e10vq
UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-Q
(Mark One)
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þ |
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QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
For the quarterly period ended June 30, 2008
or
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o |
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TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 |
Commission file number: 000-50633
CYTOKINETICS, INCORPORATED
(Exact name of registrant as specified in its charter)
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Delaware
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94-3291317 |
(State or other jurisdiction of
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(I.R.S. Employer |
incorporation or organization)
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Identification Number) |
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280 East Grand Avenue |
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South San Francisco, California
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94080 |
(Address of principal executive offices)
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(Zip Code) |
Registrants telephone number, including area code: (650) 624-3000
Indicate by check mark whether the registrant (1) has filed all reports required to be filed
by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or
for such shorter period that the registrant was required to file such reports), and (2) has been
subject to such filing requirements for the past 90 days. Yes
þ No o
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated
filer, a non-accelerated filer, or a smaller reporting company. See the definitions of large
accelerated filer, accelerated filer and smaller reporting company in Rule 12b-2 of the
Exchange Act. (Check one):
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Large accelerated filer o
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Accelerated filer þ
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Non-accelerated filer o
(Do not check if a smaller reporting company)
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Smaller reporting company o |
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of
the Exchange Act). Yes o No þ
Number of shares of common stock, $0.001 par value, outstanding as of July 31, 2008:
49,412,922.
CYTOKINETICS, INCORPORATED
TABLE OF CONTENTS FOR FORM 10-Q
FOR THE QUARTER ENDED JUNE 30, 2008
2
PART I. FINANCIAL INFORMATION
ITEM 1. FINANCIAL STATEMENTS
CYTOKINETICS, INCORPORATED
(A Development Stage Enterprise)
CONDENSED BALANCE SHEETS
(In thousands, except share and per share data)
(Unaudited)
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June 30, |
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December 31, |
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2008 |
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2007 (1) |
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ASSETS |
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Current assets: |
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Cash and cash equivalents |
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$ |
86,861 |
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$ |
116,564 |
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Short-term investments |
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3,175 |
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Related party accounts receivable |
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60 |
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87 |
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Related party notes receivable short-term portion |
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77 |
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127 |
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Prepaid and other current assets |
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2,337 |
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2,063 |
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Total current assets |
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89,335 |
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122,016 |
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Long-term investments |
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18,749 |
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20,025 |
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Property and equipment, net |
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6,728 |
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7,728 |
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Related party notes receivable long-term portion |
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39 |
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99 |
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Restricted cash |
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4,147 |
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5,167 |
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Other assets |
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368 |
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335 |
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Total assets |
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$ |
119,366 |
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$ |
155,370 |
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LIABILITIES and STOCKHOLDERS EQUITY |
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Current liabilities: |
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Accounts payable |
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$ |
1,659 |
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$ |
1,584 |
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Accrued liabilities |
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8,024 |
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8,558 |
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Related party payables and accrued liabilities |
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6 |
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22 |
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Short-term portion of equipment financing lines |
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3,029 |
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4,050 |
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Short-term portion of deferred revenue |
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12,234 |
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12,234 |
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Total current liabilities |
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24,952 |
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26,448 |
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Long-term portion of equipment financing lines |
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3,576 |
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4,639 |
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Long-term portion of deferred revenue |
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18,250 |
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24,367 |
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Total liabilities |
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46,778 |
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55,454 |
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Stockholders equity: |
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Common stock, $0.001 par value: Authorized:
170,000,000 shares; Issued and outstanding: 49,399,620
shares at June 30, 2008 and 49,282,362
shares at December 31, 2007 |
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49 |
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49 |
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Additional paid-in capital |
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382,730 |
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379,730 |
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Deferred stock-based compensation |
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(124 |
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(329 |
) |
Accumulated other comprehensive loss |
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(1,276 |
) |
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(1 |
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Deficit accumulated during the development stage |
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(308,791 |
) |
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(279,533 |
) |
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Total stockholders equity |
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72,588 |
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99,916 |
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Total liabilities and stockholders equity |
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$ |
119,366 |
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$ |
155,370 |
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(1) |
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The condensed balance sheet at December 31, 2007 has been derived from the audited financial
statements at that date but does not include all of the information and footnotes required by
accounting principles generally accepted in the United States of America for complete
financial statements. |
The accompanying notes are an integral part of these financial statements.
3
CYTOKINETICS, INCORPORATED
(A Development Stage Enterprise)
CONDENSED STATEMENTS OF OPERATIONS
(In thousands, except per share data)
(Unaudited)
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Period from |
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August 5, 1997 |
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Three Months Ended |
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Six Months Ended |
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(date of inception) |
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June 30, |
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June 30, |
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June 30, |
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June 30, |
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to June 30, |
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2008 |
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2007 |
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2008 |
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2007 |
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2008 |
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Revenues: |
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Research and development revenues
from related party |
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$ |
16 |
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$ |
119 |
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$ |
27 |
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$ |
265 |
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$ |
40,279 |
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Research and development, grant and
other revenues |
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2,955 |
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License revenues from related parties |
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3,058 |
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3,058 |
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6,117 |
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6,117 |
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32,451 |
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Total revenues |
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3,074 |
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3,177 |
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6,144 |
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6,382 |
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75,685 |
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Operating expenses: |
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Research and development (1) |
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14,859 |
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13,726 |
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28,961 |
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26,213 |
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312,449 |
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General and administrative (1) |
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4,252 |
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4,015 |
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8,409 |
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8,497 |
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93,869 |
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Total operating expenses |
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19,111 |
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17,741 |
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37,370 |
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34,710 |
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406,318 |
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Operating loss |
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(16,037 |
) |
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(14,564 |
) |
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(31,226 |
) |
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(28,328 |
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(330,633 |
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Interest and other income |
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808 |
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2,122 |
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2,249 |
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4,363 |
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26,992 |
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Interest and other expense |
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(135 |
) |
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(186 |
) |
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(281 |
) |
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(356 |
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(5,150 |
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Net loss |
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$ |
(15,364 |
) |
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$ |
(12,628 |
) |
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$ |
(29,258 |
) |
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$ |
(24,321 |
) |
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$ |
(308,791 |
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Net loss per common share basic and
diluted |
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$ |
(0.31 |
) |
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$ |
(0.27 |
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$ |
(0.59 |
) |
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$ |
(0.52 |
) |
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Weighted-average number of shares used
in computing net loss per common share
basic and diluted |
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49,366 |
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46,890 |
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49,330 |
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46,826 |
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(1) Includes the following stock-based
compensation charges: |
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Research and development |
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$ |
652 |
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$ |
684 |
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$ |
1,517 |
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$ |
1,328 |
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$ |
9,829 |
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General and administrative |
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695 |
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792 |
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1,356 |
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1,308 |
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7,792 |
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The accompanying notes are an integral part of these financial statements.
4
CYTOKINETICS, INCORPORATED
(A Development Stage Enterprise)
CONDENSED STATEMENTS OF CASH FLOWS
(In thousands)
(Unaudited)
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Period from |
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August 5, 1997 |
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Six Months Ended |
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(date of inception) |
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June 30, |
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June 30, |
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to June 30, |
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2008 |
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2007 |
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2008 |
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Cash flows from operating activities: |
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Net loss |
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$ |
(29,258 |
) |
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$ |
(24,321 |
) |
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$ |
(308,791 |
) |
Adjustments to reconcile net loss to net cash provided by (used
in) operating activities: |
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Depreciation and amortization of property and equipment |
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1,274 |
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1,500 |
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22,263 |
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Loss on disposal of property and equipment |
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4 |
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348 |
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Gain on sale of investments |
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(84 |
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Allowance for doubtful accounts |
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191 |
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Non-cash expense related to warrants issued for equipment
financing lines and facility lease |
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41 |
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Non-cash interest expense |
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46 |
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46 |
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473 |
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Non-cash forgiveness of loan to officer |
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11 |
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12 |
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375 |
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Stock-based compensation |
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2,873 |
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2,636 |
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17,621 |
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Other non-cash expenses |
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27 |
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Changes in operating assets and liabilities: |
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Related party accounts receivable |
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25 |
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42,006 |
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(402 |
) |
Prepaid and other assets |
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(351 |
) |
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(505 |
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(2,702 |
) |
Accounts payable |
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384 |
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(47 |
) |
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1,778 |
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Accrued liabilities |
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(549 |
) |
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(780 |
) |
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7,972 |
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Related party payables and accrued liabilities |
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(16 |
) |
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(88 |
) |
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7 |
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Deferred revenue |
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(6,117 |
) |
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817 |
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30,484 |
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Net cash provided by (used in) operating activities |
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(31,678 |
) |
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21,280 |
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(230,399 |
) |
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Cash flows from investing activities: |
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Purchases of investments |
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(9,400 |
) |
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(39,800 |
) |
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(654,303 |
) |
Proceeds from sales and maturities of investments |
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12,576 |
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65,720 |
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634,362 |
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Purchases of property and equipment |
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(567 |
) |
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(1,947 |
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(29,459 |
) |
Proceeds from sale of property and equipment |
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50 |
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(Increase) decrease in restricted cash |
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1,020 |
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(91 |
) |
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(4,147 |
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Issuance of related party notes receivable |
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(1,146 |
) |
Proceeds from payments of related party notes receivable |
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100 |
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99 |
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799 |
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Net cash provided by (used in) investing activities |
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3,729 |
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23,981 |
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(53,844 |
) |
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Cash flows from financing activities: |
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Proceeds from initial public offering, sale of common stock to
related party and public offerings, net of issuance costs |
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26,002 |
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193,934 |
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Proceeds from draw down of Committed Equity Financing Facility,
net of issuance costs |
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32,046 |
|
Proceeds from other issuances of common stock |
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|
331 |
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|
686 |
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|
5,889 |
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Proceeds from issuance of preferred stock, net of issuance costs |
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133,172 |
|
Repurchase of common stock |
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(68 |
) |
Proceeds from equipment financing lines |
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|
1,743 |
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|
23,696 |
|
Repayment of equipment financing lines |
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|
(2,085 |
) |
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|
(1,856 |
) |
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(17,565 |
) |
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Net cash provided by (used in) financing activities |
|
|
(1,754 |
) |
|
|
26,575 |
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|
371,104 |
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Net increase (decrease) in cash and cash equivalents |
|
|
(29,703 |
) |
|
|
71,836 |
|
|
|
86,861 |
|
Cash and cash equivalents, beginning of period |
|
|
116,564 |
|
|
|
39,387 |
|
|
|
|
|
|
|
|
|
|
|
|
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|
Cash and cash equivalents, end of period |
|
$ |
86,861 |
|
|
$ |
111,223 |
|
|
$ |
86,861 |
|
|
|
|
|
|
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|
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|
The accompanying notes are an integral part of these financial statements.
5
CYTOKINETICS, INCORPORATED
(A DEVELOPMENT STAGE ENTERPRISE)
NOTES TO UNAUDITED CONDENSED FINANCIAL STATEMENTS
Note 1. Organization and Summary of Significant Accounting Policies
Overview
Cytokinetics, Incorporated (the Company, we or our) was incorporated under the laws of
the state of Delaware on August 5, 1997. The Company is focused on developing small molecule
therapeutics for the treatment of cardiovascular disease, cancer and other diseases. The Company is
a development stage enterprise and has been primarily engaged in conducting research, developing
drug candidates and technologies, and raising capital.
The Company has funded its operations primarily through sales of common stock and convertible
preferred stock, contract payments under its collaboration agreements, debt financing arrangements,
government grants and interest income.
The Companys registration statement for its initial public offering (IPO) was declared
effective by the Securities and Exchange Commission (SEC) on April 29, 2004. The Companys common
stock commenced trading on the NASDAQ National Market, now the NASDAQ Global Market, on April 29,
2004 under the trading symbol CYTK.
Until it achieves profitable operations, the Company intends to continue to fund operations
through the additional sale of equity securities, payments from strategic collaborations,
government grant awards and debt financing.
Basis of Presentation
The accompanying unaudited condensed financial statements have been prepared in accordance
with accounting principles generally accepted in the United States of America for interim financial
information and with instructions to Form 10-Q and Rule 10-01 of
Regulation
S-X. Accordingly, they do not include all of the information and footnotes required by generally accepted accounting
principles for complete financial statements. The financial statements include all adjustments
(consisting only of normal recurring adjustments) that management believes are necessary for the
fair statement of the balances and results for the periods presented. These interim financial
statement results are not necessarily indicative of results to be expected for the full fiscal year
or any future interim period.
The balance sheet at December 31, 2007 has been derived from the audited financial statements
at that date. The financial statements and related disclosures have been prepared with the
presumption that users of the interim financial statements have read or have access to the audited
financial statements for the preceding fiscal year. Accordingly, these financial statements should
be read in conjunction with the audited financial statements and notes thereto contained in the
Companys Form 10-K for the year ended December 31, 2007.
Comprehensive Income (Loss)
Comprehensive loss consists of the net loss and other comprehensive income (loss). Other
comprehensive income (loss) (OCI) includes certain changes in stockholders equity that are
excluded from net loss. Comprehensive loss and its components for the three-and six-month periods
ended June 30, 2008 and 2007 are as follows (in thousands):
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Three months Ended |
|
|
Six Months Ended |
|
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
|
2008 |
|
|
2007 |
|
|
2008 |
|
|
2007 |
|
Net loss |
|
$ |
(15,364 |
) |
|
$ |
(12,628 |
) |
|
$ |
(29,258 |
) |
|
$ |
(24,321 |
) |
Change in unrealized gain (loss) on investments |
|
|
(328 |
) |
|
|
(6 |
) |
|
|
(1,275 |
) |
|
|
15 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Comprehensive loss |
|
$ |
(15,692 |
) |
|
$ |
(12,634 |
) |
|
$ |
(30,533 |
) |
|
$ |
(24,306 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
6
Restricted Cash
In accordance with the terms of the Companys line of credit agreements with General Electric
Capital Corporation (GE Capital) to fund certain equipment, the Company is obligated to maintain a certificate of deposit
with the lender. The balance of the certificate of deposit, which is classified as restricted cash,
was $4.1 million at June 30, 2008 and $5.2 million at December 31, 2007. At July 1, 2008, the
restricted cash balance was $2.7 million.
Fair Value of Financial Instruments
In September 2006, the Financial Statement Standard Board (FASB) issued Statement of
Financial Accounting Standard (SFAS) No. 157, Fair Value Measurements (SFAS No. 157). SFAS
No. 157 established a common definition for fair value, which is to be applied to U.S. generally
accepted accounting principles (GAAP) requiring use of fair value, and a framework for measuring
fair value, and expanded disclosure about such fair value measurements. This pronouncement applies
under the other accounting standards that require or permit fair value measurements. Accordingly,
this statement does not require any new fair value measurement. SFAS No. 157 is effective for
financial assets and financial liabilities for fiscal years beginning after November 15, 2007. In
February 2008, the FASB released a FASB Staff Position (FSP) 157-1, Application of FASB
Statement No. 157 to FASB Statement 13 and Other Accounting Pronouncements That Address Fair Value
Measurements for Purposes of Lease Classification or Measurement under Statement 13. FSP 157-1
removed leasing transactions accounted for under FASB Statement 13 and related guidance from the
scope of SFAS No. 157. FSP 157-2, Partial Deferral of the Effective Date of Statement 157,
deferred the effective date of SFAS No. 157 for all nonfinancial assets and nonfinancial
liabilities, except those are recognized or disclosed at fair value in the financial statements on
a recurring basis (at least annually) to fiscal years beginning after November 15, 2008.
SFAS No. 159, The Fair Value Option for Financial Assets and Financial Liabilities, became
effective for the Company on January 1, 2008. SFAS No. 159 includes an amendment of FASB Statement
No. 115, Accounting for Certain Investments in Debt and Equity Securities, which permits an
entity to measure certain financial assets and financial liabilities at fair value. The objective
of SFAS No. 159 is to improve financial reporting by allowing entities to mitigate volatility in
reported earnings caused by the measurement of related assets and liabilities using different
attributes, without having to apply complex hedge accounting provisions. Under SFAS No. 159,
entities that elect the fair value option (by instrument) will report unrealized gains and losses
in earnings at each subsequent reporting date. The fair value option election is irrevocable,
unless a new election date occurs. SFAS No. 159 establishes presentation and disclosure
requirements to help financial statement users understand the effect of the entitys election on
its earnings, but does not eliminate disclosure requirements of other accounting standards. Assets
and liabilities that are measured at fair value must be displayed on the face of the balance sheet.
The Company did not elect the fair value option for its financial assets and liabilities existing
at January 1, 2008, nor for its financial assets and liabilities transacted in the six months ended
June 30, 2008.
Stock-Based Compensation
Effective January 1, 2006, the Company adopted the provisions of SFAS No. 123R, Share-Based
Payment, which establishes accounting for share-based payment awards made to employees and
directors, including employee stock options and employee stock purchases. Under the provisions of
SFAS No. 123R, stock-based compensation cost is measured at the grant date based on the calculated
fair value of the award, and is recognized as an expense on a straight-line basis over the
employees requisite service period, generally the vesting period of the award.
The Company uses the Black-Scholes option pricing model to determine the fair value of stock
options and employee stock purchase plan (ESPP) shares, consistent with the provisions of SFAS
No. 123R. The key input assumptions used to estimate fair value of these awards include the
exercise price of the award, the expected option term, the expected volatility of the Companys
stock over the options expected term, the risk-free interest rate over the options expected term
and the Companys expected dividend yield, if any.
7
For employee stock options, the fair value of share-based payments was estimated on the date
of grant using the Black-Scholes option pricing model based on the following weighted average
assumptions:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
Six Months Ended |
|
|
June 30, 2008 |
|
June 30, 2007 |
|
June 30, 2008 |
|
June 30, 2007 |
Risk-free interest rate |
|
|
3.50 |
% |
|
|
4.74 |
% |
|
|
2.97 |
% |
|
|
4.52 |
% |
Volatility |
|
|
67 |
% |
|
|
74 |
% |
|
|
63 |
% |
|
|
73 |
% |
Expected life (in years) |
|
|
6.11 |
|
|
|
5.73 |
|
|
|
6.08 |
|
|
|
5.99 |
|
Expected dividend yield |
|
|
0.00 |
% |
|
|
0.00 |
% |
|
|
0.00 |
% |
|
|
0.00 |
% |
For the ESPP, the fair value of share-based payments was estimated on the date of grant using
the Black-Scholes option pricing model based on the following weighted average assumptions:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
Six Months Ended |
|
|
June 30, 2008 |
|
June 30, 2007 |
|
June 30, 2008 |
|
June 30, 2007 |
Risk-free interest rate |
|
|
2.23 |
% |
|
|
4.84 |
% |
|
|
2.23 |
% |
|
|
4.84 |
% |
Volatility |
|
|
67 |
% |
|
|
74 |
% |
|
|
67 |
% |
|
|
74 |
% |
Expected life (in years) |
|
|
1.25 |
|
|
|
1.25 |
|
|
|
1.25 |
|
|
|
1.25 |
|
Expected dividend yield |
|
|
0.00 |
% |
|
|
0.00 |
% |
|
|
0.00 |
% |
|
|
0.00 |
% |
The risk-free interest rate that the Company uses in the option pricing model is based on the
U.S. Treasury zero-coupon issues with remaining terms similar to the expected terms of the options.
The Company does not anticipate paying dividends in the foreseeable future and therefore uses an
expected dividend yield of zero in the option pricing model. The Company is required to estimate
forfeitures at the time of grant and revise those estimates in subsequent periods if actual
forfeitures differ from those estimates. Historical data is used to estimate pre-vesting option
forfeitures and record stock-based compensation expense only on those awards that are expected to
vest.
Under Staff Accounting Bulletin (SAB) No. 107, the Company used the simplified method of
estimating the expected term for stock-based compensation from January 1, 2006, the date it adopted
SFAS No. 123R, through December 31, 2007. Starting January 1, 2008, the Company ceased to use the
simplified method, and now uses its own historical exercise activity and extrapolates the life
cycle of options outstanding to arrive at its estimated expected term for new option grants.
From January 1, 2006, the date of adopting SFAS No. 123R, through December 31, 2007, the
Company estimated the volatility of its common stock by using an average of historical stock price
volatility of comparable companies due to the limited length of trading history. Starting January
1, 2008, the Company has used its own volatility history based on its stocks trading history of
approximately four years. Because its outstanding options have an expected term of approximately
six years, the Company supplemented its own volatility history by using comparable companies
volatility history for approximately two years preceding the Companys IPO.
Note 2. Net Loss Per Share
Basic net loss per common share is computed by dividing the net loss by the weighted-average
number of vested common shares outstanding during the period. Diluted net loss per common share is
computed by giving effect to all potentially dilutive common shares, including outstanding options,
common stock subject to repurchase, warrants and shares issuable under the ESPP. The following is a
reconciliation of the numerator and denominator used in the calculation of basic and diluted net
loss per common share (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
|
Six Months Ended |
|
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
|
2008 |
|
|
2007 |
|
|
2008 |
|
|
2007 |
|
Numerator net loss |
|
$ |
(15,364 |
) |
|
$ |
(12,628 |
) |
|
$ |
(29,258 |
) |
|
$ |
(24,321 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
Denominator: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Weighted-average common shares outstanding |
|
|
49,366 |
|
|
|
46,890 |
|
|
|
49,330 |
|
|
|
46,827 |
|
Less: Weighted-average shares subject to repurchase |
|
|
( |
) |
|
|
( |
) |
|
|
( |
) |
|
|
(1 |
) |
|
|
|
|
|
|
|
|
|
|
|
|
|
Weighted-average shares used in computing basic and
diluted net loss per common share |
|
|
49,366 |
|
|
|
46,890 |
|
|
|
49,330 |
|
|
|
46,826 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
8
The following outstanding instruments were excluded from the computation of diluted net loss
per common share for the periods presented, because their effect would have been antidilutive (in
thousands):
|
|
|
|
|
|
|
|
|
|
|
As of June 30, |
|
|
2008 |
|
2007 |
Options to purchase common stock |
|
|
6,590 |
|
|
|
5,250 |
|
Warrants to purchase common stock |
|
|
474 |
|
|
|
244 |
|
Shares issuable related to the ESPP |
|
|
46 |
|
|
|
38 |
|
|
|
|
|
|
|
|
|
|
Total shares |
|
|
7,110 |
|
|
|
5,532 |
|
|
|
|
|
|
|
|
|
|
Note 3. Supplemental Cash Flow Data
Supplemental cash flow data was as follows (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Period from |
|
|
|
|
|
|
|
|
|
|
August 5, 1997 |
|
|
Six Months Ended |
|
(date of inception) |
|
|
June 30, |
|
June 30, |
|
June 30, |
|
|
2008 |
|
2007 |
|
2008 |
Significant non-cash investing and financing activities: |
|
|
|
|
|
|
|
|
|
|
|
|
Deferred stock-based compensation |
|
$ |
|
|
|
$ |
|
|
|
$ |
6,940 |
|
Purchases of property and equipment through accounts payable |
|
|
65 |
|
|
|
42 |
|
|
|
65 |
|
Purchases of property and equipment through trade in value
of disposed property and equipment |
|
|
|
|
|
|
|
|
|
|
258 |
|
Penalty on restructuring of equipment financing lines |
|
|
|
|
|
|
|
|
|
|
475 |
|
Conversion of convertible preferred stock to common stock |
|
|
|
|
|
|
|
|
|
|
133,172 |
|
Unrealized loss on auction rate securities |
|
|
1,276 |
|
|
|
|
|
|
|
1,276 |
|
Note 4. Related Party Agreements
Research and Development Arrangements
GlaxoSmithKline (GSK). Pursuant to the collaboration and license agreement between
the Company and GSK (the GSK Agreement), the Company received and recorded as research and
development revenues from related party, patent expense reimbursements from GSK of $16,000 and
$119,000 in the three months ended June 30, 2008 and 2007, respectively. For the six months ended
June 30, 2008 and 2007, the Company received and recorded as research and development revenues from
related party, patent expense reimbursements from GSK of $27,000 and $265,000, respectively.
Related party accounts payable and accrued liabilities payable to GSK for outsourced services under
the GSK Agreement were zero and $20,000 at June 30, 2008 and December 31, 2007, respectively.
Amgen Inc. (Amgen). Pursuant to the collaboration and option agreement between the
Company and Amgen (the Amgen Agreement), the Company recognized license revenue of $3.1 million
and $6.1 million in both the three and six months ended June 30, 2008 and June 30, 2007. At June
30, 2008, deferred revenue related to the Amgen Agreement and its related common stock purchase
agreement was $30.5 million.
Other
Board member. Charles J. Homcy, M.D. was a member of the Companys Board of Directors
through June 30, 2008 and continues as a consultant to the Company. The Company incurred consulting
fees earned by Dr. Homcy of $8,000 and $13,000 in the six months ended June 30, 2008 and 2007,
respectively. Related party accounts payable and accrued liabilities payable to Dr. Homcy for his
consulting services were $6,300 and $2,500 as of June 30, 2008 and December 31, 2007, respectively.
Related Party Notes Receivable. Effective March 31, 2008, James Sabry voluntarily
resigned from his position as Executive Chairman of the Board of Directors of the Company, and on
April 1, 2008, assumed his new role as the non-employee Chairman of the Board of Directors, as well
as Chairman of the Companys Scientific Advisory Board and a consultant to the Company. In
accordance with the terms of Dr. Sabrys promissory note payable to the Company, the outstanding
balance of the note of $100,000 became due, and was repaid in full, on April 30, 2008.
In May 2007, $11,000 of principal and interest on a loan receivable from an officer of the
Company was forgiven in accordance with the terms of the loan agreement.
9
Note 5. Cash, cash equivalents, and investments
The amortized cost and fair value of cash, cash equivalents and short- and long-term
investments at June 30, 2008 and December 31, 2007 were as follows (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
June 30, 2008 |
|
|
|
|
|
|
|
|
|
|
|
Unrealized |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Losses in |
|
|
|
|
|
|
|
|
|
Amortized |
|
|
Unrealized |
|
|
accumulated |
|
|
Fair |
|
|
Investment Maturity |
|
|
|
Cost |
|
|
Gains |
|
|
OCI |
|
|
Value |
|
|
Dates |
|
Cash and cash equivalents |
|
$ |
86,861 |
|
|
|
|
|
|
|
|
|
|
$ |
86,861 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Long-term investments: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Student loan auction rate securities (taxable) |
|
$ |
20,025 |
|
|
|
|
|
|
|
(1,276 |
) |
|
$ |
18,749 |
|
|
|
6/20368/2045 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total long-term investments |
|
$ |
20,025 |
|
|
$ |
|
|
|
$ |
(1,276 |
) |
|
$ |
18,749 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
December 31, 2007 |
|
|
|
|
|
|
|
|
|
|
|
Unrealized |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Losses in |
|
|
|
|
|
|
|
|
|
Amortized |
|
|
Unrealized |
|
|
accumulated |
|
|
Fair |
|
|
Investment Maturity |
|
|
|
Cost |
|
|
Gains |
|
|
OCI |
|
|
Value |
|
|
Dates |
|
Cash and cash equivalents |
|
$ |
116,565 |
|
|
|
|
|
|
$ |
(1 |
) |
|
$ |
116,564 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Short-term investments: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Student loan auction rate securities (taxable) |
|
$ |
3,175 |
|
|
|
|
|
|
|
|
|
|
$ |
3,175 |
|
|
|
1/2008 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total short-term investments |
|
$ |
3,175 |
|
|
$ |
|
|
|
$ |
|
|
|
$ |
3,175 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Long-term investments: |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Student loan auction rate securities (taxable) |
|
$ |
20,025 |
|
|
|
|
|
|
|
|
|
|
$ |
20,025 |
|
|
|
6/20368/2045 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total long-term investments |
|
$ |
20,025 |
|
|
$ |
|
|
|
$ |
|
|
|
$ |
20,025 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The Companys student loan auction rate securities (ARS), which had a fair value of $18.7
million as of June 30, 2008 and $23.2 million as of December 31, 2007, are securities that are
structured with short-term interest reset dates of less than 30 days, but with maturities generally
greater than 20 years. The Company classified $18.7 million and $20.0 million of these ARS as
long-term investments as of June 30, 2008 and December 31, 2007, respectively, due to their
illiquidity and the Companys inability to use them in its current operations.
These ARS are intended to provide liquidity via an auction process that resets the applicable
interest rate at predetermined calendar intervals, allowing investors to either roll over their
holdings or gain immediate liquidity by selling such interests at par. As of December 31, 2007,
there were no ARS in an unrealized loss position, and there were no failed auctions associated with
the Companys ARS through that date. The Companys ARS with auction reset dates prior to February
13, 2008 had successful auctions at which their interest rates were reset. In February 2008, the
Company liquidated $3.2 million of its ARS at par, which were classified as short-term investments
as of December 31, 2007. The recent uncertainties in the credit markets have affected all of the
Companys holdings in ARS investments and auctions for the Companys investments in these
securities have failed to settle on their respective settlement dates since February 2008.
Consequently, the investments are not currently liquid, and the Company will not be able to access
these funds until a future auction of these investments is successful, the issuer redeems the
outstanding securities, the securities mature or a buyer is found outside of the auction process.
Maturity dates for these ARS range from 2036 to 2045. All of the ARS are AAA/Aaa rated and were in
compliance with the Companys investment policy at the time of acquisition. As of June 30, 2008,
the Company held ARS with a par value of $20.0 million, which were classified as long-term
investments because of the Companys inability to determine when its investments in these ARS would
settle. Typically the fair value of ARS investments approximates par value due to the frequent
resets through the auction process. The Company earns interest on its ARS at the contractual rates,
however, these investments are not currently trading and accordingly, the estimated fair value of these ARS no longer
approximates par value.
The Company used a discounted cash flow (DCF) model to assess the estimated fair value of
its investment in ARS as of June 30, 2008. See Footnote 8 for the assumptions used in preparing the
DCF model. As of June 30, 2008, the Company determined there was a decline in the fair value of its
ARS of $1.3 million and deemed the entire decline temporary. As
a result, the Company recorded an unrealized loss of $1.3
million associated with its ARS as a component of stockholders
equity as of June 30, 2008. The Company reviews its impairments in
accordance with SFAS No. 115, Accounting for Certain Investments in Debt and Equity Securities,
and FSP Nos. FASB 115-1 and FASB 124-1, The Meaning of Other-Than-Temporary Impairment and Its
Application to Certain Investments, in order to determine the classification of the impairment as
temporary or other-than-temporary. A temporary decline in value results
10
in an unrealized loss being recorded in the Other Comprehensive Income (Loss) component of
stockholders equity. Such an unrealized loss does not affect net income (loss) for the applicable
accounting period. An other-than-temporary decline in value is recorded as a realized loss in the
condensed statement of operations and reduces net income (loss) for the applicable accounting
period. In evaluating the impairment of any individual ARS, the Company classifies such impairment
as temporary or other-than-temporary. The differentiating factors between temporary and
other-than-temporary impairment are primarily the length of the time and the extent to which the
market value has been less than cost, the financial condition and near-term prospects of the issuer
and the Companys intent and ability to retain its investment in the issuer for a period of time
sufficient to allow for any anticipated recovery in market value. As of June 30, 2008 and December
31, 2007, the Company had not incurred any losses that were other-than-temporary. The Company
continues to monitor the ARS market and to consider the impact, if any, on the fair value of its
ARS.
Note 6. Equipment Financing Lines
In August 2007, the Company secured a new line of credit with GE Capital of up to $3.0 million
to finance certain equipment until September 30, 2008. The line of credit is subject to the Master
Security Agreement between the Company and GE Capital, dated February 2001 and amended on March 24,
2005. As of June 30, 2008, the Company has not borrowed any funds under this line.
Note 7. Stockholders Equity
Stock Option Plans
In January 2004, the Board of Directors adopted the 2004 Equity Incentive Plan (the 2004
Plan) which was approved by the stockholders in February 2004. The 2004 Plan provides for the
granting of incentive stock options, nonstatutory stock options, restricted stock purchase rights
and stock bonuses to employees, directors and consultants. Under the 2004 Plan, the number of
authorized shares automatically increases on an annual basis by a number of shares equal to the
lesser of (i) 1,500,000 shares, (ii) 3.5% of the outstanding shares on such date, or (iii) an
amount determined by the Board of Directors. Accordingly, on January 1, 2008, the number of shares
of common stock authorized for issuance under the 2004 Plan was increased by 1,500,000 shares to a
total of 2,997,296 shares. At the May 2008 Annual Stockholder Meeting, the number of shares of
common stock authorized for issuance under the 2004 Plan was increased by 2,000,000, and approved
an amended and restated 2004 Plan which eliminated the automatic increase provision.
Stock option activity for the six months ended June 30, 2008 under the 2004 Plan and the 1997
Stock Option/Stock Issuance Plan was as follows:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Options |
|
|
|
|
|
Weighted |
|
|
Available for |
|
Options |
|
Average Exercise |
|
|
Grant |
|
Outstanding |
|
Price per Share |
Balance at December 31, 2007 |
|
|
1,497,296 |
|
|
|
5,060,294 |
|
|
$ |
5.80 |
|
Increase in authorized shares |
|
|
3,500,000 |
|
|
|
|
|
|
|
|
|
Options granted |
|
|
(1,708,137 |
) |
|
|
1,708,137 |
|
|
$ |
3.41 |
|
Options exercised |
|
|
|
|
|
|
(22,400 |
) |
|
$ |
1.19 |
|
Options cancelled |
|
|
156,019 |
|
|
|
(156,019 |
) |
|
$ |
4.73 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Balance at June 30, 2008 |
|
|
3,445,178 |
|
|
|
6,590,012 |
|
|
$ |
5.22 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The weighted average fair value of options granted in the six months ended June 30, 2008 was
$2.06 per share.
Note 8 Fair Value Measurements
As stated in Note 1. Organization and Summary of Significant Accounting Policies, on
January 1, 2008, the Company adopted the methods of fair value described in SFAS No. 157 to value
its financial assets and liabilities. As defined in SFAS No. 157, fair value is the price that
would be received for asset when sold or paid to transfer a liability in an orderly transaction
between market participants at the measurement date (exit price). The Company utilizes market data
or assumptions that the Company believes market participants would use in pricing the asset or
liability, including assumptions about risk and the risks inherent in the inputs to the valuation
technique. These inputs can be readily observable, market corroborated or generally unobservable.
11
The Company primarily applies the market approach for recurring fair value measurements and
endeavors to utilize the best information available to it. Accordingly, the Company utilizes
valuation techniques that maximize the use of observable inputs and minimize the use of
unobservable inputs to the extent possible, and considers the security issuers and the third-party
insurers credit risk in its assessment of fair value.
The Company classifies the determined fair value based on the observability of those inputs.
SFAS No. 157 establishes a fair value hierarchy that prioritizes the inputs used to measure fair
value. The hierarchy gives the highest priority to unadjusted quoted prices in active markets for
identical assets or liabilities (Level 1 measurement) and the lowest priority to unobservable
inputs (Level 3 measurement). The three levels of the fair value hierarchy defined by SFAS No. 157
are as follows:
|
|
|
Level 1
|
|
Quoted prices are available in active markets for identical assets
or liabilities as of the reporting date. Active markets are those
in which transactions for the asset or liability occur in
sufficient frequency and volume to provide the most reliable
pricing information and evidence of fair value on an ongoing
basis. |
|
|
|
Level 2
|
|
Pricing inputs are other than quoted prices in active markets
included in Level 1, which are either directly or indirectly
observable as of the reporting date. Level 2 includes those
financial instruments that are valued using models or other
valuation methodologies. These models are primarily
industry-standard models that consider various assumptions,
including quoted forward prices for commodities, time value,
volatility factors, and current market and contractual prices for
the underlying instruments, as well as other relevant economic
measures. Substantially all of these assumptions are observable in
the marketplace throughout the full term of the instrument, can be
derived from observable data or are supported by observable levels
at which transactions are executed in the marketplace. |
|
|
|
Level 3
|
|
Pricing inputs include significant inputs that are generally less
observable from objective sources. These inputs may be used with
internally developed methodologies that result in managements
best estimate of fair value from the perspective of a market
participant. Instruments subject to Level 3 measurements include
those that may be more structured or otherwise tailored to
customers needs. At each balance sheet date, the Company performs
an analysis of all instruments subject to SFAS No. 157 and
includes in Level 3 all of those whose fair value is based on
significant unobservable inputs. |
Financial assets carried at fair value as of June 30, 2008 are classified in the table below
in one of the three categories described above (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Fair Value Measurements Using |
|
Assets |
|
|
Level 1 |
|
Level 2 |
|
Level 3 |
|
At Fair Value |
Cash equivalents
|
|
|
$85,923 |
|
|
|
|
|
|
|
|
|
$ |
85,923 |
|
Long-term investments ARS
|
|
|
|
|
|
|
|
|
$18,749 |
|
|
|
$ |
18,749 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
|
$85,923 |
|
|
|
|
|
$18,749 |
|
|
|
$ |
104,672 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The Company chose not to elect the fair value option as prescribed by SFAS No. 159 for its
financial assets and liabilities that had not been previously reported at fair value. Therefore,
financial assets and liabilities not reported at fair value, such as the Companys accounts
receivable, notes receivable, short- and long-term equipment financing lines and accounts payable
are still reported at their carrying values.
As of June 30, 2008, the Company applied Level 1 measurements to its holdings of money market
funds, which it classified as cash equivalents.
Temporary Impairment of Long-Term Student Loan Auction Rate Securities
The Companys financial assets measured at fair value on a recurring basis using significant
Level 3 inputs as of June 30, 2008 consisted solely of ARS. The following table summarizes the
Companys fair value measurements using Level 3 inputs, and changes therein, for the six-months
period ended June 30, 2008 (in thousands):
|
|
|
|
|
|
|
Long-term Investment |
|
Beginning balance as of December 31, 2007 |
|
$ |
|
|
Transfer-in of Level 3 hierarchy measurement from Level 1 |
|
|
20,025 |
|
Unrealized losses included in other comprehensive income |
|
|
(1,276 |
) |
|
|
|
|
Ending balance as of June 30, 2008 |
|
$ |
18,749 |
|
|
|
|
|
12
The Companys ARS holdings as of June 30, 2008 and December 31, 2007 consisted entirely of
student loan ARS. The unrealized loss of these ARS for the six months ended June 30, 2008 reflected
a decrease of fair value of the Companys long-term investments and was reported in its OCI. Due to
the lack of observable market quotes on the Companys ARS portfolio, the Company utilized DCF
valuation models that relied exclusively on Level 3 inputs including estimates for interest rates,
timing and amount of cash flows, credit quality, expected holding periods of the ARS, net loan rate
provision and percentage of portfolio guaranteed by the Federal Family and Education Loan Program.
The valuation used estimates of observable market data including yields or spreads of trading
instruments that the Company believed to be similar or comparable and assumptions that it believed
to be reasonable non-observable inputs such as illiquidity premium and likelihood of redemption.
The valuation of the Companys ARS is subject to uncertainties that are difficult to predict.
Factors that may impact its valuation include changes to credit ratings of the securities and to
the underlying assets supporting those securities, rates of default of the underlying assets,
underlying collateral value, discount rates and ongoing strength and quality of market credit and
liquidity. The Companys ARS, valued using Level 3 inputs, represent 18 percent of assets measured
at fair value under the provisions of SFAS 157.
Based on this assessment of fair value, as of June 30, 2008, the Company determined there was
a decline in the fair value of its ARS investment of $1,276,000, and deemed the entire decline
temporary. The unrealized losses are reported as a component of stockholders equity, except for
unrealized losses determined to be other than temporary which are recorded in the Statement of
Operations, in accordance with the Companys policy and FSP No. FASB 115-1 and FASB 124-1, The
Meaning of Other-Than-Temporary Impairment and Its Application to Certain Investments. As of June
30, 2008 and December 31, 2007, the Company had not incurred any losses that it deemed
other-than-temporary. The Company continues to monitor the ARS market and consider its impact, if
any, on the fair value of its ARS.
If the current market conditions deteriorate further, or the anticipated recovery in market
values does not occur, the Company may be required to record additional unrealized losses in other
comprehensive income (loss) or impairment charges in future quarters.
Note 9. Recent Accounting Pronouncements
Recently Adopted Accounting Pronouncements
The Company adopted certain requirements of SFAS No. 157 effective January 1, 2008. See Note
1, Organization and Summary of Significant Accounting Policies Fair Value of Financial
Instruments.
Effective
January 1, 2008, the Company adopted SFAS No. 159. The
Company did not elect
the fair value option for its financial assets and liabilities
existing at January 1, 2008, nor for its financial assets and liabilities transacted in the six months
ended June 30, 2008. Therefore, the adoption of SFAS No. 159 had no impact on the Companys
financial position or results of operations. See Note 1, Organization and Summary of Significant
Accounting Policies Fair Value of Financial Instruments.
The Company adopted Emerging Issues Task Force (EITF) Issue No. 07-3, Accounting for
Nonrefundable Advance Payments for Goods or Services to Be Used in Future Research and Development
Activities, on a prospective basis for new contracts entered into on or after effective January 1,
2008. EITF Issue No. 07-3 states that nonrefundable advance payments for future research and
development activities should be deferred and recognized as an expense as the goods are delivered
or the related services are performed. Entities should then continue to evaluate whether they
expect the goods to be delivered or services to be rendered and, if an entity does not expect the
goods to be delivered or services to be rendered, the capitalized advance payment should be charged
to expense. The adoption of EITF Issue No. 07-3 did not have a material effect on the Companys
financial position or results of operations.
In December 2007, the SEC issued SAB No. 110, which addresses the continued use of the
simplified method for estimating the expected term for stock based compensation. Previously, under
SAB No. 107, the use of the simplified method was intended to be discontinued after December 31,
2007. Under SAB No. 110, companies may continue to use the simplified method in certain
circumstances. The Company used the simplified method of estimating the expected term for stock
based compensation from January 1, 2006,
13
the date
it adopted SFAS No. 123R, through December 31,
2007. Starting January 1, 2008, the Company ceased to use the
simplified method under SAB No. 107. Instead, the Company uses its own historical exercise
activity and extrapolates the life cycle of options outstanding to arrive at its estimated expected
term for new option grants.
Accounting Pronouncements Not Yet Adopted
In November 2007, the EITF issued a consensus on EITF Issue No. 07-01, Accounting for
Collaboration Arrangements Related to the Development and Commercialization of Intellectual
Property, which is focused on how the parties to a collaborative agreement should account for
costs incurred and revenue generated on sales to third parties, how sharing payments pursuant to a
collaboration agreement should be presented in the income statement and certain related disclosure
questions. EITF Issue No. 07-01 is to be applied retrospectively for collaboration arrangements in
fiscal years beginning after December 15, 2008. The Company is currently evaluating the impact on
its financial statements of adopting EITF Issue No. 07-1.
In March 2008, the FASB issued SFAS No. 161, Disclosures about Derivative Instruments and
Hedging Activities, as an amendment to SFAS No. 133, Accounting for Derivative Instruments and
Hedging Activities. SFAS No. 161 requires that the objectives for using derivative instruments be
disclosed in terms of underlying risk and accounting designation. The fair value of derivative
instruments and their gains and losses will need to be presented in tabular format in order to
present a more complete picture of the effects of using derivative instruments. SFAS No. 161 is
effective for financial statements issued for fiscal years beginning after November 15, 2008. The
Company is currently evaluating the impact of adopting this pronouncement.
ITEM 2. MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
This discussion and analysis should be read in conjunction with our financial statements and
accompanying notes included elsewhere in this report. Operating results are not necessarily
indicative of results that may occur in future periods.
This report contains forward-looking statements that are based upon current expectations
within the meaning of the Private Securities Litigation Reform Act of 1995. We intend that such
statements be protected by the safe harbor created thereby. Forward-looking statements involve
risks and uncertainties and our actual results and the timing of events may differ significantly
from the results discussed in the forward-looking statements. Examples of such forward-looking
statements include, but are not limited to, statements about or relating to:
|
|
|
the initiation, progress, timing and scope of clinical trials and development for our
drug candidates and potential drug candidates by ourselves or
GlaxoSmithKline (GSK),
including the anticipated dates of data becoming available or being announced or presented
from clinical trials; |
|
|
|
|
guidance concerning revenues, research and development expenses and general and
administrative expenses for 2008; |
|
|
|
|
our and our partners plans or ability for continued research and development of drug
candidates, such as CK-1827452, ispinesib, SB-743921 and GSK-923295, and other compounds,
such as our skeletal muscle activators and our smooth muscle myosin inhibitors; |
|
|
|
|
our ability to generate clinical data sufficient to result in
Amgen Inc. (Amgen) exercising its option with respect to CK-1827452 or GSK exercising its option with respect
to either or both of ispinesib or SB-743921, or to provide such data within our expected
timeframes. |
|
|
|
|
our expected roles in research, development or commercialization under our strategic
alliances, such as with Amgen and GSK; |
|
|
|
|
the potential benefits of our drug candidates and potential drug candidates; |
|
|
|
|
the scope, conduct and results of our research and development activities and programs; |
|
|
|
|
the utility of our clinical trials programs for our drug candidates in informing future
development activities; |
14
|
|
|
our plans or ability to commercialize drugs with or without a partner, including our
intention to develop sales and marketing capabilities; |
|
|
|
|
receipt of milestone payments, royalties and other funds from our partners under
strategic alliances, such as with Amgen and GSK; |
|
|
|
|
issuance of shares of our common stock under our committed equity financing facility
entered into with Kingsbridge Capital Limited
(Kingsbridge) in 2007; |
|
|
|
|
losses, costs, expenses and expenditures; |
|
|
|
|
the sufficiency of existing resources to fund our operations for at least the next 12
months; |
|
|
|
|
capital requirements and our needs for additional financing; |
|
|
|
|
future payments under lease obligations and equipment financing lines; |
|
|
|
|
expected future sources of revenue and capital; |
|
|
|
|
increasing the number of our employees and recruiting additional key personnel; and |
|
|
|
|
expected future amortization of employee stock-based compensation. |
Such forward-looking statements involve risks and uncertainties, including, but not limited
to, those risks and uncertainties relating to:
|
|
|
difficulties or delays in development, testing, obtaining regulatory approval for, and
undertaking production and marketing of our drug candidates,
including decisions by the National Cancer Institute (NCI)
to postpone or discontinue development activities for ispinesib, or by GSK to postpone or
discontinue research or development activities relating to GSK-923295 or to
centromere-associated protein E; |
|
|
|
|
difficulties or delays in or slower than anticipated patient enrollment in our or our
partners clinical trials; |
|
|
|
|
unexpected adverse side effects or inadequate therapeutic efficacy of our drug candidates
that could slow or prevent product approval (including the risk that current and past
results of clinical trials or preclinical studies are not indicative of future results of
clinical trials); |
|
|
|
|
the possibility that the U.S. Food and Drug Administration
(FDA), or foreign regulatory
agencies may delay or limit our or our partners ability to conduct clinical trials; |
|
|
|
|
our receipt of funds under our strategic alliances, including those funds dependent upon
Amgens exercise of its option with respect to CK-1827452 and GSKs exercise of its option
with respect to either or both of ispinesib and SB-743921; |
|
|
|
|
activities and decisions of, and market conditions affecting, current and future
strategic partners; |
|
|
|
|
our ability to obtain additional financing if necessary; |
|
|
|
|
our ability to maintain the effectiveness of our registration statement permitting resale
of securities to be issued to Kingsbridge by us under, and in connection with, the 2007
committed equity financing facility; |
|
|
|
|
changing standards of care and the introduction of products by competitors or alternative
therapies for the treatment of indications we target; |
15
|
|
|
the uncertainty of our ability to obtain and maintain protection for our intellectual
property, through patents, trade secrets or otherwise; and |
|
|
|
|
our potential infringement or misappropriation of the intellectual property rights of
third parties. |
In addition such statements are subject to the risks and uncertainties discussed in the Risk
Factors section and elsewhere in this document. Operating results are not necessarily indicative
of results that may occur in future periods.
When used in this report, unless otherwise indicated, Cytokinetics, the Company, we,
our and us refers to Cytokinetics, Incorporated.
CYTOKINETICS, and our logo used alone and with the mark CYTOKINETICS, and CYTOMETRIX are
registered service marks and trademarks of Cytokinetics. PUMA is a trademark of Cytokinetics. Other
service marks, trademarks and trade names referred to in this report are the property of their
respective owners.
Overview
We are a biopharmaceutical company, incorporated in Delaware in 1997, focused on developing
small molecule therapeutics for the treatment of cardiovascular diseases, cancer and other
diseases. Our current clinical development activities are primarily directed to advancing multiple
drug candidates through clinical trials with the objective of determining the intended
pharmacodynamic effect or effects in two principal diseases: heart failure and cancer. Our drug
development pipeline consists of a drug candidate, CK-1827452, being developed in both an
intravenous and oral formulation for the potential treatment of heart failure; three drug
candidates, ispinesib, SB-743921 and GSK-923295, each being developed in an intravenous formulation
for the potential treatment of cancer; and a potential drug candidate for the potential treatment
of skeletal muscle weakness associated with neuromuscular diseases or other conditions. Our drug
candidates and potential drug candidate are all novel small molecules that arose from our research
activities and are directed toward the cytoskeleton. We believe our understanding of the
cytoskeleton enables us to discover novel and potentially safer and more effective therapeutics.
Since our inception in August 1997, we have incurred significant net losses. As of June 30,
2008, we had an accumulated deficit of $308.8 million. We expect to incur substantial and
increasing losses for the next several years if and to the extent:
|
|
|
we advance CK-1827452 through clinical development for the treatment of heart failure and
Amgen does not exercise its option to conduct later-stage development and commercialization; |
|
|
|
|
Amgen exercises its option to conduct later-stage development and commercialization of
CK-1827452 and we then exercise our option to co-fund the development of CK-1827452; |
|
|
|
|
we conduct continued Phase I, Phase II and later-stage development and commercialization
of ispinesib, SB-743921 or GSK-923295 under our collaboration and license agreement with
GSK, as amended; |
|
|
|
|
we advance ispinesib through clinical development for breast cancer and SB-743921 through
clinical development for Hodgkin and non-Hodgkin lymphoma, and GSK does not exercise its
option to conduct later-stage development and commercialization for either or both of these
drug candidates; |
|
|
|
|
we exercise our option to co-fund the development of GSK-923295 or of any other drug
candidate being developed by GSK under our strategic alliance; |
|
|
|
|
we exercise our option to co-promote any of the products for which we have elected
co-fund development under our strategic alliance with GSK; |
|
|
|
|
we advance potential drug candidates through preclinical studies and into clinical
trials; |
16
|
|
|
we expand our research programs and further develop our proprietary drug discovery
technologies; or |
|
|
|
|
we elect to fund development or commercialization of any drug candidate. |
We intend to pursue selective strategic alliances to enable us to maintain financial and
operational flexibility.
Cardiovascular
We have focused our cardiovascular research and development activities on heart failure, a
disease most often characterized by compromised contractile function of the heart that impacts its
ability to effectively pump blood throughout the body. We have discovered and optimized small
molecules that have the potential to improve cardiac systolic performance by specifically binding
to and activating cardiac myosin, a cytoskeletal protein essential for cardiac muscle contraction.
This work gave rise to our drug candidate CK-1827452, a novel small molecule cardiac myosin
activator. CK-1827452 entered clinical trials in 2006. Based on data from our first-time-in-humans
Phase I clinical trial with this drug candidate, in April 2007, we initiated a clinical trials
program for CK-1827452, comprised of Phase I and Phase IIa clinical trials designed to evaluate the
safety, tolerability, pharmacodynamics and pharmacokinetic profile of both intravenous and oral
formulations of this drug candidate in a diversity of patients, including patients with stable
heart failure and patients with ischemic cardiomyopathy. Our goal is to develop CK-1827452 as a
potential treatment across the continuum of care in heart failure, both in the hospital setting as
an intravenous formulation for the treatment of acutely decompensated heart failure and in the
outpatient setting as an oral formulation for the treatment of chronic heart failure.
In the first-time-in-humans Phase I clinical trial of CK-1827452, evaluating
a six-hour intravenous infusion of
this drug candidate in healthy volunteers, CK-1827452 was well-tolerated and statistically
significant and concentration-dependent increases in indices of left ventricular function were
demonstrated. In addition, CK-1827452 exhibited generally linear, dose-proportional
pharmacokinetics across the dose range studied. The adverse effects at intolerable doses in humans
appeared similar to the adverse findings which occurred at similar plasma concentrations in the
preclinical safety studies. These effects are believed to be related to an excess of the intended
pharmacologic effect, resulting in excessive prolongation of the systolic ejection time, and
resolved promptly with discontinuation of the infusions of CK-1827452. The activity of CK-1827452
in this trial was consistent with results from preclinical evaluations of CK-1827452 in normal
dogs. Further clinical trials are necessary to determine whether similar results will also be seen
in patients with heart failure.
In December 2006, we entered into a collaboration and option agreement with Amgen
to discover, develop and commercialize novel small-molecule therapeutics that
activate cardiac muscle contractility for potential applications in the treatment of heart failure,
including CK-1827452. The agreement provides Amgen with a non-exclusive license and access to
certain technology, as well as an option to receive an exclusive license to develop and
commercialize CK-1827452 and other drug candidates arising from the collaboration, subject to
Cytokinetics development and commercial participation rights. The option is for worldwide license
rights, excluding Japan. Amgens option is exercisable during a defined period, the ending of which
is dependent upon the satisfaction of certain conditions, primarily the delivery of Phase I and
Phase IIa clinical trials data for CK-1827452 in accordance with an agreed development plan, the
results of which may reasonably support its progression into Phase IIb clinical development.
Currently ongoing and recently completed clinical trials of CK-1827452 are as follows:
CK-1827452 (intravenous)
Phase IIa stable heart failure (safety and tolerability): In June 2008, as part of the Late
Breaking Trials Session at the 2008 Heart Failure Congress of the European Society of Cardiology in
Milan, Italy, we announced results from an interim analysis of an ongoing Phase IIa, multi-center,
double-blind, randomized, placebo-controlled, dose-escalation clinical trial of CK-1827452
administered intravenously to patients with stable heart failure. The trials primary objective is
to evaluate the safety and tolerability of CK-1827452. Its secondary objectives are to establish a
relationship between the plasma concentration and the pharmacodynamic effects of CK-1827452 and to
determine its pharmacokinetics in stable heart failure patients. In addition to routine assessments
of vital signs, blood samples and electrocardiographic monitoring, echocardiograms are being
performed to evaluate cardiac function at various pre-defined
17
time points. The clinical trial is planned to consist of at least five cohorts of
eight patients with stable heart failure. In the first four cohorts, patients undergo four
treatment periods, receiving three escalating active doses of CK-1827452 and one placebo treatment
randomized into the dose escalation sequence to maintain blinding. Patients receive a loading
infusion to rapidly achieve a target plasma concentration of CK-1827452 during the first hour,
followed by a slower infusion intended to maintain that plasma concentration during the remainder
of the infusion. The first two of these cohorts were designed to study a range of target CK-1827452
plasma concentrations, from 90 ng/ml in the lowest dose regimen in Cohort 1 to 650 ng/ml in the
highest dose regimen in Cohort 2; Cohorts 3 and 4 were designed to gain experience across the same
range plasma of concentrations, but with infusions of a longer duration. In Cohorts 1 and 2, the
second, slower, maintenance infusion was continued for one hour; in Cohort 3, the maintenance
infusion was continued for 23 hours. At the time of the interim analysis, 22 patients had been
evaluated in this clinical trial (8 patients from each of the completed Cohorts 1 and 2, and 6
patients from the then-ongoing Cohort 3.) The safety data from this analysis suggest that
CK-1827452 was well-tolerated with no serious adverse events reported in patients exposed to the
intended range of doses and plasma concentrations. A pharmacodynamic-pharmacokinetic analysis of
data from these 22 patients showed that when compared to placebo, CK-1827452 produced statistically
significant and clinically relevant increases in Doppler-derived stroke volume and fractional
shortening as a consequence of statistically significant prolongations of systolic ejection time.
At the highest CK-1827452 concentrations studied, stroke volume, the volume of blood pumped during
each heartbeat, increased versus placebo from its mean baseline value of 71 mL by 19 ± 4 mL (p <
0.0001). In addition, fractional shortening increased versus placebo by 4.0 ± 2% (p = 0.01), and
systolic ejection time by 95 ± 9 msec (p < 0.0001). These promising data reflect what we
believe is the clinically relevant activity of this novel drug candidate. Following review of
safety data from this interim analysis, we opened enrollment in a fourth cohort in this trial. This
cohort will also evaluate a one-hour loading infusion followed by 23 hours of maintenance infusion
over the same range of target CK-1827452 plasma concentrations evaluated in Cohort 3. We anticipate that final data will be available from this trial during the second half of
2008.
Phase IIa stable heart failure (cardiac catheterization): In the second quarter of 2008, we opened
enrollment in an open-label, non-randomized Phase IIa clinical trial designed to evaluate an
intravenous formulation of CK-1827452 administered to patients with stable heart failure undergoing
clinically indicated coronary angiography in a cardiac catheterization laboratory. The primary
objective of this trial is to evaluate the potential effects of CK-1827452 on myocardial
efficiency, defined as the ratio of ventricular performance to myocardial oxygen consumption. The
secondary objective of this trial is to measure the potential effects of CK-1827452 on ventricular
performance, myocardial oxygen consumption, hemodynamics, pressure-volume relationships and
systolic ejection time. We continue to screen patients for the potential initiation of this trial.
CK-1827452 (oral)
Phase I drug-drug interaction: In April 2007, we announced the initiation of a single-center,
open-label, sequential, parallel group, Phase I clinical trial of CK-1827452 designed to evaluate
the potential for drug-drug interactions occurring via each of two drug-metabolizing enzymes,
cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6
(CYP2D6). In June 2008, we announced
interim results which showed that, in CYP2D6 extensive metabolizers, the potent CYP3A4
inhibitor ketoconazole caused a modest reduction in the clearance of CK-1827452 and consequently,
a modest but statistically significant increase in the elimination half-life of CK-1827452, from 22
to 27 hours (p < 0.01). This increase in the half-life of CK-1827452 with ketoconazole resulted
in an approximate 50% increase in the area under the CK-1827452 plasma concentration versus time
curve (AUC), which reflects the overall exposure to the study drug, and which was also
statistically significant (p < 0.01). The maximum CK-1827452
plasma concentration (Cmax) was
unaffected by ketoconazole (65 versus 67 ng/mL). Diltiazem, a moderate inhibitor of CYP3A4, had
no effect on either the Cmax or AUC of CK-1827452 when the two were
co-administered to CYP2D6 extensive metabolizer subjects,
although the half-life increased slightly, from 18 to 20 hours (p < 0.01). We continue to screen
and enroll subjects with the poor metabolizer genotype for CYP2D6, who comprise approximately 5% or
less of the population. We anticipate that final data from this trial will be available in 2008.
Phase I oral multi-dose: In June 2008, we announced final results from a Phase I clinical
trial designed to evaluate the safety, tolerability, pharmacokinetics and dose-proportionality of
an oral formulation of CK-1827452 administered both as a single oral dose and as multiple oral
doses of 10 mg and 30 mg strength capsules. The primary objective of this study was to evaluate the
safety and
18
tolerability of CK-1827452 after a single oral dose and after multiple oral doses to
steady-state in healthy men and women. The secondary objective of this study was to evaluate the
pharmacokinetics of CK-1827452 after a single oral dose and after multiple oral doses to
steady-state and to compare the pharmacokinetic parameters between healthy men and women.
CK-1827452 was well-tolerated in the trial, with no drug-related serious adverse events.
Dose-proportionality between the 10 mg and 30 mg dose levels was observed in both men and women,
both after a single dose and after multiple doses to steady-state, with similar pharmacokinetics
observed between men and women.
Phase I modified release: In December 2007, we initiated a single-center, two-part,
open-label, Phase I clinical trial of up to twelve healthy male volunteers. Since an immediate
release formulation of CK-1827452 was found to be rapidly absorbed in a previous study in healthy
subjects, the purpose of developing these modified release forms was to reduce the rate of drug
absorption without significantly affecting the overall bioavailability. The primary objective of
this study was to assess the pharmacokinetics and relative bioavailability of three different oral
modified release prototypes of CK 1827452 as compared to the immediate release formulation in up to
twelve healthy male subjects. The secondary objective of the trial was to determine whether there
is an effect of food on the pharmacokinetics of one of these oral modified release prototypes of
CK-1827452. The single-dose pharmacokinetics of one formulation, in both the fasted and fed states,
demonstrated that it reduced Cmax and elevated the trough plasma concentration as compared to the
immediate release formulation without a substantial effect on overall bioavailability, resulting in
a smaller range of fluctuation in plasma concentrations as compared to oral dosing with the
immediate release formulation. This prototype modified release oral formulation of CK-1827452 has
been selected to proceed forward into further clinical testing.
CK-1827452
(intravenous to oral)
In April 2008, we initiated a double-blind, randomized, placebo-controlled Phase IIa clinical
trial designed to evaluate both an intravenous and an oral formulation of CK-1827452 in patients
with ischemic cardiomyopathy and angina. The primary objective of this trial is to assess the
effect of intravenous CK-1827452 on symptom-limited treadmill exercise tolerance. The secondary
objectives of this trial are to assess the tolerability of CK-1827452 administered as an oral
formulation, and to evaluate the resulting plasma concentrations. The target Cmax in Cohort 1 is
295 ng/mL; the target Cmax in Cohort 2 is 550 ng/mL. We recently completed enrollment of the first
cohort of patients in this trial. We are conducting an interim safety analysis of clinical data
arising from the first cohort in order to enable the initiation of the second and final cohort.
CK-1827452 is at too early a stage of development for us to predict if or when we will be in a
position to generate any revenues or material net cash flows from its commercialization. We
currently fund all research and development costs associated with this program. We recorded
research and development expenses for activities relating to our cardiovascular program of
approximately $10.5 million for the six months ended June 30, 2008, and $11.5 million for the six
months ended June 30, 2007. We anticipate that our expenditures relating to the research and
development of compounds in our cardiovascular program will increase significantly as we advance
CK-1827452 through clinical development. Our expenditures will also increase if Amgen does not
exercise its option and we elect to develop CK-1827452 or related compounds independently, or if we
elect to co-fund later-stage development of CK-1827452 or other compounds in our cardiovascular
program under our collaboration and option agreement with Amgen following Amgens exercise of its
option. If Amgen elects to exercise its option, it would be responsible for development and
commercialization of CK-1827452 and related compounds, subject to our development and commercial
participation rights. In addition, we may be eligible to receive precommercialization and
commercialization milestone payments of up to $600 million on CK-1827452 and other products arising
from the research under the collaboration, as well as escalating royalties based on increasing
levels of annual net sales of products commercialized under the agreement. The agreement also
provides for us to receive increased royalties by co-funding Phase III development costs of drug
candidates under the collaboration. If we elect to co-fund such costs, we would be entitled to
co-promote products in North America and participate in agreed commercial activities in
institutional care settings, at Amgens expense.
19
If Amgen elects not to exercise its option on CK-1827452, we may then independently proceed to
develop CK-1827452 and the collaboration with Amgen would terminate.
Oncology
In the six months ended June 30, 2008, we continued to advance our oncology development
programs for our drug candidates ispinesib and SB-743921 as they progressed in Phase I of their
respective Phase I/II clinical trials and GSK continued conducting the first-time-in-humans Phase I
clinical trial of our drug candidate GSK-923295. These three drug
candidates are being
developed in connection with our collaboration and license agreement with GSK. This strategic alliance is focused on novel small molecule therapeutics targeting a
family of cytoskeletal proteins known as mitotic kinesins for the treatment of cancer. Pursuant to
a November 2006 amendment to the GSK collaboration and license agreement, we assumed responsibility, at our expense, for the
continued research, development and commercialization of ispinesib and SB-743921, subject to GSKs
option to resume development and commercialization of either or both of ispinesib and SB-743921.
This option is exercisable until the end of 2008. For those drug candidates that GSK develops under
the strategic alliance, we can elect to co-fund certain later-stage development activities which
would increase our potential royalty rates on sales of resulting drugs and provide us with the
option to secure co-promotion rights in North America. If we elect to co-fund later-stage
development of GSK-923295, the royalty rates to be paid to us for future sales of any resulting
drugs would increase, and could result in increased payments to us based on increasing product
sales and co-funding by us. If we elect to co-fund later-stage development of ispinesib or
SB-743921, we believe that the royalty rates to be paid to us for future sales of any resulting
drugs would increase to an even higher percentage rate, and could result in increased payments to
us, based on increasing product sales and co-funding by us. If we exercise our co-promotion option,
then we are entitled to receive reimbursement from GSK for certain sales force costs we incur in
support of our commercial activities. We are also researching other compounds for the potential
treatment of cancer.
Ispinesib
The clinical trials program sponsored by GSK and the NCI for ispinesib, an inhibitor of
kinesin spindle protein, consisted of nine Phase II clinical trials and eight Phase I or Ib
clinical trials evaluating the use of this drug candidate in a variety of both solid and
hematologic cancers. We believe that the breadth of this clinical trials program took into
consideration the potential and the complexity of developing a drug candidate such as ispinesib,
and should help us to identify those tumor types and dosing regimens that are the most promising
for the continued development of ispinesib. We have reported Phase II clinical trial data for
ispinesib in metastatic breast, non-small cell lung, ovarian, colorectal, head and neck,
hepatocellular, renal and prostate cancers and in melanoma. To date,
we believe some clinical activity
for ispinesib has been observed in non-small cell lung, ovarian and breast cancers, with the most
clinical activity observed in a Phase II clinical trial evaluating ispinesib in the
treatment of patients with locally advanced or metastatic breast cancer that had failed treatment
with taxanes and anthracyclines. Under our strategic alliance with GSK, we have initiated a focused
development program for ispinesib in the treatment of patients with locally advanced or metastatic
breast cancer. This program is intended to build upon the previous data from the clinical trials
conducted by GSK and the NCI, and is designed to further define the clinical activity profile of
ispinesib in chemotherapy-naïve locally advanced or metastatic breast cancer patients in
preparation for potentially initiating a later stage clinical trials program of ispinesib for the
second-line treatment of advanced breast cancer.
Currently ongoing and recently completed clinical trials of ispinesib are as follows:
Breast Cancer: In December 2007, we initiated, at our expense, an open-label, non-randomized
Phase I/II clinical trial designed to evaluate ispinesib as monotherapy administered as a
first-line treatment in chemotherapy-naïve patients with locally advanced or metastatic breast
cancer. This trial is designed to be a proof-of-concept study to potentially amplify the signals of
clinical activity seen in GSKs Phase II monotherapy trial of ispinesib in breast cancer that had
failed to respond or progressed after treatment with an anthracycline and a taxane, and is intended
to provide the data necessary to inform ispinesibs further development, as well as to inform GSKs
potential exercise of its option to develop and commercialize ispinesib. The primary objectives of
the Phase I portion of this clinical trial are to determine the dose limiting toxicities
and maximum tolerated dose, and to assess the safety and tolerability of ispinesib
administered as a 1-hour intravenous infusion on days 1 and 15 of a 28-day cycle. The secondary
objectives are to characterize the pharmacokinetics of ispinesib on this schedule and to evaluate
the effect of ispinesib on biomarkers of cell proliferation in patients with accessible tumors.
20
In June 2008, a poster containing interim data from Phase I of this
trial was presented at the 2008 Annual Meeting of the American Society of Clinical Oncology
(ASCO) in Chicago, IL. At the interim analysis point, the
authors concluded that preliminary data suggests that ispinesib is well-tolerated when dosed on
days 1 and 15 every 28 days at doses up to 12 mg/m2. The most common toxicity in this clinical trial observed to date has been
neutropenia. No neuropathy, alopecia or Grade 2 or higher gastrointestinal toxicity has been
observed in this trial. We continue to enroll patients and dose-escalate in the Phase I portion of
this Phase I/II clinical trial. We anticipate that data from the
ongoing Phase I portion of this trial will be available in the third
quarter of 2008.
Ispinesib with capecitabine: In June 2008, we announced the results of a Phase Ib clinical
trial sponsored by GSK designed to evaluate ispinesib in combination with capecitabine, an oral
chemotherapy agent commonly used in the treatment of breast cancer. This trial was an open-label,
dose-escalation study of ispinesib in combination with capecitabine on an every 21-day schedule in
subjects with advanced solid tumors. Its primary objectives were to assess the safety and
tolerability and to determine the optimally tolerated regimen of ispinesib when
administered as a 1-hour infusion on day 1 in combination with daily administration of capecitabine
given on days 1 through 14 of the 21-day cycle. The secondary objective was to assess the clinical
activity of this combination in patients with advanced solid tumors. Although a single dose regimen
was not formally confirmed as the optimally tolerated regimen,
ispinesib administered at 18
mg/m2,
its maximum tolerated dose as
monotherapy, was well-tolerated in combination with therapeutic doses of capecitabine at daily
doses of 2000 mg/m2 and 2500 mg/m2. The investigators in this clinical trial
concluded that the combination of ispinesib with capecitabine had an acceptable tolerability
profile on the 21-day schedule investigated in the trial. The dose
limiting toxicities in this combination regimen were
consistent with the monotherapy toxicities of ispinesib (prolonged neutropenia) and capecitabine
(rash). In this trial, the best response observed among the 24 patients treated was a partial
response by Response Evaluation Criteria In Solid Tumors in a patient with advanced
breast cancer. In addition, 11 patients had a response of stable
disease by this criteria.
Pediatric Solid Tumors: In June 2008, at the ASCO annual meeting, the NCI presented final data
from a Phase I clinical trial designed to evaluate the safety, tolerability, pharmacodynamics and
pharmacokinetic profile of ispinesib as monotherapy administered as a one-hour infusion on days 1,
8 and 15 of a 28-day schedule to pediatric patients with relapsed or refractory solid tumors. Of
the 24 patients enrolled in this clinical trial, 18 were evaluable for toxicity and 23 were
evaluable for a response. The authors concluded that the maximum tolerated dose on this schedule for this patient
population was 9
mg/m2. In
this clinical trial, the dose limiting toxicities observed were neutropenia
(n=3), hyperbilirubinemia (n=1) and elevated ALT (n=1). The best response observed was stable
disease at 7 courses in one patient. Three patients experienced stable disease for longer than 3 courses of
therapy. The authors concluded that ispinesib was well-tolerated in pediatric patients, with
neutropenia and hepatotoxicity representing the most commonly
observed dose limiting toxicities.
Acute Leukemias, Chronic Myelogenous Leukemia or Advanced Myelodysplastic Syndromes: The NCI
has completed enrollment in a Phase I clinical trial designed to evaluate the safety, tolerability
and pharmacokinetic profile of ispinesib as monotherapy administered as a one-hour infusion on days
1, 2 and 3 of a 21-day cycle in adult patients with relapsed or refractory acute leukemias, chronic
myelogenous leukemia in blast crisis or advanced myelodysplastic syndromes.
We
expect that it will take several years before ispinesib can be
commercialized, if at all.
Ispinesib is at too early a stage of development for us to predict if and when we will be in a
position to generate any revenues or material net cash flows from any resulting drugs. Accordingly,
we cannot reasonably estimate when and to what extent ispinesib will generate revenues or material
net cash flows, which may vary widely depending on numerous factors, including, but not limited to,
the safety and efficacy profile of the drug, receipt of regulatory approvals, market acceptance,
then-prevailing reimbursement policies, competition and other market conditions. We have assumed
responsibility for funding the research and development costs associated with ispinesib pursuant to
the November 2006 amendment to our collaboration and license
agreement with GSK. We have initiated a focused development program
for ispinesib in the treatment of patients with locally advanced or metastatic breast cancer
designed to further define the clinical activity profile of ispinesib
in advanced breast cancer patients. If GSK
does not exercise its option to resume responsibility for some or all of the development and
commercialization activities associated with this drug candidate, and
we continue to advance the drug candidate on our own, our expenditures relating to
research and development of this drug candidate will increase significantly.
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SB-743921
SB-743921,
our second anti-cancer drug candidate, also inhibits kinesin spindle
protein but is structurally
distinct from ispinesib. SB-743921 is also being developed in connection with our strategic
alliance with GSK. Though we are aware of no clinical shortcomings of ispinesib that are addressed
by SB-743921, we believe that having two kinesin spindle
protein inhibitors in concurrent clinical development
increases the likelihood that a commercial product will result from this research and development
program.
SB-743921 was studied by GSK in a dose-escalating Phase I clinical trial evaluating its
safety, tolerability and pharmacokinetics in advanced cancer patients. The primary objectives of
this clinical trial were to determine the dose limiting toxicities
and to establish the maximum tolerated dose of SB-743921 administered
intravenously on a once every 21-day schedule. Secondary objectives included assessment of the
safety and tolerability of SB-743921, characterization of the pharmacokinetics of SB-743921 on this
schedule and a preliminary assessment of its anti-tumor activity. The observed toxicities at the
recommended Phase II dose were manageable. Dose limiting toxicities in this clinical trial consisted predominantly of
neutropenia and elevations in hepatic enzymes and bilirubin. Disease stabilization, ranging from 9
to 45 weeks, was observed in seven patients. One patient with cholangiocarcinoma had a confirmed
partial response at the maximum tolerated dose.
Phase I/II Hodgkin and non-Hodgkin Lymphoma: In 2006, we initiated, at our expense, an
additional clinical trial of SB-743921 in hematologic cancers. We continue to enroll and
dose-escalate patients in Phase I of an open-label, non-randomized Phase I/II clinical trial to
investigate the safety, tolerability, pharmacodynamics and pharmacokinetic profile of SB-743921
administered as a one-hour infusion on days 1 and 15 of a 28-day schedule in patients with Hodgkin
or non-Hodgkin lymphoma, first without, and then with, the addition of granulocyte
colony-stimulating factor (G-CSF). In June 2008, in association with proceedings at both the ASCO
annual meeting and the 10th International Conference on Malignant Lymphoma in Lugano, Switzerland,
interim data from the Phase I portion of this trial were presented. At the interim analysis point,
46 patients had been enrolled and 43 patients were treated. Of the treated patients, 43 were
evaluable for safety and 28 were evaluable for efficacy. The authors concluded that the pattern of
neutropenia onset and recovery support a dosing schedule for SB-743921 of days 1 and 15 of a 28-day
cycle. The maximum tolerated dose of SB-743921 was 6 mg/m2 when given days 1 and 15 every 28 days without
G-CSF support. This represents a greater dose density (0.43 mg/m2/day) than on the
previously studied schedule; i.e., 4 mg/m2 once every 21 days (0.19
mg/m2/day).
The only dose limiting toxicity observed without G-CSF was neutropenia; therefore further dose
escalation with empiric, prophylactic G-CSF is ongoing. The trial is currently enrolling at 8
mg/m2. The declines from baseline seen in neutrophil counts on day 8 and 22 without
G-CSF were not observed with 6 mg/m2 plus G-CSF, suggesting further dose escalation with
G-CSF may be possible. Grade 3 and 4 toxicities other than neutropenia were uncommon; in
particular, no evidence of neuropathy or alopecia was observed. To date, one objective partial
response has been observed at the maximum tolerated dose without G-CSF in a patient with Hodgkin lymphoma. We
anticipate that final data will be available from the Phase I portion of this trial in 2008.
The clinical trials program for SB-743921 may proceed for several years, and we will not be in
a position to generate any revenues or material net cash flows from
this drug candidate until and unless the
program is successfully completed, regulatory approval is achieved and a drug is commercialized.
SB-743921 is at too early a stage of development for us to predict when or if this may occur. The
November 2006 amendment to our collaboration and license
agreement with GSK provides for us to fund the future development of
SB-743921 in all cancer indications subject to GSKs option to resume responsibility for some or
all development and commercialization activities. As a result of our conduct of our current Phase
I/II clinical trial of SB-743921 in hematologic cancers, and any further development activities for
SB-743921 we may conduct under this amendment, our expenditures relating to research and
development of this drug candidate will increase significantly.
If GSK exercises its option for either or both of ispinesib and SB-743921, it will pay us an
option fee equal to the costs we independently incurred for the development of that drug candidate,
plus a premium intended to compensate us for the cost of capital associated with such costs,
subject to an agreed limit for such costs and premium. Upon GSK exercising its option for a drug
candidate, we may receive additional precommercialization milestone payments with respect to such
drug candidate and increased royalties on net sales of any resulting product, in each case, beyond
those contemplated under the original agreement.
GSK-923295
GSK-923295 is the third drug candidate to arise from our strategic alliance with GSK.
GSK-923295 is an inhibitor of a second mitotic kinesin,
centromere-associated protein E.
Centromere-associated protein E is directly involved in coordinating
the decision a cell makes to divide with the actual
trigger of the mechanics of cell division. These processes are essential for cancer cells to grow.
GSK-923295
22
causes partial and complete shrinkages of human tumors in animal models and has exhibited
properties in these studies that distinguish it from ispinesib and SB-743921.
Phase I First-Time-in-Humans: During the quarter, GSK continued to enroll patients and
dose-escalate in a first-time-in-humans Phase I clinical trial of GSK-923295. This trial is an
open-label, non-randomized, dose-finding trial designed to investigate the safety, tolerability,
pharmacodynamics and pharmacokinetic profile of GSK-923295 in patients with advanced solid tumors.
The initiation of this clinical trial in August 2007 triggered a milestone payment of $1.0 million
from GSK to Cytokinetics under our collaboration and license agreement
with GSK. An oral presentation at the April 2008 American
Association of Cancer Research Annual Meeting highlighted interim clinical data from this
trial. The authors concluded that the pharmacokinetics of GSK-923295 were generally
dose-proportional over the dose range of 10 to 80 mg/m2 and that intrapatient pharmacokinetics on
days 1 and 15 were similar. We anticipate that data from this trial
will be available in the third quarter of 2008.
In
June 2008, we amended our collaboration and license agreement
with GSK to extend the research term for an additional year
through June 19, 2009 to facilitate continued research activities under an updated research plan
focused on centromere-associated protein E. Under the June 2008 amendment, GSK will have no obligation to reimburse us for
full-time employee equivalents (FTEs) or other research-related expenses during the extension of
the research term.
The development program for GSK-923295 may proceed for several years, and we will not be in a
position to generate any revenues or material net cash flows from this potential drug candidate
unless the program is successfully completed, regulatory approval is achieved and a drug is
commercialized. GSK-923295 is at too early a stage of development for us to predict when or if this
may occur. If GSK abandons development of GSK-923295 prior to regulatory approval, we may undertake
and fund the clinical development of this drug candidate, or its commercialization, or we may seek
a new partner for such clinical development or commercialization, or curtail or abandon such
clinical development.
We recorded research and development expenses for activities relating to our mitotic kinesin
programs of approximately $4.0 million for the six months ended June 30, 2008, and $2.9 million for
the six months ended June 30, 2007. We anticipate that our expenditures relating to the development
of ispinesib and SB-743921 will increase significantly as we advance through clinical development.
Our expenditures will also increase if GSK does not exercise its option to resume responsibility
for some or all of the development and commercialization activities associated with ispinesib and
SB-743921, or if we elect to co-fund later-stage development for one or more of ispinesib,
SB-743921 and GSK-923295. For those drug candidates and potential drug candidates that GSK develops
under the strategic alliance, which currently includes GSK-923295 and which may include either or
both of ispinesib and SB-743921 if so elected by GSK pursuant to its option, we may elect to
co-fund certain later-stage development activities which would increase our potential royalty rates
on sales of resulting drugs and provide us with the option to secure co-promotion rights in North
America. We expect that the royalties to be paid on potential future sales, if any, by GSK of each
of ispinesib, SB-743921 and GSK-923295 will be based on increasing product sales and our
anticipated level of co-funding, if any. If we exercise our co-promotion option, then we will
receive reimbursement from GSK for certain sales force costs we incur in support of our commercial
activities.
Research
In April 2008, we announced the selection of a development compound directed towards the
skeletal sarcomere. Preclinical data indicates that this compound is a highly specific small
molecule activator of the troponin complex, increasing its sensitivity to calcium, and subsequently
leading to an increase in skeletal muscle contractility. This compound has demonstrated encouraging
pharmacological activity in non-clinical models that may relate to the potential treatment of
skeletal muscle weakness associated with neuromuscular diseases or other conditions. This potential
drug candidate is the fifth development compound to emerge from our research activities focused on
discovering novel therapeutics directed towards cytoskeletal biology.
23
In the second quarter, we advanced novel smooth muscle myosin inhibitors in lead optimization
activities towards the potential selection of one or more development compounds. Company
scientists have characterized compounds arising from this research in pharmacology studies and have
demonstrated encouraging evidence of efficacy for an inhaled formulation of certain of these
compounds in preclinical bronchoconstriction models related to asthma and other reactive airways
disorders.
Development Risks
The successful development of all of our drug candidates is highly uncertain. We cannot
estimate with certainty or know the exact nature, timing and estimated costs of the activities
necessary to complete the development of any of our drug candidates or the date of completion of
these development activities. We cannot estimate with certainty any of the foregoing due to the
numerous risks and uncertainties associated with developing our drug candidates, including, but not
limited to:
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the uncertainty of the timing of the initiation and completion of patient enrollment in
our clinical trials; |
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the possibility of delays in the collection of clinical trial data and the uncertainty
of the timing of the analyses of our clinical trial data after such trials have been
initiated and completed; |
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our potential inability to obtain or retain partners to
assist in the design, management and funding of later stage clinical
trials; |
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the possibility of delays in characterization, synthesis or optimization of potential
drug candidates; |
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delays or additional costs in developing appropriate formulations of our drug
candidates for clinical trial use; |
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the uncertainty of clinical trial results; |
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the uncertainty of obtaining FDA or other foreign regulatory agency approval required
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the uncertainty related to the development of commercial scale manufacturing processes
and qualification of a commercial scale manufacturing facility. |
If we fail to complete the development of any of our drug candidates in a timely manner, it
could have a material adverse effect on our operations, financial position and liquidity. In
addition, any failure by us or our partners to obtain, or any delay in obtaining, regulatory
approvals for our drug candidates could have a material adverse effect on our results of
operations. A further discussion of the risks and uncertainties associated with completing our
programs on schedule, or at all, and certain consequences of failing to do so are discussed further
in the risk factors entitled We have never generated, and may never generate, revenues from
commercial sales of our drugs and we may not have drugs to market for at least several years, if
ever, Clinical trials may fail to demonstrate the desired safety and efficacy of our drug
candidates, which could prevent or significantly delay completion of clinical development and
regulatory approval and Clinical trials are expensive, time consuming and subject to delay, as
well as other risk factors.
Revenues
Our current revenue sources are limited, and we do not expect to generate any direct revenue
from product sales for several years. We have recognized revenues from our strategic alliances with
Amgen, GSK and AstraZeneca for license fees and contract research activities.
Under
our collaboration and option agreement with Amgen, we received an upfront, non-refundable license and technology
access fee of $42.0 million. In connection with entering into the agreement, we also entered into a
common stock purchase agreement with Amgen. In January 2007, we issued 3,484,806 shares of our
common stock to Amgen for net proceeds of $32.9 million, of which the $6.9 million purchase premium
was recorded as deferred revenue. We are amortizing the upfront fee and stock premium to license
revenue ratably over the maximum term of the non-exclusive license, which is four years. We may
receive additional payments from Amgen upon achieving certain precommercialization and
commercialization milestones. Milestone payments are non-refundable and are recognized as revenue
when earned, as evidenced by achievement of the specified milestones and the absence of ongoing
performance obligations.
24
We may also be eligible to receive reimbursement for contract development activities
subsequent to Amgens option exercise, which we will record as revenue if and when the related
expenses are incurred. We record amounts received in advance of performance as deferred revenue.
Charges to GSK in 2006 were based on negotiated rates intended to approximate the costs for
our FTEs performing research under the strategic alliance and our out-of-pocket expenses, which we
recorded as the related expenses were incurred. GSK paid us an upfront licensing fee, which we
recognized ratably over the strategic alliances initial five-year research term, which ended in
June 2006. In 2007, we received a $1.0 million milestone payment from GSK relating to its
initiation of a phase I clinical trial of GSK-295. We may receive additional payments from GSK upon
achieving certain precommercialization milestones. Milestone payments are non-refundable and are
recognized as revenue when earned, as evidenced by achievement of the specified milestones and the
absence of ongoing performance obligations. We record amounts received in advance of performance as
deferred revenue. The revenues recognized to date are nonrefundable, even if the relevant research
effort is not successful.
Charges to AstraZeneca in 2005 were based on negotiated rates intended to approximate the
costs for our FTEs performing research under the strategic alliance. The revenues recognized since
inception to date are not refundable. The research term of our collaboration and license agreement
with AstraZeneca expired in December 2005, and we formally terminated that agreement in August
2006.
Because a substantial portion of our revenues for the foreseeable future will depend on
achieving development and other precommercialization milestones under our strategic alliances with
GSK and Amgen, our results of operations may vary substantially from year to year.
We expect that our future revenues will most likely be derived from royalties on sales from
drugs licensed to GSK or Amgen under our strategic alliances and from those licensed to future
partners, as well as from direct sales of our drugs. If Amgen exercises its option, we will retain
a product-by-product option to co-fund certain later-stage development activities under our
strategic alliance with Amgen, thereby potentially increasing our royalties and affording us
co-promotion rights in North America. For those products being developed by GSK under our strategic
alliance, we also retain a product-by-product option to co-fund certain later-stage development
activities, thereby potentially increasing our royalties and affording us co-promotion rights in
North America. If we exercise our co-promotion rights under either strategic alliance, we are
entitled to receive reimbursement for certain sales force costs we incur in support of our
commercial activities.
Research and Development Expenses
We incur research and development expenses associated with both partnered and unpartnered
research activities, as well as the development and expansion of our drug discovery technologies.
Research and development expenses related to our strategic alliance with GSK consisted primarily of
costs related to research and screening, lead optimization and other activities relating to the
identification of compounds for development as mitotic kinesin inhibitors for the treatment of
cancer. Prior to June 2006, certain of these costs were reimbursed by GSK on an FTE basis. From
2001 through November 2006, GSK funded the majority of the costs related to the clinical
development of ispinesib and SB-743921. Under our November 2006
amendment to our collaboration and license agreement with GSK, we
assumed responsibility for the continued research, development and commercialization of inhibitors
of kinesin spindle protein, including ispinesib and SB-743921, and
other mitotic kinesins other than centromere-associated protein E, at our
sole expense subject to GSKs option to resume responsibility for the development and
commercialization of either or both of ispinesib and SB-743921, exercisable during a defined
period. We also have the option to co-fund certain later-stage development activities for
GSK-923295. Our conduct of the research and development of ispinesib and SB-743921 and the
potential exercise of our co-funding option will result in a significant increase in research and
development expenses. We expect to incur research and development expenses in the continued conduct
of preclinical studies and clinical trials for CK-1827452 and other of our cardiac myosin activator
compounds for the treatment of heart failure and in connection with our early research programs in
other diseases, as well as the continued refinement and application of our existing and future
proprietary drug discovery technologies. Research and development expenses related to any
development and commercialization activities we elect to fund would consist primarily of employee
compensation, supplies and materials, costs for consultants and contract research, facilities costs
and depreciation of equipment. From our inception through June 30, 2008, we incurred costs of
approximately $64.2 million for research and development activities relating to mitotic kinesin
inhibitors, $114.5 million for our cardiac contractility program, $51.4 million for our proprietary
technologies and $82.3 million for other research and preclinical programs.
25
General and Administrative Expenses
General and administrative expenses consist primarily of compensation for employees in
executive and administrative functions, including, but not limited to, finance, human resources,
legal, business and commercial development and strategic planning. Other significant costs include
facilities costs and professional fees for accounting and legal services, including legal services
associated with obtaining and maintaining patents. We anticipate continued increases in general and
administrative expenses associated with operating as a publicly traded company.
Stock Compensation
The following table summarizes stock-based compensation related to employee stock options and
employee stock purchases for the three months and six months ended June 30, 2008 and June 30, 2007,
which was allocated as follows (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
|
Six Months Ended |
|
|
|
June 30, 2008 |
|
|
June 30, 2007 |
|
|
June 30, 2008 |
|
|
June 30, 2007 |
|
Research and development |
|
$ |
652 |
|
|
$ |
684 |
|
|
$ |
1,517 |
|
|
$ |
1,328 |
|
General and administrative |
|
|
695 |
|
|
|
792 |
|
|
|
1,356 |
|
|
|
1,308 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Stock-based compensation included in operating expenses |
|
$ |
1,347 |
|
|
$ |
1,476 |
|
|
$ |
2,873 |
|
|
$ |
2,636 |
|
As of June 30, 2008, there was $11.1 million of total unrecognized compensation cost related
to non-vested stock-based compensation arrangements granted under our stock option plans. That cost
is expected to be recognized over a weighted-average period of 2.78 years. In addition, we continue
to amortize deferred stock-based compensation recorded prior to adoption of Statement of Financial
Accounting Standard (SFAS) No. 123R (SFAS
123R) for stock options granted prior to the
initial public offering. At June 30, 2008, the balance of deferred stock based compensation was
$0.1 million, which we expect to amortize in the remaining quarters of 2008.
Income Taxes
We account for income taxes in accordance with SFAS 109, Accounting for Income Taxes, which
is the asset and liability method for accounting and reporting for income taxes. Under this method,
deferred tax assets and liabilities are determined based on the difference between the financial
statement and tax bases of assets and liabilities using enacted tax rates in effect for the year in
which the differences are expected to affect taxable income. Valuation allowances are established
when necessary to reduce deferred tax assets to the amounts expected to be realized. We have not
recorded an income tax provision in the quarters ended June 30, 2008 or June 30, 2007 because we
had a net taxable loss in both of those periods. Given that we have a history of recurring losses,
we have recorded a full valuation allowance against our deferred tax assets.
We
also follow the provisions of Financial Accounting Standards Board (FASB) Interpretation
No. 48, Accounting for Uncertainty in Income Taxes, an
Interpretation of SFAS 109 (FIN 48).
This standard defines the threshold for recognizing the benefits of tax return positions in the
financial statements as more-likely-than-not to be sustained by the taxing authorities based
solely on the technical merits of the position. If the recognition threshold is met, the tax
benefit is measured and recognized as the largest amount of tax benefit, in our judgment, which is
greater than 50% likely to be realized. We are currently not subject to income tax examinations
and, in general, all tax years remain open due to net operating losses.
Interest and penalties are zero, and our policy for accounting for interest and penalties is
to classify both as income tax expense in the financial statements. We do not expect our
unrecognized tax benefits to change materially over the next 12 months.
Interest and Other Income and Expense
Interest and other income and expense consist primarily of interest income and interest
expense. Interest income is primarily generated from our cash, cash equivalents and investments.
Interest expense generally relates to the borrowings under our equipment financing lines.
26
Results of Operations
Revenues
We recorded total revenues of $3.1 million and $6.1 million, in the second quarter and first
half of 2008, respectively, compared with total revenues of $3.2 million and $6.4 million,
respectively, for the same periods of 2007.
Research and development revenues from related party refers to revenues from our partner, GSK,
which is also a stockholder of the Company. Research and development revenues from GSK were $16,000
and $27,000, respectively, in the second quarter and first half of 2008, compared with $119,000 and
$265,000, respectively, for the same periods of 2007, and represented patent expense
reimbursements.
License revenues from related parties refers to license revenue from our strategic alliances
with Amgen and GSK. License revenues for the second quarter and first half of 2008 were $3.1
million and $6.1 million, respectively, and represented recognition of the upfront license fee and
the premium paid on the common stock purchase by Amgen. License revenues for the second quarter and
first half of 2007 were $3.1 million and $6.1 million, respectively, and represented recognition of
the upfront license fee and the premium paid on the common stock purchase by Amgen. As of June 30,
2008, the remaining balance of deferred revenue relating to the upfront license fee and stock
purchase premium paid by Amgen was $30.5 million. We are amortizing the Amgen deferred revenue on a
straight-line basis over the maximum term of the non-exclusive license granted to Amgen under the
collaboration and option agreement, which is four years.
We anticipate that total revenues for the year ending December 31, 2008 will be approximately
$12.0 million.
Research and Development Expenses
Research and development expenses were $14.9 million and $29.0 million in the second quarter
and first half of 2008, up from $13.7 million and $26.2 million for the same periods of 2007. The
increase in the second quarter of 2008 compared to the same period in 2007, was primarily due to an
increase of $0.9 million for clinical and preclinical outsourcing costs as we advanced our drug
candidates for the treatment of cardiovascular disease and cancer through clinical trials, and
increases of $0.2 million for compensation and benefit related costs and $0.2 million for
laboratory related expenses. For the first half of 2008 compared to the same period in 2007, the
increase in research and development was primarily due to an increase of $1.9 million for clinical
and preclinical outsourcing costs, and increases of $0.6 million for compensation and benefit
related costs and $0.5 million for laboratory related expenses.
From a program perspective, the increase in spending in the second quarter of 2008 compared to
the second quarter of 2007 was due to increases of $0.1 million related to our mitotic kinesin
inhibitor program, $0.1 million of proprietary technologies and $1.8 million for our other research
and preclinical programs, partially offset by decreases in spending for our cardiac contractility
program of $0.8 million. For the first half of 2008 compared to the first half of 2007, the
increase in research and development spending was due to increases of $1.1 million for our mitotic
kinesin inhibitors and $3.1 million for our other research and preclinical programs, partially
offset by decreases of $1.0 million in spending for cardiac contractility program and $0.4 million
for our proprietary technologies.
Research and development expenses incurred related to the following programs (in millions):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended |
|
|
Six Months Ended |
|
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
June 30, |
|
|
|
2008 |
|
|
2007 |
|
|
2008 |
|
|
2007 |
|
Mitotic kinesin inhibitors |
|
$ |
2.0 |
|
|
$ |
1.9 |
|
|
$ |
4.0 |
|
|
$ |
2.9 |
|
Cardiac contractility |
|
|
5.2 |
|
|
|
6.0 |
|
|
|
10.5 |
|
|
|
11.5 |
|
Proprietary technologies |
|
|
0.9 |
|
|
|
0.8 |
|
|
|
1.6 |
|
|
|
2.0 |
|
All other research and preclinical programs |
|
|
6.8 |
|
|
|
5.0 |
|
|
|
12.9 |
|
|
|
9.8 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total research and development expenses |
|
$ |
14.9 |
|
|
$ |
13.7 |
|
|
$ |
29.0 |
|
|
$ |
26.2 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
27
Clinical timelines, likelihood of success and total completion costs vary significantly for
each drug candidate and are difficult to estimate. We anticipate that we will make determinations
as to which early research programs to pursue and how much funding to direct to each program on an
ongoing basis in response to the scientific and clinical success of each drug candidate and
available resources. The lengthy process of seeking regulatory approvals and subsequent compliance
with applicable regulations requires the expenditure of substantial resources. Any failure by us to
obtain and maintain, or any delay in obtaining, regulatory approvals could cause our research and
development expenditures to increase and, in turn, could have a material adverse effect on our
results of operations.
We expect research and development expenditures to continue to increase in 2008. We expect to
advance research and development of our drug candidate CK-1827452 for the potential treatment of
heart failure and our drug candidates ispinesib and SB-743921 for the potential treatment of
cancer. We anticipate that research and development expenses for the year ending December 31, 2008
will be in the range of $62.0 million to $67.0 million.
General and Administrative Expenses
General and administrative expenses were $4.3 million and $8.4 million in the second quarter
and first half of 2008, respectively, compared with $4.0 million and $8.5 million for the same
periods of 2007. The increase in the second quarter of 2008 was primarily due an increase in
outside services of $0.2 million. For the first half of 2008, the decrease in general and
administrative expenses, compared to the same period in 2007, was primarily due to a decrease in
legal expenses of $0.3 million, partially offset by an increase in outside services of $0.1 million
and compensation and benefit related costs of $0.1 million.
We expect that general and administrative expenses for the full year 2008 will continue the
trend of increasing over prior years due to higher payroll-related expenses in support of our
continuing corporate development activities, business development costs, expanding operational
infrastructure, and costs associated with being a public company. We anticipate that general and
administrative expenses for the year ending December 31, 2008 will be in the range of $20.0 million
to $22.0 million.
Interest and Other Income and Expense
Interest and other income was $0.8 million and $2.2 million in the second quarter and first
half of 2008, respectively, compared with $2.1 million and $4.4 million for the same periods of
2007. The decrease in interest and other income for the periods in 2008 compared to the same
periods in 2007, was due to a decrease in interest income of $1.3 million and $2.1 million in the
second quarter and first half of 2008, respectively, resulting from lower average balances of cash,
cash equivalents and investments and from lower market interest rates earned on these investments.
Interest and other expense in the second quarter and first half of 2008 was $0.1 million and
$0.3 million, respectively, and was $0.2 million and $0.4 million, respectively, for the same
periods in 2007. Interest and other expense in all of these periods primarily consisted of interest
expense on our equipment financing line of credit.
Critical Accounting Policies
The accounting policies that we consider to be our most critical (i.e., those that are most
important to the portrayal of our financial condition and results of operations and that require
our most difficult, subjective or complex judgments), the effects of those accounting policies
applied and the judgments made in their application are summarized in Item 7Managements
Discussion and Analysis of Financial Condition and Results of OperationsCritical Accounting
Policies and Estimates in our Annual Report on Form 10-K for the fiscal year ended December 31,
2007.
In addition to the Critical Accounting Policies and Estimates summarized in our Annual Report
on Form 10-K for the fiscal year ended December 31, 2007, we applied significant judgments and
estimates in adopting SFAS No. 157, Fair Value
Measurements (SFAS 157). We used a discounted
cash flow (DCF) model to determine the estimated fair value of our investment in auction rate
securities, or ARS, as of June 30, 2008. Due to the lack of observable market quotes on our ARS
portfolio, we utilized DCF valuation models that relied exclusively on significant inputs that were
generally less observable from objective sources. Our ARS, valued using Level 3 inputs, represent
18 percent of assets measured at fair value under the provisions of SFAS 157. The valuation models
used estimates of observable market data including yields or spreads of trading instruments that we
believed to be similar or comparable
28
and assumptions that we believed to be reasonable non-observable inputs such as illiquidity
premium and likelihood of redemption. The valuation of our ARS is subject to uncertainties that are
difficult to predict. Factors that may impact their valuation include changes to credit ratings of
the securities and to the underlying assets supporting those securities, rates of default of the
underlying assets, underlying collateral value, discount rates and ongoing strength and quality of
market credit and liquidity.
Based on this assessment of fair value, as of June 30, 2008, we determined there was a decline
in the fair value of our ARS investment of $1.3 million, and deemed the entire decline temporary.
The unrealized losses are reported as a component of stockholders equity, except for unrealized
losses determined to be other than temporary which are recorded in the Statement of Operations, in
accordance with our policy and FSP No. FASB 115-1 and FASB 124-1, The Meaning of
Other-Than-Temporary Impairment and Its Application to Certain Investments. As of June 30, 2008
and December 31, 2007, we had not incurred any losses that we deemed other-than-temporary. We will
continue to monitor the ARS market and consider its impact, if any, on the fair value of our ARS.
If the current market conditions deteriorate further, or the anticipated recovery in market
values does not occur, we may be required to record additional unrealized losses in other
comprehensive income (loss) or impairment charges in future quarters.
Recent Accounting Pronouncements
Recently Adopted Accounting Pronouncements
Effective January 1, 2008, we adopted certain requirements of SFAS 157. See Note 1 ,
Organization and Summary of Significant Accounting Policies Fair Value of Financial
Instruments.
On January 1, 2008, we adopted SFAS No. 159, The Fair Value Option for Financial Assets and
Financial Liabilities, which permits entities to choose to measure many financial instruments and
certain other items at fair value that are not currently required to be measured at fair value. The
adoption of SFAS 159 had no effect on our financial position or results of operations.
We
adopted Emerging Issues Task Force (EITF) Issue No. 07-3, Accounting for Nonrefundable
Advance Payments for Goods or Services to Be Used in Future Research and Development Activities on
a prospective basis for new contracts entered into on or after January 1, 2008. EITF Issue No. 07-3
states that nonrefundable advance payments for future research and development activities should be
deferred and recognized as an expense as the goods are delivered or the related services are
performed. Entities should then continue to evaluate whether they expect the goods to be delivered
or services to be rendered and, if an entity does not expect the goods to be delivered or services
to be rendered, the capitalized advance payment should be charged to expense. The adoption of EITF
Issue No. 07-3 had no effect on our financial position or results of operations.
In
December 2007, the SEC issued Staff Accounting Bulletin (SAB) No. 110, which addresses the
continued use of the simplified method for estimating the expected term for stock based
compensation. Previously, under SAB No. 107, the use of the simplified method was intended to be
discontinued after December 31, 2007. Under SAB No. 110, companies may continue to use the
simplified method in certain circumstances. We used the simplified method of estimating the
expected term for stock based compensation from January 1, 2006, the date of adopting SFAS
123R, through December 31, 2007. Starting January 1, 2008, we ceased to use the simplified method
under SAB No. 107. Instead, we use our own historical exercise
activity and extrapolate the life cycle of options outstanding to
arrive at our estimated expected term for new option grants.
In November 2007, the EITF issued a consensus on EITF Issue No. 07-01, Accounting for
Collaboration Arrangements Related to the Development and Commercialization of Intellectual
Property, which is focused on how the parties to a collaborative agreement should account for
costs incurred and revenue generated on sales to third parties, how sharing payments pursuant to a
collaboration agreement should be presented in the income statement and certain related disclosure
questions. EITF Issue No. 07-01 is to be applied retrospectively for collaboration arrangements in
fiscal years beginning after December 15, 2008. We are currently evaluating the impact on our
financial statements of adopting EITF Issue No. 07-1.
In March 2008, the FASB issued SFAS No. 161, Disclosures about Derivative Instruments and
Hedging Activities, as an amendment to SFAS No. 133, Accounting for Derivative Instruments and
Hedging Activities. SFAS No. 161 requires that the objectives for using derivative instruments be
disclosed in terms of underlying risk and accounting designation. The fair value of derivative
instruments and their gains and losses will need to be presented in tabular format in order to
present a more complete
29
picture of the effects of using derivative instruments. SFAS No. 161 is effective for
financial statements issued for fiscal years beginning after November 15, 2008. We are currently
evaluating the impact of adopting this pronouncement.
Liquidity and Capital Resources
From August 5, 1997, our date of inception, through March 31, 2008, we funded our operations
through the sale of equity securities, equipment financings, non-equity payments from
collaborators, government grants and interest income.
Our cash, cash equivalents and investments, excluding restricted cash, totaled $105.6 million
at June 30, 2008, down $34.2 million from $139.8 million at December 31, 2007. The decrease was
primarily due to the use of cash to fund operations.
We have received net proceeds from the sale of equity securities of $315.0 million from August
5, 1997, the date of our inception, through June 30, 2008, excluding sales of equity to GSK and
Amgen. Included in these proceeds are $94.0 million received upon closing of the initial public
offering of our common stock in May 2004. In connection with execution of the GSK Agreement in
2001, GSK made a $14.0 million equity investment in the Company. GSK made additional equity
investments in the Company in 2003 and 2004 of $3.0 million and $7.0 million, respectively.
In 2005, we entered into our first committed equity financing facility with Kingsbridge pursuant to which
Kingsbridge committed to finance up to $75.0 million of capital for a three-year period. Subject to
certain conditions and limitations, from time to time under this committed equity financing facility, at our election,
Kingsbridge purchased newly-issued shares of our common stock at a price between 90% and 94% of the
volume weighted average price on each trading day during an eight day, forward-looking pricing
period. We received gross proceeds from draw downs and sales of our common stock to Kingsbridge
under this committed equity financing facility as follows: 2005 gross proceeds of $5.7 million from the sale of 887,576
shares, before offering costs of $178,000; 2006 gross proceeds of $17.0 million from the sale of
2,740,735 shares; and 2007 gross proceeds of $9.5 million from the sale of 2,075,177 shares. No
further draw downs are available to us under this committed equity financing facility.
In October 2007, we entered into a new committed equity financing facility with Kingsbridge, pursuant to
which Kingsbridge committed to finance up to $75.0 million of capital for a three-year period.
Subject to certain conditions and limitations, from time to time under this committed equity financing facility, at our
election, Kingsbridge is committed to purchase newly-issued shares of our common stock at a price
between 90% and 94% of the volume weighted average price on each trading day during an eight day,
forward-looking pricing period. The maximum number of shares we may issue in any pricing period is
the lesser of 2.5% of our market capitalization immediately prior to the commencement of the
pricing period or $15.0 million. As part of the arrangement, we issued a warrant to Kingsbridge to
purchase 230,000 shares of our common stock at a price of $7.99 per share, which represents a
premium over the closing price of our common stock on the date we entered into this committed equity financing facility. This
warrant is exercisable beginning six months after the date of grant and for a period of three years
thereafter. Under the terms of this committed equity financing facility, the maximum number of shares we may sell is 9,779,411
(exclusive of the shares underlying the warrant) which, under the rules of the NASDAQ Stock Market
LLC, is approximately the maximum number of shares we may sell to Kingsbridge without approval of
our stockholders. This limitation may further limit the amount of proceeds we are able to obtain
from this committed equity financing facility. We are not obligated to sell any of the $75.0 million of common stock available
under this committed equity financing facility and there are no minimum commitments or minimum use
penalties. This committed equity financing facility
does not contain any restrictions on our operating activities, any automatic pricing resets or any
minimum market volume restrictions. To date we have made no draw downs under this committed equity financing facility.
In January 2006, we entered into a stock purchase agreement with certain institutional
investors relating to the issuance and sale of 5,000,000 shares of our common stock at a price of
$6.60 per share, for gross offering proceeds of $33.0 million. In connection with this offering, we
paid an advisory fee to a registered broker-dealer of $1.0 million. After deducting the advisory
fee and the offering costs, we received net proceeds of approximately $32.0 million from the
offering.
In December 2006, we entered into stock purchase agreements with selected institutional
investors relating to the issuance and sale of 5,285,715 shares of our common stock at a price of
$7.00 per share, for gross offering proceeds of $37.0 million. In connection with this offering, we
paid placement agent fees to three registered broker-dealers totaling $1.9 million. After deducting
the placement agent fees and the offering costs, we received net proceeds of approximately $34.9
million from the offering.
30
In connection with our entry into the collaboration and option agreement with Amgen, we
entered into a common stock purchase agreement under which Amgen purchased 3,484,806 shares of our
common stock at a price per share of $9.47, including a premium of $1.99 per share, and an
aggregate purchase price of approximately $33.0 million. After deducting the offering costs, we
received net proceeds of approximately $32.9 million. These shares were issued, and the related
proceeds received, in January 2007.
As of June 30, 2008, we have received $54.3 million in non-equity payments from GSK and $42.0
million in non-equity payments from Amgen.
Under equipment financing arrangements, we received $23.7 million from August 5, 1997, the
date of our inception, through June 30, 2008. Interest earned on investments, excluding non-cash
amortization of purchase premiums, was $2.0 million in the first half of 2008, and $25.4 million
from August 5, 1997, the date of our inception, through June 30, 2008.
Net cash used by operating activities in the first half of 2008 was $31.7 million and
primarily resulted from our net loss of $29.3 million.
Deferred revenue decreased $6.1 million in the first half of 2008 to $30.5 million at June 30,
2008, due to the amortization of deferred Amgen license revenue.
Net cash provided by investing activities was $3.7 million in the first half 2008 and
primarily represented proceeds from the maturity of investments, net of investment purchases, of
$3.2 million, partly offset by funds used to purchase property and equipment of $0.6 million.
Restricted cash totaled $4.1 million at June 30, 2008, down from $5.2 million at December 31, 2007,
with the decrease due to the contractual semi-annual reduction in the amount of security deposit
required by our lender. At July 1, 2008, the restricted cash balance was $2.7 million.
Net cash used by financing activities was $1.8 million in the first half of 2008 and primarily
represented principal payments of $2.1 million on our lines of credit with General Electric Capital
Corporation (GE Capital) to fund certain equipment, partially offset by the proceeds of $0.3 million from our employee
stock purchase plan. In August 2007, we secured a new line of credit with GE Capital of up to $3.0
million to finance certain equipment until September 30, 2008. The line of credit is subject to our
Master Security Agreement with GE Capital, dated February 2001 and as amended on March 24, 2005.
Under the terms of the equipment financing line, funds borrowed by us from GE Capital are
collateralized by our property and equipment purchased with such borrowed funds and other
collateral. To date we have borrowed no funds under the August 2007 line.
As of June 30, 2008, our investment portfolio included $18.7 million of AAA/Aaa rated student
loan ARS, consisting of government-supported municipal debt obligations. The ARS, with total par
value of $20.0 million, were classified as long-term investments because of the inability to
determine when our investments in ARS would settle. Typically the fair value of ARS approximates
par value due to the frequent resets through the auction process. The Company earns interest on its
ARS at the contractual rates, however, these investments are not currently trading and therefore do
not currently have a readily determinable market value. Accordingly, the estimated fair value of
ARS no longer approximates par value. We have recorded an unrealized loss of $1.3 million
associated with our ARS as a component of stockholders equity.
These ARS are intended to provide liquidity via an auction process that resets the applicable
interest rate at predetermined calendar intervals, allowing investors to either roll over their
holdings or gain immediate liquidity by selling such interests at par. As of December 31, 2007,
there were no ARS in an unrealized loss position and there were no failed auctions associated with
our ARS through that date. Our ARS with auction reset dates prior to February 13, 2008 had
successful auctions at which their interest rates were reset. In February 2008, we liquidated $3.2
million of our auction rate securities at par, which were classified as short-term investment as of
December 31, 2007. The recent uncertainties in the credit markets have affected all of our holdings
in ARS and auctions for our investments in these securities have failed to settle on their
respective settlement dates since February 2008. Consequently, the investments are not currently
liquid and we will not be able to access these funds until a future auction on these investments is
successful, the issuer redeems the outstanding securities, the securities mature or we sell the
securities in the secondary market. Maturity dates for these ARS range from 2036 to 2045. These
failures resulted in the interest rates on these investments resetting to contractually stipulated
fail rates that are variable based on short-term municipal bond or other market indices, or fixed
rates that may result in us earning above-market interest rates on these investments.
31
As of June, 2008, future minimum payments under lease obligations and equipment financing
lines were as follows (in thousands):
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Within |
|
|
Two to |
|
|
Four to |
|
|
After |
|
|
|
|
|
|
One Year |
|
|
Three Years |
|
|
Five Years |
|
|
Five Years |
|
|
Total |
|
Operating leases |
|
$ |
3,089 |
|
|
$ |
6,381 |
|
|
$ |
3,900 |
|
|
$ |
313 |
|
|
$ |
13,683 |
|
Equipment financing line |
|
|
3,029 |
|
|
|
3,086 |
|
|
|
489 |
|
|
|
|
|
|
|
6,604 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total |
|
$ |
6,118 |
|
|
$ |
9,467 |
|
|
$ |
4,389 |
|
|
$ |
313 |
|
|
$ |
20,287 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Our long-term commitments under operating leases relate to payments under our two facility
leases in South San Francisco, California, which expire in 2011 and 2013.
In future periods, we expect to incur substantial costs as we continue to expand our research
programs and related research and development activities.
Our future capital uses and requirements depend on numerous forward-looking factors. These
factors include, but are not limited to, the following:
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the initiation, progress, timing, scope and completion of preclinical research,
development and clinical trials for our drug candidates and potential drug candidates; |
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the time and costs involved in obtaining regulatory approvals; |
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delays that may be caused by requirements of regulatory agencies; |
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if Amgen exercises its option, Amgens decisions with regard to funding of development
and commercialization of CK-1827452 or other compounds for the treatment of heart failure
under our collaboration; |
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GSKs decisions with regard to future funding of development of our drug candidates and
potential drug candidates, including GSK-923295 and, if GSK exercises its option, either or
both of ispinesib and SB-743921; |
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our level of funding for the development of current or future drug candidates; |
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the number of drug candidates we pursue; |
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the costs involved in filing and prosecuting patent applications and enforcing or
defending patent claims; |
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our ability to establish and maintain selected strategic alliances and activities
required for commercialization of our potential drugs; |
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our plans or ability to establish development, sales, marketing or manufacturing
capabilities and to achieve market acceptance for potential drugs; |
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expanding and advancing our research programs; |
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hiring of additional employees and consultants; |
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expanding our facilities; |
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the acquisition of technologies, products and other business opportunities that require
financial commitments; and |
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our revenues, if any, from successful development of our drug candidates and
commercialization of potential drugs. |
We believe that our existing cash and cash equivalents and interest earned on investments will
be sufficient to meet our projected operating requirements for at least the next 12 months. If, at
any time, our prospects for internally financing our research and development programs decline, we
may decide to reduce research and development expenses by delaying, discontinuing or reducing our
funding of development of one or more of our drug candidates or potential drug candidates.
Alternatively, we might raise funds
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through public or private financings, strategic relationships or other arrangements. There can
be no assurance that the funding, if needed, will be available on favorable terms, or at all.
Furthermore, any additional equity financing may be dilutive to stockholders and debt financing, if
available, may involve restrictive covenants. Similarly, financing obtained through future
co-development arrangements may require us to forego certain commercial rights to future drug
candidates. Our failure to raise capital as and when needed could have a negative impact on our
financial condition and our ability to pursue our business strategy.
Off-balance Sheet Arrangements
As of June 30, 2008, we did not have any relationships with unconsolidated entities or
financial partnerships, such as entities often referred to as structured finance or special purpose
entities, which would have been established for the purpose of facilitating off-balance sheet
arrangements or other contractually narrow or limited purposes. In addition, we do not engage in
trading activities involving non-exchange traded contracts. Therefore, we are not materially
exposed to financing, liquidity, market or credit risk that could arise if we had engaged in these
relationships. We do not have relationships or transactions with persons or entities that derive
benefits from their non-independent relationship with us or our related parties.
ITEM 3. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Our exposure to market risk has not changed materially subsequent to our disclosures in Item
7A, Quantitative and Qualitative Disclosures About Market Risk in our Annual Report on Form 10-K
for the year ended December 31, 2007.
ITEM 4. CONTROLS AND PROCEDURES
(a) Evaluation of disclosure controls and procedures
Our management evaluated, with the participation and under the supervision of our Chief
Executive Officer and our Chief Financial Officer, the effectiveness of our disclosure controls and
procedures as of the end of the period covered by this report. Based on this evaluation, our Chief
Executive Officer and our Chief Financial Officer have concluded, subject to the limitations
described below, that our disclosure controls and procedures are effective to ensure that
information we are required to disclose in reports that we file or submit under the Securities
Exchange Act of 1934 is recorded, processed, summarized and reported within the time periods
specified in Securities and Exchange Commission rules and forms, and that such information is
accumulated and communicated to management as appropriate to allow timely decisions regarding
required disclosures.
(b) Changes in internal control over financial reporting
There was no change in our internal control over financial reporting that occurred during the
period covered by this report that has materially affected, or is reasonably likely to materially
affect, our internal control over financial reporting.
(c) Limitations on the Effectiveness of Controls
A control system, no matter how well conceived and operated, can provide only reasonable, not
absolute, assurance that the objectives of the controls are met. Because of the inherent
limitations in all control systems, no evaluation of controls can provide absolute assurance that
all control issues, if any, within a company have been detected. Accordingly, our disclosure
controls and procedures are designed to provide reasonable, not absolute, assurance that the
objectives of our disclosure control system are met.
PART II. OTHER INFORMATION
ITEM 1. LEGAL PROCEEDINGS
None.
ITEM 1A. RISK FACTORS
In evaluating our business, you should carefully consider the following risks in addition to
the other information in this report. Any of the following risks could materially and adversely
affect our business, results of operations, financial condition or your investment
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in our securities, and many are beyond our control. It is not possible to predict or identify
all such factors and, therefore, you should not consider any of the above risks to be a complete
statement of all the potential risks or uncertainties that we face.
Risks Related To Our Business
Our drug candidates are in the early stages of clinical testing and we have a history of
significant losses and may not achieve or sustain profitability and, as a result, you may lose
all or part of your investment.
Our drug candidates are in the early stages of clinical testing, and we must conduct
significant additional clinical trials before we can seek the regulatory approvals necessary to
begin commercial sales of our drugs. We have incurred operating losses in each year since our
inception in 1997 due to costs incurred in connection with our research and development activities
and general and administrative costs associated with our operations. We expect to incur increasing
losses for at least several years, as we continue our research activities and conduct development
of, and seek regulatory approvals for, our drug candidates, and commercialize any approved drugs.
If our drug candidates fail or are significantly delayed in clinical trials or do not gain
regulatory approval, or if our drugs do not achieve market acceptance, we will not be profitable.
If we fail to become and remain profitable, or if we are unable to fund our continuing losses, you
could lose all or part of your investment.
We have never generated, and may never generate, revenues from commercial sales of our drugs and
we may not have drugs to market for at least several years, if ever.
We currently have no drugs for sale and we cannot guarantee that we will ever have marketable
drugs. We must demonstrate that our drug candidates satisfy rigorous standards of safety and
efficacy to the FDA and other regulatory authorities in the United States and abroad. We and our
partners will need to conduct significant additional research and preclinical and clinical testing
before we or our partners can file applications with the FDA or other regulatory authorities for
approval of our drug candidates. In addition, to compete effectively, our drugs must be easy to
use, cost-effective and economical to manufacture on a commercial scale, compared to other
therapies available for the treatment of the same conditions. We may not achieve any of these
objectives. CK-1827452, our drug candidate for the treatment of heart failure, and ispinesib,
SB-743921 and GSK-923295, our drug candidates for the treatment of cancer, are currently our only
drug candidates in clinical trials and we cannot be certain that the clinical development of these
or any future drug candidate will be successful, that they will receive the regulatory approvals
required to commercialize them, or that any of our other research programs will yield a drug
candidate suitable for clinical testing or commercialization. Our commercial revenues, if any, will
be derived from sales of drugs that we do not expect to be commercially available for several
years, if at all. The development of any one or all of these drug candidates may be discontinued at
any stage of our clinical trials programs and we may not generate revenue from any of these drug
candidates.
We currently finance and plan to continue to finance our operations through the sale of equity,
strategic alliances and debt financings, which may result in additional dilution to our
stockholders, relinquishment of valuable technology rights or the imposition of restrictive
covenants, or which may cease to be available on favorable terms or at all.
We have funded all of our operations and capital expenditures with proceeds from both private
and public sales of our equity securities, strategic alliances with GSK, Amgen, AstraZeneca and
others, equipment financings, interest on investments and government grants. We believe that our
existing cash and cash equivalents, potential payments from GSK and Amgen, interest earned on
investments, proceeds from equipment financings and potential proceeds from our 2007 committed equity financing facility with Kingsbridge will be
sufficient to meet our projected operating requirements for at least the next 12 months. To meet
our future cash requirements, we may raise funds through public or private equity offerings,
strategic alliances or debt financings. To the extent that we raise additional funds by issuing
equity securities, our stockholders may experience additional dilution. To the extent that we raise
additional funds through strategic alliance and licensing arrangements, we will likely have to
relinquish valuable rights to our technologies, research programs or drug candidates, or grant
licenses on terms that may not be favorable to us. To the extent that we raise additional funds
through debt financing, such financing may involve covenants that restrict our business activities.
In addition, there can be no assurance that any such funding, if needed, will be available to us on
favorable terms, or at all. If we can not raise the funds we need on favorable terms, or at all,
our ability to conduct our business will be significantly harmed and we may need to discontinue
certain research and development activities, and our stock price could be negatively affected.
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Clinical trials may fail to demonstrate the desired safety and efficacy of our drug candidates,
which could prevent or significantly delay completion of clinical development and regulatory
approval.
Prior to receiving approval to commercialize any of our drug candidates, we must adequately
demonstrate to the FDA and foreign regulatory authorities that such drug candidate is both
sufficiently safe and effective with substantial evidence from well-controlled clinical trials. In
clinical trials we will need to demonstrate efficacy for the treatment of specific indications and
monitor safety throughout the clinical development process and possibly following approval. None of
our drug candidates have yet been demonstrated to be safe and effective in clinical trials and
there is no assurance that they will. In addition, for each of our current preclinical compounds,
we must adequately demonstrate satisfactory chemistry, formulation, stability and toxicity in order
to file an investigational new drug application (IND) that would allow us to advance that
compound into clinical trials. If our preclinical studies, current clinical trials or future
clinical trials are unsuccessful, our business will be significantly harmed and our stock price
could be negatively affected.
All of our drug candidates are prone to the risks of failure inherent in drug development.
Preclinical studies may not yield results that would adequately support the filing of an IND (or a
foreign equivalent) with respect to our potential drug candidates. Even if these applications are
or have been filed with respect to our drug candidates, the results of preclinical studies do not
necessarily predict the results of clinical trials. For example, although preclinical testing
indicated that ispinesib causes tumor regression in a variety of tumor types, to date Phase II
clinical trials of ispinesib have not shown clinical activity in a number of different tumor types.
Similarly, Phase I clinical trials in healthy volunteers and clinical results from Phase I and II
trials in patients are not necessarily indicative of the results of later-stage clinical trials.
Data from Phase III clinical trials are necessary to establish whether a drug candidate is safe and
effective for the applicable indication. In addition, there can be no assurance that the design of
the clinical trials for any of our drug candidates is focused on appropriate indications, tumor
types, patient populations, dosing regimens, safety or efficacy parameters, or other variables
which will result in obtaining the desired safety or efficacy data to support regulatory approval
to commercialize the drug. For example, in a number of two-stage Phase II clinical trials designed
to evaluate the safety and efficacy of ispinesib as monotherapy in the first- or second-line
treatment of patients with different forms of cancer, ispinesib did not satisfy the criteria for
advancement to Stage 2. Also, there can be no assurance that the methods we select to assess
particular safety or efficacy parameters will yield the same statistical precision in their
estimation of our drug candidates effects as may other alternative methodologies. Even if we
believe the data collected from clinical trials of our drug candidates are promising, such data may
not be sufficient to support approval by the FDA or foreign regulatory authorities. Preclinical and
clinical data can be interpreted in different ways. Accordingly, the FDA or foreign regulatory
authorities could interpret such data in different ways than we or our partners do, which could
delay, limit or prevent regulatory approval.
Administering any of our drug candidates or potential drug candidates may produce undesirable
side effects, also known as adverse effects. Toxicities and adverse effects that we have observed
in preclinical studies for some compounds in a particular research and development program may also
occur in preclinical studies or clinical trials of other compounds from the same program. Potential
toxicity issues may arise from the effects of the active pharmaceutical ingredient (API) itself
or from impurities or degradants that are present in the API or could form over time in the
formulated drug candidate or the API. Such toxicities or adverse effects could delay or prevent the
filing of an IND (or a foreign equivalent) with respect to such drug candidates or potential drug
candidates or cause us to cease clinical trials with respect to any drug candidate. In clinical
trials, administering any of our drug candidates to humans may produce adverse effects. For
example, in clinical trials of ispinesib, the most commonly observed dose-limiting toxicity was
neutropenia, a decrease in the number of a certain type of white blood cell that results in an
increase in susceptibility to infection. In a Phase I clinical trial of SB-743921, the
dose-limiting toxicities observed were: prolonged neutropenia, with or without fever and with or
without infection; elevated transaminases and hyperbilirubinemia, both of which are abnormalities
of liver function; and hyponatremia, which is a low concentration of sodium in the blood. In a
Phase I clinical trial of CK-1827452, intolerable doses of CK-1827452 were associated with
complaints of chest discomfort, palpitations, dizziness and feeling hot, increases in heart rate,
declines in blood pressure, electrocardiographic changes consistent with acute myocardial ischemia
and transient rises in cardiac troponins I and T, which are markers of possible myocardial injury.
If these or other adverse effects are severe or frequent enough to outweigh the potential efficacy
of a drug candidate, our clinical trials for such drug candidate may be halted, delayed or
interrupted. Furthermore, the FDA or other regulatory authorities could deny approval of such drug
candidate for any or all targeted indications. The FDA, other regulatory authorities, our partners
or we may suspend or terminate clinical trials with our drug candidates at any time. Even if one or
more of our drug candidates were approved for sale, the occurrence of even a limited number of
toxicities or adverse effects when used in large populations may cause the FDA to impose
restrictions on, or stop, the further marketing of such drugs. Indications of potential adverse
effects or toxicities which may occur in clinical trials and which we believe are not significant
during the course of such clinical trials may later turn out to actually constitute serious adverse
effects or toxicities when a drug has been used in large populations or for extended periods of
time. Any failure or significant delay in
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completing preclinical studies or clinical trials for our drug candidates, or in receiving and
maintaining regulatory approval for the sale of any drugs resulting from our drug candidates, may
significantly harm our business and negatively affect our stock price.
Clinical trials are expensive, time-consuming and subject to delay.
Clinical trials are subject to rigorous regulatory requirements and are very expensive,
difficult and time-consuming to design and implement, especially in the heart failure and cancer
indications that we are pursuing. According to industry studies, the entire drug development and
testing process takes on average 12 to 15 years, and the fully capitalized resource cost of new
drug development averages approximately $800 million. However, individual clinical trials and
individual drug candidates may incur a range of costs or time demands above or below this average.
The length of time and number of trial sites and patients required for clinical trials vary
substantially based on the type, complexity, novelty, intended use of the drug candidate and safety
concerns. We estimate that clinical trials of our most advanced drug candidates will continue for
several years, but they may take significantly longer to complete. The commencement and completion
of our clinical trials could be delayed or prevented by many factors, including, but not limited
to:
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delays in obtaining, or inability to obtain, regulatory or other approvals to commence
and conduct clinical trials in the manner we or our partners deem necessary for the
appropriate and timely development of our drug candidates and commercialization of any
resulting drugs; |
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delays in identifying and reaching agreement, or inability to identify and reach
agreement, on acceptable terms with prospective clinical trial sites; |
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delays or additional costs in developing, or inability to develop, appropriate
formulations of our drug candidates for clinical trial use; |
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slower than expected rates of patient recruitment and enrollment, including as a result
of competition for patients with other clinical trials; limited numbers of patients that
meet the enrollment criteria; patients, investigators or trial sites reluctance to agree
to the requirements of a protocol; or the introduction of alternative therapies or drugs by
others; |
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for those drug candidates that are the subject of a strategic alliance, delays in
reaching agreement with our partner as to appropriate development strategies; |
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an investigational review board (IRB) may require changes to a protocol that then
require approval from regulatory agencies and other IRBs, or regulatory authorities may
require changes to a protocol that then require approval from the IRBs; |
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for clinical trials conducted outside of the United States, the time and resources
required to identify, interpret and comply with foreign regulatory requirements or changes
in those requirements; |
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lack of effectiveness of our drug candidates during clinical trials; |
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unforeseen safety issues; |
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inadequate supply of clinical trial materials; |
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uncertain dosing issues; |
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introduction of new therapies or changes in standards of practice or regulatory
guidance that render our clinical trial endpoints or the targeting of our proposed
indications obsolete; |
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inability to monitor patients adequately during or after treatment; and |
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inability or unwillingness of medical investigators to follow our clinical protocols. |
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We do not know whether planned clinical trials will begin on time, or whether planned or
currently ongoing clinical trials will need to be restructured or will be completed on schedule, if
at all. Significant delays in clinical trials will impede our ability to commercialize our drug
candidates and generate revenue and could significantly increase our development costs.
We have limited capacity to carry out our own clinical trials in connection with the development
of our drug candidates and potential drug candidates and, to the extent we elect to develop a
drug candidate without a strategic partner, we will need to expand our development capacity and
will require additional funding.
The development of drug candidates is complicated, and the resources that we currently have to
carry out such development are limited. Pursuant to our collaboration and option agreement with
Amgen, we are responsible for conducting Phase IIa clinical development for our drug candidate
CK-1827452. We cannot engage another strategic partner for CK-1827452 until Amgen elects not to
exercise its option to conduct later-stage clinical development for CK-1827452 or its option
expires. If Amgen elects not to exercise its option to conduct later-stage clinical development for
CK-1827452, we currently do not have an alternative strategic partner for that drug candidate.
Pursuant to our amended collaboration and license agreement with GSK, we are responsible for
conducting clinical development for our drug candidates ispinesib and SB-743921. Currently, we rely
on GSK to conduct preclinical and clinical development for GSK-923295. We cannot engage another
strategic partner for ispinesib or SB-743921 until GSKs option to conduct later-stage clinical
development for that drug candidate expires. If GSK elects to terminate its development activities
with respect to GSK-923295, or not to exercise its option to conduct later-stage clinical
development for either of ispinesib or SB-743921, we currently do not have an alternative strategic
partner for these drug candidates.
For our drug candidates for which we expect to conduct clinical trials at our expense, such as
CK-1827452, ispinesib and SB-743921, we plan to rely on contractors for the manufacture and
distribution of clinical supplies. To the extent we conduct clinical trials for a drug candidate
without support from a strategic partner, we will need to develop additional skills, technical
expertise and resources necessary to carry out such development activities on our own or through
the use of other third parties, such as contract research organizations (CROs), and will incur
significant costs.
We utilize CROs for our clinical trials within and outside of the United States. We do not
have control over many aspects of our CROs activities, and cannot fully control the amount or
timing of resources that they devote to our programs. CROs may not assign as high a priority to our
programs or pursue them as diligently as we would if we were undertaking such programs ourselves,
and therefore may not complete their respective activities on schedule. CROs may also have
relationships with our competitors and potential competitors, and may prioritize those
relationships ahead of their relationships with us. Outside of the United States, we are
particularly dependent on our CROs expertise in communicating with clinical trial sites and
regulatory authorities and ensuring that our clinical trials and related activities and regulatory
filings comply with applicable local laws. The failure of CROs to carry out development activities
on our behalf according to our requirements and the FDAs or other regulatory agencies standards
and in accordance with applicable laws, or our failure to properly coordinate and manage such
activities, could increase the cost of our operations and delay or prevent the development,
approval and commercialization of our drug candidates. In addition, if a CRO fails to perform as
agreed, our ability to collect damages may be contractually limited.
If we fail to develop the additional skills, technical expertise and resources necessary to
carry out the development of our drug candidates or to effectively manage our CROs carrying out
such development, or if such CROs fail to perform as agreed, the commercialization of our drug
candidates will be delayed or prevented.
If we fail to enter into and maintain successful strategic alliances for our drug candidates,
potential drug candidates or research and development programs,, we will have to reduce, delay or
discontinue our development of those drug candidates, potential drug candidates and programs or
increase our expenditures.
Our strategy for developing, manufacturing and commercializing our drug candidates and
potential drug candidates currently requires us to enter into and successfully maintain strategic
alliances with pharmaceutical companies or other industry participants to advance our programs and
reduce our expenditures on each program. We currently have strategic alliances with Amgen relating
to CK-1827452 and with GSK relating to ispinesib, SB-743921 and GSK-923295. Similarly, we expect
to rely on one or more strategic partners to advance and develop our potential drug candidate
directed towards the skeletal sarcomere and programs relating to skeletal muscle contractility and
smooth muscle contractility. However, we may not be able to negotiate and enter into such strategic
alliances on acceptable terms, if at all. If we are not able to maintain our existing strategic
alliances or establish and maintain additional strategic alliances, we will have to limit the size
or scope of, or delay or discontinue, one or more of our drug development programs
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or research programs or undertake and fund these programs ourselves. If we elect to continue
to conduct any of these drug development programs or research programs on our own, we will need to
obtain additional capital, which may not be available to us on acceptable terms, or at all.
If Amgen does not exercise its option for CK-1827452, we will have to reduce, delay or
discontinue our development of CK-1827452 or increase our expenditures.
Our collaboration and option agreement with Amgen grants it an option relating to development
and commercialization rights for CK-1827452. Amgens option is exercisable during a defined
period, the ending of which is dependent upon the satisfaction of certain conditions, primarily the
delivery of Phase I and Phase IIa clinical trials data for CK-1827452 in accordance with an agreed
development plan, the results of which reasonably support its progression into Phase IIb clinical
development. Amgen can exercise its option during a defined period by paying us a specified option
fee. We may be unable to provide to Amgen the necessary data to inform its decision as to whether
to exercise its option within our anticipated timeframe, or at all, or Amgen may dispute whether we
have provided sufficient information and data to require Amgen to decide whether to exercise its
option. In addition, Amgen may elect not to exercise its option, irrespective of the data that we
provide. If Amgen elects not to exercise its option for CK-1827452, we would have to seek an
alternative strategic partner for the CK-1827452 development program. However, we may not be able
to negotiate and enter into such a strategic alliance on acceptable terms, if at all. Without a
strategic partner, we would have to limit the size or scope of, or delay or discontinue,
development of CK-1827452 or undertake and fund such development ourselves. If we elect to continue
to conduct development on our own, we will need to obtain additional capital, which may not be
available to us on acceptable terms, or at all. Further, a decision by Amgen not to exercise its
option could negatively affect our stock price.
If GSK does not exercise its option for either or both of ispinesib and SB-743921, we will have
to reduce, delay or discontinue our development of those drug candidates or increase our
expenditures.
Our collaboration and license agreement with GSK grants it an option relating to development
and commercialization rights for either or both of ispinesib and SB-743921. GSKs option is
exercisable until the end of 2008. GSK can exercise its option during a defined period by paying us
a specified option fee. We may be unable to provide to GSK the necessary data to inform its
decision as to whether to exercise its option within our anticipated timeframe, or at all. In
addition, GSK may elect not to exercise its option, irrespective of the data that we provide. If
GSK elects not to exercise its option for either or both of ispinesib and SB-743921, we would have
to seek an alternative strategic partner for these programs. However, we may not be able to
negotiate and enter into such strategic alliances on acceptable terms, if at all. Without a
strategic partner, we would have to limit the size or scope of, or delay or discontinue, one or
both of our these programs or undertake and fund these programs ourselves. If we elect to continue
to conduct either program on our own, we will need to obtain additional capital, which may not be
available to us on acceptable terms, or at all. Further, a decision by GSK not to exercise its
option could negatively affect our stock price.
We depend on GSK for the conduct, completion and funding of the clinical development and
commercialization of GSK-923295.
Under our strategic alliance, GSK is responsible for the clinical development and obtaining
and maintaining regulatory approval of our drug candidate GSK-923295 for cancer and other
indications. GSK is responsible for filing applications with the FDA or other regulatory
authorities for approval of GSK-923295 and will be the owner of any marketing approvals issued by
the FDA or other regulatory authorities for GSK-923295. If the FDA or other regulatory authorities
approve GSK-923295, GSK will also be responsible for the marketing and sale of the resulting drug,
subject to our right to co-promote GSK-923295 in North America if we exercise our option to co-fund
certain later-stage development activities for GSK-923295. However, even if we do exercise our
option to co-fund the development of GSK-923295, we cannot control whether GSK will devote
sufficient attention and resources to the clinical trials program for GSK-923295 or will proceed in
an expeditious manner. In addition, even if the FDA or other regulatory agencies approve
GSK-923295, GSK may elect not to proceed with the commercialization of the resulting drug. GSK
generally has discretion to elect whether to pursue or abandon the development of GSK-923295 and
may terminate our strategic alliance for any reason upon six months prior notice. These decisions
are outside our control.
In particular, if the initial results of some of its early clinical trials do not meet GSKs
expectations, GSK may elect to terminate further development of GSK-923295 or certain of the
potential clinical trials for GSK-923295, even if the actual number of patients treated at such
time is relatively small. If GSK abandons GSK-923295, it would result in a delay in or prevent us
from commercializing GSK-923295, and would delay or prevent our ability to generate revenues.
Disputes may arise between us and GSK,
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which may delay or cause the termination of any GSK-923295 clinical trials, result in
significant litigation or arbitration, or cause GSK to act in a manner that is not in our best
interest. If development of GSK-923295 does not progress for these or any other reasons, we would
not receive further milestone payments from GSK with respect to GSK-923295. If GSK abandons
development of GSK-923295 prior to regulatory approval or if it elects not to proceed with
commercialization of the resulting drug following regulatory approval, we would have to seek a new
partner for clinical development or commercialization, curtail or abandon such clinical development
or commercialization, or undertake and fund the clinical development of GSK-923295 or
commercialization of the resulting drug ourselves. If we seek a new partner but are unable to do so
on acceptable terms, or at all, or do not have sufficient funds to conduct such development or
commercialization ourselves, we would have to curtail or abandon such development or
commercialization, which could harm our business.
The success of our development activities depends in part on the performance of our strategic
partners, over which we have little or no control.
Our ability to commercialize drugs that we develop with our partners and that generate
royalties from product sales depends on our partners abilities to assist us in establishing the
safety and efficacy of our drug candidates, obtaining and maintaining regulatory approvals and
achieving market acceptance of the drugs once commercialized. Our partners may elect to delay or
terminate development of one or more drug candidates, independently develop drugs that could
compete with ours or fail to commit sufficient resources to the marketing and distribution of drugs
developed through their strategic alliances with us. Our partners may not proceed with the
development and commercialization of our drug candidates with the same degree of urgency as we
would because of other priorities they face. In particular, we are relying on GSK to conduct
clinical development of GSK-923295. There can be no assurance that GSK will not modify its plans to
conduct such clinical development or will proceed with such clinical development diligently. In
addition, if GSK exercises its option with respect to either or both of ispinesib and SB-743921, or
if Amgen exercises its option with respect to CK-1827452, they will then be responsible for the
clinical development of those respective drug candidates. We do not control the clinical
development being conducted or that may be conducted in the future by GSK or Amgen, including the
timing of initiation, termination or completion of clinical trials, the analysis of data arising
out of such clinical trials or the timing of release of complete data concerning such clinical
trials, which may impact our ability to report on their results. If our partners fail to perform
diligently, our potential for revenue from drugs developed through our strategic alliances, if any,
could be dramatically reduced.
We have no manufacturing capacity and depend on our strategic partners or contract manufacturers
to produce our clinical trial drug supplies for each of our drug candidates and potential drug
candidates, and anticipate continued reliance on contract manufacturers for the development and
commercialization of our potential drugs.
We do not currently operate manufacturing facilities for clinical or commercial production of
our drug candidates or potential drug candidates. We have limited experience in drug formulation
and manufacturing, and we lack the resources and the capabilities to manufacture any of our drug
candidates on a clinical or commercial scale. As a result, we rely on GSK to conduct such
activities for the ongoing clinical development of GSK-923295. For CK-1827452, ispinesib,
SB-743921, we rely on a limited number of contract manufacturers, and, in particular, we rely on
single-source contract manufacturers for the active pharmaceutical ingredient and the drug product
supply for our clinical trials. We expect to rely on contract manufacturers to supply all future
drug candidates for which we conduct clinical development. If any of our existing or future
contract manufacturers fail to perform as agreed, it could delay clinical development or regulatory
approval of our drug candidates or commercialization of our drugs, producing additional losses and
depriving us of potential product revenues. In addition, if a contract manufacturer fails to
perform as agreed, our ability to collect damages may be contractually limited.
Our drug candidates require precise, high quality manufacturing. The failure to achieve and
maintain high manufacturing standards, including failure to detect or control anticipated or
unanticipated manufacturing errors or the frequent occurrence of such errors, could result in
patient injury or death, discontinuance or delay of on-going or planned clinical trials, delays or
failures in product testing or delivery, cost overruns, product recalls or withdrawals and other
problems that could seriously hurt our business. Contract drug manufacturers often encounter
difficulties involving production yields, quality control and quality assurance, as well as
shortages of qualified personnel. These manufacturers are subject to stringent regulatory
requirements, including the FDAs current good manufacturing practices regulations and similar
foreign laws and standards. Each contract manufacturer must pass a pre-approval inspection before
we can obtain marketing approval for any of our drug candidates and following approval will be
subject to ongoing periodic unannounced inspections by the FDA, the U.S. Drug Enforcement Agency
and other regulatory agencies, to ensure strict compliance with current good manufacturing
practices and other applicable government regulations and corresponding foreign laws and standards.
We seek to ensure that our contract manufacturers comply fully with all applicable regulations,
laws and
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standards. However, we do not have control over our contract manufacturers compliance with
these regulations, laws and standards. If one of our contract manufacturers fails to pass its
pre-approval inspection or maintain ongoing compliance at any time, the production of our drug
candidates could be interrupted, resulting in delays or discontinuance of our clinical trials,
additional costs and potentially lost revenues. In addition, failure of any third party
manufacturers or us to comply with applicable regulations, including pre- or post-approval
inspections and the current good manufacturing practice requirements of the FDA or other comparable
regulatory agencies, could result in sanctions being imposed on us. These sanctions could include
fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval
of our products, delay, suspension or withdrawal of approvals, license revocation, product seizures
or recalls, operational restrictions and criminal prosecutions, any of which could significantly
and adversely affect our business.
In addition, our existing and future contract manufacturers may not perform as agreed or may
not remain in the contract manufacturing business for the time required to successfully produce,
store and distribute our drug candidates. If a natural disaster, business failure, strike or other
difficulty occurs, we may be unable to replace such contract manufacturer in a timely or
cost-effective manner and the production of our drug candidates would be interrupted, resulting in
delays and additional costs.
Switching manufacturers or manufacturing sites may be difficult and time-consuming because the
number of potential manufacturers is limited. In addition, before a drug from any replacement
manufacturer or manufacturing site can be commercialized, the FDA must approve that site. Such
approval would require new testing and compliance inspections. A new manufacturer or manufacturing
site also would have to be educated in, or develop substantially equivalent processes for,
production of our drugs and drug candidates. It may be difficult or impossible to transfer certain
elements of a manufacturing process to a new manufacturer or for us to find a replacement
manufacturer on acceptable terms quickly, or at all, either of which would delay or prevent our
ability to develop drug candidates and commercialize any resulting drugs.
Our focus to date on the discovery and development of drug candidates directed against specific
proteins and pathways within the cytoskeleton is unproven, and we do not know whether we will be
able to develop any drug candidates of commercial value.
To date, we have focused our drug discovery and development activities on the cytoskeleton,
including in the areas of muscle biology and oncology. While a number of commonly used drugs and a
growing body of research validate the importance of the cytoskeleton in the origin and progression
of a number of diseases, no existing drugs specifically and directly interact with the proteins and
the pathways that our drug candidates seek to modulate. As a result, we cannot be certain that our
drug candidates and potential drug candidates will appropriately modulate the targeted proteins and
pathways or produce commercially viable drugs that safely and effectively treat heart failure,
cancer or other diseases, or that the results we have seen in preclinical models will translate
into similar results in humans. In addition, even if we are successful in developing and receiving
regulatory approval for a commercially viable drug for the treatment of a particular disease, we
cannot be certain that we will also be able to develop and receive regulatory approval for drug
candidates for the treatment of other forms of that disease or other diseases. If we or our
partners fail to develop and commercialize our drug candidates, we will not achieve commercial
success, which would materially harm our business.
Our success depends substantially upon our ability to obtain and maintain intellectual property
protection relating to our drug candidates and research technologies.
We own or hold exclusive licenses to a number of U.S. and foreign patents and patent
applications directed to our drug candidates and research technologies. Our success depends on our
ability to obtain patent protection both in the United States and in other countries for our drug
candidates, their methods of manufacture and use, and our technologies. Our ability to protect our
drug candidates and technologies from unauthorized or infringing use by third parties depends
substantially on our ability to obtain and enforce our patents. If our issued patents and patent
applications, if granted, do not adequately describe, enable or otherwise provide coverage of our
technologies and drug candidates, including CK-1827452, ispinesib, SB-743921 and GSK-923295, we
would not be able to exclude others from developing or commercializing these drug candidates.
Furthermore, the degree of future protection of our proprietary rights is uncertain because legal
means may not adequately protect our rights or permit us to gain or keep our competitive advantage.
Due to evolving legal standards relating to the patentability, validity and enforceability of
patents covering pharmaceutical inventions and the claim scope of these patents, our ability to
obtain and enforce patents that may issue from any pending or future patent applications is
uncertain and involves complex legal, scientific and factual questions. The standards which the
U.S. Patent and Trademark Office (PTO) and its foreign counterparts use to grant patents are not
always applied predictably or uniformly and are
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ultimately subject to change. To date, no consistent policy has emerged regarding the breadth
of claims allowed in biotechnology and pharmaceutical patents. Thus, we cannot be sure that any
patents will issue from any pending or future patent applications owned by or licensed to us. Even
if patents do issue, we cannot be sure that the claims of these patents will be held valid or
enforceable by a court of law, will provide us with any significant protection against competitive
products, or will afford us a commercial advantage over competitive products. For example:
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we or our licensors might not have been the first to make the inventions covered by
each of our pending patent applications and issued patents; |
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we or our licensors might not have been the first to file patent applications for these
inventions; |
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others may independently develop similar or alternative technologies or duplicate any
of our technologies without infringing our intellectual property rights; |
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some or all of our or our licensors pending patent applications may not result in
issued patents; |
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our and our licensors issued patents may not provide a basis for commercially viable
drugs or therapies, or may not provide us with any competitive advantages, or may be
challenged and invalidated by third parties; |
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our or our licensors patent applications or patents may be subject to interference,
opposition or similar administrative proceedings; |
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we may not develop additional proprietary technologies or drug candidates that are
patentable; or |
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the patents of others may prevent us or our partners from discovering, developing or
commercializing our drug candidates. |
Patent protection is afforded on a country by country basis. The laws of some foreign
jurisdictions do not protect intellectual property rights to the same extent as in the United
States. Many companies have encountered significant difficulties in protecting and defending such
rights in foreign jurisdictions. Some of our development efforts are performed in countries outside
of the United States through third party contractors. We may not be able to effectively monitor and
assess intellectual property developed by these contractors; therefore, we may not appropriately
protect this intellectual property and could thus lose valuable intellectual property rights. In
addition, the legal protection afforded to inventors and owners of intellectual property in
countries outside of the United States may not be as protective of intellectual property rights as
in the United States, and we may, therefore, be unable to acquire and protect intellectual property
developed by these contractors to the same extent as if these development activities were being
conducted in the United States. If we encounter difficulties in protecting our intellectual
property rights in foreign jurisdictions, our business prospects could be substantially harmed.
Under our license agreement with the University of California and Stanford University, we have
obtained a license to certain United States patents and pending United States and foreign patent
applications relating to certain of our research activities. If we fail to fulfill our obligations
under this license agreement, including certain diligence obligations, this agreement may be
terminated, in which case we would no longer have a license to these patents or to future patents
that may issue from the pending applications. This may impair our ability to continue to practice
the research methods covered by the issued patents, which could harm our business. Alternatively,
our license rights may become non-exclusive, which would allow the University of California and
Stanford University to grant third parties the right to practice such patents.
We rely on intellectual property assignment agreements with our corporate partners, employees,
consultants, scientific advisors and other collaborators to grant us ownership of new intellectual
property that is developed. These agreements may not result in the effective assignment to us of
that intellectual property. As a result, our ownership of key intellectual property could be
compromised.
Changes in either the patent laws or their interpretation in the United States or other
countries may diminish the value of our intellectual property or our ability to obtain patents. For
example, the U.S. Senate is currently considering a bill that could change U.S. law regarding,
among other things, post-grant review of issued patents and the calculation of damages once patent
infringement has been determined by a court of law. If enacted into law, these provisions could
severely weaken patent protection in the United States. Recently, the PTO adopted new rules that
were to become effective on November 1, 2007, regarding processes for obtaining patents in
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the United States. However, the U.S. District Court for the Eastern District of Virginia
issued a permanent injunction preventing implementation of the new rules. This decision is now
being appealed. The new rules are numerous and complex and, if made effective, generally are
expected to make it more difficult for patent applicants to obtain patents, especially with regard
to pharmaceutical products and processes. The rules changes, if they were to become effective,
would likely make it more difficult for us and others to obtain patent protection in the United
States for any future drug candidates.
If we do not obtain adequate intellectual property protection for our products in the United
States, competitors could duplicate them without repeating the extensive testing that we had been
required to undertake to obtain approval of the products by the FDA. Regardless of any patent
protection, under the current statutory framework the FDA is prohibited by law from approving any
generic version of any of our products for at least five years after it has approved our product.
Upon the expiration of that period, or if that time period is altered, the FDA could approve a
generic version of our product unless we have patent protection sufficient for us to block that
generic version. Without sufficient patent protection, the applicant for a generic version of our
product would only be required to conduct a relatively inexpensive study to show that its product
is bioequivalent to our product, and would not have to repeat the studies that we conducted to
demonstrate that the product is safe and effective. In the absence of adequate patent protection in
other countries, competitors may similarly be able to obtain regulatory approval in those countries
of products that duplicate our products.
We also rely on trade secrets to protect our technology, especially where we believe patent
protection is not appropriate or obtainable. However, trade secrets are difficult to protect. While
we endeavor to use reasonable efforts to protect our trade secrets, our or our partners employees,
consultants, contractors or scientific and other advisors may unintentionally or willfully disclose
our information to competitors. In addition, confidentiality agreements, if any, executed by such
persons may not be enforceable or provide meaningful protection for our trade secrets or other
proprietary information in the event of unauthorized use or disclosure. If we were to enforce a
claim that a third party had illegally obtained and was using our trade secrets, our enforcement
efforts would be expensive and time-consuming, and the outcome would be unpredictable. In addition,
courts outside the United States are sometimes less willing to protect trade secrets. Moreover, if
our competitors independently develop information that is equivalent to our trade secrets, it will
be more difficult for us to enforce our rights and our business could be harmed.
If we are not able to defend the patent or trade secret protection position of our
technologies and drug candidates, then we will not be able to exclude competitors from developing
or marketing competing drugs, and we may not generate enough revenue from product sales to justify
the cost of development of our drugs and to achieve or maintain profitability.
If we are sued for infringing intellectual property rights of third parties, such litigation will
be costly and time-consuming, and an unfavorable outcome would have a significant adverse effect
on our business.
Our ability to commercialize drugs depends on our ability to sell such drugs without
infringing the patents or other proprietary rights of third parties. Numerous U.S. and foreign
issued patents and pending patent applications owned by third parties exist in the therapeutic
areas in which we are developing drug candidates and exploring for new potential drug candidates.
In addition, because patent applications can take several years to issue, there may be currently
pending applications, unknown to us, which may later result in issued patents that our drug
candidates may infringe. There could also be existing patents of which we are not aware that our
drug candidates may inadvertently infringe.
Currently, we are aware of an issued U.S. patent and at least one pending U.S. patent
application assigned to Curis, Inc. (Curis), relating to certain compounds in the quinazolinone
class. Ispinesib falls into this class of compounds. The Curis U.S. patent claims a method of use
for inhibiting signaling by what is called the hedgehog pathway using certain such compounds. Curis
also has pending applications in Europe, Japan, Australia and Canada with claims covering certain
quinazolinone compounds, compositions thereof and/or methods of their use. We are also aware that
two of the Australian applications have been allowed and two of the European applications have been
granted. In Europe, Australia and elsewhere, the grant of a patent may be opposed by one or more
parties. We have opposed the granting of certain such patents to Curis in Europe and in Australia.
One of the European patents which we opposed was recently revoked and is no longer valid in Europe.
Curis has appealed this decision.
Curis or a third party may assert that the manufacture, use, importation or sale of ispinesib
may infringe one or more of these patents. We believe that we have valid defenses against the
issued U.S. patent owned by Curis if it were to be asserted against us. However, we cannot
guarantee that a court would find such defenses valid or that any additional oppositions would be
successful. We
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have not attempted to obtain a license to these patents. If we decide to seek a license to
these patents, we cannot guarantee that such a license would be available on acceptable terms, if
at all.
Other future products of ours may be impacted by patents of companies engaged in competitive
programs with significantly greater resources (such as Bayer AG, Merck & Co., Inc., Merck GmbH, Eli
Lilly and Company, Bristol-Myers Squibb, Array Biopharma Inc., ArQule, Inc., and AstraZeneca).
Further development of these products could be impacted by these patents and result in significant
legal fees.
If a third party claims that our actions infringe on their patents or other proprietary
rights, we could face a number of issues that could seriously harm our competitive position,
including, but not limited to:
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infringement and other intellectual property claims that, even if meritless, can be
costly and time-consuming to litigate and can delay the regulatory approval process and
divert managements attention from our core business strategy; |
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substantial damages for past infringement which we may have to pay if a court
determines that our drugs or technologies infringe a competitors patent or other
proprietary rights; |
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a court prohibiting us from selling or licensing our drugs or technologies unless the
holder licenses the patent or other proprietary rights to us, which it is not required to
do; and |
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if a license is available from a holder, we may have to pay substantial royalties or
grant cross licenses to our patents or other proprietary rights. |
If any of these events occur, it could significantly harm our business and negatively affect
our stock price.
We may become involved in disputes with our strategic partners over intellectual property
ownership, and publications by our research collaborators and scientific advisors could impair
our ability to obtain patent protection or protect our proprietary information, which, in either
case, would have a significant impact on our business.
Inventions discovered under our strategic alliance agreements become jointly owned by our
strategic partners and us in some cases, and the exclusive property of one of us in other cases.
Under some circumstances, it may be difficult to determine who owns a particular invention, or
whether it is jointly owned, and disputes could arise regarding ownership of those inventions.
These disputes could be costly and time-consuming, and an unfavorable outcome would have a
significant adverse effect on our business if we were not able to protect or license rights to
these inventions. In addition, our research collaborators and scientific advisors have contractual
rights to publish data and other proprietary information, subject to our prior review. Publications
by our research collaborators and scientific advisors containing such information, either with our
permission or in contravention of their agreements with us, could benefit our current or potential
competitors and may impair our ability to obtain patent protection or protect our proprietary
information, which could significantly harm our business.
We may be subject to damages resulting from claims that we or our employees have wrongfully used
or disclosed alleged trade secrets of their former employers.
Many of our employees were previously employed at universities or other biotechnology or
pharmaceutical companies, including our competitors or potential competitors. Although no claims
against us are currently pending, we may be subject to claims that these employees or we have
inadvertently or otherwise used or disclosed trade secrets or other proprietary information of
their former employers. Litigation may be necessary to defend against these claims. If we fail in
defending such claims, in addition to paying monetary damages, we may lose valuable intellectual
property rights or personnel. A loss of key research personnel or their work product could hamper
or prevent our ability to commercialize certain potential drugs, which could significantly harm our
business. Even if we are successful in defending against these claims, litigation could result in
substantial costs and distract management.
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To the extent we elect to fund the development of a drug candidate or the commercialization of a
drug at our expense, we will need substantial additional funding.
The discovery, development and commercialization of new drugs for the treatment of a wide
array of diseases is costly. As a result, to the extent we elect to fund the development of a drug
candidate or the commercialization of a drug at our expense, we will need to raise additional
capital to:
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expand our research and development and technologies; |
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fund clinical trials and seek regulatory approvals; |
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build or access manufacturing and commercialization capabilities; |
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implement additional internal systems and infrastructure; |
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maintain, defend and expand the scope of our intellectual property; and |
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hire and support additional management and scientific personnel. |
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Our future funding requirements will depend on many factors, including, but not limited to: |
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the rate of progress and cost of our clinical trials and other research and development
activities; |
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the costs and timing of seeking and obtaining regulatory approvals; |
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the costs associated with establishing manufacturing and commercialization
capabilities; |
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the costs of filing, prosecuting, defending and enforcing any patent claims and other
intellectual property rights; |
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the costs of acquiring or investing in businesses, products and technologies; |
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the effect of competing technological and market developments; and |
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the payment and other terms and timing of any strategic alliance, licensing or other
arrangements that we may establish. |
Until we can generate a sufficient amount of product revenue to finance our cash requirements,
which we may never do, we expect to continue to finance our future cash needs primarily through
public or private equity offerings, debt financings and strategic alliances. We cannot be certain
that additional funding will be available on acceptable terms, or at all. If we are not able to
secure additional funding when needed, we may have to delay, reduce the scope of or eliminate one
or more of our clinical trials or research and development programs or future commercialization
initiatives.
We expect to expand our development, clinical research, sales and marketing capabilities, and as
a result, we may encounter difficulties in managing our growth, which could disrupt our
operations.
We expect to have significant growth in expenditures, the number of our employees and the
scope of our operations, in particular with respect to those drug candidates that we elect to
develop or commercialize independently or together with a partner. To manage our anticipated future
growth, we must continue to implement and improve our managerial, operational and financial
systems, expand our facilities and continue to recruit and train additional qualified personnel.
Due to our limited resources, we may not be able to effectively manage the expansion of our
operations or recruit and train additional qualified personnel. The physical expansion of our
operations may lead to significant costs and may divert our management and business development
resources. Any inability to manage growth could delay the execution of our business plans or
disrupt our operations.
We may not be able to successfully scale-up manufacture of our drug candidates in sufficient
quality and quantity, which would delay or prevent us from developing our drug candidates and
commercializing resulting approved drugs, if any.
To date, our drug candidates have been manufactured in small quantities for preclinical
studies and early-stage clinical trials. In order to conduct larger scale or late-stage clinical
trials for a drug candidate and for commercialization of the resulting drug if that
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drug candidate is approved for sale, we will need to manufacture it in larger quantities. We
may not be able to successfully increase the manufacturing capacity for any of our drug candidates,
whether in collaboration with third-party manufacturers or on our own, in a timely or
cost-effective manner or at all. If a contract manufacturer makes improvements in the manufacturing
process for our drug candidates, we may not own, or may have to share, the intellectual property
rights to such improvements. Significant scale-up of manufacturing may require additional
validation studies, which are costly and which the FDA must review and approve. In addition,
quality issues may arise during such scale-up activities because of the inherent properties of a
drug candidate itself or of a drug candidate in combination with other components added during the
manufacturing and packaging process or during shipping and storage of the finished product or
active pharmaceutical ingredients. If we are unable to successfully scale-up manufacture of any of
our drug candidates in sufficient quality and quantity, the development of that drug candidate and
regulatory approval or commercial launch for any resulting drugs may be delayed or there may be a
shortage in supply, which could significantly harm our business.
We currently have no marketing or sales staff, and if we are unable to enter into or maintain
strategic alliances with marketing partners or if we are unable to develop our own sales and
marketing capabilities, we may not be successful in commercializing our potential drugs.
We currently have no sales, marketing or distribution capabilities. We plan to commercialize
ourselves drugs that can be effectively marketed and sold in concentrated markets that do not
require a large sales force to be competitive. To achieve this goal, we will need to establish our
own specialized sales force and marketing organization with technical expertise and with supporting
distribution capabilities. Developing such an organization is expensive and time-consuming and
could delay a product launch. In addition, we may not be able to develop this capacity efficiently,
cost-effectively or at all, which could make us unable to commercialize our drugs. To
commercialize our drugs that we determine not to market on our own, we will depend on strategic
alliances with third parties, such as GSK and Amgen, which have established distribution systems
and direct sales forces. If we are unable to enter into such arrangements on acceptable terms, we
may not be able to successfully commercialize such drugs. To the extent that we are not successful
in commercializing any drugs ourselves or through a strategic alliance, our product revenues will
suffer, our business will suffer and the price of our common stock could decrease.
Our failure to attract and retain skilled personnel could impair our drug development and
commercialization activities.
Our performance is substantially dependent on the performance of our senior management and key
scientific and technical personnel. The loss of the services of any member of our senior
management, scientific or technical staff may significantly delay or prevent the achievement of
drug development and other business objectives by diverting managements attention to transition
matters and identification of suitable replacements, and could have a material adverse effect on
our business, operating results and financial condition. We also rely on consultants and advisors
to assist us in formulating our research and development strategy. All of our consultants and
advisors are either self-employed or employed by other organizations, and they may have conflicts
of interest or other commitments, such as consulting or advisory contracts with other
organizations, that may affect their ability to contribute to us.
In addition, we believe that we will need to recruit additional executive management and
scientific and technical personnel. There is currently intense competition for skilled executives
and employees with relevant scientific and technical expertise, and this competition is likely to
continue. Our inability to attract and retain sufficient scientific, technical and managerial
personnel could limit or delay our product development activities, which would adversely affect the
development of our drug candidates and commercialization of our potential drugs and growth of our
business.
Risks Related To Our Industry
Our competitors may develop drugs that are less expensive, safer or more effective, which may
diminish or eliminate the commercial success of any drugs that we may commercialize.
We compete with companies that are also developing drug candidates that focus on the
cytoskeleton, as well as companies that have developed drugs or are developing alternative drug
candidates for cardiovascular diseases, cancer and other diseases for which our compounds may be
useful treatments. For example, if CK-1827452 or any other of our compounds is approved for
marketing by the FDA for heart failure, that compound could compete against current generically
available therapies, such as milrinone, dobutamine or digoxin or newer marketed drugs such as
nesiritide, as well as potentially against other novel drug candidates in development, such as
levosimendan, which is being developed in the United States by Abbott Laboratories, in
collaboration with Orion Pharma, and is
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commercially available in a number of countries outside of the United States, and
istaroxamine, which is being developed by Debiopharm Group.
Similarly, if approved for marketing by the FDA, depending on the approved clinical
indication, our anti-cancer drug candidates such as ispinesib, SB-743921 and GSK-923295 could
compete against existing cancer treatments such as paclitaxel, docetaxel, vincristine, vinorelbine,
navelbine, ixabepilone and potentially against other novel anti-cancer drug candidates that are
currently in development such as those that are reformulated taxanes, other tubulin binding
compounds or epothilones. We are also aware that Merck & Co., Inc., Eli Lilly and Company,
Bristol-Myers Squibb, Array Biopharma Inc., ArQule, Inc. and others are conducting research and
development focused on kinesin spindle protein and other mitotic kinesins. In addition, Bristol-Myers Squibb, Merck &
Co., Inc., Novartis, Genentech, AstraZeneca, Hoffman-La Roche Ltd. and other pharmaceutical and
biopharmaceutical companies are developing other approaches to inhibiting mitosis.
Our competitors may:
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develop drug candidates and market drugs that are less expensive or more effective than
our future drugs; |
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commercialize competing drugs before we or our partners can launch any drugs developed
from our drug candidates; |
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hold or obtain proprietary rights that could prevent us from commercializing our
products; |
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initiate or withstand substantial price competition more successfully than we can; |
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more successfully recruit skilled scientific workers from the limited pool of available
talent; |
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more effectively negotiate third-party licenses and strategic alliances; |
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take advantage of acquisition or other opportunities more readily than we can; |
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develop drug candidates and market drugs that increase the levels of safety or efficacy
that our drug candidates will need to show in order to obtain regulatory approval; or |
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introduce therapies or market drugs that render the market opportunity for our
potential drugs obsolete. |
We will compete for market share against large pharmaceutical and biotechnology companies and
smaller companies that are collaborating with larger pharmaceutical companies, new companies,
academic institutions, government agencies and other public and private research organizations.
Many of these competitors, either alone or together with their partners, may develop new drug
candidates that will compete with ours. These competitors may, and in certain cases do, operate
larger research and development programs or have substantially greater financial resources than we
do. Our competitors may also have significantly greater experience in:
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developing drug candidates; |
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undertaking preclinical testing and clinical trials; |
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building relationships with key customers and opinion-leading physicians; |
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obtaining and maintaining FDA and other regulatory approvals of drug candidates; |
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formulating and manufacturing drugs; and |
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launching, marketing and selling drugs. |
If our competitors market drugs that are less expensive, safer or more efficacious than our
potential drugs, or that reach the market sooner than our potential drugs, we may not achieve
commercial success. In addition, the life sciences industry is characterized by
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rapid technological change. Because our research approach integrates many technologies, it may
be difficult for us to stay abreast of the rapid changes in each technology. If we fail to stay at
the forefront of technological change we may be unable to compete effectively. Our competitors may
render our technologies obsolete by advances in existing technological approaches or the
development of new or different approaches, potentially eliminating the advantages in our drug
discovery process that we believe we derive from our research approach and proprietary
technologies.
The regulatory approval process is expensive, time-consuming and uncertain and may prevent our
partners or us from obtaining approvals to commercialize some or all of our drug candidates.
The research, testing, manufacturing, selling and marketing of drugs are subject to extensive
regulation by the FDA and other regulatory authorities in the United States and other countries,
which regulations differ from country to country. Neither we nor our partners are permitted to
market our potential drugs in the United States until we receive approval of a new drug
application (NDA) from the FDA. Neither we nor our partners have received marketing approval for
any of Cytokinetics drug candidates.
Obtaining NDA approval can be a lengthy, expensive and uncertain process. In addition, failure
to comply with the FDA and other applicable foreign and U.S. regulatory requirements may subject us
to administrative or judicially imposed sanctions. These include warning letters, civil and
criminal penalties, injunctions, product seizure or detention, product recalls, total or partial
suspension of production, and refusal to approve pending NDAs or supplements to approved NDAs.
Regulatory approval of an NDA or NDA supplement is never guaranteed, and the approval process
typically takes several years and is extremely expensive. The FDA and foreign regulatory agencies
also have substantial discretion in the drug approval process. Despite the time and expense
exerted, failure can occur at any stage, and we could encounter problems that cause us to abandon
clinical trials or to repeat or perform additional preclinical testing and clinical trials. The
number and focus of preclinical studies and clinical trials that will be required for approval by
the FDA and foreign regulatory agencies varies depending on the drug candidate, the disease or
condition that the drug candidate is designed to address, and the regulations applicable to any
particular drug candidate. The FDA and foreign regulatory agencies can delay, limit or deny
approval of a drug candidate for many reasons, including, but not limited to:
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they might determine that a drug candidate is not be safe or effective; |
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they might not find the data from preclinical testing and clinical trials sufficient; |
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they might not approve our or our contract manufacturers processes or facilities; or |
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they might change its approval policies or adopt new regulations. |
Even if we receive regulatory approval to manufacture and sell a drug in a particular
regulatory jurisdiction, other jurisdictions regulatory authorities may not approve that drug for
manufacture and sale. If we or our partners fail to receive and maintain regulatory approval for
the sale of any drugs resulting from our drug candidates, it would significantly harm our business
and negatively affect our stock price.
If we or our partners receive regulatory approval for our drug candidates, we will also be
subject to ongoing obligations to and continued regulatory review by the FDA and foreign
regulatory agencies, such as continued safety reporting requirements, and we may also be subject
to additional post-marketing obligations, all of which may result in significant expense and
limit our ability to commercialize our potential drugs.
Any regulatory approvals that we or our partners receive for our drug candidates may be
subject to limitations on the indicated uses for which the drug may be marketed or contain
requirements for potentially costly post-marketing follow-up studies. In addition, if the FDA or
foreign regulatory agencies approves any of our drug candidates, the labeling, packaging, adverse
event reporting, storage, advertising, promotion and record-keeping for the drug will be subject to
extensive regulatory requirements. The subsequent discovery of previously unknown problems with the
drug, including adverse events of unanticipated severity or frequency, or the discovery that
adverse effects or toxicities previously observed in preclinical research or clinical trials that
were believed to be minor actually constitute much more serious problems, may result in
restrictions on the marketing of the drug, and could include withdrawal of the drug from the
market.
47
The policies of the FDA and foreign regulatory agencies may change and additional government
regulations may be enacted that could prevent or delay regulatory approval of our drug candidates.
We cannot predict the likelihood, nature or extent of adverse government regulation that may arise
from future legislation or administrative action, either in the United States or abroad. If we are
not able to maintain regulatory compliance, we might not be permitted to market our drugs and our
business would suffer.
If physicians and patients do not accept our drugs, we may be unable to generate significant
revenue, if any.
Even if our drug candidates obtain regulatory approval, the resulting drugs, if any, may not
gain market acceptance among physicians, healthcare payors, patients and the medical community.
Even if the clinical safety and efficacy of drugs developed from our drug candidates are
established for purposes of approval, physicians may elect not to recommend these drugs for a
variety of reasons including, but not limited to:
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timing of market introduction of competitive drugs; |
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clinical safety and efficacy of alternative drugs or treatments; |
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cost-effectiveness; |
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availability of coverage and reimbursement from health maintenance organizations and
other third-party payors; |
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convenience and ease of administration; |
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prevalence and severity of adverse side effects; |
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other potential disadvantages relative to alternative treatment methods; or |
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insufficient marketing and distribution support. |
If our drugs fail to achieve market acceptance, we may not be able to generate significant
revenue and our business would suffer.
The coverage and reimbursement status of newly approved drugs is uncertain and failure to obtain
adequate coverage and reimbursement could limit our ability to market any drugs we may develop
and decrease our ability to generate revenue.
There is significant uncertainty related to the coverage and reimbursement of newly approved
drugs. The commercial success of our potential drugs in both domestic and international markets is
substantially dependent on whether third-party coverage and reimbursement is available for our
potential drugs by the medical profession for use by their patients. Medicare, Medicaid, health
maintenance organizations and other third-party payors are increasingly attempting to contain
healthcare costs by limiting both coverage and the level of reimbursement of new drugs, and, as a
result, they may not cover or provide adequate payment for our potential drugs. They may not view
our potential drugs as cost-effective and reimbursement may not be available to consumers or may
not be sufficient to allow our potential drugs to be marketed on a competitive basis. If we are
unable to obtain adequate coverage and reimbursement for our potential drugs, our ability to
generate revenue may be adversely affected. Likewise, legislative or regulatory efforts to control
or reduce healthcare costs or reform government healthcare programs could result in lower prices or
rejection of coverage and reimbursement for our potential drugs. Changes in coverage and
reimbursement policies or healthcare cost containment initiatives that limit or restrict
reimbursement for our drugs may cause our revenue to decline.
We may be subject to costly product liability or other liability claims and may not be able to
obtain adequate insurance.
The use of our drug candidates in clinical trials may result in adverse effects. We currently
maintain product liability insurance. We cannot predict all the possible harms or adverse effects
that may result from our clinical trials. We may not have sufficient resources to pay for any
liabilities resulting from a claim excluded from, or beyond the limit of, our insurance coverage.
Our insurance does not cover third parties negligence or malpractice, and our clinical
investigators and sites may have inadequate insurance or none at all. In addition, in order to
conduct clinical trials or otherwise carry out our business, we may have to contractually assume
48
liabilities for which we may not be insured. If we are unable to look to our own or a third
partys insurance to pay claims against us, we may have to pay any arising costs and damages
ourselves, which may be substantial.
In addition, once we have commercially launched drugs based on our drug candidates, we will
face even greater exposure to product liability claims. This risk exists even with respect to those
drugs that are approved for commercial sale by the FDA and foreign regulatory agencies and
manufactured in licensed and regulated facilities. We intend to secure limited product liability
insurance coverage, but may not be able to obtain such insurance on acceptable terms with adequate
coverage, or at reasonable costs. There is also a risk that third parties that we have agreed to
indemnify could incur liability, or that third parties that have agreed to indemnify us do not
fulfill their obligations. Even if we were ultimately successful in product liability litigation,
the litigation would consume substantial amounts of our financial and managerial resources and may
create adverse publicity, all of which would impair our ability to generate sales of the affected
product as well as our other potential drugs. Moreover, product recalls may be issued at our
discretion or at the direction of the FDA and foreign regulatory agencies, other governmental
agencies or other companies having regulatory control for drug sales. If product recalls occur,
they are generally expensive and often have an adverse effect on the image of the drugs being
recalled as well as the reputation of the drugs developer or manufacturer.
We use hazardous chemicals and radioactive and biological materials in our business. Responding
to any claims relating to improper handling, storage or disposal of these materials could be
time-consuming and costly.
Our research and development processes involve the controlled use of hazardous materials,
including chemicals and radioactive and biological materials. Our operations produce hazardous
waste products. We cannot eliminate the risk of accidental contamination or discharge and any
resultant injury from those materials. Federal, state and local laws and regulations govern the
use, manufacture, storage, handling and disposal of hazardous materials. We may be sued for any
injury or contamination that results from our use or the use by third parties of these materials.
Compliance with environmental laws and regulations is expensive, and current or future
environmental regulations may impair our research, development and production activities.
In addition, our partners may use hazardous materials in connection with our strategic
alliances. To our knowledge, their work is performed in accordance with applicable biosafety
regulations. In the event of a lawsuit or investigation, however, we could be held responsible for
any injury caused to persons or property by exposure to, or release of, these hazardous materials
used by these parties. Further, we may be required to indemnify our partners against all damages
and other liabilities arising out of our development activities or drugs produced in connection
with these strategic alliances, which could be costly and time-consuming and distract management.
Our facilities in California are located near an earthquake fault, and an earthquake or other
types of natural disasters, catastrophic events or resource shortages could disrupt our
operations and adversely affect our results.
Important documents and records, such as hard copies of our laboratory books and records for
our drug candidates and compounds and our electronic business records, are located in our corporate
headquarters at a single location in South San Francisco, California near active earthquake zones.
In the event of a natural disaster, such as an earthquake or flood, a catastrophic event such as a
disease pandemic or terrorist attack or localized extended outages of critical utilities or
transportation systems, we do not have a formal business continuity or disaster recovery plan, and
could therefore experience a significant business interruption. Our partners and other third
parties on which we rely may also be subject to business interruptions from such events. In
addition, California from time to time has experienced shortages of water, electric power and
natural gas. Future shortages and conservation measures could disrupt our operations and cause
expense, thus adversely affecting our business and financial results.
Risks Related To Our Common Stock
We expect that our stock price will fluctuate significantly, and you may not be able to resell
your shares at or above your investment price.
The stock market, particularly in recent years, has experienced significant volatility,
particularly with respect to pharmaceutical, biotechnology and other life sciences company stocks.
The volatility of pharmaceutical, biotechnology and other life sciences company stocks often does
not relate to the operating performance of the companies represented by the stock. Factors that
could cause volatility in the market price of our common stock include, but are not limited to:
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results from, delays in, or discontinuation of, any of the clinical trials for our drug
candidates for the treatment of heart failure or cancer, including the current and proposed
clinical trials for CK-1827452 for heart failure, ispinesib for breast cancer and leukemia,
SB-743921 for Hodgkin and non-Hodgkin lymphoma, and GSK-923295 for cancer, and including
delays resulting from slower than expected or suspended patient enrollment or
discontinuations resulting from a failure to meet pre-defined clinical end-points; |
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announcements concerning our strategic alliances with Amgen, GSK or future strategic
alliances, including, but not limited to, announcements concerning Amgens option relating
to CK-1827452 and GSKs option relating to either or both of ispinesib and SB-743921; |
49
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announcements concerning clinical trials; |
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failure or delays in entering additional drug candidates into clinical trials; |
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failure or discontinuation of any of our research programs; |
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issuance of new or changed securities analysts reports or recommendations; |
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failure or delays in establishing new strategic alliances, or the terms of such
alliances; |
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market conditions in the pharmaceutical, biotechnology and other healthcare related
sectors; |
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actual or anticipated fluctuations in our quarterly financial and operating results; |
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developments or disputes concerning our intellectual property or other proprietary
rights; |
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introduction of technological innovations or new commercial products by us or our
competitors; |
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issues in manufacturing our drug candidates or drugs; |
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market acceptance of our drugs; |
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third-party healthcare coverage and reimbursement policies; |
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FDA or other U.S. or foreign regulatory actions affecting us or our industry; |
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litigation or public concern about the safety of our drug candidates or drugs; |
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additions or departures of key personnel; or |
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volatility in the stock prices of other companies in our industry. |
These and other external factors may cause the market price and demand for our common stock to
fluctuate substantially, which may limit or prevent investors from readily selling their shares of
common stock and may otherwise negatively affect the liquidity of our common stock. In addition,
when the market price of a stock has been volatile, holders of that stock have instituted
securities class action litigation against the company that issued the stock. If any of our
stockholders brought a lawsuit against us, we could incur substantial costs defending the lawsuit.
Such a lawsuit could also divert our managements time and attention.
If the ownership of our common stock continues to be highly concentrated, it may prevent you and
other stockholders from influencing significant corporate decisions and may result in conflicts
of interest that could cause our stock price to decline.
As of July 31, 2008, our executive officers, directors and their affiliates beneficially owned
or controlled approximately 26.1% of the outstanding shares of our common stock (after giving
effect to the exercise of all outstanding vested and unvested options and warrants). Accordingly,
these executive officers, directors and their affiliates, acting as a group, will have substantial
influence over
50
the outcome of corporate actions requiring stockholder approval, including the election of
directors, any merger, consolidation or sale of all or substantially all of our assets or any other
significant corporate transactions. These stockholders may also delay or prevent a change of
control of us, even if such a change of control would benefit our other stockholders. The
significant concentration of stock ownership may adversely affect the trading price of our common
stock due to investors perception that conflicts of interest may exist or arise.
Evolving regulation of corporate governance and public disclosure may result in additional
expenses and continuing uncertainty.
Changing laws, regulations and standards relating to corporate governance and public
disclosure, including the Sarbanes-Oxley Act of 2002 (Sarbanes-Oxley), new Securities and
Exchange Commission regulations and NASDAQ Stock Market LLC rules are creating uncertainty for
public companies. We are presently evaluating and monitoring developments with respect to new and
proposed rules and cannot predict or estimate the amount of the additional costs we may incur or
the timing of such costs. For example, compliance with the internal control requirements of
Sarbanes-Oxley Section 404 has to date required the commitment of significant resources to document
and test the adequacy of our internal control over financial reporting. While our assessment,
testing and evaluation of the design and operating effectiveness of our internal control over
financial reporting resulted in our conclusion that, as of December 31, 2007, our internal control
over financial reporting was effective, we can provide no assurance as to conclusions of management
or by our independent registered public accounting firm with respect to the effectiveness of our
internal control over financial reporting in the future. These new or changed laws, regulations and
standards are subject to varying interpretations, in many cases due to their lack of specificity,
and, as a result, their application in practice may evolve over time as new guidance is provided by
regulatory and governing bodies. This could result in continuing uncertainty regarding compliance
matters and higher costs necessitated by ongoing revisions to disclosure and governance practices.
We are committed to maintaining high standards of corporate governance and public disclosure. As a
result, we intend to invest the resources necessary to comply with evolving laws, regulations and
standards, and this investment may result in increased general and administrative expenses and a
diversion of management time and attention from revenue-generating activities to compliance
activities. If our efforts to comply with new or changed laws, regulations and standards differ
from the activities intended by regulatory or governing bodies, due to ambiguities related to
practice or otherwise, regulatory authorities may initiate legal proceedings against us, which
could be costly and time-consuming, and our reputation and business may be harmed.
Volatility in the stock prices of other companies may contribute to volatility in our stock
price.
The stock market in general, and The NASDAQ Global Market (NASDAQ) and the market for
technology companies in particular, have experienced significant price and volume fluctuations that
have often been unrelated or disproportionate to the operating performance of those companies.
Further, there has been particular volatility in the market prices of securities of early stage and
development stage life sciences companies. These broad market and industry factors may seriously
harm the market price of our common stock, regardless of our operating performance. In the past,
following periods of volatility in the market price of a companys securities, securities class
action litigation has often been instituted. A securities class action suit against us could result
in substantial costs, potential liabilities and the diversion of managements attention and
resources, and could harm our reputation and business.
We have never paid dividends on our capital stock, and we do not anticipate paying any cash
dividends in the foreseeable future.
We have paid no cash dividends on any of our classes of capital stock to date and we currently
intend to retain our future earnings, if any, to fund the development and growth of our businesses.
In addition, the terms of existing or any future debts may preclude us from paying these dividends.
Our common stock is thinly traded and there may not be an active, liquid trading market for our
common stock.
There is no guarantee that an active trading market for our common stock will be maintained on
NASDAQ, or that the volume of trading will be sufficient to allow for timely trades. Investors may
not be able to sell their shares quickly or at the latest market price if trading in our stock is
not active or if trading volume is limited. In addition, if trading volume in our common stock is
limited, trades of relatively small numbers of shares may have a disproportionate effect on the
market price of our common stock.
51
Risks Related To Our Financing Vehicles and Investments
Our committed equity financing facility with Kingsbridge may not be available to us if we elect
to make a draw down, may require us to make additional blackout or other payments to
Kingsbridge, and may result in dilution to our stockholders.
In October 2007, we entered into a committed equity financing facility with Kingsbridge. This committed equity financing facility entitles us to
sell and obligates Kingsbridge to purchase, from time to time over a period of three years, shares
of our common stock for cash consideration up to an aggregate of $75.0 million, subject to certain
conditions and restrictions. Kingsbridge will not be obligated to purchase shares under this
committed equity financing facility unless certain conditions are met, which include a minimum price for our common stock; the
accuracy of representations and warranties made to Kingsbridge; compliance with laws; effectiveness
of the registration statement registering for resale the shares of common stock to be issued in
connection with this committed equity financing facility; and the continued listing of our stock on NASDAQ. In addition,
Kingsbridge is permitted to terminate this committed equity financing facility if it determines that a material and adverse
event has occurred affecting our business, operations, properties or financial condition and if
such condition continues for a period of 10 days from the date Kingsbridge provides us notice of
such material and adverse event. If we are unable to access funds
through this committed equity financing facility, or if Kingsbridge terminates this committed equity financing facility, we may be unable to access capital on favorable terms or
at
all.
We are entitled, in certain circumstances, to deliver a blackout notice to Kingsbridge to
suspend the use of the resale registration statement and prohibit Kingsbridge from selling shares
under the resale registration statement. If we deliver a blackout notice in the 15 trading days
following the settlement of a draw down, or if the registration statement is not effective in
circumstances not permitted by the agreement, then we must make a payment to Kingsbridge, or issue
Kingsbridge additional shares in lieu of this payment, calculated on the basis of the number of
shares held by Kingsbridge (exclusive of shares that Kingsbridge may hold pursuant to exercise of
the Kingsbridge warrant) and the change in the market price of our common stock during the period
in which the use of the registration statement is suspended. If the trading price of our common
stock declines during a suspension of the registration statement, the blackout or other payment
could be significant.
Should we sell shares to Kingsbridge under this committed equity financing facility, or issue shares in lieu of a
blackout payment, it will have a dilutive effective on the holdings of our current stockholders,
and may result in downward pressure on the price of our common stock. If we draw down under this committed equity financing facility, we will issue shares to Kingsbridge at a discount of up to 10 percent from the volume
weighted average price of our common stock. If we draw down amounts under this committed equity financing facility when our
share price is decreasing, we will need to issue more shares to raise the same amount than if our
stock price was higher. Issuances in the face of a declining share price will have an even greater
dilutive effect than if our share price were stable or increasing, and may further decrease our
share price.
We may be required to record impairment charges in future quarters as a result of the decline in
value of our investments in auction rate securities.
We hold interest-bearing student loan auction rate securities (ARS) that represent
investments in pools of assets. These ARS are intended to provide liquidity via an auction process
that resets the applicable interest rate at predetermined calendar intervals, allowing investors to
either roll over their holdings or gain immediate liquidity by selling such interests at par. The
recent uncertainties in the credit markets have affected all of our holdings in ARS and auctions
for our investments in these securities have failed to settle on their respective settlement dates.
Consequently, these investments are not currently liquid and we will not be able to access these
funds until a future auction of these investments is successful, the issuer redeems the outstanding
securities, the securities mature or a buyer is found outside of the auction process. Maturity
dates for these ARS range from 2036 to 2045. To date, we have recorded $1.3 million of unrealized
loss in other comprehensive income (loss) related to the ARS that we hold in our investment
portfolio. However, if the current market conditions deteriorate further, or the anticipated
recovery in market values does not occur, we may be required to record additional unrealized losses
in other comprehensive income (loss) or impairment charges in future quarters. This could adversely
impact our results of operations and financial condition. Furthermore, in light of auction failures
associated with our ARS, we re-classified our ARS as long-term investments due to the uncertainty
associated with the timing of our ability to access the funds underlying these investments. If we
are unable to access the funds underlying these investments in a timely manner, we may need to find
alternate sources of funding for certain of our operations, which may not be available on favorable
terms, or at all, and our business could be adversely effected.
ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS
We made no repurchases of our common stock during the six months ended June 30, 2008. As of
June 30, 2008, there were no remaining shares of common stock subject to repurchase by us.
52
ITEM 3. DEFAULTS UPON SENIOR SECURITIES
None.
ITEM 4. SUBMISSION OF MATTERS TO A VOTE OF SECURITY HOLDERS
Our Annual Meeting of Stockholders was held on May 22, 2008 in South San Francisco,
California. Of the 49,301,300 shares of the Companys common stock entitled to vote at the meeting,
39,048,355 shares of common stock, or 79%, of the total eligible votes to be cast, were represented
at the meeting in person or by proxy, constituting a quorum. The voting results were as follows:
The stockholders elected A. Grant Heidrich and James H. Sabry as Class I directors, each to
serve for a three-year term until their successors are duly elected and qualified. The votes were
as follows:
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Name |
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For |
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Withheld |
A. Grant Heidrich
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38,512,135
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536,220 |
James H. Sabry
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34,683,566
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4,364,789 |
Our other directors with terms of office that continued after the Annual Meeting of
Stockholders were Robert Blum, Stephen Dow, Charles Homcy, Mark McDade, Michael Schmertzler and
James Spudich.
The stockholders ratified the selection by the Audit Committee of the Board of Directors of
PricewaterhouseCoopers LLP as the Companys independent registered public accounting firm for the
fiscal year ending December 31, 2008. The votes were as follows:
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For |
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Against |
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Abstain |
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Broker Non-Vote |
39,006,038
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38,546
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3,771
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|
O |
The stockholders approved the amendment to the Amended and Restated Certificate of
Incorporation increasing the number of authorized shares of common stock from 120,000,000 shares to
170,000,000 shares. The votes were as follows:
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For |
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Against |
|
Abstain |
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Broker Non-Vote |
31,993,251
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7,112,697
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2,407
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|
O |
The stockholders approved the amended and restated 2004 Equity Incentive Plan. The votes were
as follows:
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For |
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Against |
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Abstain |
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Broker Non-Vote |
28,961,221
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3,658,269
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2,281,129
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4,147,736 |
ITEM 5. OTHER INFORMATION
In August 2008, the Company entered into an Amended and Restated Executive Employment
Agreement with each of David J. Morgans, Jr., Sharon Barbari, Michael Rabson, Andrew A. Wolff,
David W. Cragg and Jay K. Trautman, each in substantially the form
filed as Exhibit 10.68 to this
report. Also in August 2008, the Company entered into an Amended and Restated Executive
Employment Agreement with Robert I. Blum as filed as
Exhibit 10.69 to this report. These
agreements were entered into in order to comply with Section 409A of the Internal Revenue Code and
its regulations.
In
August 2008, the Company also entered into an
Indemnification Agreement with each of Robert I. Blum, David J. Morgans, Jr., Sharon Barbari,
Michael Rabson, Andrew A. Wolff, David W. Cragg and Jay K. Trautman, each in substantially the form
filed as Exhibit 10.1 to this report.
ITEM 6. EXHIBITS
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Exhibit |
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Number |
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|
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Exhibit Description |
3.1
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(1 |
) |
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Amended and Restated Certificate of Incorporation. |
53
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Exhibit |
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Number |
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|
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Exhibit Description |
3.2
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(1 |
) |
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Amended and Restated Bylaws. |
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4.1
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(2 |
) |
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Specimen Common Stock Certificate. |
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4.2
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(1 |
) |
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Fourth Amended and Restated Investors Rights Agreement, dated March 21, 2003, by and among the
Company and certain stockholders of the Company. |
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4.3
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(1 |
) |
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Master Security Agreement, dated February 2, 2001, by and between the Company and General Electric
Capital Corporation. |
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4.4
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(1 |
) |
|
Cross-Collateral and Cross-Default Agreement by and between the Company and General Electric
Capital Corporation. |
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4.5
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(3 |
) |
|
Warrant for the purchase of shares of common stock, dated October 28, 2005, issued by the Company
to Kingsbridge Capital Limited. |
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4.6
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(3 |
) |
|
Registration Rights Agreement, dated October 28, 2005, by and between the Company and Kingsbridge
Capital Limited. |
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4.7
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(4 |
) |
|
Registration Rights Agreement, dated as of December 29, 2006, by and between the Company and Amgen
Inc. |
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4.8
|
|
|
(5 |
) |
|
Warrant for the purchase of shares of common stock, dated October 15, 2007, issued by the Company
to Kingsbridge Capital Limited. |
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4.9
|
|
|
(5 |
) |
|
Registration Rights Agreement, dated October 15, 2007, by and between the Company and Kingsbridge
Capital Limited. |
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|
10.1
|
|
|
|
|
|
Form of Indemnification Agreement between the Company and each of its directors and executive officers. |
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10.3
|
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2004 Equity Incentive Plan (as amended and restated as of May 22, 2008). |
|
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|
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|
10.66*
|
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|
(6 |
) |
|
Scientific Advisory Board Consulting Agreement, dated April 1, 2008, by and between the Company
and James H. Sabry. |
|
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|
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|
10.67*
|
|
|
(7 |
) |
|
Letter Amendment to the Collaboration Agreement, dated June 18, 2008, by and between the Company
and Glaxo Group Limited, a GlaxoSmithKline company. |
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10.68
|
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|
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|
Form of Executive Employment Agreement between the Company and its executive officers. |
|
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10.69
|
|
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|
|
|
Amended and Restated Executive Employment Agreement,
dated May 21, 2007, by and between the Company and Robert I. Blum. |
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31.1
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Certification of Chief Executive Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. |
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31.2
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|
Certification of Chief Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. |
|
|
|
|
|
|
|
32.1
|
|
|
|
|
|
Certifications of the Chief Executive Officer and the Chief Financial Officer pursuant to Section
906 of the Sarbanes-Oxley Act of 2002 (18 U.S.C. Section 1350). |
|
|
|
|
|
|
|
|
|
|
* |
|
Pursuant to a request for confidential treatment, portions of this Exhibit have been redacted
from the publicly filed document and have been furnished separately to the Securities and
Exchange Commission as required by Rule 406 under the Securities Act of 1933 or Rule 24b-2
under the Securities Exchange Act of 1934, as applicable. |
|
(1) |
|
Incorporated by reference from our registration statement on Form S-1, registration number
333-112261, declared effective by the Securities and Exchange Commission on April 29, 2004. |
54
|
|
|
(2) |
|
Incorporated by reference from our Quarterly Report on Form 10-Q, filed with the Security and
Exchange Commission on May 9, 2007. |
|
(3) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on January 20, 2006. |
|
(4) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on January 3, 2007. |
|
(5) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on October 15, 2007. |
|
(6) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on April 2, 2008. |
|
(7) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on June 20, 2008. |
55
SIGNATURES
Pursuant to the requirements of the Securities Act of 1934, the registrant has duly caused
this report to be signed on its behalf by the undersigned, thereunto duly authorized.
|
|
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Dated: August 5, 2008
|
|
CYTOKINETICS, INCORPORATED |
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|
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(Registrant) |
|
|
|
|
|
|
|
|
|
/s/ Robert I. Blum
Robert I. Blum
|
|
|
|
|
President and Chief Executive Officer |
|
|
|
|
(Principal Executive Officer) |
|
|
|
|
|
|
|
|
|
/s/ Sharon Barbari
Sharon Barbari
|
|
|
|
|
Senior Vice President, Finance and Chief Financial Officer |
|
|
|
|
(Principal Financial Officer) |
|
|
56
EXHIBIT INDEX
|
|
|
|
|
|
|
Exhibit |
|
|
|
|
|
|
Number; |
|
|
|
|
|
Exhibit Description |
3.1
|
|
|
(1 |
) |
|
Amended and Restated Certificate of Incorporation. |
|
|
|
|
|
|
|
3.2
|
|
|
(1 |
) |
|
Amended and Restated Bylaws. |
|
|
|
|
|
|
|
4.1
|
|
|
(2 |
) |
|
Specimen Common Stock Certificate. |
|
|
|
|
|
|
|
4.2
|
|
|
(1 |
) |
|
Fourth Amended and Restated Investors Rights Agreement, dated March 21, 2003, by and among the
Company and certain stockholders of the Company. |
|
|
|
|
|
|
|
4.3
|
|
|
(1 |
) |
|
Master Security Agreement, dated February 2, 2001, by and between the Company and General Electric
Capital Corporation. |
|
|
|
|
|
|
|
4.4
|
|
|
(1 |
) |
|
Cross-Collateral and Cross-Default Agreement by and between the Company and General Electric
Capital Corporation. |
|
|
|
|
|
|
|
4.5
|
|
|
(3 |
) |
|
Warrant for the purchase of shares of common stock, dated October 28, 2005, issued by the Company
to Kingsbridge Capital Limited. |
|
|
|
|
|
|
|
4.6
|
|
|
(3 |
) |
|
Registration Rights Agreement, dated October 28, 2005, by and between the Company and Kingsbridge
Capital Limited. |
|
|
|
|
|
|
|
4.7
|
|
|
(4 |
) |
|
Registration Rights Agreement, dated as of December 29, 2006, by and between the Company and Amgen
Inc. |
|
|
|
|
|
|
|
4.8
|
|
|
(5 |
) |
|
Warrant for the purchase of shares of common stock, dated October 15, 2007, issued by the Company
to Kingsbridge Capital Limited. |
|
|
|
|
|
|
|
4.9
|
|
|
(5 |
) |
|
Registration Rights Agreement, dated October 15, 2007, by and between the Company and Kingsbridge
Capital Limited. |
|
|
|
|
|
|
|
10.1
|
|
|
|
|
|
Form of Indemnification Agreement between the Company and each of its directors and executive officers. |
|
|
|
|
|
|
|
10.3
|
|
|
|
|
|
2004 Equity Incentive Plan (as amended and restated as of May 22, 2008). |
|
|
|
|
|
|
|
10.66*
|
|
|
(6 |
) |
|
Scientific Advisory Board Consulting Agreement, dated April 1, 2008, by and between the Company
and James H. Sabry. |
|
|
|
|
|
|
|
10.67*
|
|
|
(7 |
) |
|
Letter Amendment to the Collaboration Agreement, dated June 18, 2008, by and between the Company
and Glaxo Group Limited, a GlaxoSmithKline company. |
|
|
|
|
|
|
|
10.68
|
|
|
|
|
|
Form of Executive Employment Agreement between the Company and its executive officers. |
|
|
|
|
|
|
|
10.69
|
|
|
|
|
|
Amended and Restated Executive Employment Agreement,
dated May 21, 2007, by and between the Company and Robert I. Blum. |
|
|
|
|
|
|
|
31.1
|
|
|
|
|
|
Certification of Chief Executive Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. |
|
|
|
|
|
|
|
31.2
|
|
|
|
|
|
Certification of Chief Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002. |
|
|
|
|
|
|
|
32.1
|
|
|
|
|
|
Certifications of the Chief Executive Officer and the Chief Financial Officer pursuant to Section
906 of the Sarbanes-Oxley Act of 2002 (18 U.S.C. Section 1350). |
|
|
|
|
|
|
|
|
|
|
* |
|
Pursuant to a request for confidential treatment, portions of this Exhibit have been redacted
from the publicly filed document and have been furnished separately to the Securities and
Exchange Commission as required by Rule 406 under the Securities Act of 1933 or Rule 24b-2
under the Securities Exchange Act of 1934, as applicable. |
57
|
|
|
(1) |
|
Incorporated by reference from our registration statement on Form S-1, registration number
333-112261, declared effective by the Securities and Exchange Commission on April 29, 2004. |
|
(2) |
|
Incorporated by reference from our Quarterly Report on Form 10-Q, filed with the Security and
Exchange Commission on May 9, 2007. |
|
(3) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on January 20, 2006. |
|
(4) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on January 3, 2007. |
|
(5) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on October 15, 2007. |
|
(6) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on April 2, 2008. |
|
(7) |
|
Incorporated by reference from our Current Report on Form 8-K, filed with the Securities and
Exchange Commission on June 20, 2008. |
58