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): November 2, 2006
ZIOPHARM
Oncology, Inc.
(Exact
name of registrant as specified in its charter)
|
Delaware
|
0-32353
|
84-1475642
|
|
(State
or other jurisdiction of
incorporation) |
(Commission
File Number)
|
(IRS
Employer Identification No.)
|
1180
Avenue of the Americas, 19th
Floor
New
York, NY 10036
(Address
of principal executive offices) (Zip Code)
(646)
214-0700
(Registrant’s
telephone number, including area code)
(Former
name or former address, if changed since last report)
Check
the
appropriate box below if the Form 8-K filing is intended to simultaneously
satisfy the filing obligation of the registrant under any of the following
provisions:
o
Written
communications
pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
o
Soliciting
material pursuant to Rule 14a-12 under the
Exchange Act (17 CFR 240.14a-12)
o
Pre-commencement
communications pursuant to Rule
14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
o
Pre-commencement
communications pursuant to Rule
13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Item
8.01. Other Events.
On
November 2, 2006 and November 3, 3006, the Company issued press releases
and such press releases are attached hereto as
Exhibits 99.1 and 99.2 and are incorporated herein by reference.
Item
9.01 Financial Statements and Exhibits.
(d) Exhibits.
99.1
Press
Release dated November 2, 2006.
99.2
Press
Release dated November 3, 2006.
SIGNATURE
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.
| Date: November 3, 2006 |
ZIOPHARM Oncology, Inc.:
(Registrant)
|
|
| |
|
|
| By: | /s/ Richard E. Bagley | |
|
RICHARD E.
BAGLEY,
President, Chief
Operating Officer and Chief Financial Officer |
||
Exhibit
Index
|
Exhibit
No.
|
Description
|
|
99.1
|
Press
Release dated November 2, 2006
|
|
99.2
|
Press
Release dated November 3, 2006
|
Exhibit
99.1
ZIO-201
Preclinical Data Demonstrate Effectiveness in Pediatric
Cancers
--
CTOS Presentations Support Phase I/II Sarcoma Trials and Planned Trial in
Pediatric Cancers --
VENICE,
ITALY - November 2, 2006
-
ZIOPHARM Oncology, Inc. (NASDAQ: ZIOP) and colleagues today presented new data
on the effect of ZIO-201 on several human pediatric sarcoma models (Ewing
sarcoma, rhabdomyosarcoma, synovial sarcoma and osteosarcoma) demonstrating
potent anti-cancer activity. Importantly, the results were comparable for
ZIO-201 administered as a single dose, a schedule currently being explored
in
phase I clinical study, or as three consecutive daily doses, as is scheduled
in
the initial phase I and the sarcoma phase I/II trials. Also, ZIO-201 was active
in cyclophosphamide-resistant osteosarcoma, the most common pediatric bone
cancer in the United States. Children presenting initially with metastatic
disease typically have a very low survival rate. Cyclophosphamide and the
related drug ifosfamide are widely used alkylating agents for treating a number
of cancers including sarcoma.
“I
think
this data is particularly exciting because it suggests that ZIO-201 may be
an
effective new agent that potentially bypasses mechanisms of resistance and
toxicity that limit the use of cyclophosphamide and ifosfamide,” commented Dr.
Anders Kolb, Assistant Professor of Pediatrics at the Albert Einstein College
of
Medicine and the lead investigator on this study. These data were presented
at
the Connective Tissue Oncology Society (CTOS) meeting in Venice, Italy. Data
from the initial ZIO-201 phase I clinical studies with intravenous (IV)
administration will also be presented at the CTOS meeting by Dr. Robert Benjamin
and colleagues from The University of Texas M. D. Anderson Cancer Center,
Karmanos Cancer Center and Premier Oncology.
Resistance
to cyclophosphamide (CPA) and ifosfamide (IFOS) is a major obstacle to overcome
in cancer treatment. CPA and IFOS are pro-drugs that cannot kill cells unless
activated by an intracellular enzyme (aldehyde dehydrogenase 3A1; ALDH). Cancer
cells typically escape killing by CPA and IFOS by developing high intracellular
levels of ALDH. Because ZIO-201 (isophosphoramide mustard) is the activated
form
of IFOS, killing of sarcoma cells is direct and immediate and does not require
activation by ALDH. Similarly, high intracellular levels of ALDH should not
inhibit sarcoma cell-killing by ZIO-201. Gorlick, Kolb and colleagues
demonstrate here that sarcoma cell lines with high intracellular ALDH-levels
were not killed by CPA but were readily killed by ZIO-201. Furthermore, mice
with xenografts of CPA-resistant human sarcoma cells had a more than 5-fold
reduction in sarcoma growth when treated with ZIO-201; CPA therapy had no
effect. These data imply that ZIO-201 should be active in CPA- and
IFOS-resistant sarcomas in humans. These data support not only the ongoing
IV
clinical studies in adult sarcoma but also are intriguing with regard to a
subsequent IV phase I/II trial in children’s cancers as well as other trials
involving different routes and form of administration.
About
ZIO-201
ZIO-201
(isophosphoramide mustard-lysine; IPM-Lys), the active moiety of IFOS, is a
bi-functional alkylator that causes irreparable inter-strand DNA cross-linking
resulting in cell death. ZIO-201 is as or more active than IFOS in diverse
cancer models. Unlike IFOS which is a pro-drug, ZIO-201 is directly active
against cancer cells. Also, unlike IFOS, ZIO-201 is not metabolized to acrolein
or chloracetaldehyde which cause bladder or central nervous system toxicities.
ZIO-201 is in phase I and I/II trials in diverse cancers exploring maximum
tolerated dose at alternate schedules. Clinical activity (stable disease) in
subjects with advanced cancers (including those resistant to IFOS) has been
seen.
About
ZIOPHARM Oncology, Inc.
ZIOPHARM
Oncology, Inc. is a biopharmaceutical company engaged in the development and
commercialization of a diverse, risk-sensitive portfolio of in-licensed cancer
drugs to address unmet medical needs. The
Company applies new insights from molecular and cancer biology to understand
the
efficacy and safety limitations of approved and developmental cancer therapies
and identifies proprietary and related molecules for better patient treatment.
For more information, visit www.ziopharm.com.
Forward-Looking
Safe Harbor Statement:
This
press release contains forward-looking statements for ZIOPHARM Oncology, Inc.
that involve risks and uncertainties that could cause the Company's actual
results to differ materially from the anticipated results and expectations
expressed in these forward-looking statements. These statements are based on
current expectations, forecasts and assumptions that are subject to risks and
uncertainties, which could cause actual outcomes and results to differ
materially from these statements. Among other things, there can be no assurance
that any of the Company's development efforts relating to its product candidates
will be successful, or such product candidates will be successfully
commercialized. Other risks that affect forward-looking information contained
in
this press release include the possibility of being unable to obtain regulatory
approval of the Company's product candidates, the risk that the results of
clinical trials may not support the Company's claims, and risks related to
the
Company's ability to protect its intellectual property and its reliance on
third
parties to develop its product candidates. The Company assumes no obligation
to
update these forward-looking statements, except as required by law.
ZIOP-G
Contact:
Suzanne
McKenna
Investors
(646)
214-0703
Tina
Posterli
Media
(917)
322-2565
tposterli@rxir.com
Exhibit
99.2
ZIOPHARM
Presents ZIO-201 Phase I Data at CTOS
--
Data Support Expanded Clinical Development Program --
VENICE,
ITALY - November 3, 2006
-
ZIOPHARM Oncology, Inc. (NASDAQ: ZIOP) announced today the presentation of
updated clinical data on ZIO-201 at the Connective Tissue Oncology Society
(CTOS) meeting in Venice. Related new preclinical data for ZIO-201 was the
subject of an earlier presentation at CTOS. ZIO-201 is a proprietary form of
the
therapeutic active metabolite of ifosfamide (IFOS), a drug that is the standard
of care in the treatment of sarcoma and is widely used in the treatment of
lymphoma and pediatric cancers. IFOS is associated with severe toxicity to
the
bladder and the central nervous system because of the presence of two other
metabolites - acrolein and chloroacetaldehyde. These toxicities can be
particularly troubling, especially in the treatment of pediatric cancers.
The
safety and dose-ranging phase I studies utilized ZIO-201 administered daily
for
three consecutive days each four weeks (1 cycle) and were conducted at the
University of Texas M. D. Anderson Cancer Center in Houston, the Karmanos Cancer
Center in Detroit and Premier Oncology in Santa Monica. The results demonstrated
evidence of clinical activity in sarcoma (2/11 patients including at least
one
who had failed IFOS therapy) and mesothelioma (1 patient with extended stable
disease). The maximum tolerated dose (MTD) of ZIO-201 on this schedule was
400
mg/me2/d. There was little bone marrow toxicity and no hemorrhagic cystitis
(bladder toxicity) or CNS toxicity. The dose limiting toxicity was characterized
by electrolyte imbalances. This MTD is comparable to IFOS doses of greater
than
25 g/me2 and this dose achieves serum levels that are 25-fold higher than doses
that kill 50% of human sarcoma cell lines.
“These
phase I results with ZIO-201 are encouraging,” commented Dr. Brian Schwartz,
Chief Medical Officer at ZIOPHARM. “Avoiding the more serious toxicities
associated with the administration of ifosfamide at doses that are much higher
than the equivalent ifosfamide dose is what we were hoping to see. We are
presently continuing the phase I trial with a single monthly administration
of
ZIO-201, a regimen that is strongly supported by the preclinical data presented
yesterday at CTOS. The phase II trial in sarcoma with the 3-day regimen
continues. We are also planning for a pediatric phase I/II trial, exploring
the
possibility of administering intrathecally for metastatic brain cancer, and
moving forward with an oral form.”
About
ZIO-201
ZIO-201
(isophosphoramide mustard-lysine; IPM-Lys), the active moiety of IFOS, is a
bi-functional alkylator that causes irreparable inter-strand DNA cross-linking
resulting in cell death. ZIO-201 is as or more active than IFOS in diverse
cancer models. Unlike IFOS which is a pro-drug, ZIO-201 is directly active
against cancer cells. Also, unlike IFOS, ZIO-201 is not metabolized to acrolein
or chloracetaldehyde which cause bladder or central nervous system toxicities.
ZIO-201 is in phase I and I/II trials in diverse cancers exploring maximum
tolerated dose at alternate schedules. Clinical activity (stable disease) in
patients with advanced cancers (including those resistant to IFOS) has been
seen.
About
ZIOPHARM Oncology, Inc.
ZIOPHARM
Oncology, Inc. is a biopharmaceutical company engaged in the development and
commercialization of a diverse, risk-sensitive portfolio of in-licensed cancer
drugs to address unmet medical needs. The Company applies new insights from
molecular and cancer biology to understand the efficacy and safety limitations
of approved and developmental cancer therapies and identifies proprietary and
related molecules for better patient treatment. For more information, visit
www.ziopharm.com.
Forward-Looking
Safe Harbor Statement:
This
press release contains forward-looking statements for ZIOPHARM Oncology, Inc.
that involve risks and uncertainties that could cause the Company's actual
results to differ materially from the anticipated results and expectations
expressed in these forward-looking statements. These statements are based on
current expectations, forecasts and assumptions that are subject to risks and
uncertainties, which could cause actual outcomes and results to differ
materially from these statements. Among other things, there can be no assurance
that any of the Company's development efforts relating to its product candidates
will be successful, or such product candidates will be successfully
commercialized. Other risks that affect forward-looking information contained
in
this press release include the possibility of being unable to obtain regulatory
approval of the Company's product candidates, the risk that the results of
clinical trials may not support the Company's claims, and risks related to
the
Company's ability to protect its intellectual property and its reliance on
third
parties to develop its product candidates. The Company assumes no obligation
to
update these forward-looking statements, except as required by law.
ZIOP-G
Contact:
Suzanne
McKenna
Investors
(646)
214-0703
Tina
Posterli
Media
(917)
322-2565
tposterli@rxir.com