Delaware
|
84-1475642
|
(State
or Other Jurisdiction of Incorporation or Organization)
|
(IRS
Employer Identification No.)
|
|
|
1180
Avenue of the Americas, 19th Floor, New York,
NY
|
10036
|
(Address
of Principal Executive Offices)
|
(Zip
Code)
|
Large accelerated filer o
|
Accelerated filer x
|
Non-accelerated
filer o
(Do not check if a smaller reporting company)
|
Smaller reporting company o
|
Page
|
|||
PART
I
|
FINANCIAL
INFORMATION
|
||
Item
1.
|
Financial
Statements
|
||
Balance
Sheets as of June 30, 2008 (unaudited) and December 31, 2007
(unaudited)
|
3
|
||
Statement
of Operations for the three and six months ended June 30, 2008 and
2007
(unaudited) and for the period from inception (September 9, 2003)
to June
30, 2008 (unaudited)
|
4
|
||
Statement
of Cash Flows for the six months ended June 30, 2008 and 2007 (unaudited)
and for the period from inception (September 9, 2003) to June 30,
2008
(unaudited)
|
5
|
||
Statement
of Changes in Convertible Preferred Stock and Stockholders’
Equity/(Deficit) for the period from inception (September 9, 2003)
to June
30, 2008 (unaudited)
|
6
|
||
Notes
to Unaudited Financial Statements
|
7
|
||
Management’s
Discussion and Analysis
|
12
|
||
Quantitative
and Qualitative Disclosure About Market Risk
|
18
|
||
Controls
and Procedures
|
18
|
||
PART
II
|
OTHER
INFORMATION
|
||
Item
1.
|
Legal
Proceedings
|
18
|
|
Item
2.
|
Unregistered
Sales of Equity Securities and Use of Proceeds
|
18
|
|
Item
3.
|
Defaults
Under Senior Securities
|
18
|
|
Item
4.
|
Submission
of Matters to a Vote of Security Holders
|
18
|
|
Item
5.
|
Other
Information
|
18
|
|
Item
6.
|
Exhibits
|
19
|
|
Signatures
|
20
|
||
Exhibit
Index
|
21
|
June 30,
|
December 31,
|
||||||
2008
|
2007
|
||||||
(Unaudited)
|
(Unaudited)
|
||||||
ASSETS
|
|||||||
Current
assets:
|
|||||||
Cash
and cash equivalents
|
$
|
21,087,264
|
$
|
35,028,798
|
|||
Prepaid
expenses and other current assets
|
237,908
|
498,864
|
|||||
Total
current assets
|
21,325,172
|
35,527,662
|
|||||
Property
and equipment, net
|
674,714
|
746,421
|
|||||
Deposits
|
98,897
|
95,497
|
|||||
Other
non-current assets
|
359,651
|
356,881
|
|||||
Total
assets
|
$
|
22,458,434
|
$
|
36,726,461
|
|||
LIABILITIES
AND STOCKHOLDERS' EQUITY
|
|||||||
Current
liabilities:
|
|||||||
Accounts
payable
|
$
|
1,900,291
|
$
|
2,909,170
|
|||
Accrued
expenses
|
4,281,177
|
3,396,480
|
|||||
Total
current liabilities
|
6,181,468
|
6,305,650
|
|||||
Deferred
rent
|
60,430
|
50,988
|
|||||
Total
liabilities
|
6,241,898
|
6,356,638
|
|||||
Commitments
and contingencies
|
|||||||
Stockholders'
equity:
|
|||||||
Common
stock, $.001 par value; 280,000,000 shares authorized; 21,398,964
and
21,298,964 shares issued and outstanding at June 30, 2008 and December
31,
2007, respectively
|
21,399
|
21,299
|
|||||
Preferred
stock, $0.01 par value; 30,000,000 shares authorized and no shares
issued
and outstanding
|
-
|
-
|
|||||
Additional
paid-in capital
|
70,644,632 | 69,674,151 | |||||
Warrants
issued
|
20,503,894
|
20,503,894
|
|||||
Deficit
accumulated during the development stage
|
(74,953,389
|
)
|
(59,829,521
|
)
|
|||
Total
stockholders' equity
|
16,216,536
|
30,369,823
|
|||||
Total
liabilities and stockholders' equity
|
$
|
22,458,434
|
$
|
36,726,461
|
|
|
|
|
|
For the Period
|
|||||||||||
For the three
|
For the three
|
For the six
|
For the six
|
from Inception
|
||||||||||||
|
months
|
months
|
months
|
months
|
(September 9, 2003)
|
|||||||||||
ended
|
ended
|
ended
|
ended
|
through
|
||||||||||||
|
June 30, 2008
|
June 30, 2007
|
June 30, 2008
|
June 30, 2007
|
June 30, 2008
|
|||||||||||
(unaudited)
|
(unaudited)
|
(unaudited)
|
(unaudited)
|
(unaudited)
|
||||||||||||
Research contract revenue
|
$
|
-
|
$
|
-
|
$
|
-
|
$
|
-
|
$
|
-
|
||||||
Operating
expenses and other income:
|
||||||||||||||||
Research
and development, including costs of research contracts
|
4,266,059
|
4,347,610
|
10,340,636
|
7,774,123
|
47,445,030
|
|||||||||||
General
and administrative
|
2,349,529
|
2,847,973
|
5,094,230
|
4,837,991
|
31,328,524
|
|||||||||||
Total
operating expenses
|
6,615,588
|
7,195,583
|
15,434,866
|
12,612,114
|
78,773,554
|
|||||||||||
Loss
from operations
|
(6,615,588
|
)
|
(7,195,583
|
)
|
(15,434,866
|
)
|
(12,612,114
|
)
|
(78,773,554
|
)
|
||||||
Interest
income
|
114,814
|
650,382
|
310,998
|
1,026,227
|
3,820,165
|
|||||||||||
Net
loss
|
$
|
(6,500,774
|
)
|
$
|
(6,545,201
|
)
|
$
|
(15,123,868
|
)
|
$
|
(11,585,887
|
)
|
$
|
(74,953,389
|
)
|
|
Basic
and diluted net loss per share
|
$
|
(0.31
|
)
|
$
|
(0.31
|
)
|
$
|
(0.71
|
)
|
$
|
(0.60
|
)
|
||||
Weighted
average common shares outstanding used to compute basic and diluted
net
loss per share
|
21,228,964
|
21,182,948
|
21,228,964
|
19,419,729
|
For the period
|
||||||||||
|
For the
|
For the
|
from inception
|
|||||||
six months
|
six months
|
(September 9, 2003)
|
||||||||
|
ended
|
ended
|
through
|
|||||||
June 30, 2008
|
June 30, 2007
|
June 30, 2008
|
||||||||
(unaudited)
|
(unaudited)
|
(unaudited)
|
||||||||
Cash flows from operating activities:
|
||||||||||
Net
loss
|
$
|
(15,123,868
|
)
|
$
|
(11,585,887
|
)
|
$
|
(74,953,389
|
)
|
|
Adjustments
to reconcile net loss to net cash used in operating activities:
|
||||||||||
Depreciation
and amortization
|
189,425
|
182,310
|
931,883
|
|||||||
Non-cash
stock-based compensation
|
970,581
|
735,751
|
6,093,698
|
|||||||
Loss
on disposal of fixed assets
|
302
|
-
|
8,725
|
|||||||
Change
in operating assets and liabilities:
|
||||||||||
(Increase)
decrease in:
|
||||||||||
Prepaid
expenses and other current assets
|
260,956
|
(355,025
|
)
|
(237,908
|
)
|
|||||
Other
noncurrent assets
|
(2,770
|
)
|
(123,398
|
)
|
(359,651
|
)
|
||||
Deposits
|
(3,400
|
)
|
(41,412
|
)
|
(98,897
|
)
|
||||
Increase
(decrease) in:
|
||||||||||
Accounts
payable
|
(1,008,879
|
)
|
712,687
|
1,900,291
|
||||||
Accrued
expenses
|
884,697
|
172,893
|
4,281,177
|
|||||||
Deferred
rent
|
9,442
|
2,547
|
60,430
|
|||||||
Net
cash used in operating activates
|
(13,823,514
|
)
|
(10,299,534
|
)
|
(62,373,641
|
)
|
||||
|
||||||||||
Cash
flows from investing activities:
|
||||||||||
Purchases
of property and equipment
|
(118,720
|
)
|
(392,159
|
)
|
(1,616,022
|
)
|
||||
Proceeds
from sale of property and equipment
|
700
|
-
|
700
|
|||||||
Decrease
in short-term investments
|
-
|
1,555,164
|
-
|
|||||||
Net
cash provided by (used in) investing activities
|
(118,020
|
)
|
1,163,005
|
(1,615,322
|
)
|
|||||
|
||||||||||
Cash
flows from financing activities:
|
||||||||||
Proceeds
from the exercise of stock options
|
-
|
-
|
65,596
|
|||||||
Stockholders'
capital contribution
|
-
|
-
|
500,000
|
|||||||
Proceeds
from issuance of common stock and warrants, net
|
-
|
28,970,915
|
67,751,035
|
|||||||
Proceeds
from issuance of preferred stock, net
|
-
|
-
|
16,759,596
|
|||||||
Net
cash provided by financing activities
|
-
|
28,970,915
|
85,076,227
|
|||||||
|
||||||||||
Net
increase (decrease) in cash and cash equivalents
|
(13,941,534
|
)
|
19,834,386
|
21,087,264
|
||||||
|
||||||||||
Cash
and cash equivalents, beginning of period
|
35,028,798
|
26,855,450
|
-
|
|||||||
|
||||||||||
Cash
and cash equivalents, end of period
|
$
|
21,087,264
|
$
|
46,689,836
|
$
|
21,087,264
|
||||
|
||||||||||
Supplementary
disclosure of cash flow information:
|
||||||||||
Cash
paid for interest
|
$
|
-
|
$
|
-
|
$
|
-
|
||||
|
||||||||||
Cash
paid for income taxes
|
$
|
-
|
$
|
-
|
$
|
-
|
||||
|
||||||||||
Supplementary
disclosure of noncash investing and financing
activities:
|
||||||||||
|
||||||||||
Warrants
issued to placement agents and investors, in connection with with
private placement
|
$
|
-
|
$
|
5,432,793
|
$
|
20,208,217
|
||||
|
||||||||||
|
||||||||||
Preferred
stock conversion to common stock
|
$
|
-
|
$
|
-
|
$
|
16,759,596
|
||||
|
||||||||||
Warrants
converted to common shares
|
$
|
-
|
$
|
-
|
$
|
17,844
|
Convertible Preferred Stock and Warrants
|
Stockholder's Equity (Deficit)
|
|||||||||||||||||||||||||||
Warrants to Purchase
|
||||||||||||||||||||||||||||
Series A
|
Series A Convertible
|
|||||||||||||||||||||||||||
Convertible Preferred Stock
|
Preferred Stock
|
Common Stock
|
Deficit Accumulated
|
Total
|
||||||||||||||||||||||||
|
Additional Paid-
|
During The
|
Stockholders' Equity/
|
|||||||||||||||||||||||||
Shares
|
Amount
|
Warrants
|
Shares
|
Amount
|
in Capital
|
Warrants
|
Development Stage
|
(Deficit)
|
||||||||||||||||||||
Stockholders'
contribution, September 9, 2003
|
-
|
$
|
-
|
$
|
-
|
250,487
|
$
|
250
|
$
|
499,750
|
$
|
-
|
$
|
-
|
$
|
500,000
|
||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(160,136
|
)
|
(160,136
|
)
|
|||||||||||||||||
Balance
at December 31, 2003
|
-
|
-
|
-
|
250,487
|
250
|
499,750
|
-
|
(160,136
|
)
|
339,864
|
||||||||||||||||||
Issuance
of common stock
|
-
|
-
|
-
|
2,254,389
|
2,254
|
4,497,746
|
-
|
-
|
4,500,000
|
|||||||||||||||||||
Issuance
of common stock for services
|
-
|
-
|
-
|
256,749
|
257
|
438,582
|
-
|
-
|
438,839
|
|||||||||||||||||||
Fair
value of options/warrants issued for nonemployee
services
|
-
|
-
|
-
|
-
|
-
|
13,240
|
251,037
|
-
|
264,277
|
|||||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(5,687,297
|
)
|
(5,687,297
|
)
|
|||||||||||||||||
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||
Balance
at December 31, 2004
|
-
|
-
|
-
|
2,761,625
|
2,761
|
5,449,318
|
251,037
|
(5,847,433
|
)
|
(144,317
|
)
|
|||||||||||||||||
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||
Issuance
of Series A convertible preferred stock (net of expenses of
$1,340,263 and warrant cost of $1,682,863)
|
4,197,946
|
15,076,733
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|||||||||||||||||||
|
|
|
|
|
|
|
|
|
|
|||||||||||||||||||
Fair
value of warrants to purchase Series A convertible preferred
stock
|
-
|
-
|
1,682,863
|
-
|
-
|
-
|
-
|
-
|
-
|
|||||||||||||||||||
Issuance
of Common stock to EasyWeb Shareholders
|
-
|
-
|
-
|
189,922
|
190
|
(190
|
)
|
-
|
-
|
-
|
||||||||||||||||||
Conversion
of Series A convertible preferred stock @ $0.001 into
$0.001 common stock on September 13, 2005 at an exchange ratio
of .500974
|
(4,197,946
|
)
|
(15,076,733
|
)
|
(1,682,863
|
)
|
4,197,823
|
4,198
|
15,072,535
|
1,682,863
|
-
|
16,759,596
|
||||||||||||||||
Issuance
of common stock for options
|
-
|
-
|
-
|
98,622
|
99
|
4,716
|
|
-
|
4,815
|
|||||||||||||||||||
Fair
value of options/warrants issued for nonemployee
services
|
-
|
-
|
-
|
-
|
-
|
54,115
|
44,640
|
-
|
98,755
|
|||||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(9,516,923
|
)
|
(9,516,923
|
)
|
|||||||||||||||||
|
|
|||||||||||||||||||||||||||
Balance
at December 31, 2005
|
-
|
-
|
-
|
7,247,992
|
7,248
|
20,580,494
|
1,978,540
|
(15,364,356
|
)
|
7,201,926
|
||||||||||||||||||
|
|
|||||||||||||||||||||||||||
Issuance
of common stock in private placement, net of expenses
$2,719,395
|
-
|
-
|
-
|
7,991,256
|
7,991
|
21,179,568
|
-
|
-
|
21,187,559
|
|||||||||||||||||||
Issuance
of warrants
|
-
|
-
|
-
|
-
|
-
|
-
|
13,092,561
|
-
|
13,092,561
|
|||||||||||||||||||
Issuance
of common stock for services rendered
|
-
|
-
|
-
|
25,000
|
25
|
106,225
|
-
|
-
|
106,250
|
|||||||||||||||||||
Stock
based compensation for employees
|
-
|
-
|
-
|
-
|
-
|
2,776,408
|
-
|
-
|
2,776,408
|
|||||||||||||||||||
Issuance
of common stock due to exercise of stock
options
|
-
|
-
|
-
|
5,845
|
6
|
25,186
|
-
|
-
|
25,192
|
|||||||||||||||||||
Issuance
of common stock due to exercise of stock
warrants
|
-
|
-
|
-
|
2,806
|
3
|
(3
|
)
|
-
|
-
|
-
|
||||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(17,856,919
|
)
|
(17,856,919
|
)
|
|||||||||||||||||
|
|
|||||||||||||||||||||||||||
Balance
at December 31, 2006
|
-
|
-
|
-
|
15,272,899
|
15,273
|
44,667,878
|
15,071,101
|
(33,221,275
|
)
|
26,532,977
|
||||||||||||||||||
Issuance
of common stock in private placement, net of expenses
$1,909,090
|
-
|
-
|
-
|
5,910,049
|
5,910
|
23,532,212
|
-
|
-
|
23,538,122
|
|||||||||||||||||||
Issuance
of warrants
|
-
|
-
|
-
|
-
|
-
|
-
|
5,432,793
|
-
|
5,432,793
|
|||||||||||||||||||
Stock-based
compensation for employees
|
-
|
-
|
-
|
-
|
-
|
1,318,096
|
-
|
-
|
1,318,096
|
|||||||||||||||||||
Stock-based
compensation for non-employee
|
-
|
-
|
-
|
-
|
-
|
120,492
|
-
|
-
|
120,492
|
|||||||||||||||||||
Issuance
of common stock due to exercise of stock
options
|
-
|
-
|
-
|
46,016
|
46
|
35,543
|
-
|
-
|
35,589
|
|||||||||||||||||||
Issuance
of restricted stock
|
-
|
-
|
-
|
70,000
|
70
|
(70
|
)
|
-
|
-
|
-
|
||||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(26,608,246
|
)
|
(26,608,246
|
)
|
|||||||||||||||||
|
||||||||||||||||||||||||||||
Balance
at December 31, 2007
|
-
|
-
|
-
|
21,298,964
|
21,299
|
69,674,151
|
20,503,894
|
(59,829,521
|
)
|
30,369,823
|
||||||||||||||||||
Stock-based
compensation for employees
|
-
|
-
|
-
|
-
|
-
|
970,581
|
-
|
-
|
970,581
|
|||||||||||||||||||
Issuance
of restricted stock
|
-
|
-
|
-
|
100,000
|
100
|
(100
|
)
|
-
|
-
|
-
|
||||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
(15,123,868
|
)
|
(15,123,868
|
)
|
|||||||||||||||||
Balance
at June 30, 2008
|
-
|
$
|
-
|
$
|
-
|
21,398,964
|
$
|
21,399
|
$
|
70,644,632
|
$
|
20,503,894
|
$
|
(74,953,389
|
)
|
$
|
16,216,536
|
1. |
BASIS
OF PRESENTATION AND
OPERATIONS
|
2. |
RECENT
ACCOUNTING PRONOUNCEMENTS
|
3. |
STOCK-BASED
COMPENSATION AND STOCK OPTION
PLAN
|
Three months
|
Three months
|
Six months
|
Six months
|
||||||||||
|
ended June 30, 2008
|
ended June 30, 2007
|
ended June 30, 2008
|
ended June 30, 2007
|
|||||||||
|
|||||||||||||
Research
and development, including costs of research contracts
|
$
|
204,857
|
$
|
229,048
|
$
|
384,968
|
$
|
372,258
|
|||||
General
and administrative
|
298,168
|
183,009
|
585,613
|
363,493
|
|||||||||
Share
based compensation expense before tax
|
503,025
|
412,057
|
970,581
|
735,751
|
|||||||||
Income
tax benefit
|
-
|
-
|
-
|
-
|
|||||||||
Net
compensation expense
|
$
|
503,025
|
$
|
412,057
|
$
|
970,581
|
$
|
735,751
|
3. |
STOCK-BASED
COMPENSATION AND STOCK OPTION
PLAN…CONTINUED
|
|
Number
of
Shares
|
Weighted-
Average
Exercise Price
|
Weighted-
Average
Remaining
Contractual
Term
(Years)
|
Aggregate
Intrinsic
Value
|
|||||||||
Outstanding,
January 1, 2008
|
2,797,000
|
$
|
3.81
|
||||||||||
Granted
|
161,000
|
2.72
|
|||||||||||
Exercised
|
—
|
—
|
|||||||||||
Canceled
|
77,500
|
4.77
|
|||||||||||
Outstanding,
June 30, 2008
|
2,880,500
|
$
|
3.73
|
8.08
|
$
|
624,963
|
|||||||
Options
exercisable, June 30, 2008
|
1,544,083
|
$
|
3.70
|
7.17
|
$
|
624,363
|
|
Restricted
Stock
|
Weighted-
Average Grant
Date Fair Value
|
|||||
Non-vested
at January 1, 2008
|
70,000
|
$
|
2.73
|
||||
Granted
|
100,000
|
3.25
|
|||||
Vested
|
—
|
—
|
|||||
Canceled
|
—
|
—
|
|||||
Non-vested
at June 30, 2008
|
170,000
|
$
|
3.04
|
4. |
INCOME
TAXES
|
|
·
|
Darinaparsin
is an organic arsenic compound covered by issued patents and pending
patent applications in the U.S. and in foreign countries. A form
of
commercially available inorganic arsenic (arsenic trioxide [Trisenox
®];
“ATO”) has been approved in the United States and the European Union for
the treatment of acute promyelocytic leukemia (“APL”), a precancerous
condition. ATO is on the compendia listing for the therapy of multiple
myeloma, and has been studied for the treatment of various other
cancers.
Nevertheless, ATO has been shown to be toxic to the heart, liver,
and
brain, which limits its use as an anti-cancer agent. Inorganic arsenic
has
also been shown to cause cancer of the skin and lung in humans. The
toxicity of arsenic is generally correlated to its accumulation in
organs
and tissues. Our preclinical and clinical studies to date have
demonstrated that darinaparsin is considerably less toxic than inorganic
arsenic, particularly with regard to cardiac toxicity. In
vitro
testing of darinaparsin using the National Cancer Institute’s human cancer
cell panel detected activity against lung, colon, brain, melanoma,
ovarian, and kidney cancer. Moderate activity was detected against
breast
and prostate cancer. In addition to solid tumors, in
vitro
testing in both the National Cancer Institute’s cancer cell panel and
in
vivo
testing in a leukemia animal model demonstrated substantial activity
against hematological cancers (cancers of the blood and blood-forming
tissues) such as leukemia, lymphoma, myelodysplastic syndromes, and
multiple myeloma. Preclinical studies have also established
anti-angiogenic properties of darinaparsin, provided support for
the
development of an oral form of the drug, and established synergy
of
darinaparsin in combination with other approved anti-cancer
agents.
|
|
|
Phase
I testing of the intravenous form of darinaparsin in solid tumors
and
hematological cancers has been completed. The Company has reported
clinical activity and, importantly, a safety profile from these studies
as
predicted by preclinical results. The Company is nearing completion
of
Phase II studies in advanced myeloma, in certain other hematological
cancers, and primary liver cancer. In addition, the Company has recently
initiated two Phase I studies with an oral form of darinaparsin.
Preliminary favorable results from the trial with IV-administered
darinaparsin in hematologic cancers have been reported. Initial study
results indicate efficacy and a favorable safety profile in various
types
of blood cancers. This ongoing Phase II trial, as well as one of
the two
trials with orally administered drug, will now be focused on non-Hodgkin's
lymphoma. The Company is actively seeking a partner or partners to
progress the program.
|
|
|
|
|
·
|
Several
proprietary forms of palifosfamide, or isophosphoramide mustard (“IPM”),
the active metabolite of ifosfamide that is also chemically related
to the
active metabolite of cyclophosphamide, have been developed. Patent
applications for pharmaceutical composition and method of use have
been
filed in the U.S. and internationally. Like cyclophosphamide and
ifosfamide, palifosfamide is an alkylating agent. The Company believes
that cyclophosphamide is the most widely used alkylating agent in
cancer
therapy, with significant use in the treatment of breast cancer and
non-Hodgkin’s lymphoma. Ifosfamide has been shown to be effective at high
doses in the treatment of sarcoma and lymphoma, either by itself
or in
combination with other anticancer agents. Unlike cyclophosphamide,
ifosfamide is approved by the U.S. Food and Drug Administration
("FDA") only as a treatment for testicular cancer. Although
ifosfamide-based treatment generally represents the standard of care
for
sarcoma, it is not licensed for this indication by the FDA. Preclinical
studies have shown that palifosfamide has activity against leukemia
and
solid tumors. These studies also indicate that palifosfamide may
have a
better safety profile than ifosfamide or cyclophosphamide because
it does
not appear to produce known toxic metabolites, such as acrolein and
chloroacetaldehyde. Acrolein, which is toxic to the kidneys and bladder,
can mandate the administration of a protective agent called mesna,
which
is inconvenient and expensive. Chloroacetaldehyde is toxic to the
central
nervous system, causing “fuzzy brain” syndrome for which there is
currently no protective measure. Similar toxicity concerns pertain
to
high-dose cyclophosphamide, which is widely used in bone marrow and
blood
cell transplantation. Palifosfamide has evidenced activity against
ifosfamide- and/or cyclophosphamide-resistant cancer cell lines.
Also in
preclinical cancer models, encouraging results have been obtained
with
palifosfamide in combination with doxorubicin, an agent approved
to
treat sarcoma.
|
|
|
|
|
|
Phase
II testing of the intravenous form of palifosfamide as a single agent
to
treat advanced sarcoma has been completed. In both Phase I and Phase
II
testing, palifosfamide has been administered without the “uroprotectant”
mesna, and the toxicities associated with acrolein and chloroacetaldehyde
have not been observed. Kidney toxicity, however, in the form of
Fanconi’s
Syndrome has been identified as the dose limiting toxicity. The Company
has reported clinical activity in the single agent Phase II study.
Following review of the preclinical combination studies, clinical
data,
and discussion with sarcoma experts, the Company has initiated a
Phase I
study of palifosfamide in combination with doxorubicin in patients
with
soft tissue sarcoma. The Company is now preparing a Phase II
randomized study designed to compare doxorubicin plus palifosfamide
to
doxorubicin alone in patients with front and second-line soft
tissue sarcoma to be initiated in the third quarter of 2008. The
Company is developing an oral form of palifosfamide to be studied
clinically following completion of additional preclinical studies
and with
further data from the IV trials.
|
|
·
|
Indibulin
is a novel, orally available small molecular-weight inhibitor of
tubulin polymerization that was acquired from Baxter Healthcare.
The
microtubule component, tubulin, is one of the more well-established
drug
targets in cancer. Microtubule inhibitors interfere with the dynamics
of
tubulin polymerization, resulting in inhibition of chromosome segregation
during mitosis and consequently inhibition of cell division. A number
of
marketed IV anticancer drugs target tubulin, such as the taxane family
members, paclitaxel (Taxol ®,
Abraxane®),
docetaxel (Taxotere ®)
,
and the Vinca
alkaloid family members, vincristine and vinorelbine. This class
of agents
is typically the mainstay of therapy in a wide variety of indications.
In
spite of their effectiveness, the use of these drugs is associated
with
significant toxicities, notably peripheral neurotoxicity.
Preclinical
studies with indibulin demonstrate significant and broad antitumor
activity, including activity against taxane-refractory cell lines.
The
cytotoxic activity of indibulin was demonstrated in several rodent
and
human tumor cell lines derived from prostate, brain, breast, pancreas,
lung, ovary, and cervical tumor tissues and in rodent tumor and human
tumor xenograft models. In addition, indibulin was effective against
multidrug resistant tumor cell lines (breast, lung, and leukemia)
both in
vitro
and in
vivo.
Indibulin is potentially safer than other tubulin inhibitors. No
neurotoxicity has been observed at therapeutic doses in rodents and
in the
ongoing Phase I trials. Indibulin has also demonstrated synergy with
approved anti-cancer agents in preclinical studies. The availability
of an
oral formulation of indibulin creates significant commercial opportunity
because no oral formulations of paclitaxel or related compounds are
currently on the market in the United States.
There
are three ongoing Phase I studies, which are nearing completion,
in
patients with advanced solid tumors. The Company has reported signs
of
clinical activity at well-tolerated doses using a continuous dosing
scheme
without the development of clinically relevant peripheral neuropathy.
Following encouraging results obtained with indibulin in combination
with
erlotinib, and 5-FU in preclinical models, two Phase I/II
combination studies have been initiated.
|
·
|
Clinical
trial expenses, including the costs incurred with respect to the
conduct
of clinical trials for darinaparsin, palifosfamide and
indibulin;
|
· |
Fees
and milestone payments required under the license agreements relating
to
our existing product candidates;
|
· |
Costs
related to the scale-up of palifosfamide and the manufacture of all
three
product candidates;
|
· |
Rent
for our facilities; and
|
· |
General
corporate and working capital, including general and administrative
expenses.
|
|
·
|
Changes
in the focus and direction of our research and development programs,
including the acquisition and pursuit of development of new product
candidates;
|
|
·
|
Competitive
and technical advances;
|
|
·
|
Costs
of commercializing any of the product candidates;
and
|
|
·
|
Costs
of filing, prosecuting, defending and enforcing any patent claims
and any
other intellectual property rights, or other
developments.
|
Payments due by Period
|
|
||||||||||||||||||
|
|
Total
|
|
2009
|
|
2010
|
|
2011
|
|
2012
|
|
2013 and
thereafter
|
|||||||
Operating
leases
|
$
|
1,347,464
|
$
|
508,018
|
$
|
431,633
|
$
|
184,500
|
$
|
191,250
|
32,063
|
Affirmative
Votes
|
Authority
Withheld
|
Abstained
|
|
Jonathan
Lewis, M.D., Ph.D.
|
11,663,482
|
838,557
|
0
|
Richard
E. Bagley
|
11,662,382
|
839,657
|
0
|
Murray
Brennan, M.D.
|
12,457,603
|
44,436
|
0
|
James
Cannon
|
12,457,603
|
44,436
|
0
|
Senator
Wyche Fowler, Jr., J.D.
|
12,457,103
|
44,936
|
0
|
Gary
S. Fragin
|
12,458,203
|
43,836
|
0
|
Timothy
McInerney
|
12,460,596
|
41,443
|
0
|
Michael
Weiser, M.D., Ph.D.
|
12,437,385
|
64,654
|
0
|
Affirmative
Votes
|
Votes
Against
|
Abstentions
|
12,462,217
|
17,313
|
22,509
|
Exhibit
No.
|
|
Description
|
10.1
(*)
|
|
Employment
Agreement dated as of June 25, 2008 between ZIOPHARM Oncology,
Inc. and
Richard E. Bagley.
|
|
|
|
31.1
|
|
Certification
of Chief Executive Officer pursuant to Securities Exchange Act
Rule
13a-15(e)/15d-15(e) as adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
|
|
|
|
31.2
|
|
Certification
of Chief Financial Officer pursuant to Securities Exchange Act
Rule
13a-15(e)/15d-15(e) as adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
|
|
|
|
32.1
|
|
Certification
of Chief Executive Officer pursuant to 18 U.S.C. Section 1350,
as adopted
pursuant to Section 906 of the Sarbanes-Oxley Act of
2002.
|
|
|
|
32.2
|
|
Certification
of Chief Financial Officer pursuant to 18 U.S.C. Section 1350,
as adopted
pursuant to Section 906 of the Sarbanes-Oxley Act of
2002.
|
(*)
|
|
Compensatory
plan or arrangement.
|
|
ZIOPHARM
ONCOLOGY, INC.
|
|
|
|
|
Date: July
30, 2008
|
By:
|
/s/ Jonathan
Lewis
|
|
|
Jonathan
Lewis, M.D., Ph.D.
Chief
Executive Officer
(Principal
Executive Officer)
|
Date:
July 30, 2008
|
By:
|
/s/ Richard
Bagley
|
|
|
Richard
Bagley
Chief
Financial Officer
(Principal
Financial and Accounting
Officer)
|
Exhibit
No.
|
|
Description
|
10.1
(*)
|
|
Employment
Agreement dated as of June 25, 2008 between ZIOPHARM Oncology,
Inc. and
Richard E. Bagley.
|
|
|
|
31.1
|
|
Certification
of Chief Executive Officer pursuant to Securities Exchange Act
Rule
13a-15(e)/15d-15(e) as adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
|
|
|
|
31.2
|
|
Certification
of Chief Financial Officer pursuant to Securities Exchange Act
Rule
13a-15(e)/15d-15(e) as adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
|
|
|
|
32.1
|
|
Certification
of Chief Executive Officer pursuant to 18 U.S.C. Section 1350,
as adopted
pursuant to Section 906 of the Sarbanes-Oxley Act of
2002.
|
|
|
|
32.2
|
|
Certification
of Chief Financial Officer pursuant to 18 U.S.C. Section 1350,
as adopted
pursuant to Section 906 of the Sarbanes-Oxley Act of
2002.
|
(*)
|
|
Compensatory
plan or arrangement.
|