· |
ZIO-101
is an organic arsenic compound covered by an issued U.S. patent
and
applications internationally. A form of commercially available
inorganic
arsenic (arsenic trioxide (Trisenox®) or ATO) has been approved for the
treatment of acute promyelocytic leukemia (APL), a precancerous
condition,
and is on the compendia listing for the therapy of multiple myeloma
as
well as having been studied for the treatment of various other
cancers.
Nevertheless, ATO has been shown to be toxic to the heart and
liver,
limiting 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 generally is correlated to its accumulation in organs
and tissues.
Our preclinical studies to date have demonstrated that ZIO-101
(and
organic arsenic in general) is considerably less toxic than inorganic
arsenic, particularly with regard to heart toxicity. In vitro
testing of
ZIO-101 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.
|
· |
ZIO-201,
or isophosphoramide mustard (IPM), is a proprietary stabilized
metabolite
of ifosfamide that is also related to cyclophosphamide. A patent
application for pharmaceutical composition has been filed.
Cyclophosphamide and ifosfamide are alkylating agents. Cyclophosphamide
is
the most widely used alkylating agent in cancer therapy and is
used to
treat breast cancer and non-Hodgkin’s lymphoma. Ifosfamide has been shown
to be effective in high dose by itself, or in combination in
treating
sarcoma and lymphoma. Although ifosfamide-based treatment generally
represents the standard of care for sarcoma, it is not licensed
for this
indication by the FDA. Our preclinical studies have shown that,
in animal
and laboratory models, IPM evidences activity against leukemia
and solid
tumors. These studies also indicate that ZIO-201 has a better
pharmacokinetic and safety profile than ifosfamide or cyclophosphamide,
offering the possibility of safer and more efficacious therapy
with
ZIO-201. Ifosfamide is metabolized to IPM. In addition to IPM,
another
metabolite of ifosfamide is acrolein, which is toxic to the kidneys
and
bladder. The presence of acrolein can mandate the administration
of a
protective agent called Mesna®, which is inconvenient and expensive.
Chloroacetaldehyde is another metabolite of ifosfamide and 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. Because ZIO-201 is independently active—without
acrolein or chloroacetaldehyde metabolites—we believe that the
administration of ZIO-201 may avoid the toxicities of ifosfamide
and
cyclophosphamide without compromising efficacy. In addition to
anticipated
lower toxicity, ZIO-201 may have other advantages over ifosfamide
and
cyclophosphamide. ZIO-201 likely cross-links DNA differently
than
ifosfamide or cyclophosphamide metabolites, resulting in a different
activity profile. Moreover, in some instances ZIO-201 appears
to show
activity in ifosfamide- and/or cyclophosphamide-resistant cancer
cells.
|
· |
fees
and milestone payments required under the license agreements relating
to
our existing product candidates;
|
· |
clinical
trial expenses, including the costs incurred with respect to the
conduct
of clinical trials for ZIO-101 and ZIO-201 and preclinical costs
associated with back-up candidates ZIO-102 and ZIO-202;
|
· |
costs
related to the scale-up and manufacture of ZIO-101 and
ZIO-201;
|
· |
rent
for our facilities; and
|
· |
general
corporate and working capital, including general and administrative
expenses.
|
Balance
Sheets as of September 30, 2005 and December 31, 2004
(unaudited)
|
F-2
|
|
Statement
of Operations for the three and nine months ended September 30,
2005 and 2004 and for the period
from
inception (September 9, 2003) to September 30,
2005 (unaudited)
|
F-3
|
|
Statement
of Cash Flows for the nine months ended September 30, 2005
and 2004 and for the period
from
inception (September 9, 2003) to September 30, 2005
(unaudited)
|
F-4
|
|
Statement
of changes in Convertible Preferred Stock and Stockholders’ Equity
(Deficit) for the nine months
ended
September 30, 2005 (unaudited), for the year ended December 31,
2004 and
for the period from inception
(September
9, 2003) to December 31,
2003
|
F-5
|
|
Notes
to Unaudited Financial Statements
|
F-6
|
ZIOPHARM
Oncology, Inc.
|
|||||||
(A
Development Stage Enterprise)
|
|||||||
Balance
Sheets
|
|||||||
September
30, 2005
|
December
31, 2004
|
||||||
|
Unaudited
|
||||||
ASSETS
|
|||||||
Current
assets:
|
|||||||
Cash
and cash equivalents
|
$
|
10,740,639
|
$
|
1,026,656
|
|||
Prepaid
expenses and other current assets
|
209,816
|
117,571
|
|||||
Total
current assets
|
10,950,455
|
1,144,227
|
|||||
Property
and equipment, net
|
232,862
|
240,733
|
|||||
Deposits
|
36,032
|
60,046
|
|||||
Other
non current assets
|
92,812
|
-
|
|||||
Total
assets
|
$
|
11,312,161
|
$
|
1,445,006
|
|||
LIABILITIES
AND STOCKHOLDERS' EQUITY (DEFICIT)
|
|||||||
Current
liabilities:
|
|||||||
Accounts
payable
|
$
|
477,389
|
$
|
709,947
|
|||
Accrued
expenses
|
1,270,624
|
879,376
|
|||||
Total
current liabilities
|
1,748,013
|
1,589,323
|
|||||
|
- |
-
|
|||||
Commitments
and contingencies
|
|||||||
Stockholders'
deficit:
|
|||||||
Common
stock, $.001 par value; 280,000,000 shares
authorized;
|
|||||||
7,241,211
and 2,761,621 shares issued and outstanding
|
|||||||
at September
30, 2005 and December 31, 2004, respectively
|
7,241
|
2,761
|
|||||
Additional
paid-in capital
|
22,460,147
|
5,700,355
|
|||||
Deficit
accumulated during the development stage
|
(12,903,240
|
)
|
(5,847,433
|
)
|
|||
Total
stockholders' equity (deficit)
|
9,564,148
|
(144,317
|
)
|
||||
Total
liabilities and stockholders' equity (deficit)
|
$
|
11,312,161
|
$
|
1,445,006
|
ZIOPHARM
Oncology, Inc.
|
||||||||||||||||
(A
Development Stage Enterprise)
|
||||||||||||||||
Statements
of Operations
|
||||||||||||||||
For
the three and nine months ended September 30, 2005 and
2004 and for the
period from inception (September 9, 2003) through September
30, 2005
(unaudited)
|
||||||||||||||||
|
|
|
|
|
|
|
|
For
the Period
|
|
|||||||
|
|
|
|
|
|
|
|
|
|
from
Inception
|
|
|||||
For
the three
|
|
For
the three
|
|
For
the nine
|
|
For
the nine
|
|
(September
9,
|
||||||||
months
|
months
|
months
|
months
|
2003)
|
||||||||||||
|
|
ended
|
|
ended
|
|
ended
|
|
ended
|
|
through
|
|
|||||
|
|
September
30, 2005
|
|
September
30,
2004
|
|
September
30,
2005
|
|
September
30,
2004
|
|
September
30,
2005
|
||||||
Revenue
|
$
|
-
|
$
|
-
|
$
|
-
|
$
|
-
|
$
|
-
|
||||||
Operating
expenses and other income:
|
||||||||||||||||
Research
and development, including
|
||||||||||||||||
costs
of research contracts
|
1,318,608
|
425,428
|
4,279,687
|
425,428
|
6,406,294
|
|||||||||||
General
and administrative
|
1,541,740
|
928,174
|
2,953,830
|
2,646,084
|
6,696,423
|
|||||||||||
Total
operating expenses
|
2,860,348
|
1,353,602
|
7,233,517
|
3,071,512
|
13,102,717
|
|||||||||||
Loss
from operations
|
(2,860,348
|
)
|
(1,353,602
|
)
|
(7,233,517
|
)
|
(3,071,512
|
)
|
(13,102,717
|
)
|
||||||
Interest
income
|
94,231
|
5,229
|
177,710
|
15,471
|
199,477
|
|||||||||||
Net
loss
|
$
|
(2,766,117
|
)
|
$
|
(1,348,373
|
)
|
$
|
(7,055,807
|
)
|
$
|
(3,056,041
|
)
|
$
|
(12,903,240
|
)
|
|
Basic
and diluted net loss per share
|
$
|
(0.77
|
)
|
$
|
(0.52
|
)
|
$
|
(2.32
|
)
|
$
|
(1.34
|
)
|
||||
Weighted
average common shares outstanding used to
|
||||||||||||||||
compute
basic and diluted net loss per share
|
3,593,109
|
2,611,873
|
3,041,829
|
2,280,832
|
||||||||||||
ZIOPHARM
Oncology, Inc.
|
||||||||||
(A
Development Stage Enterprise)
|
||||||||||
Statements
of Cash Flows
|
||||||||||
For
the nine months ended September 30, 2005 and 2004 and
for the period from
inception(September 9, 2003) through September 30, 2005
(unaudited)
|
||||||||||
|
|
|
|
|
|
|||||
|
|
|
|
|
|
For
the Period
|
|
|||
For
the
|
For
the
|
from
Inception
|
||||||||
|
|
Nine
months
|
|
Nine
months
|
|
(September
9, 2003)
|
|
|||
|
|
ended
|
|
ended
|
|
through
|
|
|||
|
|
September
30, 2005
|
|
September
30, 2004
|
|
September
30, 2005
|
||||
Cash
flows from operating activities:
|
||||||||||
Net
loss
|
$
|
(7,055,807
|
)
|
$
|
(3,056,041
|
)
|
$
|
(12,903,240
|
)
|
|
Adjustments
to reconcile net loss to net cash
|
||||||||||
used
in operating activities:
|
||||||||||
Depreciation
and amortization
|
72,519
|
25,177
|
106,472
|
|||||||
Stock-based
compensation
|
-
|
- |
703,116
|
|||||||
Change
in operating assets and liabilities:
|
||||||||||
Increase
in:
|
||||||||||
Prepaid
expenses and other current assets
|
(92,245
|
)
|
(52,054
|
)
|
(209,816
|
)
|
||||
Other
noncurrent assets
|
(92,812
|
)
|
-
|
(92,812
|
)
|
|||||
Increase
(decrease) in:
|
||||||||||
Deposits
|
24,014
|
(69,246
|
)
|
(36,032
|
)
|
|||||
Accounts
payable
|
(232,558
|
)
|
202,673
|
477,389
|
||||||
Accrued
expenses
|
391,248
|
387,103
|
1,270,624
|
|||||||
Net
cash used in operating activates
|
(6,985,641
|
)
|
(2,562,388
|
)
|
(10,684,299
|
)
|
||||
Cash
flows from investing activities:
|
||||||||||
Purchases
of property and equipment
|
(64,648
|
)
|
(133,077
|
)
|
(339,334
|
)
|
||||
Net
cash used in investing activities
|
(64,648
|
)
|
(133,077
|
)
|
(339,334
|
)
|
||||
Cash
flows from financing activities:
|
||||||||||
Stockholders'
capital contribution
|
-
|
-
|
500,000
|
|||||||
Proceeds
from issuance of common stock, net
|
4,676
|
4,500,000
|
4,504,676
|
|||||||
Proceeds
from issuance of preferred stock, net
|
16,759,596
|
-
|
16,759,596
|
|||||||
Net
cash provided by financing activities
|
16,764,272
|
4,500,000
|
21,764,272
|
|||||||
Net
increase in cash and cash equivalents
|
9,713,983
|
1,804,535
|
10,740,639
|
|||||||
Cash
and cash equivalents, beginning of period
|
1,026,656
|
402,363
|
-
|
|||||||
Cash
and cash equivalents, end of period
|
$
|
10,740,639
|
$
|
2,206,898
|
$
|
10,740,639
|
||||
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 agent, in connection with
|
||||||||||
preferred
stock issuance
|
$
|
1,682,863
|
$
|
-
|
$
|
1,682,863
|
||||
ZIOPHARM Oncology,
Inc.
|
|||||||||||||||||||||||||
(A Development Stage
Enterprise)
|
|||||||||||||||||||||||||
Statement
of Changes in Convertible Preferred Stock and Stockholders'
Equity
(Deficit)
|
|||||||||||||||||||||||||
For
the nine months ended September 30, 2005 (unaudited), For
the Year ended
December 31, 2004 and
|
|||||||||||||||||||||||||
For
the Period from Inception (September 9, 2003) to December
31,
2003
|
|||||||||||||||||||||||||
Convertible
Preferred Stock and Warrants
|
|
Stockholder's
Equity (Deficit)
|
|
||||||||||||||||||||||
|
|
|
|
|
|
Warrants
to
|
|
|
|
|
|
|
|
|
|
|
|
||||||||
|
|
|
|
Purchase
Series
A
|
|
|
|
|
|
|
|
Deficit
|
|
|
|
||||||||||
|
|
Series
A
|
|
Convertible
|
|
|
|
|
|
|
|
Accumulated
|
|
Total
|
|
||||||||||
|
|
Convertible
|
|
Preferred
|
Additional
|
during
the
|
Stockholders'
|
||||||||||||||||||
|
|
Preferred
Stock
|
|
Stock
|
|
Common
Stock
|
|
Paid-in
|
|
Development
|
|
Equity/
|
|
||||||||||||
|
|
Shares
|
|
Amount
|
|
Warrants
|
|
Shares
|
|
Amount
|
|
Capital
|
|
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 (audited)
|
-
|
-
|
-
|
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
|
-
|
-
|
-
|
-
|
-
|
264,277
|
-
|
264,277
|
|||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
(5,687,297
|
)
|
(5,687,297
|
)
|
|||||||||||||||
Balance
at December 31, 2004 (audited)
|
-
|
-
|
-
|
2,761,625
|
2,761
|
5,700,355
|
(5,847,433
|
)
|
(144,317
|
)
|
|||||||||||||||
Issuance
of Series A convertible preferred stock
|
8,379,564
|
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
|
(8,379,564
|
)
|
(15,076,733
|
)
|
(1,682,863
|
)
|
4,197,946
|
4,198
|
16,755,398
|
-
|
16,759,596
|
||||||||||||||
Issuance
of common stock due to exercise of stock options
|
-
|
-
|
-
|
91,718
|
92
|
4,584
|
-
|
4,676
|
|||||||||||||||||
Net
loss
|
-
|
-
|
-
|
-
|
-
|
-
|
(7,055,807
|
)
|
(7,055,807
|
)
|
|||||||||||||||
Balance
at September 30, 2005 (unaudited)
|
-
|
$
|
-
|
$
|
-
|
7,241,211
|
$
|
7,241
|
$
|
22,460,147
|
$
|
(12,903,240
|
)
|
$
|
9,564,148
|
1.
|
BASIS
OF PRESENTATION AND
OPERATIONS
|
2. |
STOCK
BASED COMPENSATION
|
Three
months ended
September
30,
|
Nine
months ended
September
30,
|
||||||||||||
2005
|
2004
|
2005
|
2004
|
||||||||||
Net
loss:
|
|||||||||||||
As
reported
|
$
|
(2,766,117
|
)
|
$
|
(1,348,373
|
)
|
$
|
(7,055,807
|
$
|
(3,056,041
|
)
|
||
Stock-based
compensation expense included in reported net loss
|
---
|
---
|
---
|
---
|
|||||||||
Stock-based
compensation expense under the fair value-based method
|
(176,297
|
)
|
(33,958
|
)
|
(340,197
|
)
|
(60,683
|
)
|
|||||
Pro
forma net loss
|
$
|
(2,942,414
|
)
|
$
|
(1,382,331
|
)
|
$
|
(7,396,004
|
)
|
$
|
(3,116,724
|
)
|
|
Basic
and diluted net loss per share:
|
|||||||||||||
As
reported
|
$
|
(0.77
|
)
|
$
|
(0.52
|
)
|
$
|
(2.32
|
)
|
$
|
(1.34
|
)
|
|
Pro
forma
|
$
|
(0.82
|
)
|
$
|
(0.53
|
)
|
$
|
(2.43
|
)
|
$
|
(1.37
|
)
|
Three
months ended
September
30,
|
Nine
months ended
September
30,
|
||||||
2005
|
2004
|
2005
|
2004
|
||||
Expected
life
|
5
years
|
5
years
|
5
years
|
5
years
|
|||
Expected
volatility
|
172%
|
134%
|
172%
|
114%
|
|||
Dividend
yield
|
0%
|
0%
|
0%
|
0%
|
|||
Weighted
average risk-free interest rate
|
4.01%
|
3.60%
|
4.01%
|
3.60%
|
3.
|
CONVERTIBLE
PREFERRED STOCK AND STOCKHOLDERS’
EQUITY
|
4.
|
RELATED
PARTY TRANSACTIONS
|
5.
|
STOCK
OPTION PLAN
|
6.
|
COMMITMENTS
AND CONTIGENCIES
|