Form 8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(d)

OF THE SECURITIES EXCHANGE ACT OF 1934

Date of report (Date of earliest event reported): June 18, 2015

 

 

ZIOPHARM Oncology, Inc.

(Exact Name of Registrant as Specified in Charter)

 

 

 

Delaware   001-33038   84-1475672

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

One First Avenue, Parris Building 34, Navy Yard Plaza

Boston, Massachusetts

  02129
(Address of Principal Executive Offices)   (Zip Code)

(617) 259-1970

(Registrant’s telephone number, including area code)

Not applicable

(Former Name or Former Address, if Changed Since Last Report)

 

 

Check the appropriate box below if the Form 8-K is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425).

 

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12).

 

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)).

 

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)).

 

 

 


Item 7.01 Regulation FD Disclosure

The Company will be presenting a slide presentation as part of the Mizuho Boston BioPharma Bus Tour: The Road to Healing, a copy of which is furnished as Exhibit 99.1 hereto. From time to time, the Company intends to conduct meetings with third parties in which this presentation will be presented.

This information, including the information contained in the presentation furnished as Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not incorporated by reference into any of the Company’s filings, whether made before or after the date hereof, regardless of any general incorporation language in any such filing.

 

Item 9.01 Financial Statements and Exhibits

 

  (d) Exhibits

 

Exhibit
No.

  

Description

99.1    Presentation of the Company dated June 18, 2015

 

2


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

ZIOPHARM Oncology, Inc.
By:

/s/ Kevin G. Lafond

Date: June 18, 2015 Name: Kevin G. Lafond
Title: Vice President, Chief Accounting Officer and Treasurer

 

3


INDEX OF EXHIBITS

 

Exhibit
No.

  

Description

99.1    Presentation of the Company dated June 18, 2015

 

4

EX-99.1
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