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): September 10, 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

On September 10, 2015, ZIOPHARM Oncology, Inc., or the Company, will present the attached presentation of its immuno-oncology programs at the 2015 Wells Fargo Healthcare Conference in Boston, Massachusetts, being held on September 9 - 10, 2015.

A copy of the above referenced presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K. This information, including the information contained in the press release 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 September 10, 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: September 10, 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 September 10, 2015

 

4

EX-99.1
Wells Fargo
Healthcare Conference
SEPTEMBER 2015
Exhibit 99.1


2
Forward-looking Statements
This presentation contains certain forward-looking information about ZIOPHARM Oncology, Inc. 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, and in some cases can be identified by terms
such as "may," "will," "could," "expects," "plans," "anticipates," and "believes." These statements include, but are not limited to,
statements regarding the progress, timing and results of preclinical and clinical trials involving the Company's drug candidates,
and the progress of the Company's research and development programs. 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 by, the forward-looking statements. These risks and uncertainties
include, but are not limited to: whether chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-IL-12, TCR and NK cell-
based therapies, or any of our other therapeutic candidates will advance further in the pre-clinical or 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 chimeric antigen receptor T cell (CAR T) approaches, Ad-RTS-IL-12, TCR
and NK cell-based therapies, and our other therapeutic products will be successfully marketed if approved; the strength and
enforceability of our intellectual property rights; competition from other pharmaceutical and biotechnology companies; and the
other risk factors contained in our periodic and interim SEC reports filed from time to time with the Securities and Exchange
Commission, including but not limited to, our Annual Report on Form 10-K for the fiscal year ended December 31, 2014, and our
Quarterly Report on Form 10Q for the quarter ended June 30, 2015. Readers are 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.


3
NASDAQ: ZIOP
Robust synthetic immunology pipeline
Virotherapy
& adoptive cell therapy
Multiple partnerships
Differentiated technology platforms
Gene switch, non-viral integration and viral-based delivery
Multiple trial launches in 2015/2016
Well capitalized
Cash and equivalents of $176.1 million (Pro forma)
Sufficient to fund our planned operations into Q1 2018
Highlights


4
Delivering on the Premise and Promise of
Gene and Immune-based Therapies
Fully Aligned with research and
development (Intrexon)
Big pharma partnership (CARs)
Bio-processing for next-generation
products
Aligned with academic centers for
manufacturing of cells for
investigator-initiated trials
Contract manufacturing for ZIOP-
sponsored trials in place
Established suite of correlative
studies
Undertaking multi-center gene
therapy trials
Multi-faceted approach to gene
therapy (non-viral and viral)
Ability to manipulate the immune
response in situ (generate immune
response within patient)
Ability to provide an immune
response (infuse immune cells)
Ability to manipulate virus after
infusion
Ability to manipulate immune cells
after infusion
Immune cells targeting tumor
through CAR, TCR, and NK
Infuse patient-derived immune cells
Infuse 3
rd
party (allogeneic) immune
cells


Virotherapy
RTS
®
Gene Switches
Viral & Non-viral Gene
Integration
Cell Therapy
CAR-T, TCR
and NK
Cells
Autologous and Allogeneic
Our Approach
5


IL-12 Virotherapy
Adenoviral vector engineered
to express IL-12 utilizing
RheoSwitch Therapeutic
System
®
(RTS
®
) 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
6


Improved persistence and
survival in tumor
microenvironment
Limits on-target, off-tumor
toxicities
Administer virus locally to
achieve systemic anti-tumor
effects (Breast)
Administer virus locally to
achieve local anti-tumor effects
(GBM)
RTS®
Gene Switch Technology
7


Expression of functional IL-12 in human subjects by direct intra-tumoral
injection of Ad-RTS-hIL-12 + oral veledimex generates downstream IFNg
production and rapid systemic elevation of IL-10 and IP-10
Documented systemic immune activation and clinical effect in advanced,
heavily pretreated melanoma and breast cancer patients
Adverse event profile, including cytokine release syndrome, of Ad-RTS-hIL-12
+ veledimex is predictable, controllable, and fully and rapidly reversible on
stopping veledimex. Several subjects then restarted on veledimex
Ad-RTS-IL-12 Gene Therapy
Clinical Response To Date
8


Early Response Data Expected in 4Q 2015
Phase 1 Study of IL-12 Gene Therapy in Recurrent
or Progressive Glioblastoma/Grade III Malignant Glioma
A Multi-Center Gene Therapy Study
A single cycle of Ad-RTS-hIL-12 +
escalating veledimex
1O : Safety and tolerability
2O : 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
9


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
Suspend
chemotherapy
phase of
treatment
(HER2 therapy
permitted)
Phase 1b/2 Study of IL-12 Gene Therapy in
Locally Advanced/Metastatic Breast Cancer
Early Response Data Expected in 4Q 2015
10


11
Pipeline
Demonstrated the ability of Veledimex
to cross
blood-brain barrier in animal models (AACR 2014)
Proof-of-concept in humans being explored in
ongoing multi-center gene therapy trial
Combination therapies
Veledimex
for activation of genetically modified T
cells in brain


12
CAR
+
T cells
Target cell surface tumor-
associated antigens (TAAs)
independent of HLA
“Public” cell surface antigens
TCR
+
T cells
Target intracellular TAAs
dependent on HLA
“Private” intra-cellular
antigens
NK cells
Target tumor with loss of
HLA
No “antigens”
Cell Therapy


13
Sleeping Beauty (SB) Non-viral Gene
Integration
Step 1 (safety)
Step 2
(efficacy)
Step 3
(scale)


14
Pre-emptive donor lymphocyte Infusion with CD19-
directed
CAR
+
T
cells
infused
after
autologous
hematopoietic stem-cell transplantation (HSCT)
Population
7 patients with advanced non-Hodgkin
lymphoma (NHL)
Safety
Patients have not demonstrated any
acute
or
late
toxicity
to
CAR
+
T-cell
infusions
Efficacy
100% of patients remain alive following
a single CAR
+
T-cell infusion with a
median follow-up of 24 months
86%
of
patients
(n=6)
remain
alive
and
in complete remission (CR)
Trial at MDACC; Will be submitted for publication


15
Pre-emptive donor lymphocyte infusion with CD19-
directed,
CAR
+
T
cells
infused
after
allogeneic
HSCT
*Wilhelm et al. J Oncol
Pharm Practice, 2014, 20:257
Population
19
patients
with
advanced
CD19
+
ALL
(n=17) or
NHL (n=2)
Safety
3 patients developed GVHD which is lower than the
expected
range
after
allogeneic
HSCT
alone
Efficacy
58% of patients (n=11/19) remain in complete
remission (CR) and 10/19 remain alive and in CR (1
death in CR) following CAR
+
T-cell infusion with a
median follow-up of 6.5 months post transplant
among survivors.
Among 8 patients who received haplo-HCST and
CAR, 100% of remain alive and 75% remain in
remission
Rate
of
CMV
reactivation
after
CAR
+
T-cell
administration was 24% vs. 41% previously reported
for our patients without infusion
Trial at MDACC, Updated from EHA 2015; Will be submitted for publication


16
Persistence
of
Infused
CAR
+
T
Cells
Trial at MDACC, Updated from EHA 2015; Will be submitted for publication


17
Improving
Therapeutic
Potential
of
CAR
+
T
Cells
Signals 1 & 2
Signal 3


18
1.
New CAR designs for patients
with hematologic malignancies
and solid tumors
2.
Combining CAR with cytokines
IL-12
IL-15
TCR-based T-cell therapy
NK-cell immunotherapy
Next-generation Adoptive Cell-based Clinical
Trials


19
How do we achieve on-target anti-cancer activity?
The Promise and Challenges of DNA-based
Immuno-Oncology
Avoid


20
Strategies to widen therapeutic index to
Target Solid Tumors


21
Off-the-shelf T Cells


22
Elimination of Endogenous TCR


23
Fitting Together the Pieces of the Puzzle
NK cells
T cells
TCRs
CARs
Virotherapy
Cytokines
Remote
Controlled


24
Clinical Programs
Ziopharm
2015
Ad-RTS-IL12
Multicenter
CARs
MDACC


25
Clinical Programs
Ziopharm
2016+
Ad-RTS-IL12
CARs and
interleukin
Multicenter
NK cells
TCRs
CARs
Multicenter
MDACC
MDACC
Multicenter


26
Abstracts
European Hematology Association (June 2015)
Donor-derived, CD19-directed, CAR-modified T cells infused after allogeneic hematopoietic stem-cell transplantation as pre-
emptive donor lymphocyte infusion in patients with CD19+ malignances
CRI-CIMT-EATI-AACR (September 2015)
Demonstration of systemic antitumor immunity via intratumoral regulated expression of IL-12 in advanced breast cancer and
melanoma patients
Demonstration of systemic antitumor immunity via intratumoral regulated expression of IL-12 as a gene therapy approach to
treatment of cancer
Bio-engineered Dectin-1 CAR+ T cells to control invasive fungal infection
Ex-vivo generation of clinical grade T cells by using activating and propagating feeder cells to cross-link T cell receptor
Designing CARs for personalized immunotherapy: rapid assembly of CARs from principal components using “EZ-CAR” platform
Transcriptional
and
epigenetic
signatures
of
ex
vivo
propagated
three
distinct
TCR
V
1,
TCR
V
2
and
TCR
V
3
cell
subtypes
with broad specificity for malignancies
Papers
Sleeping Beauty Transposition of Chimeric Antigen Receptors Targeting Receptor Tyrosine Kinase-Like Orphan Receptor-1
(ROR1) into Diverse Memory T-Cell Populations. PLoS
One. 2015 Jun 1;10(6):e0128151 PMID: 26030772
Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma. Clin
Cancer Res. 2015 Mar 31. [Epub
ahead of print] PMID: 25829402
Moving from tinkering in the garage to assembly line production: the manufacture of genetically modified T cells expressing
chimeric antigen receptors (CARs) comes on line. Cancer Gene Ther. 2015 Mar;22(2):64-6. PMID: 25675874
Manufacture of T cells using the Sleeping Beauty system to enforce expression of a CD19-specific chimeric antigen receptor.
Cancer Gene Ther. 2015 Mar;22(2):95-100. PMID: 25591810
Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity.
Cancer Res. 2015 Sep 1;75(17):3505-18. PMID: 26330164
Extensive Data Outreach…


27
CRI-CIMT-EATI-AACR Immunotherapy Conference September 16-19, NY, NY
SITC November 4-8, National Harbor, MD
SNO
November 19-23, San Antonio, TX
CAR-T Summit November 12-13, Boston, MA
ASH
December 5-8, Orlando FL
SABCS
December 9-12, San Antonio TX
Additional papers
…With More to Come for 2015


28
ZIOPHARM Oncology Pipeline
Solid
Tumors
2016+
Heme
2015+
Virotherapy
Multi-
center
trials
2015+
Multi
Modal
2016+
Expanded
Indications
2016+
Single
Agent
2015+
CAR
Cytokine
2016+
Adoptive Cell Therapy
TCR
2016+
CAR
2015+
NK cells
2016+
T cells
2015+
Allogeneic
2016+
Autologous
2015+


Wells Fargo
Healthcare Conference
SEPTEMBER 2015