialization of T cells

30

The N=1 approach has been shown for

non-genetically modified T cells

31

www.ziopharm.com

The Future of Cancer Therapy