UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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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
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For the quarterly period ended March 31, 2009
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
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For
the transition period from
to
Commission File Number 000-50743
ALNYLAM PHARMACEUTICALS, INC.
(Exact Name of Registrant as Specified in Its Charter)
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Delaware
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77-0602661
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(State or Other Jurisdiction of
Incorporation or Organization)
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(I.R.S. Employer
Identification No.)
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300 Third Street, Cambridge, MA
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02142
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(Address of Principal Executive
Offices)
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(Zip Code)
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(617) 551-8200
(Registrants Telephone Number, Including Area Code)
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 has submitted electronically and posted on its
corporate Web site, if any, every Interactive Data File required to be submitted and posted
pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months
(or for such shorter period that the registrant was required to submit and post such files). Yes
o
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:
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Large accelerated filer
þ
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Accelerated filer
o
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Non-accelerated filer
o
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Smaller reporting company
o
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(Do not check if a smaller reporting company)
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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
As of April 30, 2009, the registrant had 41,502,140 shares of Common Stock, $0.01 par value
per share, outstanding.
ALNYLAM PHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share amounts)
(Unaudited)
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March 31,
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December 31,
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2009
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2008
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ASSETS
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Current assets:
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Cash and cash equivalents
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$
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227,268
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$
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191,792
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Marketable securities
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180,786
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238,596
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Collaboration receivables
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5,831
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4,188
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Prepaid expenses and other current assets
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5,454
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4,674
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Restricted cash
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2,999
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Total current assets
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419,339
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442,249
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Marketable securities
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96,647
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82,321
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Property and equipment, net
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19,321
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19,194
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Deferred tax assets
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5,606
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5,382
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Investment in joint venture (Regulus Therapeutics Inc.)
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9,713
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1,583
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Intangible assets, net
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751
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795
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Restricted cash, net of current portion
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3,152
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3,152
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Total assets
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$
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554,529
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$
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554,676
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LIABILITIES AND STOCKHOLDERS EQUITY
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Current liabilities:
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Accounts payable
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$
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8,729
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$
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2,588
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Accrued expenses
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10,389
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9,328
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Income taxes payable
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1,033
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6,111
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Deferred rent
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1,561
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1,561
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Deferred revenue
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82,539
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79,864
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Total current liabilities
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104,251
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99,452
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Deferred rent, net of current portion
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2,342
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2,732
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Deferred revenue, net of current portion
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248,959
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250,121
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Other long-term liabilities
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233
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246
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Total liabilities
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355,785
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352,551
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Commitments and contingencies
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Stockholders equity:
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Preferred stock, $0.01 par value, 5,000,000
shares authorized and no shares issued and
outstanding at March 31, 2009 and December
31, 2008
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Common stock, $0.01 par value, 125,000,000
shares authorized; 41,442,690 shares issued
and outstanding at March 31, 2009;
41,413,828 shares issued and outstanding at
December 31, 2008
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414
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414
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Additional paid-in capital
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457,838
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452,767
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Accumulated other comprehensive income
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623
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1,186
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Accumulated deficit
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(260,131
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)
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(252,242
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)
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Total stockholders equity
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198,744
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202,125
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Total liabilities and stockholders equity
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$
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554,529
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$
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554,676
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The accompanying notes are an integral part of these condensed consolidated financial statements.
2
ALNYLAM PHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(In thousands, except per share amounts)
(Unaudited)
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Three Months Ended March 31,
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2009
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2008
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Net revenues from research collaborators
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$
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25,057
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$
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22,192
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Operating expenses:
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Research and development
(1)
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25,321
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20,277
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General and administrative
(1)
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7,716
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5,872
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Total operating expenses
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33,037
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26,149
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Loss from operations
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(7,980
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(3,957
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)
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Other income (expense):
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Equity in loss of joint venture (Regulus Therapeutics Inc.)
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(1,470
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(1,629
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Interest income
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2,048
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4,702
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Interest expense
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(232
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Other income
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178
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82
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Total other income (expense)
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756
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2,923
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Loss before income taxes
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(7,224
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(1,034
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Provision for income taxes
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(665
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(205
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)
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Net loss
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$
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(7,889
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$
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(1,239
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Net loss per
common share - basic and diluted
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$
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(0.19
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$
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(0.03
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)
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Weighted average common shares used to compute
basic and diluted net loss per common share
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41,399
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40,736
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Comprehensive loss:
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Net loss
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$
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(7,889
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)
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$
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(1,239
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)
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Foreign currency translation
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(90
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)
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10
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Unrealized (loss) gain on marketable securities
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(473
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)
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336
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Comprehensive loss
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$
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(8,452
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)
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$
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(893
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)
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(1) Non-cash stock-based compensation expenses
included in operating expenses are as follows:
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Research and development
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$
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3,034
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$
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2,314
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General and administrative
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2,103
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1,506
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The accompanying notes are an integral part of these condensed consolidated financial statements.
3
ALNYLAM PHARMACEUTICALS, INC.
CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
(Unaudited)
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Three Months Ended March 31,
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2009
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2008
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Cash flows from operating activities:
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Net loss
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$
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(7,889
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)
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$
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(1,239
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)
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Adjustments to reconcile net loss to net cash provided by (used
in) operating activities:
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Depreciation and amortization
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1,802
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951
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Deferred
income taxes
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(237
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)
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(16
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)
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Non-cash stock-based compensation
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4,736
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4,004
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Charge for 401(k) company stock match
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125
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90
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Equity in loss of joint venture (Regulus Therapeutics Inc.)
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1,870
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1,445
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Changes in operating assets and liabilities:
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Collaboration receivables
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(1,643
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)
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(4,649
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)
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Prepaid expenses and other assets
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(780
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)
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1,004
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Accounts payable
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6,141
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5,258
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Income taxes payable
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(5,078
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)
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(47
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)
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Accrued expenses and other
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671
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(2,405
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)
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Deferred revenue
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1,513
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(13,054
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)
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Net cash provided by (used in) operating activities
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1,231
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(8,658
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)
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Cash flows from investing activities:
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Purchases of property and equipment
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(1,885
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)
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(2,945
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)
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Decrease in restricted cash
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2,999
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Purchases of marketable securities
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(93,687
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)
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(101,689
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)
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Sales and maturities of marketable securities
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136,698
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204,878
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Investment in joint venture (Regulus Therapeutics Inc.)
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(10,000
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)
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Net cash provided by investing activities
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34,125
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100,244
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Cash flows from financing activities:
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Proceeds from issuance of common stock
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210
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443
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Repayments of notes payable
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(915
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)
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Net cash provided by (used in) financing activities
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210
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(472
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)
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Effect of exchange rate on cash
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(90
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)
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10
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Net increase in cash and cash equivalents
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35,476
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91,124
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Cash and cash equivalents, beginning of period
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191,792
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105,157
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Cash and cash equivalents, end of period
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$
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227,268
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$
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196,281
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The accompanying notes are an integral part of these condensed consolidated financial statements.
4
ALNYLAM PHARMACEUTICALS, INC.
NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS
(Unaudited)
1. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES
Basis of Presentation and Principles of Consolidation
The accompanying condensed consolidated financial statements of Alnylam Pharmaceuticals, Inc.
(the Company or Alnylam) are unaudited and have been prepared in accordance with accounting
principles generally accepted in the United States of America applicable to interim periods and, in
the opinion of management, include all normal and recurring adjustments that are necessary to
present fairly the results of operations for the reported periods. The Companys condensed
consolidated financial statements have also been prepared on a basis substantially consistent with,
and should be read in conjunction with, the Companys audited consolidated financial statements for
the year ended December 31, 2008, which were included in the Companys Annual Report on Form 10-K
filed with the Securities and Exchange Commission (the SEC) on March 2, 2009. The year-end
condensed balance sheet date was derived from audited financial statements, but does not include
all disclosures required by accounting principles generally accepted in the United States of
America (GAAP). The results of the Companys operations for any interim period are not necessarily
indicative of the results of the Companys operations for any other interim period or for a full
fiscal year.
The accompanying condensed consolidated financial statements reflect the operations of the
Company and its wholly-owned subsidiaries, Alnylam U.S., Inc., Alnylam Europe AG (Alnylam Europe)
and Alnylam Securities Corporation. All significant intercompany accounts and transactions have
been eliminated. The Company uses the equity method of accounting to account for its investment in
Regulus Therapeutics Inc., formerly Regulus Therapeutics LLC (Regulus).
Use of Estimates
The preparation of financial statements in conformity with accounting principles generally
accepted in the United States of America requires management to make estimates and assumptions that
affect the reported amounts of assets and liabilities and the disclosure of contingent assets and
liabilities at the date of the condensed consolidated financial statements and the reported amounts
of revenues and expenses during the reporting period. Actual results could differ from those
estimates.
Net Loss Per Common Share
The Company accounts for and discloses net loss per common share in accordance with Statement
of Financial Accounting Standards (SFAS) No. 128,
Earnings per Share.
Basic net loss per common
share is computed by dividing net loss attributable to common stockholders by the weighted average
number of common shares outstanding. Diluted net loss per common share is computed by dividing net
loss attributable to common stockholders by the weighted average number of common shares and
dilutive potential common share equivalents then outstanding. Potential common shares consist of
shares issuable upon the exercise of stock options (using the treasury stock method), and unvested
restricted stock awards. Because the inclusion of potential common shares would be anti-dilutive
for all periods presented, diluted net loss per common share is the same as basic net loss per
common share.
The following table sets forth for the periods presented the potential common shares (prior to
consideration of the treasury stock method) excluded from the calculation of net loss per common
share because their inclusion would be anti-dilutive, in thousands:
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Three Months Ended
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March 31,
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2009
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2008
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Options to purchase common stock
|
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|
7,014
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5,494
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Unvested restricted common stock
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|
29
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|
57
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|
|
|
|
|
|
|
|
|
|
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7,043
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|
|
|
5,551
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|
|
|
|
|
|
|
|
|
|
Fair Value Measurements
Effective January 1, 2009, the Company implemented SFAS No. 157,
Fair Value Measurements
(SFAS 157), for all nonfinancial assets and nonfinancial liabilities not recognized or disclosed
at fair value in the financial statements on a recurring basis.
5
The implementation of SFAS 157 for those assets and liabilities did not have a material impact
on the Companys operating results or financial position, however, could have an impact in future
periods. The Company did not have any nonfinancial assets or nonfinancial liabilities that would
be recognized or disclosed at fair value on a recurring basis for the three months ended March 31,
2009.
The following tables present information about the Companys assets that are measured at fair
value on a recurring basis as of March 31, 2009 and December 31, 2008, and indicate the fair value
hierarchy of the valuation techniques the Company utilized to determine such fair value. In
general, fair values determined by Level 1 inputs utilize quoted prices (unadjusted) in active
markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data
points that are observable, such as quoted prices (adjusted), interest rates and yield curves. Fair
values determined by Level 3 inputs utilize unobservable data points for the asset or liability,
and include situations where there is little, if any, market activity for the asset or liability.
Financial assets measured at fair value on a recurring basis are summarized as follows, in
thousands:
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Quoted
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|
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Prices in
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Significant
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Significant
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As of
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Active
|
|
|
Observable
|
|
|
Unobservable
|
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|
|
March 31,
|
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Markets
|
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|
Inputs
|
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|
Inputs
|
|
Description
|
|
2009
|
|
|
(Level 1)
|
|
|
(Level 2)
|
|
|
(Level 3)
|
|
Cash equivalents
|
|
$
|
225,845
|
|
|
$
|
223,647
|
|
|
$
|
2,198
|
|
|
$
|
|
|
Marketable securities (fixed income)
|
|
|
276,382
|
|
|
|
|
|
|
|
276,382
|
|
|
|
|
|
Marketable securities (equity holdings)
|
|
|
1,051
|
|
|
|
|
|
|
|
1,051
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
$
|
503,278
|
|
|
$
|
223,647
|
|
|
$
|
279,631
|
|
|
$
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Quoted
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Prices in
|
|
|
Significant
|
|
|
Significant
|
|
|
|
As of
|
|
|
Active
|
|
|
Observable
|
|
|
Unobservable
|
|
|
|
December 31,
|
|
|
Markets
|
|
|
Inputs
|
|
|
Inputs
|
|
Description
|
|
2008
|
|
|
(Level 1)
|
|
|
(Level 2)
|
|
|
(Level 3)
|
|
Cash equivalents
|
|
$
|
187,057
|
|
|
$
|
167,293
|
|
|
$
|
19,764
|
|
|
$
|
|
|
Marketable securities (fixed income)
|
|
|
320,269
|
|
|
|
|
|
|
|
320,269
|
|
|
|
|
|
Marketable securities (equity holdings)
|
|
|
648
|
|
|
|
|
|
|
|
648
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
|
$
|
507,974
|
|
|
$
|
167,293
|
|
|
$
|
340,681
|
|
|
$
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The carrying amounts reflected in the Companys condensed consolidated balance sheets for
cash, collaboration receivables, other current assets, accounts payable and accrued expenses
approximate fair value due to their short-term maturities.
Recent Accounting Pronouncements
In December 2007, the Financial Accounting Standards Board (FASB) reached a consensus on
Emerging Issues Task Force (EITF) Issue No. 07-1,
Accounting for Collaborative Arrangements
(EITF 07-1). EITF 07-1 requires collaborators to present the results of activities for which they
act as the principal on a gross basis and report any payments received from (made to) other
collaborators based on other applicable GAAP or, in the absence of other applicable GAAP, based on
analogy to authoritative accounting literature or a reasonable, rational and consistently applied
accounting policy election. Further, EITF 07-1 clarifies that the determination of whether
transactions within a collaborative arrangement are part of a vendor-customer (or analogous)
relationship subject to EITF Issue No. 01-9,
Accounting for Consideration Given by a Vendor to a
Customer (Including a Reseller of the Vendors Products)
(EITF 01-9). EITF 07-1 became
effective on January 1, 2009. The adoption of EITF 07-1 did not have a material impact on the
Companys condensed consolidated financial statements, however,
it resulted in enhanced disclosures for the Companys
collaboration activities.
2. SIGNIFICANT AGREEMENTS
Platform Alliances
Roche Alliance
In July 2007, the Company and, for limited purposes, Alnylam Europe, entered into a license
and collaboration agreement (the LCA) with F. Hoffmann-La Roche Ltd (Roche Basel) and
Hoffman-La Roche Inc. (together with Roche Basel, Roche). Under the LCA, which became effective
in August 2007, the Company granted Roche a non-exclusive license to the Companys
6
intellectual property to develop and commercialize therapeutic products that function through
RNA interference, or RNAi, subject to the Companys existing contractual obligations to third
parties. The license is initially limited to the therapeutic areas of oncology, respiratory
diseases, metabolic diseases and certain liver diseases, and may be expanded to include up to 18
additional therapeutic areas, comprising substantially all other fields of human disease, as
identified and agreed upon by the parties, upon payment to the Company by Roche of an additional
$50.0 million for each additional therapeutic area, if any.
In consideration for the rights granted to Roche under the LCA, Roche paid the Company $273.5
million in upfront cash payments. In addition, in exchange for the Companys contributions under
the LCA, for each RNAi therapeutic product successfully developed by Roche, its affiliates or
sublicensees under the LCA, if any, the Company is entitled to receive milestone payments upon
achievement of specified development and sales events, totaling up to an aggregate of $100.0
million per therapeutic target, together with royalty payments based on worldwide annual net sales,
if any.
Under the LCA, the Company and Roche also agreed to collaborate on the discovery of RNAi
therapeutic products directed to one or more disease targets (Discovery Collaboration), subject
to the Companys existing contractual obligations to third parties. The collaboration between Roche
and the Company will be governed by a joint steering committee for a period of five years that is
comprised of an equal number of representatives from each party. In exchange for the Companys
contributions to the collaboration, Roche will be required to make additional milestone and royalty
payments to the Company.
In July 2007, the Company executed a common stock purchase agreement (the Common Stock
Purchase Agreement) with Roche Finance Ltd, an affiliate of Roche (Roche Finance). Under the
terms of the Common Stock Purchase Agreement, on August 9, 2007, Roche Finance purchased 1,975,000
shares of the Companys common stock at $21.50 per share, for an aggregate purchase price of $42.5
million. The Company recorded this issuance using the closing price of the Companys common stock
on August 9, 2007, the date the shares were issued to Roche. Based on the closing price of $25.98,
the fair value of the shares issued was $51.3 million, which was $8.8 million in excess of the
proceeds received from Roche for the issuance of the Companys common stock. As a result, the
Company allocated $8.8 million of the upfront payment from the LCA to the common stock issuance.
Under the terms of the Common Stock Purchase Agreement, in the event the Company proposes to
sell or issue any of its equity securities, subject to specified exceptions, it has agreed to grant
to Roche Finance the right to acquire, at fair value, additional securities, such that Roche
Finance would be able to maintain its ownership percentage in the Company.
In connection with the execution of the LCA and the Common Stock Purchase Agreement, the
Company also executed a Share Purchase Agreement (the Alnylam Europe Purchase Agreement) with
Alnylam Europe and Roche Beteiligungs GmbH, an affiliate of Roche (Roche Germany). Under the
terms of the Alnylam Europe Purchase Agreement, which became effective in August 2007, the Company
created a new, wholly-owned German limited liability company (Roche Kulmbach) into which
substantially all of the non-intellectual property assets of Alnylam Europe were transferred, and
Roche Germany purchased from the Company all of the issued and outstanding shares of Roche Kulmbach
for an aggregate purchase price of $15.0 million. The Alnylam Europe Purchase Agreement also
included transition services that were performed by Roche Kulmbach employees at various levels
through August 2008. The Company reimbursed Roche for these services at an agreed-upon rate. The
Company recorded contra revenue (a reduction of revenues) of $0.3 million for these services for
the three months ended March 31, 2008.
In addition, in connection with the closing of the Alnylam Europe Purchase Agreement, the
Company granted restricted stock of the Company to certain employees of Roche Kulmbach. In
connection with the closing, the Company also accelerated the unvested portion of the outstanding
stock options of certain Alnylam Europe employees.
In summary, the Company received upfront payments totaling $331.0 million under the Roche
alliance, which included an upfront payment under the LCA of $273.5 million, $42.5 million under
the Common Stock Purchase Agreement and $15.0 million for the Roche Kulmbach shares under the
Alnylam Europe Purchase Agreement.
The Company recorded $278.2 million as deferred revenue in connection with the Roche alliance.
This amount represents the aggregate proceeds received from Roche of $331.0 million, net of the
amount allocated to the common stock issuance of $51.3 million, and the net book value of Alnylam
Europe of $1.5 million.
When evaluating multiple element arrangements, the Company considers whether the components of
the arrangement represent separate units of accounting as defined in EITF Issue No. 00-21,
Revenue
Arrangements with Multiple Deliverables
(EITF 00-21). Application of this standard requires
subjective determinations and requires management to make judgments about the value of each
individual element and whether it is separable from the other aspects of the contractual
relationship. The Company
7
has determined that the deliverables under the Roche alliance include the license, the Alnylam
Europe assets and employees, the steering committees (joint steering committee and future
technology committee) and the services that the Company will be obligated to perform under the
Discovery Collaboration. The Company has concluded that, pursuant to paragraph 9 of EITF 00-21, the
license and assets of Alnylam Europe are not separable from the undelivered services (i.e., the
steering committees and Discovery Collaboration) and, accordingly, the license and the services are
being treated as a single unit of accounting. When multiple deliverables are accounted for as a
single unit of accounting, the Company bases its revenue recognition pattern on the final
deliverable. Under the Roche alliance, the steering committee services and the Discovery
Collaboration services are the final deliverables and all such services will end, contractually,
five years from the effective date of the LCA. The Company is recognizing the Roche-related revenue
on a straight-line basis over five years because the Company cannot reasonably estimate the total
level of effort required to complete its service obligations under the LCA. The Company will
continue to reassess whether it can reasonably estimate the level of effort required to fulfill its
obligations under the Roche alliance. In particular, when the Discovery Collaboration commences,
the Company may be able to make such an estimate. When, and if, the Company can make a reasonable
estimate of its remaining efforts under the collaboration, the Company would modify its method of
recognition and utilize a proportional performance method. As future substantive milestones are
achieved, a portion of the milestone payment, equal to the percentage of the performance period
completed when the milestone is achieved, multiplied by the amount of the milestone payment, will
be recognized as revenue upon achievement of such milestone. The remaining portion of the milestone
will be recognized over the remaining performance period on a straight-line basis.
Takeda Alliance
In May 2008, the Company entered into a license and collaboration agreement (the Takeda
Collaboration Agreement) with Takeda Pharmaceutical Company Limited (Takeda) to pursue the
development and commercialization of RNAi therapeutics. Under the Takeda Collaboration Agreement,
the Company granted Takeda a non-exclusive, worldwide, royalty-bearing license to the Companys
intellectual property to develop, manufacture, use and commercialize RNAi therapeutics, subject to
the Companys existing contractual obligations to third parties. The license initially is limited
to the fields of oncology and metabolic disease and may be expanded at Takedas option to include
other therapeutic areas, subject to specified conditions. Under the Takeda Collaboration Agreement,
Takeda will be the Companys exclusive platform partner in the Asian territory, as defined in the
Takeda Collaboration Agreement, for a period of five years.
In consideration for the rights granted to Takeda under the Takeda Collaboration Agreement,
Takeda agreed to pay the Company $150.0 million in upfront and near-term technology transfer
payments. In addition, the Company has the option, exercisable until the start of Phase III
development, to opt-in under a 50-50 profit sharing agreement to the development and
commercialization in the United States of up to four Takeda licensed products, and would be
entitled to opt-in rights for two additional products for each additional field expansion, if any,
elected by Takeda under the Takeda Collaboration Agreement. In June 2008, Takeda paid the Company
an upfront payment of $100.0 million. Takeda is also required to make the additional $50.0 million
in payments to the Company upon achievement of specified technology transfer milestones, $20.0
million of which was achieved in September 2008 and paid in October 2008, $20.0 million of which is
required to be paid upon achievement of specified technology transfer activities, but no later than
24 months after execution of the Takeda Collaboration Agreement, and $10.0 million of which is required
to be paid upon achievement of specified technology transfer
activities within 24 to 36 months after
execution of the Takeda Collaboration Agreement (collectively, the Technology Transfer
Milestones). If Takeda elects to expand its license to additional therapeutic areas, Takeda will
be required to pay the Company $50.0 million for each of up to approximately 20 total additional
fields selected, comprising substantially all other fields of human disease, as identified and
agreed upon by the parties. In addition, for each RNAi therapeutic product developed by Takeda, its
affiliates and sublicensees, if any, the Company is entitled to receive specified development and
commercialization milestones, totaling up to $171.0 million per product, together with royalty
payments based on worldwide annual net sales, if any.
Pursuant to the Takeda Collaboration Agreement, the Company and Takeda have also agreed to
collaborate on the research of RNAi therapeutics directed to one or two disease targets agreed to
by the parties (the Research Collaboration), subject to the Companys existing contractual
obligations with third parties. Takeda also has the option, subject to certain conditions, to
collaborate with the Company on the research and development of RNAi drug delivery technology for
targets agreed to by the parties. In addition, Takeda has a right of first negotiation for the
development and commercialization of the Companys RNAi therapeutic products in the Asian
territory, excluding the Companys ALN-RSV01 program. In addition to the 50-50 profit sharing
option, the Company has a similar right of first negotiation to participate with Takeda in the
development and commercialization in the United States of licensed products. The collaboration
between the Company and Takeda is governed by a joint technology transfer committee (the JTTC), a
joint research collaboration committee (the JRCC) and a joint delivery collaboration committee
(the JDCC), each of which is comprised of an equal number of representatives from each party.
8
The Company has determined that the deliverables under the Takeda agreement include the
license, the joint committees (the JTTC, JRCC and JDCC), the technology transfer activities and the
services that the Company will be obligated to perform under the Research Collaboration. The
Company has determined that, pursuant to EITF 00-21, the license and undelivered services (i.e.,
the joint committees and the Research Collaboration) are not separable and, accordingly, the
license and services are being treated as a single unit of accounting.
When multiple deliverables are accounted for as a single unit of accounting, the Company bases
its revenue recognition pattern on the final deliverable. Under the Takeda Collaboration Agreement,
the last elements to be delivered are the JDCC and JTTC services, each of which has a life of no
more than seven years. The Company is recognizing the upfront payment of $100.0 million, the first
Technology Transfer Milestone of $20.0 million and the $30.0 million of remaining Technology
Transfer Milestones, the receipt of which the Company believes is probable, on a straight-line
basis over seven years because the Company is unable to reasonably estimate the level of effort to
fulfill these obligations, primarily because the effort required under the Research Collaboration
is largely unknown. As future substantive milestones are achieved, a portion of the milestone
payment, equal to the percentage of the performance period completed when the milestone is
achieved, multiplied by the amount of the milestone payment, will be recognized as revenue upon
achievement of such milestone. The remaining portion of the milestone will be recognized over the
remaining performance period on a straight-line basis. The Company will continue to reassess
whether it can reasonably estimate the level of effort required to fulfill its obligations under
the Takeda Collaboration Agreement. When, and if, the Company can make a reasonable estimate of its
remaining efforts under the collaboration, the Company would modify its method of recognition and
utilize a proportional performance method.
In connection with the Takeda Collaboration Agreement, the Company paid $5.0 million of
license fees to the Companys licensors, primarily Isis Pharmaceuticals, Inc. (Isis), during
2008, in accordance with the applicable license agreements with those parties. These fees were
charged to research and development expense.
Discovery and Development Alliances
Novartis Broad Alliance
In the second half of 2005, the Company entered into a series of transactions with Novartis
Pharma AG and its affiliate, Novartis Institutes for BioMedical Research, Inc. (collectively,
Novartis). In September 2005, the Company and Novartis executed a stock purchase agreement (the
Stock Purchase Agreement) and an investor rights agreement (the Investor Rights Agreement). In
October 2005, in connection with the closing of the transactions contemplated by the Stock Purchase
Agreement, the Investor Rights Agreement became effective and the Company and Novartis executed a
research collaboration and license agreement (the Collaboration and License Agreement). The
Collaboration and License Agreement had an initial term of three years, with an option for two
additional one-year extensions at the election of Novartis. In July 2008, Novartis elected to
extend the initial term for an additional year, through October 2009. Novartis retains the right to
extend the term for a second additional year, which right must be exercised no later than July
2009.
Under the terms of the Stock Purchase Agreement, in October 2005, Novartis purchased 5,267,865
shares of the Companys common stock at a purchase price of $11.11 per share for an aggregate
purchase price of $58.5 million, which, after such issuance, represented 19.9% of the Companys
outstanding common stock as of the date of issuance. In addition, under the Investor Rights
Agreement, the Company granted Novartis rights to acquire additional equity securities in the event
that the Company proposes to sell or issue any equity securities, subject to specified exceptions,
as described in the Investor Rights Agreement, such that Novartis would be able to maintain its
then-current ownership percentage in the Companys outstanding common stock. Pursuant to terms of
the Investor Rights Agreement, in May 2008, Novartis purchased 213,888 shares of the Companys
common stock at a purchase price of $25.29 per share resulting in a payment to the Company of $5.4
million. In May 2009, Novartis purchased 65,922 shares of the Companys common stock at a purchase
price of $17.50 per share, resulting in a payment to the Company of
$1.2 million. This purchase allows Novartis to maintain
its ownership position of 13.4% of the Companys outstanding common stock. The
exercise of this right does not result in any changes to existing rights or any additional rights
to Novartis. Further, during the term described in the Investor Rights Agreement, Novartis is
permitted to own no more than 19.9% of the Companys outstanding shares.
Under the terms of the Collaboration and License Agreement, the parties will work together on
a defined number of selected targets, as defined in the Collaboration and License Agreement, to
discover and develop therapeutics based on RNAi. In consideration for the rights granted to
Novartis under the Collaboration and License Agreement, Novartis made upfront payments totaling
$10.0 million to the Company in October 2005, partly to reimburse prior costs incurred by the
Company to develop
in vivo
RNAi
9
technology. The Collaboration and License Agreement also includes terms under which Novartis
will provide the Company with research funding and milestone payments as well as royalties on
annual net sales of products resulting from the Collaboration and License Agreement, if any. The
amount of research funding provided by Novartis under the Collaboration and License Agreement
during the research term is dependent upon the number of active programs on which the Company is
collaborating with Novartis at any given time and the number of Company employees that are working
on those programs, in respect of which Novartis reimburses the Company at an agreed upon rate.
Under the terms of the Collaboration and License Agreement, Novartis has the right to select up to
30 exclusive targets to include in the collaboration, which number may be increased to 40 under
certain circumstances and upon additional payments. For RNAi therapeutic products successfully
developed under the Collaboration and License Agreement, if any, the Company would be entitled to
receive milestone payments upon achievement of certain specified development and annual net sales
events, up to an aggregate of $75.0 million per therapeutic product.
Under the terms of the Collaboration and License Agreement, the Company retains the right to
discover, develop, commercialize and manufacture compounds that function through the mechanism of
RNAi, or products that contain such compounds as an active ingredient, with respect to targets not
selected by Novartis for inclusion in the collaboration, provided that Novartis has a right of
first offer with respect to an exclusive license for additional targets before the Company partners
any of those additional targets with third parties.
The Collaboration and License Agreement also provides Novartis with a non-exclusive option to
integrate into its operations the Companys intellectual property relating to RNAi technology,
excluding any technology related to delivery of nucleic acid-based molecules (the Integration
Option). Novartis may exercise this Integration Option at any point during the research term, as
defined in the Collaboration and License Agreement. The research term expires in October 2009 and
may be extended until October 2010 at Novartis election. In connection with the exercise of the
Integration Option, Novartis would be required to make additional payments to the Company totaling
$100.0 million, payable in full at the time of exercise, which payments would include an option
exercise fee, a milestone based on the overall success of the collaboration and pre-paid milestones
and royalties that could become due as a result of future development of products using the
Companys technology. In addition, under this license grant, Novartis may be required to make
milestone and royalty payments to the Company in connection with the successful development and
commercialization of RNAi therapeutic products, if any. The license grant under the integration
option, if exercised by Novartis, would be structured similarly to the Companys non-exclusive
platform licenses with Roche and Takeda.
The Company initially deferred the non-refundable $10.0 million upfront payment and the $6.4
million premium received that represents the difference between the purchase price and the closing
price of the common stock of the Company on the date of the stock purchase from Novartis. These
payments, in addition to research funding and certain milestone payments, the receipt of which is
considered probable, are being amortized into revenue using the proportional performance method
over the estimated duration of the Collaboration and License Agreement or ten years. Under this
model, the Company estimates the level of effort to be expended over the term of the agreement and
recognizes revenue based on the lesser of the amount calculated based on proportional performance
of total expected revenue or the amount of non-refundable payments
earned. The Company recognized $2.7 million and $3.3 million in revenues in its condensed consolidated statements of operations for the three months ended March 31, 2009 and 2008, respectively, related to the Collaboration and License Agreement.
As future substantive milestones are achieved, and to the extent they are within the period of
performance, milestone payments will be recognized as revenue on a proportional performance basis
over the contracts entire performance period, starting with the contracts commencement. A portion
of the milestone payment, equal to the percentage of total performance completed when the milestone
is achieved, multiplied by the milestone payment, will be recognized as revenue upon achievement of
the milestone. The remaining portion of the milestone will be recognized over the remaining
performance period under the proportional performance method.
The Company believes the estimated period of performance under the Collaboration and License
Agreement includes the three-year term of the agreement, two one-year extensions at the election of
Novartis and limited support as part of a technology transfer until the fifth anniversary of the
termination of the agreement. In July 2008, Novartis elected to extend the initial term for an
additional year, through October 2009. The Company continues to use an expected term of ten years
in its proportional performance model. The Company reevaluates the expected term when new
information is known that could affect the Companys estimate. In the event the Companys period of
performance is different than estimated, revenue recognition will be adjusted on a prospective
basis.
Product Alliances
Kyowa Hakko Alliance
In June 2008, the Company entered into a license and collaboration agreement (the Kyowa Hakko
Agreement) with Kyowa
10
Hakko Kirin Co., Ltd. (Kyowa Hakko). Under the Kyowa Hakko Agreement, the Company granted Kyowa
Hakko an exclusive license to its intellectual property in Japan and other markets in Asia (the
Licensed Territory) for the development and commercialization of ALN-RSV01, an RNAi therapeutic
for the treatment of respiratory syncytial virus (RSV) infection, for which the Company is
currently conducting Phase II clinical trials. The Kyowa Hakko Agreement also covers additional
RSV-specific RNAi therapeutic compounds that comprise the ALN-RSV program (Additional Compounds).
The Company retains all development and commercialization rights worldwide outside of the Licensed
Territory.
Under the terms of the Kyowa Hakko Agreement, in June 2008, Kyowa Hakko paid the Company an
upfront cash payment of $15.0 million. In addition, Kyowa Hakko is required to make payments to the
Company upon achievement of specified development and sales milestones totaling up to $78.0
million, and royalty payments based on annual net sales, if any, of ALN-RSV01 by Kyowa Hakko, its
affiliates and sublicensees in the Licensed Territory.
The collaboration between Kyowa Hakko and the Company is governed by a joint steering
committee that is comprised of an equal number of representatives from each party. Under the
agreement, Kyowa Hakko is establishing a development plan for ALN-RSV01 relating to the development
activities to be undertaken in the Licensed Territory, with the initial focus on Japan. Kyowa Hakko
is responsible, at its expense, for all development activities under the development plan that are
reasonably necessary for the regulatory approval and commercialization of ALN-RSV01 in Japan and
the rest of the Licensed Territory. The Company will be responsible for supply of the product to
Kyowa Hakko under a supply agreement unless Kyowa Hakko elects, prior to the first commercial sale
of the product in the Licensed Territory, to manufacture the product itself or arrange for a third
party to manufacture the product.
The Company has determined that the deliverables under the Kyowa Hakko Agreement include the
license, the joint steering committee, the manufacturing services and any Additional Compounds. The
Company has determined that, pursuant to EITF 00-21, the individual deliverables are not separable
and, accordingly, must be accounted for as a single unit of accounting.
When multiple deliverables are accounted for as a single unit of accounting, the Company bases
its revenue recognition pattern on the final deliverable. The Company is currently unable to
reasonably estimate its period of performance under the Kyowa Hakko Agreement, as it is unable to
estimate the timeline of its deliverables related to the fixed-price option granted to Kyowa Hakko
for any Additional Compounds. The Company is deferring all revenue under the Kyowa Hakko Agreement
until it is able to reasonably estimate its period of performance. The Company will continue to
reassess whether it can reasonably estimate the period of performance to fulfill its obligations
under the Kyowa Hakko Agreement.
Cubist Alliance
In January 2009, the Company entered into a license and collaboration agreement (the Cubist
Agreement) with Cubist Pharmaceuticals, Inc. (Cubist) to develop and commercialize therapeutic
products (Licensed Products) based on certain of the Companys RNAi technology for the treatment
of RSV. Licensed Products include ALN-RSV01, as well as several other second-generation RNAi-based
RSV inhibitors, which currently are in pre-clinical studies.
Under the terms of the Cubist Agreement, the Company and Cubist will share responsibility for
developing Licensed Products in North America and will each bear one-half of the related
development costs. The Companys collaboration with Cubist for the development of Licensed Products
in North America will be governed by a joint steering committee (the JSC) comprised of an equal
number of representatives from each party. Cubist will have the sole right to commercialize
Licensed Products in North America with costs associated with such activities and any resulting
profits or losses to be split equally between the Company and Cubist. Throughout the rest of the
world (the Royalty Territory), excluding Asia, where the Company has previously partnered its
ALN-RSV program with Kyowa Hakko, Cubist will have an exclusive, royalty-bearing license to develop
and commercialize Licensed Products.
In consideration for the rights granted to Cubist under the Cubist Agreement, Cubist made a
$20.0 million upfront cash payment to the Company. Cubist also has an obligation under the Cubist
Agreement to pay the Company milestone payments, totaling up to an aggregate of $82.5 million, upon
the achievement of specified development and sales events in the Royalty Territory. In addition, if
Licensed Products are successfully developed, Cubist will be required to pay to the Company
royalties on net sales of Licensed Products in the Royalty Territory, if any, subject to
offsets under certain circumstances. Upon achievement of certain development milestones, the
Company will have the right to convert the North American co-development and profit sharing
arrangement into a royalty-bearing license and, in addition to royalties on net sales in North
America, will be entitled to receive additional milestone payments totaling up to an aggregate of
$130.0 million upon achievement of specified development and sales
11
events in North America, subject to the timing of the conversion by the Company and the regulatory
status of a Licensed Product at the time of conversion. If the Company makes the conversion to a
royalty-bearing license with respect to North America, then North America becomes part of the
Royalty Territory.
During the term of the Cubist Agreement, neither party nor its affiliates may develop,
manufacture or commercialize anywhere in the world, outside of Asia, a therapeutic or prophylactic
product that specifically targets RSV, except for Licensed Products developed, manufactured or
commercialized pursuant to the Cubist Agreement.
The Company has determined that the deliverables under the Cubist Agreement include the
licenses, technology transfer related to the ALN-RSV program, the JSC, and the development and
manufacturing services that the Company will be obligated to perform. The Company has determined
that, pursuant to EITF 00-21, the deliverables and undelivered services are not separable and,
accordingly, the licenses and services are being treated as a single unit of accounting.
When multiple deliverables are accounted for as a single unit of accounting, the Company bases
its revenue recognition pattern on the final deliverable. Under the Cubist Agreement, the last
element to be delivered is the JSC service, which has an expected life of no more than seven years.
The Company is recognizing the upfront payment of $20.0 million on a straight-line basis over seven
years because the Company is unable to reasonably estimate the level of effort to fulfill its
performance obligations. As future substantive milestones are achieved, a portion of the milestone
payment, equal to the percentage of the performance period completed when the milestone is
achieved, multiplied by the amount of the milestone payment, will be recognized as revenue upon
achievement of such milestone. The remaining portion of the milestone will be recognized over the
remaining performance period on a straight-line basis. The Company will continue to reassess
whether it can reasonably estimate the level of effort required to fulfill its obligations under
the Cubist Agreement. When, and if, the Company can make a reasonable estimate of its remaining
efforts under the collaboration, the Company would modify its method of recognition and utilize a
proportional performance method.
Under the terms of the Cubist Agreement, the Company and Cubist will share responsibility for
developing Licensed Products in North America and will each bear one-half of the related
development costs. For revenue generating arrangements that involve
cost sharing between both parties, the Company applies the provisions of
EITF 07-1. EITF 07-1 requires collaborators to present the results of activities for which they act
as the principal on a gross basis and report any payments received from (made to) other
collaborators based on other applicable GAAP or, in the absence of other applicable GAAP,
analogy to authoritative accounting literature or a reasonable, rational and consistently applied
accounting policy election. As the Company is not considered the principal in this agreement,
pursuant to EITF 07-1, the Company will record any amounts due from Cubist as a reduction of
research and development costs. For the three months ended March 31,
2009, the Company and Cubist incurred $3.6 million under the Cubist
Agreement. Amounts due from Cubist of $1.8 million have been recorded
as a reduction of research and development expense. As such, the
Company recorded net research and development expenses of $1.8
million in its condensed consolidated statements of operations for
the three months ended March 31, 2009.
Government Funding
NIH Contract
In September 2006, the National Institute of Allergy and Infectious Diseases (NIAID) awarded
the Company a contract for up to $23.0 million over four years to advance the development of a
broad spectrum RNAi anti-viral therapeutic for hemorrhagic fever virus, including the Ebola virus.
Of the $23.0 million in funding, the government initially committed to pay the Company up to $14.2
million over the first two years of the contract. In June 2008, as a result of the progress of the
program, the government awarded the Company an additional $7.5 million, to be paid through
September 2009 for the third year of the contract, together with any remaining funds carried over
from the funding allocated for the first two years of the contract. The Company recognizes revenue
under government cost reimbursement contracts as it performs the underlying research and
development activities.
Department of Defense Contract
In August 2007, the Defense Threat Reduction Agency (DTRA) of the United States Department
of Defense awarded the Company a contract to advance the development of a broad spectrum RNAi
anti-viral therapeutic for hemorrhagic fever virus. The government initially committed to pay the
Company up to $10.9 million through February 2009, which included a six-month extension granted by
DTRA in July 2008. Following a program review in early 2009, the Company and DTRA have determined
not to continue this program and accordingly, the remaining funds of up to $27.7 million will not
be accessed. The Company recognizes revenue under government cost reimbursement contracts as it
performs the underlying research and development activities.
12
3. INCOME TAXES
During the three months ended March 31, 2009, the Company recorded a provision for income
taxes of $0.7 million. The Company records income tax expense for federal alternative minimum tax,
state and foreign taxes. The Company expects to generate U.S. taxable income during 2009 due to
the recognition of certain proceeds received from the Takeda alliance. The Companys U.S. taxable
income is expected to be offset by net operating loss carryforwards and other deferred tax
attributes. However, the Company will continue to be subject to federal alternative minimum tax
and state income taxes.
At December 31, 2008, the Company recorded net deferred tax assets to the extent it is more
likely than not that the assets will be utilized. These deferred tax assets were related to the
recognition of Roche revenue for tax purposes. The Company expects the recognition of certain
deferred tax attributes to generate net operating losses in 2010 and 2011 that will be carried back
to 2008 and 2009 to offset taxable income. The remaining deferred tax assets are subject to a
valuation allowance as it is more likely than not that those assets will not be realized.
At December 31, 2008, the state net operating loss carryforward was $8.6 million and the state
research and development tax credit carryforward was $0.5 million. These attributes are available
to reduce future tax liabilities and expire at various dates through 2023. Ownership changes, as
defined in the Internal Revenue Code of 1986, as amended (the Code), including those resulting
from the issuance of common stock in connection with the Companys public offerings, may limit the
amount of net operating loss and tax credit carryforwards that can be utilized to offset future
taxable income or tax liability. The Company has determined that there is no limitation on the
utilization of net operating loss and tax credit carryforwards in accordance with Section 382 of
the Code in 2008.
On January 1, 2007, the Company adopted the provisions of FASB Interpretation No. 48,
Accounting for Uncertainty in Income Taxes an interpretation of FASB Statement 109
(FIN 48),
which was issued in July 2006. The implementation of FIN 48 did not result in any adjustment to the
Companys beginning tax positions. The Company continues to recognize fully its tax benefits which
are offset by a valuation allowance to the extent that it is more likely than not that the deferred
tax assets will not be realized. At March 31, 2009, the Company had an unrecognized tax benefit of
$0.3 million.
4. REGULUS THERAPEUTICS INC.
In September 2007, the Company and Isis established Regulus, a company focused on the
discovery, development and commercialization of microRNA-based therapeutics, a potential new class
of drugs to treat the pathways of human disease. Regulus, which was initially established as a
limited liability company, converted to a C corporation in January 2009 and changed its name to
Regulus Therapeutics Inc. In consideration for the Companys and Isis initial interests in
Regulus, the Company and Isis each granted Regulus exclusive licenses to its intellectual property
for certain microRNA-based therapeutic applications as well as certain patents in the microRNA
field. In addition, the Company made an initial cash contribution to Regulus of $10.0 million,
resulting in the Company and Isis making initial capital contributions to Regulus of approximately
equal aggregate value. Additionally, in March 2009, the Company and Isis each purchased $10.0
million of Series A preferred stock of Regulus under a founders investor rights agreement (the
Investor Rights Agreement). The Company and Isis
currently own approximately 49% and 51%, respectively, of
Regulus and there are currently no other third party investors in
Regulus. Regulus continues to operate as an independent company
with a separate board of directors, scientific advisory board and management team, some of whom
have options to purchase common stock of Regulus. Members of the board of
directors of Regulus who are employees of the Company or Isis are not
eligible to receive options to purchase Regulus common stock.
The Company, Isis and Regulus also have entered into a license and collaboration agreement
(the Regulus Collaboration Agreement) to pursue the discovery, development and commercialization
of therapeutic products directed to microRNAs. Under the terms of the Regulus Collaboration
Agreement, the Company and Isis each assigned to Regulus specified patents and contracts covering
microRNA-specific technology. In addition, each of the Company and Isis granted to Regulus an
exclusive, worldwide license under its rights to other microRNA-related patents and know-how to
develop and commercialize therapeutic products containing compounds that are designed to interfere
with or inhibit a particular microRNA, subject to the Companys and Isis existing contractual
obligations to third parties. Regulus was also granted the right to request a license from the
Company and Isis to develop and commercialize therapeutic products directed to other microRNA
compounds, which license is subject to the Companys and Isis approval and to each such partys
existing contractual obligations to third parties. Regulus also granted to the Company and Isis an
exclusive license to technology developed or acquired by Regulus for use solely within the
Companys and Isis respective fields (as defined in the Regulus Collaboration Agreement), but
specifically excluding the right to develop, manufacture or commercialize the therapeutic products
for which the Company and Isis granted rights to Regulus.
The Company and Isis have also executed a services agreement (the Services Agreement) with
Regulus. Under the terms of
13
the Services Agreement, the Company and Isis provide to Regulus, for the benefit of Regulus,
certain research and development and general and administrative services for which they are paid by
Regulus.
In April 2008, Regulus entered into a worldwide strategic alliance with GlaxoSmithKline
(GSK) to discover, develop and commercialize up to four novel microRNA-targeted therapeutics to
treat inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. In
connection with this alliance, Regulus received $20.0 million in upfront payments from GSK,
including a $15.0 million option fee and a loan of $5.0 million evidenced by a promissory note
(guaranteed by Isis and the Company) that will convert into Regulus common stock under certain
specified circumstances. Regulus could be eligible to receive development, regulatory and sales
milestone payments for each of the microRNA-targeted therapeutics discovered and developed as part
of the alliance. Regulus would also receive royalty payments on worldwide sales of products
resulting from the alliance.
The Company has concluded that Regulus qualifies as a variable interest entity under FASB
Interpretation No. 46R,
Consolidation of Variable Interest Entities an interpretation of
Accounting Research Bulletin No. 51
(FIN 46R). The Investor Rights Agreement contains transfer
restrictions on each of Isis and the Companys interests and, as a result, Isis and the Company
are considered related parties under paragraph 16(d)(1) of FIN 46R. The Company has assessed which
entity would be considered the primary beneficiary under FIN 46R and has concluded that Isis is the
primary beneficiary and, accordingly, the Company has not consolidated Regulus.
The Company accounts for its investment in Regulus using the equity method of accounting.
Through December 31, 2008, the Company was recognizing the first $10.0 million of losses of Regulus
as equity in loss of joint venture (Regulus Therapeutics Inc.) in its condensed consolidated statements of operations
because the Company was responsible for funding those losses through its initial $10.0 million cash
contribution. Beginning in January 2009, in connection with the conversion of Regulus to a C
corporation, the Company is recognizing approximately 49% of the
income and losses of Regulus. The carrying value of the Companys
investment in joint venture (Regulus Therapeutics LLC) immediately
prior to the conversion to a C corporation exceeded 49% of the net assets of Regulus by approximately $0.8 million.
Upon conversion, this amount was allocated to the intellectual
property of Regulus and, because the intellectual property was
determined to be in-process research and development, the $0.8
million was recorded as a charge to expense. This charge was included
in equity in loss of joint venture (Regulus Therapeutics Inc.) in
the condensed consolidated statements of operations for the three
months ended March 31, 2009. Under the equity method, the
reimbursement of expenses to the Company is recorded as a reduction to research and development
expenses. At March 31, 2009, the Companys investment in the joint venture was $9.7 million, which
is recorded as an investment in joint venture (Regulus Therapeutics Inc.) in the condensed consolidated balance
sheets under the equity method. Summary results of Regulus operations for the three months ended
March 31, 2009 and 2008 and balance sheets as of March 31, 2009 and December 31, 2008 are presented
in the tables below, in thousands:
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended
|
|
|
|
March 31,
|
|
|
|
2009
|
|
|
2008
|
|
Statement of Operations Data:
|
|
|
|
|
|
|
|
|
Net revenues
|
|
$
|
638
|
|
|
$
|
92
|
|
Operating expenses (1)
|
|
|
2,515
|
|
|
|
1,993
|
|
|
|
|
|
|
|
|
Loss from operations
|
|
|
(1,877
|
)
|
|
|
(1,901
|
)
|
Other income
|
|
|
19
|
|
|
|
82
|
|
|
|
|
|
|
|
|
Net loss
|
|
$
|
(1,858
|
)
|
|
$
|
(1,819
|
)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
(1) Non-cash stock-based compensation
included in operating expenses
|
|
$
|
(310
|
)
|
|
$
|
375
|
|
|
|
|
|
|
|
|
|
|
|
|
March 31,
|
|
December 31,
|
|
|
2009
|
|
2008
|
Balance Sheet Data:
|
|
|
|
|
|
|
|
|
Cash and cash equivalents
|
|
$
|
37,768
|
|
|
$
|
22,411
|
|
Working capital
|
|
|
33,420
|
|
|
|
16,467
|
|
Total assets
|
|
|
39,171
|
|
|
|
23,678
|
|
Note payable
|
|
|
5,219
|
|
|
|
5,179
|
|
Total stockholders equity
|
|
|
19,577
|
|
|
|
1,745
|
|
5. SUBSEQUENT EVENT
In April 2009, the Company and Isis amended and restated their existing strategic
collaboration and license agreement (as amended and restated, the Amended and Restated Isis
Agreement). As part of the Amended and Restated Isis Agreement, the Company and Isis have
expanded their collaborative efforts to focus on the development of single-stranded RNAi (ssRNAi)
technology. Under the Amended and Restated Isis Agreement, the Company obtained from Isis
a co-exclusive, worldwide
14
license to Isis current and future patents and patent applications relating to chemistry and
RNA-targeting mechanisms to research, develop and commercialize ssRNAi products for a limited
number of gene targets to be designated by the Company. Each of the Company and Isis will have the
opportunity to discover and develop drugs employing the ssRNAi technology. In addition to entering
into the new collaboration, the Company and Isis also agreed to extend the broad cross-licensing
arrangement regarding double-stranded RNAi that was established in 2004.
Under the terms of the Amended and Restated Isis Agreement, the Company will potentially pay
Isis up to an aggregate of $31.0 million in license fees, payable in four tranches, that include
$11.0 million on signing, $10.0 million 18 months
following signing, or if and when
in vivo
efficacy
in rodents is demonstrated if sooner, $5.0 million upon achievement of
in vivo
efficacy in non-human
primates, and $5.0 million upon initiation of the first clinical
trial with an ssRNAi drug, subject to the Companys right to unilaterally terminate the research program. The
Company will fund research activities at a minimum of $3.0 million each year for three years with
research development activities conducted by both the Company and Isis. If the Company develops and
commercializes drugs utilizing ssRNAi technology on its own or with a partner, Isis could
potentially receive milestone payments, totaling up to
$18.5 million per product, as well as royalties.
Also, initially, Isis is eligible to receive up to 50 percent of any sublicense payments
due to the Company from a third party based on the Companys partnering of ssRNAi products, which
amount will decline over time as the Companys investment in the technology and drugs increases. In
turn, the Company is eligible to receive up to five percent of any sublicense payments due to Isis
from a third party based on Isis partnering of ssRNAi products.
The Company has the unilateral right to terminate the research program before September 30,
2010, in which event any licenses to ssRNAi products granted by Isis to the Company under the
Amended and Restated Isis Agreement, and any obligation thereunder by the Company to pay milestone
payments, royalties or sublicense payments to Isis for such ssRNAi products, would also terminate.
15
ITEM 2. MANAGEMENTS DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
This Quarterly Report on Form 10-Q contains forward-looking statements that involve risks and
uncertainties. The statements contained in this Quarterly Report on Form 10-Q that are not purely
historical are forward-looking statements within the meaning of Section 27A of the Securities Act
of 1933 and Section 21E of the Securities Exchange Act of 1934. Without limiting the foregoing, the
words may, will, should, could, expects, plans, intends, anticipates, believes,
estimates, predicts, potential, continue, target and similar expressions are intended to
identify forward-looking statements. All forward-looking statements included in this Quarterly
Report on Form 10-Q are based on information available to us up to, and including, the date of this
document, and we assume no obligation to update any such forward-looking statements. Our actual
results could differ materially from those anticipated in these forward-looking statements as a
result of certain important factors, including those set forth below under this Item 2
Managements Discussion and Analysis of Financial Condition and Results of Operations, Part II,
Item 1A Risk Factors and elsewhere in this Quarterly Report on Form 10-Q. You should carefully
review those factors and also carefully review the risks outlined in other documents that we file
from time to time with the Securities and Exchange Commission, or SEC.
Overview
We are a biopharmaceutical company developing novel therapeutics based on RNA interference, or
RNAi. RNAi is a naturally occurring biological pathway within cells for selectively silencing and
regulating the expression of specific genes. Since many diseases are caused by the inappropriate
activity of specific genes, the ability to silence genes selectively through RNAi could provide a
new way to treat a wide range of human diseases. We believe that drugs that work through RNAi have
the potential to become a broad new class of drugs, like small molecule, protein and antibody
drugs. Using our intellectual property and the expertise we have built in RNAi, we are developing a
set of biological and chemical methods and know-how that we apply in a systematic way to develop
RNAi therapeutics for a variety of diseases.
We are applying our technological expertise to build a pipeline of RNAi therapeutics to
address significant medical needs, many of which cannot effectively be addressed with small
molecules or antibodies, the current major classes of drugs. Our lead RNAi therapeutic program,
ALN-RSV01, is in Phase II clinical trials for the treatment of human respiratory syncytial virus,
or RSV, infection, which is reported to be the leading cause of hospitalization in infants in the
United States and also occurs in the elderly and in immune compromised adults. In February 2008,
we reported positive results from our Phase II experimental RSV infection clinical trial, referred
to as the GEMINI study. The GEMINI study was designed to evaluate the safety, tolerability and
anti-viral activity of ALN-RSV01. In this study, ALN-RSV01 was found to be safe and well tolerated
and demonstrated statistically significant anti-viral activity, including an approximately 40%
reduction in viral infection and a 95% increase in infection-free patients (p<0.01), as compared
to placebo. In April 2008, we initiated a second Phase II human clinical trial, which is currently
ongoing, to assess the safety and tolerability of aerosolized ALN-RSV01 versus placebo in adult
lung transplant patients naturally infected with RSV. We have formed collaborations with Cubist
Pharmaceuticals, Inc., or Cubist, and Kyowa Hakko Kirin Co., Ltd., or Kyowa Hakko, for the
development and commercialization of products for RSV. We will jointly develop and commercialize
products for RSV with Cubist in North America, Cubist has responsibility for developing and
commercializing these products in the rest of the world outside of Asia, and Kyowa Hakko has the
responsibility for developing and commercializing these products in Asia.
In December 2008, we submitted an investigational new drug application, or IND, to the United
States Food and Drug Administration, or FDA, for ALN-VSP, our first systemically delivered RNAi
therapeutic candidate. We are developing ALN-VSP for the treatment of liver cancers, including
hepatocellular carcinoma and other solid tumors with liver involvement. We received clearance from
the FDA in January 2009 and initiated the Phase I study in March 2009. The Phase I study, being
conducted in the United States, is a multi-center, open label, dose escalation study to evaluate
the safety, tolerability, pharmacokinetics and pharmacodynamics of intravenous ALN-VSP in
approximately 55 patients with advanced solid tumors with liver involvement, who have failed to
respond to or have progressed after standard treatment.
We are also working on a number of programs in pre-clinical development, including:
|
|
|
ALN-PCS, an RNAi therapeutic targeting a gene called proprotein convertase
subtilisin/kexin type 9, or PCSK9, for the treatment of hypercholesterolemia;
|
|
|
|
|
ALN-TTR, an RNAi therapeutic candidate targeting the transthyretin, or TTR, gene
for the treatment of TTR amyloidosis, which we advanced to a development program during
2008; and
|
16
|
|
|
ALN-HTT, an RNAi therapeutic for the treatment of Huntingtons disease, which we
are developing in collaboration with Medtronic, Inc., or Medtronic.
|
In addition to these development efforts, we are conducting research activities to discover
RNAi therapeutics to treat various diseases. The diseases for which we have discovery programs
include: viral hemorrhagic fever, including the Ebola virus, which can cause severe, often fatal
infection and poses a potential biological safety risk and bioterrorism threat; progressive
multifocal leukoencephalopathy, or PML, which is a disease of the central nervous system caused by
viral infection in immune compromised patients; and Parkinsons disease, a progressive brain
disease which is characterized by uncontrollable tremor, and in some cases, may result in dementia.
We are also pursuing many other undisclosed internal programs.
In addition to these programs, as part of our collaborations with Novartis Pharma AG, or
Novartis, and Takeda Pharmaceutical Company Limited, or Takeda, we have research activities to
discover RNAi therapeutics directed to a number of undisclosed targets. Our alliance with F.
Hoffmann-La Roche Ltd, or Roche, also contemplates such research activities.
We are working internally and with third-party collaborators to develop capabilities to
deliver our RNAi therapeutics directly to specific sites of disease, such as the delivery of
ALN-RSV01 to the lungs, which we refer to as Direct RNAi. We also are working to extend our
capabilities to advance the development of RNAi therapeutics that are administered by intravenous,
subcutaneous or intramuscular approaches, which we refer to as Systemic RNAi. We have numerous RNAi
therapeutic delivery collaborations and intend to continue to collaborate with government, academic
and corporate third parties to evaluate different delivery options, including with respect to
Direct RNAi and Systemic RNAi. For example, in May of 2007, we entered into an agreement with the
Massachusetts Institute of Technology, or MIT, Center for Cancer Research under which we are
sponsoring an exclusive five-year research program focused on the delivery of RNAi therapeutics. In
addition, during 2007, we obtained an exclusive worldwide license to the liposomal delivery
formulation technology of Tekmira Pharmaceuticals Corporation, or Tekmira, for the discovery,
development and commercialization of lipid-based nanoparticle formulations for the delivery of RNAi
therapeutics. In May 2008, Tekmira acquired Protiva Biotherapeutics Inc., or Protiva. In connection
with this acquisition, we entered into new agreements with Tekmira and Protiva, which provide us
access to key existing and future technology and intellectual property for the systemic delivery of
RNAi therapeutics with liposomal delivery technologies. Under the new agreements with Tekmira and
Protiva, we continue to have exclusive rights to the Semple (U.S. Patent No. 6,858,225) and Wheeler
(U.S. Patent Nos. 5,976,567 and 6,815,432) patents for RNAi, which we believe are critical for the
use of cationic liposomal delivery technology.
As noted above, we are developing ALN-VSP, a systemically delivered RNAi therapeutic
candidate, for the treatment of liver cancers, including hepatocellular carcinoma and other solid
tumors with liver involvement. ALN-VSP comprises two siRNAs formulated using stable nucleic
acid-lipid particles, or SNALP, technology from Tekmira. We also have rights to use SNALP
technology in the advancement of our other systemically delivered RNAi therapeutic programs,
including ALN-PCS for the treatment of hypercholesterolemia and ALN-TTR for the treatment of TTR
amyloidosis.
We rely on the strength of our intellectual property portfolio relating to the development and
commercialization of small interfering RNAs, or siRNAs, as therapeutics. This includes ownership
of, or exclusive rights to, issued patents and pending patent applications claiming fundamental
features of siRNAs and RNAi therapeutics as well as those claiming crucial chemical modifications
and promising delivery technologies. We believe that no other company possesses a portfolio of such
broad and exclusive rights to the patents and patent applications required for the
commercialization of RNAi therapeutics. Given the importance of our intellectual property portfolio
to our business operations, we intend to vigorously enforce our rights and defend against any
challenges that have arisen or may arise in this area.
In addition, our expertise in RNAi therapeutics and broad intellectual property estate have
allowed us to form alliances with leading companies, including Isis Pharmaceuticals, Inc., or Isis,
Medtronic, Novartis, Biogen Idec Inc., or Biogen Idec, Roche, Takeda, Kyowa Hakko and Cubist. In
April 2009, we expanded our existing agreement with Isis to focus on the development of
single-stranded RNAi, or ssRNAi, technology. We have also entered into contracts with government
agencies, including the National Institute of Allergy and Infectious Diseases, or NIAID, a
component of the National Institutes of Health, or NIH. We have established collaborations with
and, in some instances, received funding from major medical and disease associations. Finally, to
further enable the field and monetize our intellectual property rights, we also grant licenses to
biotechnology companies for the development and commercialization of RNAi therapeutics for
specified targets in which we have no direct strategic interest under our InterfeRx
tm
program and to research companies that commercialize RNAi reagents or services under our research
product licenses.
We also seek opportunities to form new ventures in areas outside our core strategic focus. For
example, in 2007, we and Isis
17
established Regulus Therapeutics Inc., formerly Regulus Therapeutics
LLC, or Regulus, a company focused on the discovery, development and commercialization of
microRNA-based therapeutics. Because microRNAs are believed to regulate whole networks of genes
that can be involved in discrete disease processes, microRNA-based therapeutics represent a
possible new approach to target the pathways of human disease. Given the broad applications for
RNAi technology, we believe additional opportunities exist for new ventures to be formed.
As noted above, in January 2009, we entered into a license and collaboration agreement with
Cubist to develop and commercialize therapeutic products based on certain of our RNAi technology
for the treatment of RSV. Under the Cubist agreement, licensed products include ALN-RSV01, which
is currently in Phase II clinical development for the treatment of RSV infection in adult lung
transplant patients, as well as several other second-generation RNAi-based RSV inhibitors, which
currently are in pre-clinical studies. Under the terms of the Cubist agreement, we and Cubist will
share responsibility for developing licensed products in North America and will each bear one-half
of the related development costs. Cubist will have the sole right to commercialize licensed
products in North America with costs associated with such activities and any resulting profits or
losses to be split equally between the us and Cubist. Throughout the rest of the world, excluding
Asia, where we have partnered our ALN-RSV program with Kyowa Hakko, Cubist will have an exclusive,
royalty-bearing license to develop and commercialize licensed products. In consideration for the
rights granted to Cubist under the Cubist agreement, Cubist made a $20.0 million upfront cash
payment to us. Cubist also has an obligation to pay us milestone payments, totaling up to an
aggregate of $82.5 million, upon the achievement of specified development and sales events in the
royalty territory. In addition, if licensed products are successfully developed, Cubist will be
required to pay us double digit royalties on net sales of licensed products in the royalty
territory, if any, subject to offsets under certain circumstances. A more complete description of
the Cubist agreement is set forth below under Strategic Alliances.
We commenced operations in June 2002. We have focused our efforts since inception primarily on
business planning, research and development, acquiring, filing and expanding intellectual property
rights, recruiting management and technical staff, and raising capital. Since our inception, we
have generated significant losses. As of March 31, 2009, we had an accumulated deficit of $260.1
million. Through March 31, 2009, we have funded our operations primarily through the net proceeds
from the sale of equity securities and payments we have received under strategic alliances. Through
March 31, 2009, a substantial portion of our total net revenues have been collaboration revenues
derived from our strategic alliances with Roche, Takeda and Novartis, and from the United States
government in connection with our development of treatments for hemorrhagic fever viruses,
including Ebola. We expect our revenues to continue to be derived primarily from new and existing
strategic alliances, government and foundation funding and license fee revenues.
We currently have programs focused in a number of therapeutic areas. However, we are unable to
predict when, if ever, we will successfully develop or be able to commence sales of any product. We
have never achieved profitability on an annual basis and we expect to incur additional losses over
the next several years. We expect our net losses to continue due primarily to research and
development activities relating to our drug development programs, collaborations and other general
corporate activities. We anticipate that our operating results will fluctuate for the foreseeable
future. Therefore, period-to-period comparisons should not be relied upon as predictive of the
results in future periods. Our sources of potential funding for the next several years are expected
to be derived primarily from payments under new and existing strategic alliances, which may include
license and other fees, funded research and development payments and milestone payments, government
and foundation funding and proceeds from the sale of equity.
Research and Development
Since our inception, we have focused on drug discovery and development programs. Research and
development expenses represent a substantial percentage of our total operating expenses. Our most
advanced program is focused on the treatment of RSV infection and is in Phase II clinical studies.
In January 2009, we received clearance from the FDA to proceed with a Phase I study of ALN-VSP for
the treatment of patients with advanced solid tumors with liver involvement. We initiated our
ALN-VSP Phase I study in March 2009. Our other development programs are focused on the treatment
of hypercholesterolemia, TTR amyloidosis and Huntingtons disease. In addition to these
development programs, we have discovery programs to develop RNAi therapeutics for the treatment of
a broad range of diseases, such as viral hemorrhagic fever, including the Ebola virus, PML,
Parkinsons disease and many other undisclosed programs, as well as several other diseases that are
the subject of our strategic alliances. We are also working internally and with third-party
collaborators to develop capabilities to deliver our RNAi therapeutics both directly to the
specific sites of disease and systemically, and we intend to continue to collaborate with
government, academic and corporate third parties to evaluate different delivery options.
There is a risk that any drug discovery or development program may not produce revenue for a
variety of reasons, including
the possibility that we will not be able to adequately demonstrate the safety and efficacy of
the product candidate. Moreover, there are
18
uncertainties specific to any new field of drug discovery, including RNAi. The successful development of any product candidate we develop is highly
uncertain. Due to the numerous risks associated with developing drugs, we cannot reasonably
estimate or know the nature, timing and estimated costs of the efforts necessary to complete the
development of, or the period, if any, in which material net cash inflows will commence from, any
potential product candidate. These risks include the uncertainty of:
|
|
|
our ability to progress product candidates into pre-clinical and clinical trials;
|
|
|
|
|
the scope, rate and progress of our pre-clinical trials and other research and
development activities, including those related to developing safe and effective ways of
delivering siRNAs into cells and tissues;
|
|
|
|
|
the scope, rate of progress and cost of any clinical trials we commence;
|
|
|
|
|
clinical trial results;
|
|
|
|
|
the cost of filing, prosecuting, defending and enforcing any patent claims and other
intellectual property rights;
|
|
|
|
|
the terms, timing and success of any collaborative, licensing and other arrangements that we
may establish;
|
|
|
|
|
the cost, timing and success of regulatory filings and approvals or potential
changes in regulations that govern our industry or the way in which they are interpreted
or enforced;
|
|
|
|
|
the cost and timing of establishing sufficient sales, marketing and distribution
capabilities;
|
|
|
|
|
the cost and timing of establishing sufficient clinical and commercial supplies
of any products that we may develop; and
|
|
|
|
|
the effect of competing technological and market developments.
|
Any failure to complete any stage of the development of any potential products in a timely
manner could have a material adverse effect on our operations, financial position and liquidity. A
discussion of some of the risks and uncertainties associated with completing our projects on
schedule, or at all, and the potential consequences of failing to do so, are set forth in Part II,
Item 1A below under the heading Risk Factors.
Strategic Alliances
A significant component of our business plan is to enter into strategic alliances and
collaborations with pharmaceutical and biotechnology companies, academic institutions, research
foundations and others, as appropriate, to gain access to funding, capabilities, technical
resources and intellectual property to further our development efforts and to generate revenues.
Our collaboration strategy is to form (1) non-exclusive platform alliances where our collaborators
obtain access to our capabilities and intellectual property to develop their own RNAi therapeutic
products; and (2) 50-50 co-development and/or ex-U.S. market geographic partnerships on specific
RNAi therapeutic programs. We have entered into broad, non-exclusive platform license agreements
with Roche and Takeda, under which we will also collaborate with each of Roche and Takeda on RNAi
drug discovery for one or more disease targets. We are pursuing 50-50 co-development programs with
Cubist and Medtronic for the development and commercialization of ALN-RSV and ALN-HTT,
respectively. In addition, we have entered into a product alliance with Kyowa Hakko for the
development and commercialization of ALN-RSV in territories not covered by the Cubist agreement,
which include Japan and other markets in Asia. We also have discovery and development alliances
with Isis, Novartis and Biogen Idec.
We also seek opportunities to form new ventures in areas outside our core strategic focus. For
example, we formed Regulus, together with Isis, to capitalize on our technology and intellectual
property in the field of microRNA-based therapeutics. Given the broad applications for RNAi
technology, we believe additional opportunities exist for new ventures to be formed.
To generate revenues from our intellectual property rights, we also grant licenses to
biotechnology companies under our InterfeRx program for the development and commercialization of
RNAi therapeutics for specified targets in which we have no direct strategic interest. We also
license key aspects of our intellectual property to companies active in the research products and
services market, which includes the manufacture and sale of reagents. Our InterfeRx and research
product licenses aim to generate modest near-term revenues that we can re-invest in the development
of our proprietary RNAi therapeutics pipeline. As of March 31, 2009, we had granted such licenses,
on both an exclusive and nonexclusive basis, to approximately 20
companies.
19
Since delivery of RNAi therapeutics remains a major objective of our research activities, we
also look to form collaboration and licensing agreements with other companies and academic
institutions to gain access to delivery technologies. For example, we have formed agreements with
Tekmira and MIT, among others, to focus on various delivery strategies. We have also entered into
license agreements with Isis, Max Planck Innovation, Tekmira and MIT, as well as a number of other
entities, to obtain rights to important intellectual property in the field of RNAi. In April 2009,
we expanded our existing agreement with Isis to focus on the development of ssRNAi technology.
Finally, we seek funding for the development of our proprietary RNAi therapeutics pipeline
from foundations and government sources. In 2006, NIAID awarded us a contract to advance the
development of a broad spectrum RNAi anti-viral therapeutic against hemorrhagic fever virus,
including the Ebola virus. In 2007, the Defense Threat Reduction Agency, or DTRA, an agency of the
United States Department of Defense, awarded us a contract to advance the development of a broad
spectrum RNAi anti-viral therapeutic for hemorrhagic fever virus, which contract ended in February
2009. In addition, we have obtained funding for pre-clinical discovery programs from organizations
such as The Michael J. Fox Foundation.
Cubist Alliance.
In January 2009, we entered into a license and collaboration agreement with
Cubist to develop and commercialize therapeutic products based on certain of our RNAi technology
for the treatment of RSV, including ALN-RSV01, which is currently in Phase II clinical trials for
the treatment of RSV infection in adult lung transplant patients, as well as several other
second-generation RNAi-based RSV inhibitors, which currently are in pre-clinical studies.
Under the terms of the Cubist agreement, we and Cubist will share responsibility for
developing licensed products in North America and will each bear one-half of the related
development costs. Our collaboration with Cubist for the development of licensed products in North
America will be governed by a joint steering committee comprised of an equal number of
representatives from each party. Cubist will have the sole right to commercialize licensed products
in North America with costs associated with such activities and any resulting profits or losses to
be split equally between us and Cubist. Throughout the rest of the world, referred to as the
Royalty Territory, excluding Asia, where we have previously partnered our ALN-RSV program with
Kyowa Hakko, Cubist will have an exclusive, royalty-bearing license to develop and commercialize
licensed products.
In consideration for the rights granted to Cubist under the agreement, in January 2009, Cubist
paid us an upfront cash payment of $20.0 million. Cubist also has an obligation under the agreement
to pay us milestone payments, totaling up to an aggregate of $82.5 million, upon the achievement of
specified development and sales events in the Royalty Territory. In addition, if licensed products
are successfully developed, Cubist will be required to pay us double digit royalties on net sales
of licensed products in the Royalty Territory, if any, subject to offsets under certain
circumstances. Upon achievement of certain development milestones, we will have the right to
convert the North American co-development and profit sharing arrangement into a royalty-bearing
license and, in addition to royalties on net sales in North America, will be entitled to receive
additional milestone payments totaling up to an aggregate of $130.0 million upon achievement of
specified development and sales events in North America, subject to the timing of the conversion by
us and the regulatory status of a licensed product at the time of conversion. If we make the
conversion to a royalty-bearing license with respect to North America, then North America becomes
part of the Royalty Territory. Due to the uncertainty of pharmaceutical development and the high
historical failure rates generally associated with drug development, we may not receive any
milestone or royalty payments from Cubist.
Unless terminated earlier in accordance with the agreement, the agreement expires on a
country-by-country and licensed product-by-licensed product basis, (a) with respect to the Royalty
Territory, upon the latest to occur of (1) the expiration of the last-to-expire Alnylam patent
covering a licensed product, (2) the expiration of the Regulatory-Based Exclusivity Period (as
defined in the Cubist agreement) and (3) ten years from first commercial sale in such country of
such licensed product by Cubist or its affiliates or sublicensees, and (b) with respect to
North America, if we have not converted North America into the Royalty Territory, upon the
termination of the agreement by Cubist upon specified prior written notice. We estimate that our
fundamental RNAi patents covered under the Cubist agreement will expire both in and outside of the
United States generally between 2016 and 2025. Allowed claims covering ALN-RSV01 in the United
States would expire in 2026. These patent rights are subject to any potential patent term
extensions and/or supplemental protection certificates extending such term extensions in countries
where such extensions may become available. In addition, more patent filings relating to the
collaboration may be made in the future. Cubist has the right to terminate the agreement at any
time (1) upon three months prior written notice if such notice is given prior to the acceptance
for filing of the first application for regulatory approval of a licensed product or (2) upon nine
months prior written notice if such notice is given after the acceptance for filing of the first
application for regulatory approval. Either party may terminate the agreement in the event the
other party fails to cure a material breach or upon patent-related challenges by the other party.
During the term of the Cubist agreement, neither party nor its affiliates may develop,
manufacture or commercialize
20
anywhere in the world, outside of Asia, a therapeutic or prophylactic product that
specifically targets RSV, except for licensed products developed, manufactured or commercialized
pursuant to the agreement.
We have determined that the deliverables under the Cubist agreement include the licenses,
technology transfer related to the ALN-RSV program, the joint steering committee, and the
development and manufacturing services that we will be obligated to perform. We have determined
that, pursuant to Emerging Issues Task Force, or EITF, Issue No. 00-21, Revenue Arrangements with
Multiple Deliverables, or EITF 00-21, the deliverables and undelivered services are not separable
and, accordingly, the licenses and services are being treated as a single unit of accounting.
When multiple deliverables are accounted for as a single unit of accounting, we base our
revenue recognition pattern on the final deliverable. Under the Cubist agreement, the last element
to be delivered is the joint steering committee service, which has an expected life of no more than
seven years. We are recognizing the upfront payment of $20.0 million on a straight-line basis over
seven years because we are unable to reasonably estimate the level of effort to fulfill our
performance obligations. As future substantive milestones are achieved, a portion of the milestone
payment, equal to the percentage of the performance period completed when the milestone is
achieved, multiplied by the amount of the milestone payment, will be recognized as revenue upon
achievement of such milestone. The remaining portion of the milestone will be recognized over the
remaining performance period on a straight-line basis. We will continue to reassess whether we can
reasonably estimate the level of effort required to fulfill our obligations under the Cubist
agreement. When, and if, we can make a reasonable estimate of its remaining efforts under the
collaboration, we will modify our method of recognition and utilize a proportional performance
method.
Under the terms of the Cubist agreement, we and Cubist will share responsibility for
developing Licensed Products in North America and will each bear one-half of the related
development costs. For revenue generating arrangements that
involve cost sharing between both parties, we apply the provisions of
EITF Issue No. 07-1
Accounting for Collaborative Arrangements, or EITF 07-1. EITF 07-1 requires collaborators to
present the results of activities for which they act as the principal on a gross basis and report
any payments received from (made to) other collaborators based on other applicable GAAP or, in the
absence of other applicable GAAP, analogy to authoritative accounting literature or a
reasonable, rational and consistently applied accounting policy election. As we are not considered
the principal in this agreement, pursuant to EITF 07-1, we will record any amounts due from Cubist
as a reduction of research and development costs. For the three
months ended March 31, 2009, we and Cubist incurred $3.6 million
under the Cubist agreement. Amounts due from Cubist of $1.8 million
have been recorded as a reduction of research and development
expense. As such, we recorded net research and development expenses
of $1.8 million in our condensed consolidated statements of
operations for the three months ended March 31, 2009.
Amended and Restated Isis Collaboration.
In May 2009, we and Isis amended and restated our
existing strategic collaboration and license agreement. As part of the amended and restated Isis
agreement, we and Isis have expanded our collaborative efforts to focus on the development of
ssRNAi technology. As it is known to occur in nature, the RNAi pathway is mediated by short
double-stranded RNA oligonucleotides called siRNAs. To date, efforts aimed at harnessing this
pathway to silence disease-causing proteins have used double-stranded siRNAs. Using its expertise,
in oligonucleotide chemistry and design, Isis has discovered strategies for designing
single-stranded oligonucleotides that may act through the RNAi mechanism. With further development,
these chemically modified, single-stranded, RNA-like oligonucleotides could have improved
properties for systemic administration while harnessing certain advantages of the RNAi mechanism.
Under
the amended and restated Isis agreement, we obtained from Isis a co-exclusive,
worldwide license to Isis current and future patents and patent applications relating to chemistry
and RNA-targeting mechanisms to research, develop and commercialize ssRNAi products for a limited
number of gene targets to be designated by us. We and Isis will have the opportunity to discover
and develop drugs employing the ssRNAi technology. In addition to entering into the new
collaboration, we and Isis also agreed to extend our broad cross-licensing arrangement regarding
double-stranded RNAi that was established in 2004.
Under the terms of the amended and restated Isis agreement, we will potentially pay Isis up to
an aggregate of $31.0 million in license fees, payable in four tranches, that include $11.0 million
on signing, $10.0 million 18 months following signing, or
if and when
in vivo
efficacy in rodents is
demonstrated if sooner, $5.0 million upon achievement of
in vivo
efficacy in non-human primates, and
$5.0 million upon initiation of the first clinical trial with an ssRNAi drug, subject to our right to unilaterally terminate the research program. We will fund research
activities at a minimum of $3.0 million each year for three years with research development
activities conducted by both us and Isis. If we develop and commercialize drugs utilizing ssRNAi
technology on our own or with a partner, Isis could potentially
receive milestone payments, totaling up to
$18.5 million, as well as royalties. Also, initially, Isis is eligible to receive up to
50 percent of any sublicense payments due to us from a third party based on our partnering of
ssRNAi products, which amount will decline over time as the our investment in the technology and
drugs increases. In turn, we are eligible to receive up to five percent of any sublicense
payments due to Isis from a third party based on Isis partnering of ssRNAi products.
21
We have the unilateral right to terminate the research program before September 30, 2010, in
which event any licenses to ssRNAi products granted by Isis
to us under the amended and restated
Isis agreement, and any obligation thereunder by us to pay milestone payments, royalties or
sublicense payments to Isis for such ssRNAi products, would also terminate.
Regulus
In September 2007, we and Isis established Regulus, a company focused on the discovery,
development and commercialization of microRNA-based therapeutics. Regulus combines our and Isis
technologies, know-how and intellectual property relating to microRNA-based therapeutics. Since
microRNAs are believed to regulate the expression of broad networks of genes and biological
pathways, microRNA-based therapeutics define a new and potentially high-impact strategy to target
multiple points on disease pathways. Regulus, which had initially been established as a limited
liability company, converted to a C corporation as of January 2, 2009 and changed its name to
Regulus Therapeutics Inc.
In consideration for our and Isis initial interests in Regulus, we and Isis each granted
Regulus exclusive licenses to our intellectual property for certain microRNA-based therapeutics as
well as certain patents in the microRNA field. In addition, we made an initial cash contribution
to Regulus of $10.0 million, resulting in us and Isis making initial capital contributions to
Regulus of approximately equal aggregate value. In addition, in March 2009, we and Isis each
purchased $10.0 million of Series A preferred stock of
Regulus. We and Isis currently own approximately 49%
and 51%, respectively, of Regulus and there are currently no other third party investors in Regulus. Regulus continues to operate as an
independent company with a separate board of directors, scientific advisory board and management
team, some of whom have options to purchase common stock of Regulus. Members of the board of directors of Regulus who are our employees or Isis employees are not eligible to receive options to purchase Regulus common stock.
We, Isis and Regulus have also entered into a license and collaboration agreement to pursue
the discovery, development and commercialization of therapeutic products directed to microRNAs.
Under the terms of the license and collaboration agreement, we and Isis assigned to Regulus
specified patents and contracts covering microRNA-specific technology. In addition, each of us
granted to Regulus an exclusive, worldwide license under our rights to other microRNA-related
patents and know-how to develop and commercialize therapeutic products containing compounds that
are designed to interfere with or inhibit a particular microRNA, subject to our and Isis existing
contractual obligations to third parties. Regulus also has the right to request a license from us
and Isis to develop and commercialize therapeutic products directed to other microRNA compounds,
which license is subject to our and Isis approval and to each such partys existing contractual
obligations to third parties. Regulus granted to us and Isis an exclusive license to technology
developed or acquired by Regulus for use solely within our respective fields (as defined in the
license and collaboration agreement), but specifically excluding the right to develop, manufacture
or commercialize the therapeutic products for which we and Isis granted rights to Regulus.
Regulus most advanced program, which is in pre-clinical research, is a microRNA-based
therapeutic candidate that targets miR-122, an endogenous host gene required for viral infection by
the hepatitis C virus, or HCV. HCV infection is a significant disease worldwide, for which emerging
therapies target viral genes and, therefore, are prone to viral resistance. Regulus is also
pursuing a program that targets miR-21. Pre-clinical studies by Regulus and collaborators have
shown that miR-21 is implicated in several therapeutic areas, including heart failure and fibrosis.
In addition to these programs, Regulus is also actively exploring additional areas for development
of microRNA-based therapeutics, including cancer, other viral diseases, metabolic disorders and
inflammatory diseases.
In April 2008, Regulus entered into a worldwide strategic alliance with GlaxoSmithKline, or
GSK, to discover, develop and market novel microRNA-targeted therapeutics to treat inflammatory
diseases such as rheumatoid arthritis and inflammatory bowel disease. In connection with this
alliance, Regulus received $20.0 million in upfront payments from GSK, including a $15.0 million
option fee and a loan of $5.0 million evidenced by a promissory note (guaranteed by Isis and us)
that will convert into Regulus common stock under certain specified circumstances. Regulus could be
eligible to receive development, regulatory and sales milestone payments for each of the four
microRNA-targeted therapeutics discovered and developed as part of the alliance, and would also
receive royalty payments on worldwide sales of products resulting from the alliance, if any.
Intellectual Property
The strength of our intellectual property portfolio relating to the development and
commercialization of siRNAs as therapeutics is essential to our business strategy. We own or
license issued patents and pending patent applications in the United States and in key markets
around the world claiming fundamental features of siRNAs and RNAi therapeutics as well as those
claiming crucial chemical modifications and promising delivery technologies. Specifically, we have
a portfolio of patents, patent applications
22
and other intellectual property covering: fundamental aspects of the structure and uses of
siRNAs, including their use as therapeutics, and RNAi-related mechanisms; chemical modifications to
siRNAs that improve their suitability for therapeutic uses; siRNAs directed to specific targets as
treatments for particular diseases; delivery technologies, such as in the field of cationic
liposomes; and all aspects of our specific development candidates.
We believe that no other company possesses a portfolio of such broad and exclusive rights to
the patents and patent applications required for the commercialization of RNAi therapeutics. Our
intellectual property estate for RNAi therapeutics includes over 1,800 active cases and over 700
granted or issued patents, of which over 300 are issued or granted in the United States, the
European Union and Japan. We continue to seek to grow our portfolio through the creation of new
technology in this field. In addition, we are very active in our evaluation of third-party
technology, as most recently evidenced by our acquisition of the intellectual property in the
emerging biological field of RNAa.
Our expertise in RNAi therapeutics and broad intellectual property estate have allowed us to
form alliances with leading companies, including Isis, Medtronic, Novartis, Biogen, Roche, Takeda,
Kyowa Hakko and Cubist, as well as license agreements with other biotechnology companies interested
in developing RNAi therapeutic products and research companies that commercialize RNAi reagents or
services.
Given the importance of our intellectual property portfolio to our business operations, we
intend to vigorously enforce our rights and defend against any challenges that have arisen or may
arise in this area.
Critical Accounting Policies and Estimates
There have been no significant changes to our critical accounting policies since the
beginning of this fiscal year. Our critical accounting policies are described in the Managements
Discussion and Analysis of Financial Condition and Results of Operations section of our Annual
Report on Form 10-K for the year ended December 31, 2008, which we filed with the Securities and
Exchange Commission on March 2, 2009.
Results of Operations
The following data summarizes the results of our operations for the periods indicated,
in thousands:
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended
|
|
|
March 31,
|
|
|
2009
|
|
2008
|
Net revenues
|
|
$
|
25,057
|
|
|
$
|
22,192
|
|
Operating expenses
|
|
|
33,037
|
|
|
|
26,149
|
|
Loss from operations
|
|
|
(7,980
|
)
|
|
|
(3,957
|
)
|
Net loss
|
|
$
|
(7,889
|
)
|
|
$
|
(1,239
|
)
|
Revenues
The following table summarizes our total consolidated net revenues, for the periods indicated,
in thousands:
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended
|
|
|
March 31,
|
|
|
2009
|
|
2008
|
Roche
|
|
|
$ 13,828
|
|
|
|
$ 13,411
|
|
Takeda
|
|
|
5,417
|
|
|
|
|
|
Novartis
|
|
|
2,679
|
|
|
|
3,252
|
|
Government contract
|
|
|
1,804
|
|
|
|
4,933
|
|
Other research collaborator
|
|
|
883
|
|
|
|
238
|
|
InterfeRx program, research reagent license and other
|
|
|
446
|
|
|
|
358
|
|
|
|
|
|
|
|
|
|
|
Total net revenues from research collaborators
|
|
|
$ 25,057
|
|
|
|
$ 22,192
|
|
|
|
|
|
|
|
|
|
|
Revenues increased for the three months ended March 31, 2009 as compared to the three months
ended March 31, 2008
23
primarily as a result of our alliance with Takeda. In June 2008, we received upfront cash
payments totaling $100.0 million under the Takeda alliance and in October 2008, we received the
first technology transfer milestone payment of $20.0 million. Takeda is required to make an
additional $30.0 million in near-term payments to us upon achievement of specified technology
transfer milestones. The $150.0 million in upfront and technology transfer milestone payments made
or due to us under the Takeda alliance are being recognized as revenue on a straight-line basis
over seven years.
For the three months ended March 31, 2009 as compared to the three months ended March 31,
2008, government contract revenues decreased significantly primarily due to the wind down of our
collaboration with DTRA. Following a program review, in February 2009 we and DTRA determined not to
continue this program and accordingly, no additional funds will be accessed.
The decrease in Novartis revenues in the three months ended March 31, 2009 as compared to the
three months ended March 31, 2008 was due in part to a reduction in the number of resources
allocated to the broad Novartis alliance.
For the three months ended March 31, 2009 as compared to the three months ended March 31,
2008, other research collaborator revenues increased due primarily to our alliance with Cubist. In
consideration for the rights granted to Cubist under the agreement, in January 2009, Cubist paid us
an upfront cash payment of $20.0 million. We are recognizing this $20.0 million payment as revenue
on a straight-line basis over seven years.
Total deferred revenue of $331.5 million at March 31, 2009 consists of payments we have
received from collaborators, primarily Roche, Takeda, Kyowa Hakko and Cubist, but have not yet
recognized pursuant to our revenue recognition policies.
For the foreseeable future, we expect our revenues to continue to be derived primarily from
our alliances with Roche, Takeda, Novartis and Cubist, as well as other strategic alliances,
collaborations, government contracts and licensing activities.
Operating expenses
The following table summarizes our operating expenses for the periods indicated, in
thousands and as a percentage of total operating expenses, together with the changes, in thousands
and percentages:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
|
|
|
% of Total
|
|
|
Three Months
|
|
|
% of Total
|
|
|
|
|
|
|
Ended
|
|
|
Operating
|
|
|
Ended
|
|
|
Operating
|
|
|
Increase
|
|
|
|
March 31, 2009
|
|
|
Expenses
|
|
|
March 31, 2008
|
|
|
Expenses
|
|
|
$
|
|
|
%
|
|
Research and development
|
|
$
|
25,321
|
|
|
|
77
|
%
|
|
$
|
20,277
|
|
|
|
78
|
%
|
|
$
|
5,044
|
|
|
|
25
|
%
|
General and administrative
|
|
|
7,716
|
|
|
|
23
|
%
|
|
|
5,872
|
|
|
|
22
|
%
|
|
|
1,844
|
|
|
|
31
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total operating expenses
|
|
$
|
33,037
|
|
|
|
100
|
%
|
|
$
|
26,149
|
|
|
|
100
|
%
|
|
$
|
6,888
|
|
|
|
26
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and development.
The following table summarizes the components of our research and
development expenses for the periods indicated, in thousands and as a percentage of total research
and development expenses, together with the changes, in thousands and percentages:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
|
|
|
|
|
|
|
Three Months
|
|
|
% of
|
|
|
|
|
|
|
Ended
|
|
|
% of Expense
|
|
|
Ended March 31,
|
|
|
Expense
|
|
|
Increase (Decrease)
|
|
|
|
March 31, 2009
|
|
|
Category
|
|
|
2008
|
|
|
Category
|
|
|
$
|
|
|
%
|
|
Research and development
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Compensation and related
|
|
$
|
5,573
|
|
|
|
22
|
%
|
|
$
|
3,803
|
|
|
|
19
|
%
|
|
$
|
1,770
|
|
|
|
47
|
%
|
Clinical trial and manufacturing
|
|
|
4,648
|
|
|
|
18
|
%
|
|
|
4,640
|
|
|
|
23
|
%
|
|
|
8
|
|
|
|
*
|
%
|
External services
|
|
|
4,219
|
|
|
|
17
|
%
|
|
|
5,663
|
|
|
|
28
|
%
|
|
|
(1,444
|
)
|
|
|
(26
|
)%
|
Facilities-related
|
|
|
2,939
|
|
|
|
12
|
%
|
|
|
1,913
|
|
|
|
10
|
%
|
|
|
1,026
|
|
|
|
54
|
%
|
Non-cash stock-based compensation
|
|
|
3,034
|
|
|
|
11
|
%
|
|
|
2,314
|
|
|
|
11
|
%
|
|
|
720
|
|
|
|
31
|
%
|
License fees
|
|
|
2,260
|
|
|
|
9
|
%
|
|
|
37
|
|
|
|
*
|
%
|
|
|
2,223
|
|
|
|
6008
|
%
|
Lab supplies and materials
|
|
|
2,185
|
|
|
|
9
|
%
|
|
|
1,432
|
|
|
|
7
|
%
|
|
|
753
|
|
|
|
53
|
%
|
Other
|
|
|
463
|
|
|
|
2
|
%
|
|
|
475
|
|
|
|
2
|
%
|
|
|
(12
|
)
|
|
|
(3
|
)%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total research and development
expenses
|
|
$
|
25,321
|
|
|
|
100
|
%
|
|
$
|
20,277
|
|
|
|
100
|
%
|
|
$
|
5,044
|
|
|
|
25
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
24
Research and development expenses increased during the three months ended March 31, 2009 as
compared to the three months ended March 31, 2008 due primarily to higher license fees payable to
certain entities, primarily Isis, as a result of the Cubist alliance and the initiation of our
ALN-VSP Phase I clinical study. Compensation and related expenses, lab supplies and materials, and
facilities-related expenses increased during the three months ended March 31, 2009 as compared to
the three months ended March 31, 2008 due to additional research and development headcount to
support our alliances and expanding product pipeline. Partially offsetting these increases was a
decrease in external services primarily due to the wind down of our collaboration with DTRA.
Following a program review, in February 2009 we and DTRA determined not to continue this program and, accordingly, no additional expenses for this program will be incurred. In
addition, under the terms of our January 2009 agreement with Cubist, we and Cubist each bear
one-half of the development costs for our ALN-RSV program. Accordingly, for the three months ended
March 31, 2009, we recorded a reduction of research and development expenses of $1.8 million.
We expect to continue to devote a substantial portion of our resources to research and
development expenses and we expect that research and development expenses will remain consistent or
increase slightly in 2009 as we continue development of our and our collaborators product
candidates and focus on continuing to develop drug delivery-related technologies.
We do not track actual costs for most of our research and development programs or our
personnel and personnel-related costs on a project-by-project basis because all of our programs are
in the early stages of development. In addition, a significant portion of our research and
development costs are not tracked by project as they benefit multiple projects or our technology
platform. However, our collaboration agreements contain cost-sharing arrangements whereby certain
costs incurred under the project are reimbursed. Costs reimbursed under the agreements typically
include certain direct external costs and a negotiated full-time equivalent labor rate for the
actual time worked on the project. In addition, we are reimbursed under our government contracts
for certain allowable costs including direct internal and external costs. As a result, although a
significant portion of our research and development expenses are not tracked on a
project-by-project basis, we do track direct external costs attributable to, and the actual time
our employees worked on, our collaborations and government contracts.
General and administrative.
The following table summarizes the components of our general and
administrative expenses for the periods indicated, in thousands and as a percentage of total
general and administrative expenses, together with the changes, in thousands and percentages:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three Months
|
|
|
% of
|
|
|
Three Months
|
|
|
% of
|
|
|
Increase
|
|
|
|
Ended
|
|
|
Expense
|
|
|
Ended
|
|
|
Expense
|
|
|
(Decrease)
|
|
|
|
March 31, 2009
|
|
|
Category
|
|
|
March 31, 2008
|
|
|
Category
|
|
|
$
|
|
|
%
|
|
General and administrative
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Consulting and professional services
|
|
$
|
2,333
|
|
|
|
30
|
%
|
|
$
|
1,648
|
|
|
|
28
|
%
|
|
$
|
685
|
|
|
|
42
|
%
|
Non-cash stock-based compensation
|
|
|
2,103
|
|
|
|
27
|
%
|
|
|
1,506
|
|
|
|
26
|
%
|
|
|
597
|
|
|
|
40
|
%
|
Compensation and related
|
|
|
1,724
|
|
|
|
22
|
%
|
|
|
1,430
|
|
|
|
24
|
%
|
|
|
294
|
|
|
|
21
|
%
|
Facilities-related
|
|
|
660
|
|
|
|
9
|
%
|
|
|
726
|
|
|
|
12
|
%
|
|
|
(66
|
)
|
|
|
(9
|
)%
|
Insurance
|
|
|
189
|
|
|
|
3
|
%
|
|
|
148
|
|
|
|
3
|
%
|
|
|
41
|
|
|
|
28
|
%
|
Other
|
|
|
707
|
|
|
|
9
|
%
|
|
|
414
|
|
|
|
7
|
%
|
|
|
293
|
|
|
|
71
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total general and administrative
Expenses
|
|
$
|
7,716
|
|
|
|
100
|
%
|
|
$
|
5,872
|
|
|
|
100
|
%
|
|
$
|
1,844
|
|
|
|
31
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The increase in general and administrative expenses during the three months ended March 31,
2009 as compared to the three months ended March 31, 2008 was due primarily to higher professional
service fees related to business activities, an increase in general and administrative headcount over the past year to support our
growth and higher non-cash stock-based compensation.
Other income (expense)
Equity in loss of joint venture (Regulus Therapeutics Inc.) was $1.5 million and $1.6 million for the three
months ended March 31, 2009 and 2008, respectively, related to our share of the net losses incurred
by Regulus, which was formed in September 2007. Through December 31, 2008, we were recognizing the
first $10.0 million of losses of Regulus as equity in loss of joint venture (Regulus Therapeutics Inc.) in our
condensed consolidated statements of operations because we were responsible for funding those
losses through our initial $10.0 million cash contribution. Beginning in January 2009, in
connection with the conversion of Regulus to a C corporation, we are recognizing approximately 49%
of the income and losses of Regulus.
25
Interest income was $2.0 million for the three months ended March 31, 2009 as compared to
$4.7 million for the three months ended March 31, 2008. The decrease was due to significantly
lower average interest rates, partially offset by higher average cash, cash equivalent and
marketable securities balances resulting primarily from the $120.0 million in proceeds we received
in 2008 from our alliance with Takeda.
Interest expense was zero for the three months ended March 31, 2009 as compared to
$0.2 million for the three months ended March 31, 2008. Interest expense in the three months ended
March 31, 2008 was related to borrowings under our lines of credit used to finance capital
equipment purchases. In December 2008, we defeased the aggregate outstanding balance under these
credit lines and expect to have no interest expense in 2009.
Income tax expense, primarily as a result of our alliances with Roche and Takeda, was $0.7
million for the three months ended March 31, 2009 as compared to $0.2 million for the three months
ended March 31, 2008.
Liquidity and Capital Resources
The following table summarizes our cash flow activities for the periods indicated, in
thousands:
|
|
|
|
|
|
|
|
|
|
|
Three Months Ended March 31,
|
|
|
|
2009
|
|
|
2008
|
|
Net loss
|
|
$
|
(7,889
|
)
|
|
$
|
(1,239
|
)
|
Adjustments to reconcile net loss to net cash
provided by operating activities
|
|
|
8,296
|
|
|
|
6,474
|
|
Changes in operating assets and liabilities
|
|
|
824
|
|
|
|
(13,893
|
)
|
|
|
|
|
|
|
|
Net cash provided by (used in) operating activities
|
|
|
1,231
|
|
|
|
(8,658
|
)
|
Net cash provided by investing activities
|
|
|
34,125
|
|
|
|
100,244
|
|
Net cash provided by (used in) financing activities
|
|
|
210
|
|
|
|
(472
|
)
|
Effect of exchange rate on cash
|
|
|
(90
|
)
|
|
|
10
|
|
|
|
|
|
|
|
|
Net increase in cash and cash equivalents
|
|
|
35,476
|
|
|
|
91,124
|
|
Cash and cash equivalents, beginning of period
|
|
|
191,792
|
|
|
|
105,157
|
|
|
|
|
|
|
|
|
Cash and cash equivalents, end of period
|
|
$
|
227,268
|
|
|
$
|
196,281
|
|
|
|
|
|
|
|
|
Since we commenced operations in 2002, we have generated significant losses. As of March 31,
2009, we had an accumulated deficit of $260.1 million. As of March 31, 2009, we had cash, cash
equivalents and marketable securities of $504.7 million, compared to cash, cash equivalents and
marketable securities of $512.7 million as of December 31, 2008. We invest primarily in cash
equivalents, U.S. government obligations, high-grade corporate notes and commercial paper. Our
investment objectives are, primarily, to assure liquidity and preservation of capital and,
secondarily, to obtain investment income. All of our investments in debt securities are recorded at
fair value and are available-for-sale. Fair value is determined based on quoted market prices and
models using observable data inputs. We have not recorded any impairment charges to our fixed
income marketable securities during the three months ended March 31, 2009.
Operating activities
We have required significant amounts of cash to fund our operating activities as a
result of net losses since our inception. For the three months ended March 31, 2009 as compared
to the three months ended March 31, 2008, cash provided by operating activities of $1.2 million was
due primarily to the proceeds received from our 2008 alliance with Takeda and our January 2009
alliance with Cubist. Offsetting the proceeds from the Takeda and Cubist alliances, the main
components of our use of cash in operating activities for the three months ended March 31, 2009
consisted of the net loss, the net decrease in income taxes payable of $5.1 million and other changes in our working capital. Cash provided by operating activities
is adjusted for non-cash items to reconcile net loss to net cash provided by or used in operating
activities. These non-cash adjustments consist primarily of stock-based compensation, equity in
loss of joint venture and depreciation and amortization. We had an increase in deferred revenue of
$1.5 million for the three months ended March 31, 2009, as well as an increase in accounts payable
of $6.1 million.
We expect that we will require significant amounts of cash to fund our operating activities
for the foreseeable future as we continue to develop and advance our research and development
initiatives. The actual amount of overall expenditures will depend on
26
numerous factors, including the timing of expenses, the timing and terms of collaboration
agreements or other strategic transactions, if any, and the timing and progress of our research and
development efforts.
Investing activities
For the three months ended March 31, 2009, net cash provided by investing activities of
$34.1 million resulted primarily from net sales and maturities of marketable securities of
$43.0 million. Partially offsetting this amount was an additional $10.0 million investment in
Regulus, and purchases of property and equipment of $1.9 million related to the expansion of our
Cambridge facility. For the three months ended March 31, 2008, net cash provided by investing
activities of $100.2 million resulted primarily from net sales of marketable securities of
$103.2 million offset by $2.9 million in purchases of property and equipment.
Financing activities
For the three months ended March 31, 2009, net cash provided by financing activities was $0.2
million and was due to proceeds from the issuance of common stock. For the three months ended March
31, 2008, net cash used in financing activities was $0.5 million and resulted from $0.9 million
paid under notes payable, offset by $0.4 million of proceeds received from the issuance of common
stock.
During the current downturn in global financial markets, some companies have experienced
difficulties accessing their cash equivalents, investment securities and raising capital generally,
which have had a material adverse impact on their liquidity. In addition, the current economic
downturn has severely diminished the availability of capital and may limit our ability to access
these markets to obtain financing in the future. Based on our current operating plan, we believe
that our existing cash, cash equivalents and fixed income marketable securities, for which we have
not recognized any impairment charges, together with the cash we expect to generate under our
current alliances, including our Novartis, Roche, Takeda and Cubist alliances, will be sufficient
to fund our planned operations for at least the next several years, during which time we expect to
further the development of our product candidates, conduct clinical trials, extend the capabilities
of our technology platform and continue to prosecute patent applications and otherwise build and
maintain our patent portfolio. However, we may require significant additional funds earlier than we
currently expect in order to develop, commence clinical trials for and commercialize any product
candidates.
In the longer term, we may seek additional funding through additional collaborative
arrangements and public or private financings. Additional funding may not be available to us on
acceptable terms or at all. In addition, the terms of any financing may adversely affect the
holdings or the rights of our stockholders. For example, if we raise additional funds by issuing
equity securities, further dilution to our existing stockholders may result. If we are unable to
obtain funding on a timely basis, we may be required to significantly curtail one or more of our
research or development programs. We also could be required to seek funds through arrangements with
collaborators or others that may require us to relinquish rights to some of our technologies or
product candidates that we would otherwise pursue.
Even if we are able to raise additional funds in a timely manner, our future capital
requirements may vary from what we expect and will depend on many factors, including:
|
|
|
our progress in demonstrating that siRNAs can be active as drugs;
|
|
|
|
|
our ability to develop relatively standard procedures for selecting and modifying siRNA drug
candidates;
|
|
|
|
|
progress in our research and development programs, as well as the magnitude of these
programs;
|
|
|
|
|
the timing, receipt and amount of milestone and other payments, if any, from
present and future collaborators, if any;
|
|
|
|
|
the timing, receipt and amount of funding under current and future government contracts, if
any;
|
|
|
|
|
our ability to maintain and establish additional collaborative arrangements;
|
|
|
|
|
the resources, time and costs required to successfully initiate and complete our
pre-clinical and clinical trials, obtain regulatory approvals, protect our intellectual
property and obtain and maintain licenses to third-party intellectual property;
|
27
|
|
|
the cost of preparing, filing, prosecuting, maintaining and enforcing patent claims;
|
|
|
|
|
progress in the research and development programs of Regulus; and
|
|
|
|
|
the timing, receipt and amount of sales and royalties, if any, from our potential products.
|
Contractual Obligations and Commitments
The disclosure of our contractual obligations and commitments is set forth under the heading
Managements Discussion and Analysis of Financial Condition and Results of OperationsContractual
Obligations and Commitments in our Annual Report on Form 10-K for the year ended December 31,
2008. In January 2009, we and Tekmira entered into a manufacturing and supply agreement under
which we committed to pay Tekmira up to Cdn. $11.2 million ($9.0 million at March 31, 2009) over a three year period beginning
in January 2009.
Recent Accounting Pronouncements
In December 2007, the Financial Accounting Standards Board, or FASB, reached a consensus on
EITF 07-1, which requires
collaborators to present the results of activities for which they act as the principal on a gross
basis and report any payments received from (made to) other collaborators based on other applicable
GAAP or, in the absence of other applicable GAAP, based on analogy to authoritative accounting
literature or a reasonable, rational and consistently applied accounting policy election. Further,
EITF 07-1 clarifies that the determination of whether transactions within a collaborative
arrangement are part of a vendor-customer (or analogous) relationship subject to EITF 01-9.
EITF 07-1 became effective on January 1, 2009. The adoption of EITF 07-1 did not have a material
impact on our condensed consolidated financial statements, however, it resulted in enhanced disclosures for our collaboration activities.
ITEM 3. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
As part of our investment portfolio, we own financial instruments that are sensitive to market
risks. The investment portfolio is used to preserve our capital until it is required to fund
operations, including our research and development activities. Our marketable securities consist of
U.S. government obligations, high-grade corporate notes and commercial paper. All of our
investments in debt securities are classified as available-for-sale and are recorded at fair
value. Our available-for-sale investments in debt securities are sensitive to changes in interest
rates and changes in the credit ratings of the issuers. Interest rate changes would result in a
change in the net fair value of these financial instruments due to the difference between the
market interest rate and the market interest rate at the date of purchase of the financial
instrument. A 10% decrease in market interest rates at March 31, 2009 would impact the net fair
value of such interest-sensitive financial instruments by $2.0 million. A downgrade in the credit
rating of an issuer of a debt security or further deterioration of the credit markets could result
in a decline in the fair value of the debt instruments. Our investment guidelines prohibit
investment in auction rate securities and we do not believe we have any direct exposure to losses
relating from mortgage-based securities or derivatives related thereto such as credit-default
swaps. We have not recorded any impairment charges to our fixed income marketable securities as of
March 31, 2009.
ITEM 4. CONTROLS AND PROCEDURES
Our management, with the participation of our chief executive officer and vice president
of finance and treasurer, evaluated the effectiveness of our disclosure controls and procedures as
of March 31, 2009. The term disclosure controls and procedures, as defined in Rules 13a-15(e) and
15d-15(e) under the Securities Exchange Act of 1934, as amended, or the Exchange Act, means
controls and other procedures of a company that are designed to ensure that information required to
be disclosed by a company in the reports that it files or submits under the Exchange Act is
recorded, processed, summarized and reported within the time periods specified in the SECs rules
and forms. Disclosure controls and procedures include, without limitation, controls and procedures
designed to ensure that information required to be disclosed by a company in the reports that it
files or submits under the Exchange Act is accumulated and communicated to the companys
management, including its principal executive and principal financial officers, as appropriate to
allow timely decisions regarding required disclosure. Management recognizes that any controls and
procedures, no matter how well designed and operated, can provide only reasonable assurance of
achieving their objectives and management necessarily applies its judgment in evaluating the
cost-benefit relationship of possible controls and procedures. Based on the evaluation of our
disclosure controls and procedures as of March 31, 2009, our chief executive officer and vice
president of finance and treasurer concluded that, as of such date, our disclosure controls and
procedures were effective at the reasonable assurance
28
level.
No change in our internal control over financial reporting (as defined in
Rules 13a-15(d) and 15d-15(d) under the Exchange Act) occurred during the three months ended March
31, 2009 that has materially affected, or is reasonably likely to materially affect, our internal
control over financial reporting.
PART II. OTHER INFORMATION
ITEM 1A. RISK FACTORS.
Our business is subject to numerous risks. We caution you that the following important
factors, among others, could cause our actual results to differ materially from those expressed in
forward-looking statements made by us or on our behalf in filings with the SEC, press releases,
communications with investors and oral statements. Any or all of our forward-looking statements in
this Quarterly Report on Form 10-Q and in any other public statements we make may turn out to be
wrong. They can be affected by inaccurate assumptions we might make or by known or unknown risks
and uncertainties. Many factors mentioned in the discussion below will be important in determining
future results. Consequently, no forward-looking statement can be guaranteed. Actual future results
may vary materially from those anticipated in forward-looking statements. We undertake no
obligation to update any forward-looking statements, whether as a result of new information, future
events or otherwise. You are advised, however, to consult any further disclosure we make in our
reports filed with the SEC.
Risks Related to Our Business
Risks Related to Being an Early Stage Company
Because we have a short operating history, there is a limited amount of information about us upon
which you can evaluate our business and prospects.
Our operations began in 2002 and we have only a limited operating history upon which you can
evaluate our business and prospects. In addition, as an early-stage company, we have limited
experience and have not yet demonstrated an ability to successfully overcome many of the risks and
uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly
in the biopharmaceutical area. For example, to execute our business plan, we will need to
successfully:
|
|
|
execute product development activities using unproven technologies related to
both RNAi and to the delivery of siRNAs to the relevant cell tissue;
|
|
|
|
|
build and maintain a strong intellectual property portfolio;
|
|
|
|
|
gain acceptance for the development of our product candidates and any products we
commercialize;
|
|
|
|
|
develop and maintain successful strategic alliances; and
|
|
|
|
|
manage our spending as costs and expenses increase due to clinical trials,
regulatory approvals and commercialization.
|
If we are unsuccessful in accomplishing these objectives, we may not be able to develop
product candidates, commercialize products, raise capital, expand our business or continue our
operations.
The approach we are taking to discover and develop novel RNAi therapeutics is unproven and may
never lead to marketable products.
We have concentrated our efforts and therapeutic product research on RNAi technology, and our
future success depends on the successful development of this technology and products based on it.
Neither we nor any other company has received regulatory approval to market therapeutics utilizing
siRNAs, the class of molecule we are trying to develop into drugs. The scientific discoveries that
form the basis for our efforts to discover and develop new drugs are relatively new. The scientific
evidence to support the feasibility of developing drugs based on these discoveries is both
preliminary and limited. Skepticism as to the feasibility of developing RNAi therapeutics has been
expressed in scientific literature. For example, there are potential challenges to achieving safe
29
RNAi therapeutics based on the so-called off-target effects and activation of the interferon
response.
Relatively few drug candidates based on these discoveries have ever been tested in animals or
humans. siRNAs may not naturally possess the inherent properties typically required of drugs, such
as the ability to be stable in the body long enough to reach the tissues in which their effects are
required, nor the ability to enter cells within these tissues in order to exert their effects. We
currently have only limited data, and no conclusive evidence, to suggest that we can introduce
these drug-like properties into siRNAs. We may spend large amounts of money trying to introduce
these properties, and may never succeed in doing so. In addition, these compounds may not
demonstrate in patients the chemical and pharmacological properties ascribed to them in laboratory
studies, and they may interact with human biological systems in unforeseen, ineffective or harmful
ways. As a result, we may never succeed in developing a marketable product. If we do not
successfully develop and commercialize drugs based upon our technological approach, we may not
become profitable and the value of our common stock will decline.
Further, our focus solely on RNAi technology for developing drugs, as opposed to multiple,
more proven technologies for drug development, increases the risks associated with the ownership of
our common stock. If we are not successful in developing a product candidate using RNAi technology,
we may be required to change the scope and direction of our product development activities. In that
case, we may not be able to identify and implement successfully an alternative product development
strategy.
Risks Related to Our Financial Results and Need for Financing
We have a history of losses and may never be profitable.
We have experienced significant operating losses since our inception. As of March 31, 2009, we
had an accumulated deficit of $260.1 million. To date, we have not developed any products nor
generated any revenues from the sale of products. Further, we do not expect to generate any such
revenues in the foreseeable future. We expect to continue to incur annual net operating losses over
the next several years and will require substantial resources over the next several years as we
expand our efforts to discover, develop and commercialize RNAi therapeutics. We anticipate that the
majority of any revenue we generate over the next several years will be from alliances with
pharmaceutical companies or funding from contracts with the government, but cannot be certain that
we will be able to secure or maintain these alliances or contracts, or meet the obligations or
achieve any milestones that we may be required to meet or achieve to receive payments.
To become and remain consistently profitable, we must succeed in discovering, developing and
commercializing novel drugs with significant market potential. This will require us to be
successful in a range of challenging activities, including pre-clinical testing and clinical trial
stages of development, obtaining regulatory approval for these novel drugs and manufacturing,
marketing and selling them. We may never succeed in these activities, and may never generate
revenues that are significant enough to achieve profitability. Even if we do achieve profitability,
we may not be able to sustain or increase profitability on a quarterly or annual basis. If we
cannot become and remain consistently profitable, the market price of our common stock could
decline. In addition, we may be unable to raise capital, expand our business, diversify our product
offerings or continue our operations.
We will require substantial additional funds to complete our research and development activities
and if additional funds are not available, we may need to critically limit, significantly scale
back or cease our operations.
We have used substantial funds to develop our RNAi technologies and will require substantial
funds to conduct further research and development, including pre-clinical testing and clinical
trials of any product candidates, and to manufacture and market any products that are approved for
commercial sale. Because the successful development of our products is uncertain, we are unable to
estimate the actual funds we will require to develop and commercialize them.
Our future capital requirements and the period for which we expect our existing resources to
support our operations may vary from what we expect. We have based our expectations on a number of
factors, many of which are difficult to predict or are outside of our control, including:
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our progress in demonstrating that siRNAs can be active as drugs;
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our ability to develop relatively standard procedures for selecting and modifying siRNA
drug candidates;
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progress in our research and development programs, as well as the magnitude of these
programs;
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the timing, receipt and amount of milestone and other payments, if any, from
present and future collaborators, if any;
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the timing, receipt and amount of funding under current and future government contracts,
if any;
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our ability to maintain and establish additional collaborative arrangements;
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the resources, time and costs required to initiate and complete our pre-clinical
and clinical trials, obtain regulatory approvals, protect our intellectual property and
obtain and maintain licenses to third-party intellectual property;
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the cost of preparing, filing, prosecuting, maintaining and enforcing patent claims;
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progress in the research and development programs of Regulus; and
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the timing, receipt and amount of sales and royalties, if any, from our potential
products.
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If our estimates and predictions relating to these factors are incorrect, we may need to
modify our operating plan.
We will be required to seek additional funding in the future and intend to do so through
either collaborative arrangements, public or private equity offerings or debt financings, or a
combination of one or more of these funding sources. Additional funds may not be available to us on
acceptable terms or at all. In addition, the terms of any financing may adversely affect the
holdings or the rights of our stockholders. For example, if we raise additional funds by issuing
equity securities, further dilution to our stockholders will result. In addition, our investor
rights agreement with Novartis provides Novartis with the right generally to maintain its ownership
percentage in us and our common stock purchase agreement with Roche contains a similar provision.
In May 2008, Novartis purchased 213,888 shares of our common stock at a purchase price of $25.29
per share. In May 2009, Novartis purchased 65,922 shares of our common stock at a purchase price of
$17.50 per share, allowing Novartis to maintain its current
ownership position of 13.4% of
the Companys outstanding common stock. While the exercise of these rights by Novartis has
provided us with an aggregate of $6.6 million in cash, and the exercise in the future by Novartis
or Roche may provide us with additional funding under some circumstances, this exercise and any
future exercise of these rights by Novartis or Roche will also cause further dilution to our
stockholders. Debt financing, if available, may involve restrictive covenants that could limit our
flexibility in conducting future business activities. If we are unable to obtain funding on a
timely basis, we may be required to significantly curtail one or more of our research or
development programs. We also could be required to seek funds through arrangements with
collaborators or others that may require us to relinquish rights to some of our technologies,
product candidates or products that we would otherwise pursue on our own.
If the estimates we make, or the assumptions on which we rely, in preparing our condensed
consolidated financial statements prove inaccurate, our actual results may vary from those
reflected in our projections and accruals.
Our condensed consolidated financial statements have been prepared in accordance with
accounting principles generally accepted in the United States. The preparation of these condensed
consolidated financial statements requires us to make estimates and judgments that affect the
reported amounts of our assets, liabilities, revenues and expenses, the amounts of charges accrued
by us and related disclosure of contingent assets and liabilities. We base our estimates on
historical experience and on various other assumptions that we believe to be reasonable under the
circumstances. We cannot assure you, however, that our estimates, or the assumptions underlying
them, will be correct.
The investment of our cash balance and our investments in marketable debt securities are subject
to risks which may cause losses and affect the liquidity of these investments.
At March 31, 2009, we had $504.7 million in cash, cash equivalents and marketable securities.
We historically have invested these amounts in corporate bonds, commercial paper, securities issued
by the U.S. government, certificates of deposit and money market funds meeting the criteria of our
investment policy, which is focused on the preservation of our capital. These investments are
subject to general credit, liquidity, market and interest rate risks, which may be affected by
U.S. sub-prime mortgage defaults that have affected various sectors of the financial markets and
caused credit and liquidity issues. We may realize losses in the fair value of these investments or
a complete loss of these investments, which would have a negative effect on our condensed
consolidated financial statements. In addition, should our investments cease paying or reduce the
amount of interest paid to us, our interest income would suffer. For example, due to recent market
conditions, interest rates have fallen, and accordingly, despite a higher average cash
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balance for the three months ended March 31, 2009 as compared to the three months ended March
31, 2008, our interest income decreased to $2.0 million from $4.7 million, respectively. These
market risks associated with our investment portfolio may have a negative adverse effect on our
results of operations, liquidity and financial condition.
Risks Related to Our Dependence on Third Parties
Our collaboration with Novartis is important to our business. If this collaboration is
unsuccessful, Novartis terminates this collaboration or this collaboration results in competition
between us and Novartis for the development of drugs targeting the same diseases, our business
could be adversely affected.
In October 2005, we entered into a collaboration agreement with Novartis. Under this
agreement, Novartis can select up to 30 exclusive targets to include in the collaboration, which
number may be increased to 40 under certain circumstances and upon additional payments. Novartis
pays the costs to develop these drug candidates and will commercialize and market any products
derived from this collaboration. For RNAi therapeutic products successfully developed under the
agreement, if any, we would be entitled to receive milestone payments upon achievement of certain
specified development and annual net sales events, up to an aggregate of $75.0 million per
therapeutic product, as well as royalties on the annual net sales, if any. The Novartis agreement
has an initial term of three years, with the option for two additional one-year extensions at the
election of Novartis. In July 2008, Novartis elected to extend the initial term for an additional
year, through October 2009. Novartis retains the right to extend the term for a second additional
year, which right must be exercised no later than July 2009. Novartis may elect to terminate this
collaboration in the event of a material uncured breach by us. We expect that a substantial amount
of funding will come from this collaboration. If this collaboration is unsuccessful, or if it is
terminated, our business could be adversely affected.
This agreement also provides Novartis with a non-exclusive option to integrate into its
operations our intellectual property relating to RNAi technology, excluding any technology related
to delivery of nucleic acid based molecules. Novartis may exercise this integration option at any
point during the research term, as defined in the collaboration and license agreement. The research
term expires in October 2009 and may be extended until October 2010 at Novartis election. The
license grant under the integration option, if exercised, would be structured similarly to our
non-exclusive platform licenses with Roche and Takeda. If Novartis elects to exercise this option,
Novartis could become a competitor of ours in the development of RNAi-based drugs targeting the
same diseases. Novartis has significantly greater financial resources and far more experience than
we do in developing and marketing drugs, which could put us at a competitive disadvantage if we
were to compete with Novartis in the development of RNAi-based drugs targeting the same disease.
Accordingly, the exercise by Novartis of this option could adversely affect our business.
Our agreement with Novartis allows us to continue to develop products on an exclusive basis on
our own with respect to targets not selected by Novartis for inclusion in the collaboration. We may
need to form additional alliances to develop products. However, our agreement with Novartis
provides Novartis with a right of first offer, for a defined term, in the event that we propose to
enter into an agreement with a third party with respect to such targets. This right of first offer
may make it difficult for us to form future alliances around specific targets with other parties.
Our license and collaboration agreements with Roche and Takeda are important to our business. If
Roche and/or Takeda do not successfully develop drugs pursuant to these agreements or these
agreements result in competition between us and Roche and/or Takeda for the development of drugs
targeting the same diseases, our business could be adversely affected.
In July 2007, we entered into a license and collaboration agreement with Roche. Under the
license and collaboration agreement we granted Roche a non-exclusive license to our intellectual
property to develop and commercialize therapeutic products that function through RNAi, subject to
our existing contractual obligations to third parties. The license is limited to the therapeutic
areas of oncology, respiratory diseases, metabolic diseases and certain liver diseases and may be
expanded to include up to 18 additional therapeutic areas, comprising substantially all other
fields of human disease, as identified and agreed upon by the parties, upon payment to us by Roche
of an additional $50.0 million for each additional therapeutic area, if any. In addition, in
exchange for our contributions under the collaboration agreement, for each RNAi therapeutic product
successfully developed by Roche, its affiliates, or sublicensees under the collaboration agreement,
if any, we are entitled to receive milestone payments upon achievement of specified development and
sales events, totaling up to an aggregate of $100.0 million per therapeutic target, together with
royalty payments based on worldwide annual net sales, if any. In May 2008, we entered into a
similar license and collaboration agreement with Takeda, which is limited to the therapeutic areas
of oncology and metabolic diseases, and which may be expanded to include up to 20 additional
therapeutic areas, comprising substantially all other fields of human disease, as identified and
agreed upon by the parties, upon payment to us by Takeda of an additional $50.0 million for each
additional therapeutic area, if any. For each RNAi therapeutic product successfully developed by
Takeda, its affiliates and sublicensees, if any, we are entitled to receive specified development
and commercialization milestones, totaling up to $171.0 million per product, together with royalty
payments based on
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worldwide annual net sales, if any. In addition, we have agreed that for a period of five
years, we will not grant any other party rights to develop RNAi therapeutics in the Asian
territory.
If Roche or Takeda fails to successfully develop products using our technology, we may not
receive any milestone or royalty payments under these agreements. In addition, even if Takeda is
not successful in its efforts, for a period of five years we will be limited in our ability to form
alliances with other parties in the Asia territory. We also have the option under the Takeda
agreement, exercisable until the start of Phase III development, to opt-in under a 50-50 profit
sharing agreement to the development and commercialization in the United States of up to four
Takeda licensed products, and would be entitled to opt-in rights for two additional products for
each additional field expansion, if any, elected by Takeda under the collaboration agreement. If
Takeda fails to successfully develop products, we may not realize any economic benefit from these
opt-in rights.
Finally, either Roche or Takeda could become a competitor of ours in the development of
RNAi-based drugs targeting the same diseases. Each of these companies has significantly greater
financial resources than we do and has far more experience in developing and marketing drugs, which
could put us at a competitive disadvantage if we were to compete with either Roche or Takeda in the
development of RNAi-based drugs targeting the same disease.
We may not be able to execute our business strategy if we are unable to enter into alliances with
other companies that can provide business and scientific capabilities and funds for the
development and commercialization of our drug candidates. If we are unsuccessful in forming or
maintaining these alliances on favorable terms, our business may not succeed.
We do not have any capability for sales, marketing or distribution and have limited
capabilities for drug development. In addition, we believe that other companies are expending
substantial resources in developing safe and effective means of delivering siRNAs to relevant cell
and tissue types. Accordingly, we have entered into alliances with other companies and
collaborators that we believe can provide such capabilities, and we intend to enter into additional
alliances in the future. For example, we intend to enter into (1) non-exclusive platform alliances
which will enable our collaborators to develop RNAi therapeutics and will bring in additional
funding with which we can develop our RNAi therapeutics, and (2) alliances to jointly develop
specific drug candidates and to jointly commercialize RNAi therapeutics, if they are approved,
and/or ex-U.S. market geographic partnerships on specific RNAi therapeutic programs. In such
alliances, we may expect our collaborators to provide substantial capabilities in delivery of RNAi
therapeutics to the relevant cell or tissue type, clinical development, regulatory affairs, and/or
marketing, sales and distribution. For example, under our collaboration with Medtronic, we are
jointly developing ALN-HTT, an RNAi therapeutic for Huntingtons disease, which would be delivered
using an implanted infusion device developed by Medtronic. The success of this collaboration will
depend, in part, on Medtronics expertise in the area of delivery by infusion device. In other
alliances, we may expect our collaborators to develop, market and sell certain of our product
candidates. We may have limited or no control over the sales, marketing and distribution activities
of these third parties. Our future revenues may depend heavily on the success of the efforts of
these third parties. For example, we will jointly develop and commercialize products for RSV with
Cubist in North America. We will rely entirely on Cubist for the development and commercialization
of products for RSV in the rest of the world outside of Asia, where we will rely on Kyowa Hakko for
development and commercialization of products for RSV. If Cubist and Kyowa Hakko are not successful
in their commercialization efforts, our future revenues for RSV may be adversely affected.
We may not be successful in entering into such alliances on favorable terms due to various
factors, including Novartis right of first offer on our drug targets. Even if we do succeed in
securing such alliances, we may not be able to maintain them if, for example, development or
approval of a drug candidate is delayed or sales of an approved drug are disappointing.
Furthermore, any delay in entering into collaboration agreements could delay the development and
commercialization of our drug candidates and reduce their competitiveness even if they reach the
market. Any such delay related to our collaborations could adversely affect our business.
For certain drug candidates that we may develop, we have formed collaborations to fund all or
part of the costs of drug development and commercialization, such as our collaborations with
Novartis, as well as collaborations with Cubist, Medtronic and NIAID. We may not, however, be able
to enter into additional collaborations, and the terms of any collaboration agreement we do secure
may not be favorable to us. If we are not successful in our efforts to enter into future
collaboration arrangements with respect to a particular drug candidate, we may not have sufficient
funds to develop that or any other drug candidate internally, or to bring any drug candidates to
market. If we do not have sufficient funds to develop and bring our drug candidates to market, we
will not be able to generate sales revenues from these drug candidates, and this will substantially
harm our business.
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If any collaborator terminates or fails to perform its obligations under agreements with us, the
development and commercialization of our drug candidates could be delayed or terminated.
Our dependence on collaborators for capabilities and funding means that our business could be
adversely affected if any collaborator terminates its collaboration agreement with us or fails to
perform its obligations under that agreement. Our current or future collaborations, if any, may not
be scientifically or commercially successful. Disputes may arise in the future with respect to the
ownership of rights to technology or products developed with collaborators, which could have an
adverse effect on our ability to develop and commercialize any affected product candidate.
Our current collaborations allow, and we expect that any future collaborations will allow,
either party to terminate the collaboration for a material breach by the other party. Our agreement
with Kyowa Hakko for the development and commercialization of ALN-RSV01 for the treatment of RSV
infection in Japan and other major markets in Asia may be terminated by Kyowa Hakko without cause
upon 180-days prior written notice to us, subject to certain conditions, and our agreement with
Cubist relating to the development and commercialization of RSV therapeutics in territories outside
of Asia may be terminated by Cubist at any time upon as little as three months prior written
notice, if such notice is given prior to the acceptance for filing of the first application for
regulatory approval of a licensed product. If we were to lose a commercialization collaborator, we
would have to attract a new collaborator or develop internal sales, distribution and marketing
capabilities, which would require us to invest significant amounts of financial and management
resources.
In addition, if a collaborator terminates its collaboration with us, for breach or otherwise,
it would be difficult for us to attract new collaborators and could adversely affect how we are
perceived in the business and financial communities. A collaborator, or in the event of a change in
control of a collaborator, the successor entity, could determine that it is in its financial
interest to:
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pursue alternative technologies or develop alternative products, either on its
own or jointly with others, that may be competitive with the products on which it is
collaborating with us or which could affect its commitment to the collaboration with us;
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pursue higher-priority programs or change the focus of its development programs,
which could affect the collaborators commitment to us; or
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if it has marketing rights, choose to devote fewer resources to the marketing of
our product candidates, if any are approved for marketing, than it does for product
candidates developed without us.
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If any of these occur, the development and commercialization of one or more drug candidates
could be delayed, curtailed or terminated because we may not have sufficient financial resources or
capabilities to continue such development and commercialization on our own.
We depend on government contracts to partially fund our research and development efforts and may
enter into additional government contracts in the future. If current or future government funding,
if any, is reduced or delayed, our drug development efforts for such funded programs may be
negatively affected.
In September 2006, NIAID awarded us a contract for up to $23.0 million over four years to
advance the development of a broad spectrum RNAi anti-viral therapeutic for hemorrhagic fever
virus, including the Ebola virus. Of the $23.0 million in funding, the government initially
committed to pay us up to $14.2 million over the first two years of the contract. In June 2008, as
a result of the progress of the program, the government awarded us an additional $7.5 million, to
be paid through September 2009 for the third year of the contract, together with any remaining
funds carried over from the funding allocated for the first two years of the contract. We cannot be
certain that the government will appropriate the funds necessary for this contract in future
budgets. In addition, the government can terminate the agreement in specified circumstances. If we
do not receive the $23.0 million we expect to receive under this contract, we may not be able to
develop therapeutics to treat Ebola.
For example, in August 2007, DTRA awarded us a contract to advance the development of a broad
spectrum RNAi anti-viral therapeutic for hemorrhagic fever virus infection. When granted, this
federal contract provided for potential funding of up to $38.6 million through February 2011. Of
this amount, the government initially committed to pay us up to $10.9 million through February
2009, which term includes a six-month extension granted by DTRA in July 2008. However, following a
program review in early 2009, we and DTRA have determined not to continue this program and
accordingly, the remaining funds will not be accessed.
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Regulus is important to our business. If Regulus does not successfully develop drugs pursuant to
this license and collaboration agreement or Regulus is sold to Isis or a third-party, our business
could be adversely affected.
In September 2007, we and Isis formed Regulus, of which we currently own approximately 49%, to discover,
develop and commercialize microRNA-based therapeutics. Regulus intends to address therapeutic
opportunities that arise from abnormal expression or mutations in microRNAs. Generally, we do not
have rights to pursue microRNA-based therapeutics independently of Regulus. If Regulus is unable to
discover, develop and commercialize microRNA-based therapeutics, our business could be adversely
affected.
In addition, subject to certain conditions, we and Isis each have the right to initiate a
buy-out of Regulus assets, including Regulus intellectual property and rights to licensed
intellectual property. Following the initiation of such a buy-out, we and Isis will mutually
determine whether to sell Regulus to us, Isis or a third party. We may not have sufficient funds to
buy out Isis interest in Regulus and we may not be able to obtain the financing to do so. In
addition, Isis may not be willing to sell their interest in Regulus. If Regulus is sold to Isis or
a third party, we may lose our rights to participate in the development and commercialization of
microRNA-based therapeutics. If we and Isis are unable to negotiate a sale of Regulus, Regulus will
distribute and assign its rights, interests and assets to us and Isis in accordance with our
percentage interests, except for Regulus intellectual property and license rights, to which each
of us and Isis will receive co-exclusive rights, subject to certain specified exceptions. In this
event, we could face competition from Isis in the development of microRNA-based therapeutics.
We have very limited manufacturing experience or resources and we must incur significant costs to
develop this expertise or rely on third parties to manufacture our products.
We have very limited manufacturing experience. Our internal manufacturing capabilities are
limited to small-scale production of non-good manufacturing practice material for use in
in vitro
and
in vivo
experiments. Our products utilize specialized formulations, such as liposomes, whose
scale-up and manufacturing could be very difficult. We also have very limited experience in such
scale-up and manufacturing, requiring us to depend on third parties, who might not be able to
deliver in a timely manner, or at all. In order to develop products, apply for regulatory approvals
and commercialize our products, we will need to develop, contract for, or otherwise arrange for the
necessary manufacturing capabilities. We may manufacture clinical trial materials ourselves or we
may rely on others to manufacture the materials we will require for any clinical trials that we
initiate. Only a limited number of manufacturers supply synthetic siRNAs. We currently rely on
several contract manufacturers for our supply of synthetic siRNAs. There are risks inherent in
pharmaceutical manufacturing that could affect the ability of our contract manufacturers to meet
our delivery time requirements or provide adequate amounts of material to meet our needs. Included
in these risks are synthesis and purification failures and contamination during the manufacturing
process, which could result in unusable product and cause delays in our development process, as
well as additional expense to us. To fulfill our siRNA requirements, we may also need to secure
alternative suppliers of synthetic siRNAs. In addition to the manufacture of the synthetic siRNAs,
we may have additional manufacturing requirements related to the technology required to deliver the
siRNA to the relevant cell or tissue type. In some cases, the delivery technology we utilize is
highly specialized or proprietary, and for technical and legal reasons, we may have access to only
one or a limited number of potential manufacturers for such delivery technology. Failure by these
manufacturers to properly formulate our siRNAs for delivery could also result in unusable product
and cause delays in our discovery and development process, as well as additional expense to us.
The manufacturing process for any products that we may develop is subject to the FDA and
foreign regulatory authority approval process and we will need to contract with manufacturers who
can meet all applicable FDA and foreign regulatory authority requirements on an ongoing basis. In
addition, if we receive the necessary regulatory approval for any product candidate, we also expect
to rely on third parties, including our commercial collaborators, to produce materials required for
commercial supply. We may experience difficulty in obtaining adequate manufacturing capacity for
our needs. If we are unable to obtain or maintain contract manufacturing for these product
candidates, or to do so on commercially reasonable terms, we may not be able to successfully
develop and commercialize our products.
To the extent that we enter into manufacturing arrangements with third parties, we will depend
on these third parties to perform their obligations in a timely manner and consistent with
regulatory requirements, including those related to quality control and quality assurance. The
failure of a third-party manufacturer to perform its obligations as expected could adversely affect
our business in a number of ways, including:
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we may not be able to initiate or continue clinical trials of products that are under
development;
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we may be delayed in submitting regulatory applications, or receiving regulatory
approvals, for our product candidates;
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we may lose the cooperation of our collaborators;
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we may be required to cease distribution or recall some or all batches of our
products; and
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ultimately, we may not be able to meet commercial demands for our products.
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If a third-party manufacturer with whom we contract fails to perform its obligations, we may
be forced to manufacture the materials ourselves, for which we may not have the capabilities or
resources, or enter into an agreement with a different third-party manufacturer, which we may not
be able to do with reasonable terms, if at all. In some cases, the technical skills required to
manufacture our product may be unique to the original manufacturer and we may have difficulty
transferring such skills to a back-up nor alternate supplier, or we may be unable to transfer such
skills at all. In addition, if we are required to change manufacturers for any reason, we will be
required to verify that the new manufacturer maintains facilities and procedures that comply with
quality standards and with all applicable regulations and guidelines. The delays associated with
the verification of a new manufacturer could negatively affect our ability to develop product
candidates in a timely manner or within budget. Furthermore, a manufacturer may possess technology
related to the manufacture of our product candidate that such manufacturer owns independently. This
would increase our reliance on such manufacturer or require us to obtain a license from such
manufacturer in order to have another third party manufacture our products.
We have no sales, marketing or distribution experience and would have to invest significant
financial and management resources to establish these capabilities.
We have no sales, marketing or distribution experience. We currently expect to rely heavily on
third parties to launch and market certain of our product candidates, if approved. However, if we
elect to develop internal sales, distribution and marketing capabilities, we will need to invest
significant financial and management resources. For products where we decide to perform sales,
marketing and distribution functions ourselves, we could face a number of additional risks,
including:
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we may not be able to attract and build a significant marketing or sales force;
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the cost of establishing a marketing or sales force may not be justifiable in
light of the revenues generated by any particular product; and
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our direct sales and marketing efforts may not be successful.
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If we are unable to develop our own sales, marketing and distribution capabilities, we will not be
able to successfully commercialize our products without reliance on third parties.
The current credit and financial market conditions may exacerbate certain risks affecting our
business.
Due to the recent tightening of global credit, there may be a disruption or delay in the
performance of our third-party contractors, suppliers or collaborators. We rely on third parties
for several important aspects of our business, including significant portions of our manufacturing
needs, development of product candidates and conduct of clinical trials. If such third parties are
unable to satisfy their commitments to us, our business could be adversely affected.
Risks Related to Managing Our Operations
If we are unable to attract and retain qualified key management and scientists, staff consultants
and advisors, our ability to implement our business plan may be adversely affected.
We are highly dependent upon our senior management and scientific staff. The loss of the
service of any of the members of our senior management, including Dr. John Maraganore, our Chief
Executive Officer, may significantly delay or prevent the achievement of product development and
other business objectives. Our employment agreements with our key personnel are terminable without
notice. We do not carry key man life insurance on any of our employees.
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Although we have generally been successful in our recruiting efforts, as well as our retention
of employees, we face intense competition for qualified individuals from numerous pharmaceutical
and biotechnology companies, universities, governmental entities and other research institutions,
many of which have substantially greater resources with which to reward qualified individuals than
we do. We may be unable to attract and retain suitably qualified individuals, and our failure to do
so could have an adverse effect on our ability to implement our business plan.
We may have difficulty managing our growth and expanding our operations successfully as we seek to
evolve from a company primarily involved in discovery and pre-clinical testing into one that
develops and commercializes drugs.
Since we commenced operations in 2002, we have grown substantially. As of March 31, 2009, we
had approximately 173 employees in our facility in Cambridge, Massachusetts. Our rapid and
substantial growth may place a strain on our administrative and operational infrastructure. If drug
candidates we develop enter and advance through clinical trials, we will need to expand our
development, regulatory, manufacturing, marketing and sales capabilities or contract with other
organizations to provide these capabilities for us. As our operations expand, we expect that we
will need to manage additional relationships with various collaborators, suppliers and other
organizations. Our ability to manage our operations and growth will require us to continue to
improve our operational, financial and management controls, reporting systems and procedures. We
may not be able to implement improvements to our management information and control systems in an
efficient or timely manner and may discover deficiencies in existing systems and controls.
Risks Related to Our Industry
Risks Related to Development, Clinical Testing and Regulatory Approval of Our Drug Candidates
Any drug candidates we develop may fail in development or be delayed to a point where they do not
become commercially viable.
Pre-clinical testing and clinical trials of new drug candidates are lengthy and expensive and
the historical failure rate for drug candidates is high. We are developing our most advanced
product candidate, ALN-RSV01, for the treatment of RSV infection. In January 2008, we completed our
GEMINI study, a Phase II trial designed to evaluate the safety, tolerability and anti-viral
activity of ALN-RSV01 in adult subjects experimentally infected with RSV. We commenced a second
Phase II trial in April 2008 to assess the safety and tolerability of ALN-RSV01 in adult lung
transplant patients naturally infected with RSV and we intend to continue the clinical development
of ALN-RSV01. In addition, in December 2008, we submitted an IND to the FDA for ALN-VSP, our first
systemically delivered RNAi therapeutic. We are developing ALN-VSP for the treatment of certain
liver cancers. We received clearance from the FDA in January 2009 to proceed with a Phase I study
and initiated this study in March 2009. However, we may not be able to further advance these or any
other product candidate through clinical trials. If we successfully enter into clinical studies,
the results from pre-clinical testing or early clinical trials of a drug candidate may not predict
the results that will be obtained in subsequent human clinical trials. For example, ALN-VSP and our
other systemically delivered therapeutic candidates employ novel delivery formulations that have
yet to be evaluated in human studies and have yet to be proven safe and effective in clinical
trials. We, the FDA or other applicable regulatory authorities, or an institutional review board,
or IRB, may suspend clinical trials of a drug candidate at any time for various reasons, including
if we or they believe the subjects or patients participating in such trials are being exposed to
unacceptable health risks. Among other reasons, adverse side effects of a drug candidate on
subjects or patients in a clinical trial could result in the FDA or foreign regulatory authorities
suspending or terminating the trial and refusing to approve a particular drug candidate for any or
all indications of use.
Clinical trials of a new drug candidate require the enrollment of a sufficient number of
patients, including patients who are suffering from the disease the drug candidate is intended to
treat and who meet other eligibility criteria. Rates of patient enrollment are affected by many
factors, including the size of the patient population, the age and condition of the patients, the
nature of the protocol, the proximity of patients to clinical sites, the availability of effective
treatments for the relevant disease, the seasonality of infections and the eligibility criteria for
the clinical trial. Delays in patient enrollment can result in increased costs and longer
development times.
Clinical trials also require the review and oversight of IRBs, which approve and continually
review clinical investigations and protect the rights and welfare of human subjects. Inability to
obtain or delay in obtaining IRB approval can prevent or delay the initiation and completion of
clinical trials, and the FDA may decide not to consider any data or information derived from a
clinical investigation not subject to initial and continuing IRB review and approval in support of
a marketing application.
Our drug candidates that we develop may encounter problems during clinical trials that will
cause us, an IRB or regulatory
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authorities to delay, suspend or terminate these trials, or that will delay the analysis of
data from these trials. If we experience any such problems, we may not have the financial resources
to continue development of the drug candidate that is affected, or development of any of our other
drug candidates. We may also lose, or be unable to enter into, collaborative arrangements for the
affected drug candidate and for other drug candidates we are developing.
Delays in clinical trials could reduce the commercial viability of our drug candidates. Any of
the following could, among other things, delay our clinical trials:
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delays in filing initial drug applications;
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conditions imposed on us by the FDA or comparable foreign authorities regarding
the scope or design of our clinical trials;
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problems in engaging IRBs to oversee trials or problems in obtaining or maintaining IRB
approval of trials;
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delays in enrolling patients and volunteers into clinical trials;
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high drop-out rates for patients and volunteers in clinical trials;
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negative or inconclusive results from our clinical trials or the clinical trials
of others for drug candidates similar to ours;
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inadequate supply or quality of drug candidate materials or other materials
necessary for the conduct of our clinical trials;
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serious and unexpected drug-related side effects experienced by participants in
our clinical trials or by individuals using drugs similar to our product candidates; or
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unfavorable FDA or other regulatory agency inspection and review of a clinical
trial site or records of any clinical or pre-clinical investigation.
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Even if we successfully complete clinical trials of our drug candidates, any given drug
candidate may not prove to be an effective treatment for the diseases for which it was being
tested.
The FDA approval process may be delayed for any drugs we develop that require the use of
specialized drug delivery devices.
Some drug candidates that we develop may need to be administered using specialized drug
delivery devices that deliver RNAi therapeutics directly to diseased parts of the body. For
example, we believe that product candidates we develop for Parkinsons disease, HD or other central
nervous system diseases may need to be administered using such a device. For neurodegenerative
diseases, we have entered into a collaboration agreement with Medtronic to pursue potential
development of drug-device combinations incorporating RNAi therapeutics. We may not achieve
successful development results under this collaboration and may need to seek other collaboration
partners to develop alternative drug delivery systems, or utilize existing drug delivery systems,
for the direct delivery of RNAi therapeutics for these diseases. While we expect to rely on drug
delivery systems that have been approved by the FDA or other regulatory agencies to deliver drugs
like ours to similar physiological sites, we, or our collaborator, may need to modify the design or
labeling of such delivery device for some products we may develop. In such an event, the FDA may
regulate the product as a combination product or require additional approvals or clearances for the
modified delivery device. Further, to the extent the specialized delivery device is owned by
another company, we would need that companys cooperation to implement the necessary changes to the
device, or its labeling, and to obtain any additional approvals or clearances. In cases where we do
not have an ongoing collaboration with the company that makes the device, obtaining such additional
approvals or clearances and the cooperation of such other company could significantly delay and
increase the cost of obtaining marketing approval, which could reduce the commercial viability of
our drug candidate. In summary, we may be unable to find, or experience delays in finding, suitable
drug delivery systems to administer RNAi therapeutics directly to diseased parts of the body, which
could negatively affect our ability to successfully commercialize these RNAi therapeutics.
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We may be unable to obtain United States or foreign regulatory approval and, as a result, be
unable to commercialize our drug candidates.
Our drug candidates are subject to extensive governmental regulations relating to, among other
things, research, testing, development, manufacturing, safety, efficacy, recordkeeping, labeling,
marketing and distribution of drugs. Rigorous pre-clinical testing and clinical trials and an
extensive regulatory approval process are required to be successfully completed in the United
States and in many foreign jurisdictions before a new drug can be marketed. Satisfaction of these
and other regulatory requirements is costly, time consuming, uncertain and subject to unanticipated
delays. It is possible that none of the drug candidates we may develop will obtain the appropriate
regulatory approvals necessary for us or our collaborators to begin selling them.
We have very limited experience in conducting and managing the clinical trials necessary to
obtain regulatory approvals, including approval by the FDA. The time required to obtain FDA and
other approvals is unpredictable but typically takes many years following the commencement of
clinical trials, depending upon the complexity of the drug candidate. Any analysis we perform of
data from pre-clinical and clinical activities is subject to confirmation and interpretation by
regulatory authorities, which could delay, limit or prevent regulatory approval. We may also
encounter unexpected delays or increased costs due to new government regulations, for example, from
future legislation or administrative action, or from changes in FDA policy during the period of
product development, clinical trials and FDA regulatory review. For example, the Food and Drug
Administration Amendments Act of 2007, or FDAAA, may make it more difficult and costly for us to
obtain regulatory approval of our product candidates and to produce, market and distribute products
after approval. The FDAAA granted a variety of new powers to the FDA, many of which are aimed at
improving the safety of drug products before and after approval. In particular, it authorizes the
FDA to, among other things, require post-approval studies and clinical trials, mandate changes to
drug labeling to reflect new safety information, and require risk evaluation and mitigation
strategies, or REMS, for certain drugs, including certain currently approved drugs. In addition, it
significantly expanded the federal governments clinical trial registry and results databank and
creates new restrictions on the advertising and promotion of drug products. Under the FDAAA,
companies that violate the new law are subject to substantial civil monetary penalties.
Because the drugs we are intending to develop may represent a new class of drug, the FDA has
not yet established any definitive policies, practices or guidelines in relation to these drugs.
While the product candidates that we are currently developing are regulated as a new drug under the
Federal Food, Drug, and Cosmetic Act, the FDA could decide to regulate them or other products we
may develop as biologics under the Public Health Service Act. The lack of policies, practices or
guidelines may hinder or slow review by the FDA of any regulatory filings that we may submit.
Moreover, the FDA may respond to these submissions by defining requirements we may not have
anticipated. Such responses could lead to significant delays in the clinical development of our
product candidates. In addition, because there may be approved treatments for some of the diseases
for which we may seek approval, in order to receive regulatory approval, we will need to
demonstrate through clinical trials that the product candidates we develop to treat these diseases,
if any, are not only safe and effective, but safer or more effective than existing products.
Furthermore, in recent years, there has been increased public and political pressure on the FDA
with respect to the approval process for new drugs, and the number of approvals to market new drugs
has declined.
Any delay or failure in obtaining required approvals could have a material adverse effect on
our ability to generate revenues from the particular drug candidate. Furthermore, any regulatory
approval to market a product may be subject to limitations on the indicated uses for which we may
market the product. These limitations may limit the size of the market for the product and affect
reimbursement by third-party payors.
We are also subject to numerous foreign regulatory requirements governing, among other things,
the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party
reimbursement. The foreign regulatory approval process includes all of the risks associated with
FDA approval described above as well as risks attributable to the satisfaction of local regulations
in foreign jurisdictions. Approval by the FDA does not assure approval by regulatory authorities
outside the United States and vice versa.
If our pre-clinical testing does not produce successful results or our clinical trials do not
demonstrate safety and efficacy in humans, we will not be able to commercialize our drug
candidates.
Before obtaining regulatory approval for the sale of our drug candidates, we must conduct, at
our own expense, extensive pre-clinical tests and clinical trials to demonstrate the safety and
efficacy in humans of our drug candidates. Pre-clinical and clinical testing is expensive,
difficult to design and implement, can take many years to complete and is uncertain as to outcome.
Success in pre-clinical testing and early clinical trials does not ensure that later clinical
trials will be successful, and interim results of a clinical trial do not necessarily predict final
results.
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A failure of one of more of our clinical trials can occur at any stage of testing. We may
experience numerous unforeseen events during, or as a result of, pre-clinical testing and the
clinical trial process that could delay or prevent our ability to receive regulatory approval or
commercialize our drug candidates, including:
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regulators or IRBs may not authorize us to commence or continue a clinical trial
or conduct a clinical trial at a prospective trial site;
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our pre-clinical tests or clinical trials may produce negative or inconclusive
results, and we may decide, or regulators may require us, to conduct additional
pre-clinical testing or clinical trials, or we may abandon projects that we expect to be
promising;
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enrollment in our clinical trials may be slower than we anticipate or
participants may drop out of our clinical trials at a higher rate than we anticipate,
resulting in significant delays;
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our third party contractors may fail to comply with regulatory requirements or
meet their contractual obligations to us in a timely manner;
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we might have to suspend or terminate our clinical trials if the participants are
being exposed to unacceptable health risks;
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IRBs or regulators, including the FDA, may require that we hold, suspend or
terminate clinical research for various reasons, including noncompliance with regulatory
requirements;
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the cost of our clinical trials may be greater than we anticipate;
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the supply or quality of our drug candidates or other materials necessary to
conduct our clinical trials may be insufficient or inadequate;
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effects of our drug candidates may not be the desired effects or may include
undesirable side effects or the drug candidates may have other unexpected
characteristics; and
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effects of our drug candidates may not be clear, or we may disagree with
regulatory authorities, including the FDA, about how to interpret the data generated in
our clinical trials.
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Even if we obtain regulatory approvals, our marketed drugs will be subject to ongoing regulatory
review. If we fail to comply with continuing United States and foreign regulations, we could lose
our approvals to market drugs and our business would be seriously harmed.
Following any initial regulatory approval of any drugs we may develop, we will also be subject
to continuing regulatory review, including the review of adverse drug experiences and clinical
results that are reported after our drug products are made commercially available. This would
include results from any post-marketing tests or vigilance required as a condition of approval. The
manufacturer and manufacturing facilities we use to make any of our drug candidates will also be
subject to periodic review and inspection by the FDA. The discovery of any new or previously
unknown problems with the product, manufacturer or facility may result in restrictions on the drug
or manufacturer or facility, including withdrawal of the drug from the market. We do not have, and
currently do not intend to develop, the ability to manufacture material for our clinical trials or
on a commercial scale. We may manufacture clinical trial materials or we may contract a third party
to manufacture these materials for us. Reliance on third-party manufacturers entails risks to which
we would not be subject if we manufactured products ourselves, including reliance on the
third-party manufacturer for regulatory compliance. Our product promotion and advertising is also
subject to regulatory requirements and continuing regulatory review.
If we fail to comply with applicable continuing regulatory requirements, we may be subject to
fines, suspension or withdrawal of regulatory approval, product recalls and seizures, operating
restrictions and criminal prosecution.
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Even if we receive regulatory approval to market our product candidates, the market may not be
receptive to our product candidates upon their commercial introduction, which will prevent us from
becoming profitable.
The product candidates that we are developing are based upon new technologies or therapeutic
approaches. Key participants in pharmaceutical marketplaces, such as physicians, third-party payors
and consumers, may not accept a product intended to improve therapeutic results based on RNAi
technology. As a result, it may be more difficult for us to convince the medical community and
third-party payors to accept and use our product, or to provide favorable reimbursement.
Other factors that we believe will materially affect market acceptance of our product
candidates include:
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the timing of our receipt of any marketing approvals, the terms of any approvals
and the countries in which approvals are obtained;
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the safety, efficacy and ease of administration of our product candidates;
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the willingness of patients to accept potentially new routes of administration;
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the success of our physician education programs;
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the availability of government and third-party payor reimbursement;
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the pricing of our products, particularly as compared to alternative treatments; and
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availability of alternative effective treatments for the diseases that product
candidates we develop are intended to treat and the relative risks, benefits and costs
of the treatments.
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Even if we develop an RNAi therapeutic product for the prevention or treatment of infection by
hemorrhagic fever viruses such as Ebola, governments may not elect to purchase such a product,
which could adversely affect our business.
We expect that governments will be the only purchasers of any products we may develop for the
prevention or treatment of hemorrhagic fever viruses such as Ebola. In the future, we may also
initiate additional programs for the development of product candidates for which governments may be
the only or primary purchasers. However, governments will not be required to purchase any such
products from us and may elect not to do so, which could adversely affect our business. For
example, although the focus of our Ebola program is to develop RNAi therapeutic targeting gene
sequences that are highly conserved across known Ebola viruses, if the sequence of any Ebola virus
that emerges is not sufficiently similar to those we are targeting, any product candidate that we
develop may not be effective against that virus. Accordingly, while we expect that any RNAi
therapeutic we develop for the treatment of Ebola could be stockpiled by governments as part of
their biodefense preparations, they may not elect to purchase such product, or if they purchase our
products, they may not do so at prices and volume levels that are profitable for us.
If we or our collaborators, manufacturers or service providers fail to comply with regulatory laws
and regulations, we or they could be subject to enforcement actions, which could affect our
ability to market and sell our products and may harm our reputation.
If we or our collaborators, manufacturers or service providers fail to comply with applicable
federal, state or foreign laws or regulations, we could be subject to enforcement actions, which
could affect our ability to develop, market and sell our products successfully and could harm our
reputation and lead to reduced acceptance of our products by the market. These enforcement actions
include:
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warning letters;
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product recalls or public notification or medical product safety alerts to healthcare
professionals;
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restrictions on, or prohibitions against, marketing our products;
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restrictions on importation or exportation of our products;
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suspension of review or refusal to approve pending applications;
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exclusion from participation in government-funded healthcare programs;
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exclusion from eligibility for the award of government contracts for our products;
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suspension or withdrawal of product approvals;
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product seizures;
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injunctions; and
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civil and criminal penalties and fines.
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Any drugs we develop may become subject to unfavorable pricing regulations, third-party
reimbursement practices or healthcare reform initiatives, thereby harming our business.
The regulations that govern marketing approvals, pricing and reimbursement for new drugs vary
widely from country to country. Some countries require approval of the sale price of a drug before
it can be marketed. In many countries, the pricing review period begins after marketing or product
licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains
subject to continuing governmental control even after initial approval is granted. Although we
intend to monitor these regulations, our programs are currently in the early stages of development
and we will not be able to assess the impact of price regulations for a number of years. As a
result, we might obtain regulatory approval for a product in a particular country, but then be
subject to price regulations that delay our commercial launch of the product and negatively impact
the revenues we are able to generate from the sale of the product in that country.
Our ability to commercialize any products successfully also will depend in part on the extent
to which reimbursement for these products and related treatments will be available from government
health administration authorities, private health insurers and other organizations. Even if we
succeed in bringing one or more products to the market, these products may not be considered
cost-effective, and the amount reimbursed for any products may be insufficient to allow us to sell
our products on a competitive basis. Because our programs are in the early stages of development,
we are unable at this time to determine their cost effectiveness or the likely level or method of
reimbursement. Increasingly, the third-party payors who reimburse patients, such as government and
private insurance plans, are requiring that drug companies provide them with predetermined
discounts from list prices, and are seeking to reduce the prices charged for pharmaceutical
products. If the price we are able to charge for any products we develop is inadequate in light of
our development and other costs, our profitability could be adversely affected.
We currently expect that any drugs we develop may need to be administered under the
supervision of a physician. Under currently applicable United States law, drugs that are not
usually self-administered may be eligible for coverage by the Medicare program if:
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they are incident to a physicians services;
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they are reasonable and necessary for the diagnosis or treatment of the illness
or injury for which they are administered according to accepted standard of medical
practice;
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they are not excluded as immunizations; and
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they have been approved by the FDA.
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There may be significant delays in obtaining coverage for newly-approved drugs, and coverage
may be more limited than the purposes for which the drug is approved by the FDA. Moreover,
eligibility for coverage does not imply that any drug will be reimbursed in all cases or at a rate
that covers our costs, including research, development, manufacture, sale and distribution. Interim
payments for new drugs, if applicable, may also not be sufficient to cover our costs and may not be
made permanent. Reimbursement may be based on payments allowed for lower-cost drugs that are
already reimbursed, may be incorporated into existing payments for other services and may reflect
budgetary constraints or imperfections in Medicare data. Net prices for drugs may be reduced by
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mandatory discounts or rebates required by government health care programs or private payors
and by any future relaxation of laws that presently restrict imports of drugs from countries where
they may be sold at lower prices than in the United States. Third party payors often rely upon
Medicare coverage policy and payment limitations in setting their own reimbursement rates. Our
inability to promptly obtain coverage and profitable reimbursement rates from both
government-funded and private payors for new drugs that we develop could have a material adverse
effect on our operating results, our ability to raise capital needed to commercialize products, and
our overall financial condition.
We believe that the efforts of governments and third-party payors to contain or reduce the
cost of healthcare will continue to affect the business and financial condition of pharmaceutical
and biopharmaceutical companies. A number of legislative and regulatory proposals to change the
healthcare system in the United States and other major healthcare markets have been proposed in
recent years. These proposals have included prescription drug benefit legislation that was enacted
and took effect in January 2006 and healthcare reform legislation recently enacted by certain
states. Further federal and state legislative and regulatory developments are possible and we
expect ongoing initiatives in the United States to increase pressure on drug pricing. Such reforms
could have an adverse effect on anticipated revenues from drug candidates that we may successfully
develop.
Another development that may affect the pricing of drugs is Congressional action regarding
drug reimportation into the United States. Recent proposed legislation has been introduced in
Congress that, if enacted, would permit more widespread reimportation of drugs from foreign
countries into the United States. This could include reimportation from foreign countries where
the drugs are sold at lower prices than in the United States. Such legislation, or similar
regulatory changes, could lead to a decrease in the price we receive for any approved products,
which, in turn, could impair our ability to generate revenue. Alternatively, in response to
legislation such as this, we might elect not to seek approval for or market our products in foreign
jurisdictions in order to minimize the risk of reimportation, which could also reduce the revenue
we generate from our product sales.
There is a substantial risk of product liability claims in our business. If we are unable to
obtain sufficient insurance, a product liability claim against us could adversely affect our
business.
Our business exposes us to significant potential product liability risks that are inherent in
the development, manufacturing and marketing of human therapeutic products. Product liability
claims could delay or prevent completion of our clinical development programs. If we succeed in
marketing products, such claims could result in an FDA investigation of the safety and
effectiveness of our products, our manufacturing processes and facilities or our marketing
programs, and potentially a recall of our products or more serious enforcement action, limitations
on the indications for which they may be used, or suspension or withdrawal of approvals. We
currently have product liability insurance that we believe is appropriate for our stage of
development and may need to obtain higher levels prior to marketing any of our drug candidates. Any
insurance we have or may obtain may not provide sufficient coverage against potential liabilities.
Furthermore, clinical trial and product liability insurance is becoming increasingly expensive. As
a result, we may be unable to obtain sufficient insurance at a reasonable cost to protect us
against losses caused by product liability claims that could have a material adverse effect on our
business.
If we do not comply with laws regulating the protection of the environment and health and human
safety, our business could be adversely affected.
Our research and development involves the use of hazardous materials, chemicals and various
radioactive compounds. We maintain quantities of various flammable and toxic chemicals in our
facilities in Cambridge that are required for our research and development activities. We are
subject to federal, state and local laws and regulations governing the use, manufacture, storage,
handling and disposal of these hazardous materials. We believe our procedures for storing, handling
and disposing these materials in our Cambridge facility comply with the relevant guidelines of the
City of Cambridge and the Commonwealth of Massachusetts. Although we believe that our safety
procedures for handling and disposing of these materials comply with the standards mandated by
applicable regulations, the risk of accidental contamination or injury from these materials cannot
be eliminated. If an accident occurs, we could be held liable for resulting damages, which could be
substantial. We are also subject to numerous environmental, health and workplace safety laws and
regulations, including those governing laboratory procedures, exposure to blood-borne pathogens and
the handling of biohazardous materials.
Although we maintain workers compensation insurance to cover us for costs and expenses we may
incur due to injuries to our employees resulting from the use of these materials, this insurance
may not provide adequate coverage against potential liabilities. We do not maintain insurance for
environmental liability or toxic tort claims that may be asserted against us in connection with our
storage or disposal of biological, hazardous or radioactive materials. Additional federal, state
and local laws and regulations affecting our operations may be adopted in the future. We may incur
substantial costs to comply with, and substantial fines or penalties if we violate, any of these
laws or regulations.
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Risks Related to Patents, Licenses and Trade Secrets
If we are not able to obtain and enforce patent protection for our discoveries, our ability to
develop and commercialize our product candidates will be harmed.
Our success depends, in part, on our ability to protect proprietary methods and technologies
that we develop under the patent and other intellectual property laws of the United States and
other countries, so that we can prevent others from unlawfully using our inventions and proprietary
information. However, we may not hold proprietary rights to some patents required for us to
commercialize our proposed products. Because certain U.S. patent applications are confidential
until the patents issue, such as applications filed prior to November 29, 2000, or applications
filed after such date which will not be filed in foreign countries, third parties may have filed
patent applications for technology covered by our pending patent applications without our being
aware of those applications, and our patent applications may not have priority over those
applications. For this and other reasons, we may be unable to secure desired patent rights, thereby
losing desired exclusivity. Further, we may be required to obtain licenses under third-party
patents to market our proposed products or conduct our research and development or other
activities. If licenses are not available to us on acceptable terms, we will not be able to market
the affected products or conduct the desired activities.
Our strategy depends on our ability to rapidly identify and seek patent protection for our
discoveries. In addition, we may rely on third-party collaborators to file patent applications
relating to proprietary technology that we develop jointly during certain collaborations. The
process of obtaining patent protection is expensive and time-consuming. If our present or future
collaborators fail to file and prosecute all necessary and desirable patent applications at a
reasonable cost and in a timely manner, our business will be adversely affected. Despite our
efforts and the efforts of our collaborators to protect our proprietary rights, unauthorized
parties may be able to obtain and use information that we regard as proprietary. While issued
patents are presumed valid, this does not guarantee that the patent will survive a validity
challenge or be held enforceable. Any patents we have obtained, or obtain in the future, may be
challenged, invalidated, adjudged unenforceable or circumvented by parties attempting to design
around our intellectual property. Moreover, third parties or the U.S. Patent and Trademark Office, or USPTO,
may commence interference
proceedings involving our patents or patent applications. Any challenge to, finding of
unenforceability or invalidation or circumvention of, our patents or patent applications would be
costly, would require significant time and attention of our management and could have a material
adverse effect on our business.
Our pending patent applications may not result in issued patents. The patent position of
pharmaceutical or biotechnology companies, including ours, is generally uncertain and involves
complex legal and factual considerations. The standards that the USPTO and its foreign counterparts
use to grant patents are not always applied predictably or uniformly and can change. Adding to the
uncertainty of our current intellectual property portfolio and our ability to secure and enforce
future patent rights are the outcome of a legal dispute surrounding the implementation of certain
continuation and claims rules promulgated by the USPTO, which were scheduled to take effect
November 1, 2007, but which are now enjoined and on appeal, and the outcome of Congressional
efforts to reform the Patent Act of 1952. There is also no uniform, worldwide policy regarding the
subject matter and scope of claims granted or allowable in pharmaceutical or biotechnology patents.
Accordingly, we do not know the degree of future protection for our proprietary rights or the
breadth of claims that will be allowed in any patents issued to us or to others.
We also rely to a certain extent on trade secrets, know-how and technology, which are not
protected by patents, to maintain our competitive position. If any trade secret, know-how or other
technology not protected by a patent were to be disclosed to or independently developed by a
competitor, our business and financial condition could be materially adversely affected.
We license patent rights from third party owners. If such owners do not properly maintain or
enforce the patents underlying such licenses, our competitive position and business prospects will
be harmed.
We are a party to a number of licenses that give us rights to third party intellectual
property that is necessary or useful for our business. In particular, we have obtained licenses
from, among others, Isis, MIT, the Whitehead Institute for Biomedical Research, Max Planck
Innovation, Stanford University, Tekmira and The University of Texas Southwestern Medical Center. We also intend to enter into additional licenses
to third party intellectual property in the future.
Our success will depend in part on the ability of our licensors to obtain, maintain and
enforce patent protection for our licensed intellectual property, in particular, those patents to
which we have secured exclusive rights. Our licensors may not successfully prosecute the patent
applications to which we are licensed. Even if patents issue in respect of these patent
applications,
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our licensors may fail to maintain these patents, may determine not to pursue litigation
against other companies that are infringing these patents, or may pursue such litigation less
aggressively than we would. Without protection for the intellectual property we license, other
companies might be able to offer substantially identical products for sale, which could adversely
affect our competitive business position and harm our business prospects.
Other companies or organizations may challenge our patent rights or may assert patent rights that
prevent us from developing and commercializing our products.
RNA interference is a relatively new scientific field, the commercial exploitation of which
has resulted in many different patents and patent applications from organizations and individuals
seeking to obtain patent protection in the field. We have obtained grants and issuances of RNAi
patents and have licensed many of these patents from third parties on an exclusive basis. The
issued patents and pending patent applications in the United States and in key markets around the
world that we own or license claim many different methods, compositions and processes relating to
the discovery, development, manufacture and commercialization of RNAi therapeutics. Specifically,
we have a portfolio of patents, patent applications and other intellectual property covering:
fundamental aspects of the structure and uses of siRNAs, including their manufacture and use as
therapeutics, and RNAi-related mechanisms; chemical modifications to siRNAs that improve their
suitability for therapeutic uses; siRNAs directed to specific targets as treatments for particular
diseases; and delivery technologies, such as in the field of cationic liposomes.
As the field of RNAi therapeutics is maturing, patent applications are being fully processed
by national patent offices around the world. There is uncertainty about which patents will issue,
and, if they do, as to when, to whom, and with what claims. It is likely that there will be
significant litigation and other proceedings, such as interference, reexamination and opposition
proceedings, in various patent offices relating to patent rights in the RNAi field. For example,
various third parties have initiated oppositions to patents in our Kreutzer-Limmer and Tuschl II
series in the EPO and in other jurisdictions. We expect that additional oppositions will be filed
in the EPO and elsewhere, and other challenges will be raised relating to other patents and patent
applications in our portfolio. In many cases, the possibility of appeal exists for either us or our
opponents, and it may be years before final, unappealable rulings are made with respect to these
patents in certain jurisdictions. The timing and outcome of these and other proceedings is
uncertain and may adversely affect our business if we are not successful in defending the
patentability and scope of our pending and issued patent claims. In addition, third parties may
attempt to invalidate our intellectual property rights. Even if our rights are not directly
challenged, disputes could lead to the weakening of our intellectual property rights. Our defense
against any attempt by third parties to circumvent or invalidate our intellectual property rights
could be costly to us, could require significant time and attention of our management and could
have a material adverse effect on our business and our ability to successfully compete in the field
of RNAi.
There are many issued and pending patents that claim aspects of oligonucleotide chemistry that
we may need to apply to our siRNA drug candidates. There are also many issued patents that claim
targeting genes or portions of genes that may be relevant for siRNA drugs we wish to develop. Thus,
it is possible that one or more organizations will hold patent rights to which we will need a
license. If those organizations refuse to grant us a license to such patent rights on reasonable
terms, we may not be able to market products or perform research and development or other
activities covered by these patents.
If we become involved in patent litigation or other proceedings related to a determination of
rights, we could incur substantial costs and expenses, substantial liability for damages or be
required to stop our product development and commercialization efforts.
Third parties may sue us for infringing their patent rights. Likewise, we may need to resort
to litigation to enforce a patent issued or licensed to us or to determine the scope and validity
of proprietary rights of others. In addition, a third party may claim that we have improperly
obtained or used its confidential or proprietary information. Furthermore, in connection with a
license agreement, we have agreed to indemnify the licensor for costs incurred in connection with
litigation relating to intellectual property rights. The cost to us of any litigation or other
proceeding relating to intellectual property rights, even if resolved in our favor, could be
substantial, and the litigation would divert our managements efforts. Some of our competitors may
be able to sustain the costs of complex patent litigation more effectively than we can because they
have substantially greater resources. Uncertainties resulting from the initiation and continuation
of any litigation could limit our ability to continue our operations.
If any parties successfully claim that our creation or use of proprietary technologies
infringes upon their intellectual property rights, we might be forced to pay damages, potentially
including treble damages, if we are found to have willfully infringed on such parties patent
rights. In addition to any damages we might have to pay, a court could require us to stop the
infringing activity or obtain a license. Any license required under any patent may not be made
available on commercially acceptable terms, if at all. In addition, such licenses are likely to be
non-exclusive and, therefore, our competitors may have access to the same technology licensed
45
to us. If we fail to obtain a required license and are unable to design around a patent, we
may be unable to effectively market some of our technology and products, which could limit our
ability to generate revenues or achieve profitability and possibly prevent us from generating
revenue sufficient to sustain our operations. Moreover, we expect that a number of our
collaborations will provide that royalties payable to us for licenses to our intellectual property
may be offset by amounts paid by our collaborators to third parties who have competing or superior
intellectual property positions in the relevant fields, which could result in significant
reductions in our revenues from products developed through collaborations.
If we fail to comply with our obligations under any licenses or related agreements, we could lose
license rights that are necessary for developing and protecting our RNAi technology and any
related product candidates that we develop, or we could lose certain exclusive rights to grant
sublicenses.
Our current licenses impose, and any future licenses we enter into are likely to impose,
various development, commercialization, funding, royalty, diligence, sublicensing, insurance and
other obligations on us. If we breach any of these obligations, the licensor may have the right to
terminate the license or render the license non-exclusive, which could result in us being unable to
develop, manufacture and sell products that are covered by the licensed technology or enable a
competitor to gain access to the licensed technology. In addition, while we cannot currently
determine the amount of the royalty obligations we will be required to pay on sales of future
products, if any, the amounts may be significant. The amount of our future royalty obligations will
depend on the technology and intellectual property we use in products that we successfully develop
and commercialize, if any. Therefore, even if we successfully develop and commercialize products,
we may be unable to achieve or maintain profitability.
Confidentiality agreements with employees and others may not adequately prevent disclosure of
trade secrets and other proprietary information.
In order to protect our proprietary technology and processes, we rely in part on
confidentiality agreements with our collaborators, employees, consultants, outside scientific
collaborators and sponsored researchers and other advisors. These agreements may not effectively
prevent disclosure of confidential information and may not provide an adequate remedy in the event
of unauthorized disclosure of confidential information. In addition, others may independently
discover trade secrets and proprietary information, and in such cases we could not assert any trade
secret rights against such party. Costly and time-consuming litigation could be necessary to
enforce and determine the scope of our proprietary rights, and failure to obtain or maintain trade
secret protection could adversely affect our competitive business position.
Risks Related to Competition
The pharmaceutical market is intensely competitive. If we are unable to compete effectively with
existing drugs, new treatment methods and new technologies, we may be unable to commercialize
successfully any drugs that we develop.
The pharmaceutical market is intensely competitive and rapidly changing. Many large
pharmaceutical and biotechnology companies, academic institutions, governmental agencies and other
public and private research organizations are pursuing the development of novel drugs for the same
diseases that we are targeting or expect to target. Many of our competitors have:
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much greater financial, technical and human resources than we have at every stage
of the discovery, development, manufacture and commercialization of products;
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more extensive experience in pre-clinical testing, conducting clinical trials,
obtaining regulatory approvals, and in manufacturing, marketing and selling
pharmaceutical products;
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product candidates that are based on previously tested or accepted technologies;
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products that have been approved or are in late stages of development; and
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collaborative arrangements in our target markets with leading companies and research
institutions.
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We will face intense competition from drugs that have already been approved and accepted by
the medical community for the treatment of the conditions for which we may develop drugs. We also
expect to face competition from new drugs that enter the market. We believe a significant number of
drugs are currently under development, and may become commercially available in the future, for the
treatment of conditions for which we may try to develop drugs. For instance, we are currently
evaluating RNAi
46
therapeutics for RSV, liver cancer, hypercholesterolemia, TTR amyloidosis and HD, and have a
number of additional discovery programs targeting other diseases. Virazole and Synagis are
currently marketed for the treatment of certain RSV patients, and numerous drugs are currently
marketed or used for the treatment of liver cancer, hypercholesterolemia and HD as well. These
drugs, or other of our competitors products, may be more effective, safer, less expensive or
marketed and sold more effectively, than any products we develop.
If we successfully develop drug candidates, and obtain approval for them, we will face
competition based on many different factors, including:
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the safety and effectiveness of our products;
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the ease with which our products can be administered and the extent to which
patients accept relatively new routes of administration;
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the timing and scope of regulatory approvals for these products;
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the availability and cost of manufacturing, marketing and sales capabilities;
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price;
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reimbursement coverage; and
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patent position.
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Our competitors may develop or commercialize products with significant advantages over any
products we develop based on any of the factors listed above or on other factors. Our competitors
may therefore be more successful in commercializing their products than we are, which could
adversely affect our competitive position and business. Competitive products may make any products
we develop obsolete or noncompetitive before we can recover the expenses of developing and
commercializing our drug candidates. Furthermore, we also face competition from existing and new
treatment methods that reduce or eliminate the need for drugs, such as the use of advanced medical
devices. The development of new medical devices or other treatment methods for the diseases we are
targeting could make our drug candidates noncompetitive, obsolete or uneconomical.
We face competition from other companies that are working to develop novel drugs using technology
similar to ours. If these companies develop drugs more rapidly than we do or their technologies,
including delivery technologies, are more effective, our ability to successfully commercialize
drugs will be adversely affected.
In addition to the competition we face from competing drugs in general, we also face
competition from other companies working to develop novel drugs using technology that competes more
directly with our own. We are aware of several companies that are working in the field of RNAi. In
addition, we granted licenses or options for licenses to Isis, GeneCare Research Institute Co.,
Ltd., Benitec Ltd., Calando Pharmaceuticals, Inc., Tekmira, Quark Biotech, Inc. and others under
which these companies may independently develop RNAi therapeutics against a limited number of
targets. Any of these companies may develop its RNAi technology more rapidly and more effectively
than us. Merck & Co., Inc., or Merck, was one of our collaborators and a licensee under our
intellectual property for specified disease targets until September 2007, at which time we and
Merck agreed to terminate our collaboration. As a result of its acquisition of Sirna Therapeutics
Inc. in December 2006, and in light of the mutual termination of our collaboration, Merck, which
has substantially more resources and experience in developing drugs than we do, may become a direct
competitor.
In addition, as a result of agreements that we have entered into, Roche and Takeda have
obtained, and Novartis has the right to obtain, broad, non-exclusive licenses to certain aspects of
our technology that give them the right to compete with us in certain circumstances.
We also compete with companies working to develop antisense-based drugs. Like RNAi product
candidates, antisense drugs target messenger RNAs, or mRNAs, in order to suppress the activity of
specific genes. Isis is currently marketing an antisense drug and has several antisense drug
candidates in clinical trials. The development of antisense drugs is more advanced than that of
RNAi therapeutics, and antisense technology may become the preferred technology for drugs that
target mRNAs to silence specific genes.
47
In addition to competition with respect to RNAi and with respect to specific products, we face
substantial competition to discover and develop safe and effective means to deliver siRNAs to the
relevant cell and tissue types. Safe and effective means to deliver siRNAs to the relevant cell and
tissue types may be developed by our competitors, and our ability to successfully commercialize a
competitive product would be adversely affected. In addition, substantial resources are being
expended by third parties in the effort to discover and develop a safe and effective means of
delivering siRNAs into the relevant cell and tissue types, both in academic laboratories and in the
corporate sector. Some of our competitors have substantially greater resources than we do, and if
our competitors are able to negotiate exclusive access to those delivery solutions developed by
third parties, we may be unable to successfully commercialize our product candidates.
Risks Related to Our Common Stock
If our stock price fluctuates, purchasers of our common stock could incur substantial losses.
The market price of our common stock may fluctuate significantly in response to factors that
are beyond our control. The stock market in general has recently experienced extreme price and
volume fluctuations. The market prices of securities of pharmaceutical and biotechnology companies
have been extremely volatile, and have experienced fluctuations that often have been unrelated or
disproportionate to the operating performance of these companies. These broad market fluctuations
could result in extreme fluctuations in the price of our common stock, which could cause purchasers
of our common stock to incur substantial losses.
We may incur significant costs from class action litigation due to our expected stock volatility.
Our stock price may fluctuate for many reasons, including as a result of public announcements
regarding the progress of our development efforts, the addition or departure of our key personnel,
variations in our quarterly operating results and changes in market valuations of pharmaceutical
and biotechnology companies. Recently, when the market price of a stock has been volatile as our
stock price may be, holders of that stock have occasionally brought securities class action
litigation against the company that issued the stock. If any of our stockholders were to bring a
lawsuit of this type against us, even if the lawsuit is without merit, we could incur substantial
costs defending the lawsuit. The lawsuit could also divert the time and attention of our
management.
Novartis ownership of our common stock could delay or prevent a change in corporate control or
cause a decline in our common stock should Novartis decide to sell all or a portion of its shares.
Following their purchase in May 2009 of an additional 65,922 shares of our common stock,
Novartis holds 13.4% of our outstanding common stock and has the right to maintain its ownership
percentage through the expiration or termination of our broad alliance. This concentration of
ownership may harm the market price of our common stock by:
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delaying, deferring or preventing a change in control of our company;
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impeding a merger, consolidation, takeover or other business combination involving our
company; or
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discouraging a potential acquirer from making a tender offer or otherwise
attempting to obtain control of our company.
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In addition, if Novartis decides to sell all or a portion of its shares in a rapid or
disorderly manner, our stock price could be negatively impacted.
Anti-takeover provisions in our charter documents and under Delaware law and our stockholder
rights plan could make an acquisition of us, which may be beneficial to our stockholders, more
difficult and may prevent attempts by our stockholders to replace or remove our current
management.
Provisions in our certificate of incorporation and our bylaws may delay or prevent an
acquisition of us or a change in our management. In addition, these provisions may frustrate or
prevent any attempts by our stockholders to replace or remove our current management by making it
more difficult for stockholders to replace members of our board of directors. Because our board of
directors is responsible for appointing the members of our management team, these provisions could
in turn affect any attempt by our stockholders to replace current members of our management team.
These provisions include:
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a classified board of directors;
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48
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a prohibition on actions by our stockholders by written consent;
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limitations on the removal of directors; and
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advance notice requirements for election to our board of directors and for
proposing matters that can be acted upon at stockholder meetings.
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In addition, our board of directors has adopted a stockholder rights plan, the provisions of
which could make it difficult for a potential acquirer of Alnylam to consummate an acquisition
transaction.
Moreover, because we are incorporated in Delaware, we are governed by the provisions of
Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of
15% of our outstanding voting stock from merging or combining with us for a period of three years
after the date of the transaction in which the person acquired in excess of 15% of our outstanding
voting stock, unless the merger or combination is approved in a prescribed manner. These provisions
would apply even if the proposed merger or acquisition could be considered beneficial by some
stockholders.
49
ITEM 6. EXHIBITS
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10.1
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2009 Annual Incentive Program
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10.2
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License and Collaboration Agreement entered into as of January 9,
2009 by and between the Registrant and Cubist Pharmaceuticals, Inc.
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10.3
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Amended and Restated License and Collaboration Agreement, entered
into as of January 1, 2009, by and among the Registrant, Isis
Pharmaceuticals, Inc. and Regulus Therapeutics Inc.
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10.4
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Founding Investor Rights Agreement entered into as of January 1,
2009, by and among Regulus Therapeutics Inc., Isis Pharmaceuticals,
Inc. and the Registrant
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31.1
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Certification of principal executive officer pursuant to
Rule 13a-14(a) promulgated under the Securities Exchange Act of
1934, as amended.
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31.2
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Certification of principal financial officer pursuant to
Rule 13a-14(a) promulgated under the Securities Exchange Act of
1934, as amended.
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32.1
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Certification of principal executive officer pursuant to
Rule 13a-14(b) promulgated under the Securities Exchange Act of
1934, as amended, and Section 1350 of Chapter 63 of Title 18 of the
United States Code.
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32.2
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Certification of principal financial officer pursuant to
Rule 13a-14(b) promulgated under the Securities Exchange Act of
1934, as amended, and Section 1350 of Chapter 63 of Title 18 of the
United States Code.
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Indicates confidential treatment requested as to certain portions,
which portions were omitted and filed separately with the Securities
and Exchange Commission pursuant to a Confidential Treatment Request.
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50
SIGNATURES
Pursuant to the requirements of the Securities Exchange
Act of 1934, the Registrant has duly caused this Report
to be signed on its behalf by the undersigned, thereunto
duly authorized.
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ALNYLAM PHARMACEUTICALS, INC.
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Date: May 7, 2009
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/s/ John M. Maraganore
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John M. Maraganore, Ph.D.
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Chief Executive Officer
(Principal Executive Officer)
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Date: May 7, 2009
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/s/ Patricia L. Allen
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Patricia L. Allen
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Vice President of Finance and Treasurer
(Principal Financial and Accounting Officer)
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51
Exhibit 10.2
EXECUTION COPY
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
LICENSE AND COLLABORATION AGREEMENT
BY AND BETWEEN
ALNYLAM PHARMACEUTICALS, INC.
AND
CUBIST PHARMACEUTICALS, INC.
TABLE OF CONTENTS
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Page
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ARTICLE I DEFINITIONS
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1
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Section 1.1
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Action
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1
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Section 1.2
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Affiliate
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1
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Section 1.3
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Alnylam Collaboration IP
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2
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Section 1.4
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Alnylam In-License
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2
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Section 1.5
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Alnylam Know-How
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2
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Section 1.6
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Alnylam Patent Rights
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2
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Section 1.7
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Alnylam Sequence Specific Patent Rights
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2
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Section 1.8
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Alnylam Sequence Specific Know-How
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3
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Section 1.9
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Alnylam Technology
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3
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Section 1.10
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API Bulk Drug Substance
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3
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Section 1.11
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Asia
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3
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Section 1.12
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Asian Partner
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3
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Section 1.13
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Business Day
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3
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Section 1.14
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Calendar Quarter
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3
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Section 1.15
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Calendar Year
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3
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Section 1.16
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Clinical Investigation Laws
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4
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Section 1.17
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Clinical Regulatory Filings
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4
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Section 1.18
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Clinical Study
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4
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Section 1.19
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CMC
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4
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Section 1.20
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Collaboration
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4
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Section 1.21
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Commercialization or Commercialize
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4
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Section 1.22
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Commercialization Costs
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4
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Section 1.23
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Confidential Information
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5
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Section 1.24
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Control or Controlled
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5
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Section 1.25
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Cost of Goods Sold
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5
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Section 1.26
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Cover, Covering or Covered
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6
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Section 1.27
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CPI
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6
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Section 1.28
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Cubist Collaboration IP
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6
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Section 1.29
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Cubist In-License
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6
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Section 1.30
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Cubist Know-How
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7
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Section 1.31
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Cubist Patent Rights
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7
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Section 1.32
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Cubist Technology
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7
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Section 1.33
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Development or Develop
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7
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Section 1.34
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Development Costs
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7
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Section 1.35
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Development Plan
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8
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Section 1.36
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Diligent Efforts
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8
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Section 1.37
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Directly Competitive Product
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8
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Section 1.38
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Distribution Costs
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9
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Section 1.39
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DMF
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9
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Section 1.40
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Drug Regulation Laws
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9
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Section 1.41
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EMEA
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9
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TABLE OF CONTENTS
(continued)
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Page
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Section 1.42
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European Union or EU
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9
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Section 1.43
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Executive Officers
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9
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Section 1.44
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Existing Alnylam In-Licenses
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9
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Section 1.45
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FDA
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10
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Section 1.46
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Field
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10
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Section 1.47
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Finished Product
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10
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Section 1.48
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First Commercial Sale
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10
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Section 1.49
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First Opt-Out Milestone
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10
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Section 1.50
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FTE
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10
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Section 1.51
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FTE Cost
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10
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Section 1.52
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GAAP
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10
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Section 1.53
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Generic Competition
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11
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Section 1.54
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Generic Product
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11
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Section 1.55
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Good Clinical Practice
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11
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Section 1.56
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Good Laboratory Practice
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11
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Section 1.57
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Governmental Authority
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11
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Section 1.58
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Government Health Care Programs
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11
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Section 1.59
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Government Order
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12
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Section 1.60
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Health Care Laws
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12
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Section 1.61
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ICH
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12
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Section 1.62
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IND
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12
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Section 1.63
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Investigator Sponsored Clinical Study
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12
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Section 1.64
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Joint Collaboration IP
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12
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Section 1.65
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Know-How
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12
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Section 1.66
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Knowledge of Alnylam
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13
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Section 1.67
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Kyowa Agreement
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13
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Section 1.68
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Kyowa Hakko
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13
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Section 1.69
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Law
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13
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Section 1.70
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Legal Exclusivity Period
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13
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Section 1.71
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Licensed Product
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13
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Section 1.72
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Major EU Country
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13
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Section 1.73
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Manufacturing or Manufacture
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13
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Section 1.74
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N.A. Pre-Tax Profit or Loss
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13
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Section 1.75
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Necessary Third Party IP
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14
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Section 1.76
|
|
Net Sales
|
|
|
14
|
|
|
|
Section 1.77
|
|
New Drug Application or NDA
|
|
|
16
|
|
|
|
Section 1.78
|
|
North America or N.A.
|
|
|
16
|
|
|
|
Section 1.79
|
|
Parties
|
|
|
16
|
|
|
|
Section 1.80
|
|
Party
|
|
|
16
|
|
|
|
Section 1.81
|
|
Patent-Based Exclusivity Period
|
|
|
16
|
|
|
|
Section 1.82
|
|
Patent Rights
|
|
|
16
|
|
|
|
Section 1.83
|
|
Person
|
|
|
16
|
|
|
|
Section 1.84
|
|
Phase I Clinical Study
|
|
|
16
|
|
-ii-
TABLE OF CONTENTS
(continued)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page
|
|
|
|
|
|
|
|
|
|
|
|
Section 1.85
|
|
Phase II Clinical Study
|
|
|
17
|
|
|
|
Section 1.86
|
|
Phase III Clinical Study
|
|
|
17
|
|
|
|
Section 1.87
|
|
Pivotal Clinical Study
|
|
|
17
|
|
|
|
Section 1.88
|
|
Post-Approval Study
|
|
|
17
|
|
|
|
Section 1.89
|
|
Private Health Care Plans
|
|
|
17
|
|
|
|
Section 1.90
|
|
Post Approval Medical and Regulatory Activities
|
|
|
17
|
|
|
|
Section 1.91
|
|
Product Liability Costs
|
|
|
17
|
|
|
|
Section 1.92
|
|
Profit-Share Territory
|
|
|
18
|
|
|
|
Section 1.93
|
|
Product Trademark
|
|
|
18
|
|
|
|
Section 1.94
|
|
Regulatory Approval
|
|
|
18
|
|
|
|
Section 1.95
|
|
Regulatory Authority
|
|
|
18
|
|
|
|
Section 1.96
|
|
Regulatory-Based Exclusivity Period
|
|
|
18
|
|
|
|
Section 1.97
|
|
Related Party
|
|
|
18
|
|
|
|
Section 1.98
|
|
RNAi Product
|
|
|
18
|
|
|
|
Section 1.99
|
|
Royalty Territory
|
|
|
19
|
|
|
|
Section 1.100
|
|
RSV
|
|
|
19
|
|
|
|
Section 1.101
|
|
RSV01 Product
|
|
|
19
|
|
|
|
Section 1.102
|
|
RSV02 Product
|
|
|
19
|
|
|
|
Section 1.103
|
|
Safety Data
|
|
|
19
|
|
|
|
Section 1.104
|
|
Sales Representative
|
|
|
19
|
|
|
|
Section 1.105
|
|
Second Opt-Out Milestone
|
|
|
19
|
|
|
|
Section 1.106
|
|
Sublicensee
|
|
|
19
|
|
|
|
Section 1.107
|
|
Sublicense Income
|
|
|
19
|
|
|
|
Section 1.108
|
|
Territory
|
|
|
20
|
|
|
|
Section 1.109
|
|
Third Party
|
|
|
20
|
|
|
|
Section 1.110
|
|
United States or U.S.
|
|
|
20
|
|
|
|
Section 1.111
|
|
Valid Claim
|
|
|
20
|
|
|
|
Section 1.112
|
|
Additional Definitions
|
|
|
20
|
|
|
|
|
|
|
|
|
|
|
ARTICLE II MANAGEMENT OF COLLABORATIVE ACTIVITIES
|
|
|
22
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 2.1
|
|
Joint Steering Committee
|
|
|
22
|
|
|
|
Section 2.2
|
|
Appointment of Subcommittees, Project
Teams and Collaboration Managers
|
|
|
24
|
|
|
|
Section 2.3
|
|
Reports and Minutes
|
|
|
24
|
|
|
|
Section 2.4
|
|
Decision-Making
|
|
|
24
|
|
|
|
Section 2.5
|
|
Deadlocks
|
|
|
24
|
|
|
|
Section 2.6
|
|
Dissolution of JSC
|
|
|
25
|
|
|
|
Section 2.7
|
|
Collaboration Guidelines
|
|
|
26
|
|
|
|
|
|
|
|
|
|
|
ARTICLE III LICENSE GRANTS
|
|
|
26
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 3.1
|
|
Alnylam Grants
|
|
|
26
|
|
|
|
Section 3.2
|
|
Cubist Grants
|
|
|
29
|
|
-iii-
TABLE OF CONTENTS
(continued)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page
|
|
|
|
|
|
|
|
|
|
|
|
Section 3.3
|
|
Sublicensing Terms; Liability
|
|
|
30
|
|
|
|
Section 3.4
|
|
Joint Collaboration IP
|
|
|
30
|
|
|
|
Section 3.5
|
|
Section 365(n) of the Bankruptcy Code
|
|
|
30
|
|
|
|
Section 3.6
|
|
Retained Rights
|
|
|
31
|
|
|
|
|
|
|
|
|
|
|
ARTICLE IV DEVELOPMENT OF
LICENSED PRODUCTS; ADDITIONAL RSV PRODUCTS; OPT-OUT RIGHTS
|
|
|
31
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 4.1
|
|
Overview
|
|
|
31
|
|
|
|
Section 4.2
|
|
Development Plan; Amendments; Development Responsibilities
|
|
|
31
|
|
|
|
Section 4.3
|
|
Development Efforts; Manner of Performance; Records and Reports
|
|
|
32
|
|
|
|
Section 4.4
|
|
Joint Development Costs
|
|
|
33
|
|
|
|
Section 4.5
|
|
Reimbursement of Development Costs
|
|
|
34
|
|
|
|
Section 4.6
|
|
Additional RSV Products
|
|
|
34
|
|
|
|
Section 4.7
|
|
Alnylam Opt-Out Option
|
|
|
34
|
|
|
|
Section 4.8
|
|
Technology Transfer and Exchange of Know-How
|
|
|
40
|
|
|
|
|
|
|
|
|
|
|
ARTICLE V COMMERCIALIZATION AND CERTAIN OTHER RESPONSIBILITIES
|
|
|
41
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 5.1
|
|
Diligent Efforts
|
|
|
41
|
|
|
|
Section 5.2
|
|
Joint Commercialization Team
|
|
|
41
|
|
|
|
Section 5.3
|
|
Commercialization Plan
|
|
|
42
|
|
|
|
Section 5.4
|
|
Regulatory Filings
|
|
|
43
|
|
|
|
Section 5.5
|
|
Advertising and Promotional Materials
|
|
|
44
|
|
|
|
Section 5.6
|
|
Sales and Distribution
|
|
|
44
|
|
|
|
Section 5.7
|
|
Reporting Obligations
|
|
|
44
|
|
|
|
Section 5.8
|
|
Other Responsibilities
|
|
|
45
|
|
|
|
Section 5.9
|
|
Adverse Event and Licensed Product Complaint Reporting Procedures;
Notice of Information Affecting Marketability of Licensed Product
|
|
|
45
|
|
|
|
Section 5.10
|
|
Recalls, Market Withdrawals or Corrective Actions
|
|
|
46
|
|
|
|
Section 5.11
|
|
Medical Inquiries
|
|
|
47
|
|
|
|
Section 5.12
|
|
Export Monitoring
|
|
|
47
|
|
|
|
|
|
|
|
|
|
|
ARTICLE VI MANUFACTURE AND SUPPLY
|
|
|
47
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 6.1
|
|
Supply Obligations; Alnylams Existing Manufacturing Arrangements
|
|
|
47
|
|
|
|
Section 6.2
|
|
Transition of Manufacturing Responsibilities to Cubist
|
|
|
48
|
|
|
|
Section 6.3
|
|
Supply Agreement
|
|
|
49
|
|
|
|
Section 6.4
|
|
Technology Transfer
|
|
|
50
|
|
-iv-
TABLE OF CONTENTS
(continued)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page
|
|
|
|
|
|
|
|
|
|
ARTICLE VII FINANCIAL PROVISIONS
|
|
|
50
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 7.1
|
|
Upfront Fee
|
|
|
50
|
|
|
|
Section 7.2
|
|
Development Milestones
|
|
|
50
|
|
|
|
Section 7.3
|
|
Sales Milestones
|
|
|
51
|
|
|
|
Section 7.4
|
|
N.A. Pre-Tax Profit or Loss
|
|
|
52
|
|
|
|
Section 7.5
|
|
Licensed Product Royalties in the Royalty Territory
|
|
|
53
|
|
|
|
Section 7.6
|
|
Adjustments for Necessary Third Party IP Payments in the Royalty
Territory
|
|
|
54
|
|
|
|
Section 7.7
|
|
Necessary Third Party IP in the Profit-Share Territory
|
|
|
54
|
|
|
|
Section 7.8
|
|
Royalty Adjustments for Generic Products
|
|
|
55
|
|
|
|
Section 7.9
|
|
Minimum Payments in the Royalty Territory
|
|
|
55
|
|
|
|
Section 7.10
|
|
Royalty Reports; Payments
|
|
|
56
|
|
|
|
Section 7.11
|
|
Payments from Alnylam to Cubist; Reports
|
|
|
56
|
|
|
|
Section 7.12
|
|
Audits
|
|
|
56
|
|
|
|
Section 7.13
|
|
Tax Matters
|
|
|
57
|
|
|
|
Section 7.14
|
|
United States Dollars
|
|
|
57
|
|
|
|
Section 7.15
|
|
Currency Exchange
|
|
|
57
|
|
|
|
Section 7.16
|
|
Blocked Payments
|
|
|
58
|
|
|
|
Section 7.17
|
|
Late Payments
|
|
|
58
|
|
|
|
Section 7.18
|
|
No Overlapping Royalties
|
|
|
58
|
|
|
|
Section 7.19
|
|
Reporting
|
|
|
58
|
|
|
|
Section 7.20
|
|
Resolution of Disputes
|
|
|
58
|
|
|
|
|
|
|
|
|
|
|
ARTICLE VIII INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS
|
|
|
59
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 8.1
|
|
Inventorship
|
|
|
59
|
|
|
|
Section 8.2
|
|
Ownership
|
|
|
59
|
|
|
|
Section 8.3
|
|
Prosecution and Maintenance of Patent Rights
|
|
|
59
|
|
|
|
Section 8.4
|
|
Third Party Infringement
|
|
|
61
|
|
|
|
Section 8.5
|
|
Claimed Infringement; Third Party Challenges to Patent Rights
|
|
|
62
|
|
|
|
Section 8.6
|
|
Third Party Technology
|
|
|
63
|
|
|
|
Section 8.7
|
|
Patent Marking
|
|
|
64
|
|
|
|
Section 8.8
|
|
Trademarks
|
|
|
64
|
|
|
|
|
|
|
|
|
|
|
ARTICLE IX CONFIDENTIALITY AND PUBLICITY
|
|
|
66
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 9.1
|
|
Confidential Information
|
|
|
66
|
|
|
|
Section 9.2
|
|
Employee, Consultant and Advisor Obligations and Disclosure to
Regulatory Authorities
|
|
|
67
|
|
|
|
Section 9.3
|
|
Certain Disclosures by Alnylam or Cubist
|
|
|
67
|
|
|
|
Section 9.4
|
|
Publicity
|
|
|
67
|
|
|
|
Section 9.5
|
|
Publications
|
|
|
68
|
|
-v-
TABLE OF CONTENTS
(continued)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page
|
|
|
|
|
|
|
|
|
|
|
|
Section 9.6
|
|
Asian Partner
|
|
|
68
|
|
|
|
Section 9.7
|
|
Coordination with Alnylams Asian Partner
|
|
|
68
|
|
|
|
|
|
|
|
|
|
|
ARTICLE X REPRESENTATIONS AND WARRANTIES; CERTAIN COVENANTS; INDEMNIFICATION
|
|
|
69
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 10.1
|
|
Exclusivity Covenant
|
|
|
69
|
|
|
|
Section 10.2
|
|
Representations of Authority
|
|
|
69
|
|
|
|
Section 10.3
|
|
Consents
|
|
|
69
|
|
|
|
Section 10.4
|
|
No Conflict
|
|
|
69
|
|
|
|
Section 10.5
|
|
Enforceability
|
|
|
69
|
|
|
|
Section 10.6
|
|
Sales Representatives
|
|
|
70
|
|
|
|
Section 10.7
|
|
Additional Representations and Warranties of Alnylam
|
|
|
70
|
|
|
|
Section 10.8
|
|
Cubist Representation Regarding Cubist In-Licenses
|
|
|
72
|
|
|
|
Section 10.9
|
|
No Warranties
|
|
|
72
|
|
|
|
Section 10.10
|
|
No Debarment
|
|
|
72
|
|
|
|
Section 10.11
|
|
Indemnification
|
|
|
73
|
|
|
|
Section 10.12
|
|
Limitation of Liability
|
|
|
74
|
|
|
|
Section 10.13
|
|
Insurance
|
|
|
75
|
|
|
|
|
|
|
|
|
|
|
ARTICLE XI TERM AND TERMINATION
|
|
|
75
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 11.1
|
|
Term
|
|
|
75
|
|
|
|
Section 11.2
|
|
Termination Rights
|
|
|
75
|
|
|
|
Section 11.3
|
|
Effect of Termination
|
|
|
76
|
|
|
|
Section 11.4
|
|
Payments to Cubist
|
|
|
78
|
|
|
|
Section 11.5
|
|
Effect of Expiration or Termination; Survival
|
|
|
83
|
|
|
|
|
|
|
|
|
|
|
ARTICLE XII FINAL DECISION-MAKING; DISPUTE RESOLUTION
|
|
|
84
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 12.1
|
|
Disputes
|
|
|
84
|
|
|
|
Section 12.2
|
|
Arbitration
|
|
|
84
|
|
|
|
|
|
|
|
|
|
|
ARTICLE XIII MISCELLANEOUS
|
|
|
85
|
|
|
|
|
|
|
|
|
|
|
|
|
Section 13.1
|
|
Choice of Law
|
|
|
85
|
|
|
|
Section 13.2
|
|
Notices
|
|
|
85
|
|
|
|
Section 13.3
|
|
Severability
|
|
|
86
|
|
|
|
Section 13.4
|
|
Captions
|
|
|
86
|
|
|
|
Section 13.5
|
|
Integration
|
|
|
86
|
|
|
|
Section 13.6
|
|
Independent Contractors; No Agency
|
|
|
86
|
|
|
|
Section 13.7
|
|
Submission to Jurisdiction
|
|
|
87
|
|
|
|
Section 13.8
|
|
Assignment; Successors
|
|
|
87
|
|
|
|
Section 13.9
|
|
No Consequential or Punitive Damages
|
|
|
88
|
|
-vi-
TABLE OF CONTENTS
(continued)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Page
|
|
|
|
|
|
|
|
|
|
|
|
Section 13.10
|
|
Performance by Affiliates
|
|
|
88
|
|
|
|
Section 13.11
|
|
Force Majeure
|
|
|
88
|
|
|
|
Section 13.12
|
|
Construction
|
|
|
88
|
|
|
|
Section 13.13
|
|
Execution in Counterparts; Facsimile Signatures
|
|
|
89
|
|
EXHIBITS
|
|
|
EXHIBIT A
|
|
Alnylam Patent Rights
|
EXHIBIT B
|
|
ALN-RSV01
|
EXHIBIT C
|
|
Existing Alnylam In-Licenses
|
EXHIBIT D
|
|
Existing Alnylam Out-Licenses That Include Rights or
Options to Licensed Products
|
EXHIBIT E
|
|
Development Plan
|
EXHIBIT F
|
|
Material Agreements Related to Licensed Products in the Territory
|
EXHIBIT G
|
|
Supply Agreement Term Sheet
|
EXHIBIT H
|
|
Milestone Payments Under the Existing Alnylam In-Licenses
|
EXHIBIT I
|
|
Press Release
|
Schedule 10.7 Disclosure Schedule
|
-vii-
LICENSE AND COLLABORATION AGREEMENT
This License and Collaboration Agreement (this
Agreement
) is entered into as of the
9
th
day of January, 2009 (the
Effective Date
), by and between Alnylam
Pharmaceuticals, Inc., a corporation organized and existing under the laws of the State of Delaware
and having its principal office at 300 Third Street, Cambridge, Massachusetts 02142
(
Alnylam
), and Cubist Pharmaceuticals, Inc., a corporation organized and existing under
the laws of the State of Delaware and having its principal office at 65 Hayden Avenue, Lexington,
Massachusetts 02421 (
Cubist
).
INTRODUCTION
WHEREAS, Alnylam owns or controls certain fundamental intellectual properties relating to RNA
interference, and is developing therapeutic products targeting respiratory syncytial virus that
function through RNA interference, including the proprietary Alnylam product known as ALN-RSV01;
WHEREAS, Cubist desires to develop and commercialize such therapeutic RNA interference
products for the treatment of respiratory infections in humans caused by RSV, throughout the world,
excluding Japan and certain other countries in Asia;
WHEREAS, Alnylam and Cubist believe that a license and collaboration for such purpose on the
terms and conditions of this Agreement would be desirable.
NOW, THEREFORE, in consideration of the foregoing premises and the mutual covenants herein
contained, the Parties hereby agree as follows:
ARTICLE I
DEFINITIONS
As used in this Agreement, the following terms shall have the meanings set forth below:
Section 1.1
Action
. Action means any threatened, pending or completed claim,
action, cause of action or suit (whether in contract or tort or otherwise), litigation (whether at
law or in equity, whether civil or criminal), controversy, assessment, arbitration, investigation,
hearing, charge, complaint, demand, notice or proceeding of, to, from, by or before, or threatened
to be brought to, from, by or before, any Governmental Authority, including interferences,
oppositions and patent invalidity suits as described in Section 8.5.
Section 1.2
Affiliate
. Affiliate means with respect to any Party, any Person
controlling, controlled by or under common control with such Party. For purposes of this Section
1.2, control means (a) in the case of a Person that is a corporate entity, direct or indirect
ownership of fifty percent (50%) or more of the stock or shares having the right to vote for the
election of directors of such Person, and (b) in the case of a Person that is an entity, but is not
a corporate entity, the possession, directly or indirectly, of the power to direct, or cause the
direction of, the
management or policies of such Person, whether through the ownership of voting securities, by
contract or otherwise.
Section 1.3
Alnylam Collaboration IP
. Alnylam Collaboration IP means (a) any
improvement, discovery or Know-How, patentable or otherwise, first identified, discovered or
developed solely by employees of Alnylam or its Affiliates or other persons not employed by Cubist
or any of its Affiliates acting on behalf of Alnylam or any of its Affiliates in the conduct of the
Collaboration, and (b) any Patent Rights that claim or cover such improvements, discoveries or
Know-How and are owned or otherwise Controlled by Alnylam or, subject to Section 13.8, any of its
Affiliates, at any time during the Term. Alnylam Collaboration IP excludes Alnylams interest in
Joint Collaboration IP.
Section 1.4
Alnylam In-License
. Alnylam In-License means (a) the Existing Alnylam
In-Licenses, and (b) any other agreement between Alnylam and a Third Party, executed during the
Term, pursuant to which Alnylam has rights and obligations with respect to, or which otherwise
Cover, a Licensed Product and where (i) the intellectual property that is the subject of such
agreement is included within Alnylam Technology, and (ii) such Alnylam Technology is necessary or
reasonably useful to Develop, Commercialize or Manufacture Licensed Product in the Field.
Section 1.5
Alnylam Know-How
. Alnylam Know-How means Know-How owned or otherwise
Controlled by Alnylam or any of its Affiliates as of the Effective Date or as to which Alnylam or,
subject to Section 13.8, any of its Affiliates, obtains Control during the Term that is necessary
or reasonably useful for Cubist and its Related Parties to perform their obligations or exploit
their rights under this Agreement with respect to Licensed Product, including their rights to
Develop, Manufacture, or Commercialize Licensed Product (other than Alnylams rights in Joint
Collaboration IP and Alnylam Collaboration IP).
Section 1.6
Alnylam Patent Rights
. Alnylam Patent Rights means those Patent Rights
owned or otherwise Controlled by Alnylam or any of its Affiliates as of the Effective Date or as to
which Alnylam or, subject to Section 13.8, any of its Affiliates, obtains Control during the Term
that are necessary or reasonably useful for Cubist and its Related Parties to perform their
obligations or exploit their rights under this Agreement with respect to Licensed Product,
including their rights to Develop, Manufacture, or Commercialize Licensed Product (other than
Alnylams rights in Joint Collaboration IP and Alnylam Collaboration IP), including the Patent
Rights set forth in
Exhibit A
.
Section 1.7
Alnylam Sequence Specific Patent Rights
. Alnylam Sequence Specific
Patent Rights means claim(s) contained in Patent Rights comprising Alnylam Technology that are
specifically directed to particular sequences of Licensed Products in the Territory.
Section 1.8
Alnylam Sequence Specific Know-How
. Alnylam Sequence Specific Know-How
means Know-How that is specific to RSV01 Product or to any other particular sequence of Licensed
Product, including composition information and any preclinical and clinical test data related to
any of the foregoing.
Section 1.9
Alnylam Technology
. Alnylam Technology means, collectively, Alnylam
Know-How, Alnylam Patent Rights, Alnylam Collaboration IP and Alnylams interest in Joint
Collaboration IP, and any Third Party Technology that is included in the definition of Alnylam
Technology after the Effective Date in accordance with Section 8.6.
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Section 1.10
API Bulk Drug Substance
. API Bulk Drug Substance means Licensed
Product in bulk form manufactured for use as an active pharmaceutical ingredient.
Section 1.11
Asia
. Asia means Brunei, Cambodia, China (including Hong Kong and
Macao, but excluding Taiwan), Indonesia, Japan, Laos, Malaysia, Myanmar, North Korea, Philippines,
Singapore, South Korea, Taiwan, Thailand and Vietnam.
Section 1.12
Asian Partner
. Asian Partner means Kyowa Hakko or any other Third
Party to whom Alnylam grants licenses under the Alnylam Technology to Develop or Commercialize
Licensed Products for use in the Field in Asia, but shall not include a Third Party engaged by
Alnylam or any of its Affiliates merely to perform specific discreet tasks as contract services in
connection with Alnylams Development or Commercialization of Licensed Product.
Section 1.13
Business Day
. Business Day means a weekday on which banking
institutions in Boston, Massachusetts are open for business. For purposes of clarity, a Business
Day shall not include any Saturday or Sunday or federal or Commonwealth of Massachusetts holiday.
Section 1.14
Calendar Quarter
. Calendar Quarter means the respective periods of
three (3) consecutive calendar months ending on March 31, June 30, September 30 and December 31;
provided
that
the first Calendar Quarter of the Term shall begin on the Effective
Date and end on March 31, 2009, and the last Calendar Quarter of the Term shall end on the last day
of the Term.
Section 1.15
Calendar Year
. Calendar Year means each successive period of twelve
(12) months commencing on January 1 and ending on December 31;
provided
that
the
first Calendar Year of the Term shall begin on the Effective Date and end on December 31, 2009 and
the last Calendar Year of the Term shall end on the last day of the Term.
Section 1.16
Clinical Investigation Laws
. Clinical Investigation Laws means Laws
relating to human clinical investigations, including 21 C.F.R. Parts 50, 54, 56 and 312, and
then-current Good Clinical Practice, each as in effect and as amended from time to time.
Section 1.17
Clinical Regulatory Filings
. Clinical Regulatory Filings means data,
filings or materials relating to Licensed Product submitted to the applicable Regulatory
Authorities, including (a) data derived from Clinical Studies, (b) data derived from non-clinical
studies, and (c) data, filings or materials relating to or contained in the CMC or a DMF.
Section 1.18
Clinical Study
. Clinical Study means a Phase I Clinical Study, Phase
II Clinical Study, Phase III Clinical Study or Pivotal Clinical Study, as applicable, but excluding
any Post-Approval Studies.
Section 1.19
CMC
. CMC means the chemistry, manufacturing and controls section of
an IND or NDA in the United States, or the equivalent section of regulatory filings made outside
the United States.
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Section 1.20
Collaboration
. Collaboration means the collaboration of the Parties
in the activities governed by this Agreement, including such activities relating to the Development
and Regulatory Approval of Licensed Product.
Section 1.21
Commercialization
or
Commercialize
. Commercialization or
Commercialize means (a) pre-launch, launch or post launch activities directed to obtaining pricing
and reimbursement approvals, marketing, promoting, distributing, importing or selling a product,
and (b) solely for definitional purposes in implementing the terms of this Agreement, all
Post-Approval Medical and Regulatory Activities. Commercialization includes strategic marketing,
market research, sales force recruitment, training and meetings, sales force detailing, sample
drops, activities related to managed care accounts and other similar accounts and government
programs, activities related to reimbursement, advertising, market and product support, customer
support, educational initiatives, product distribution, invoicing, and sales activities.
Commercialization shall not include any activities related to Manufacturing.
Section 1.22
Commercialization Costs
. Commercialization Costs means, with respect
to Licensed Product in the Field in the Profit-Share Territory, whether or not occurring during
Development or Commercialization (a) the costs and expenses incurred by a Party or any of its
Related Parties in the Commercialization of Licensed Product, including the costs of advertising,
detailing, sales, marketing and promotion of Licensed Product and medical,
customer or regulatory support and a reasonable allocation (subject to the oversight of the
JCT) of [**] for sales force management and support, (b) infrastructure required to support and
maintain patient/safety surveillance as required by applicable Regulatory Authorities directly
attributable to Licensed Product, including the costs of maintaining the global safety database
contemplated under Section 5.9, (c) reasonable out-of-pocket [**] costs and expenses incurred by a
Party or any of its Related Parties with respect to [**], (d) reasonable out-of-pocket [**]
incurred by a Party or any of its Related Parties regarding [**] under Section 8.4 to the extent
such enforcement action is approved by the JSC and reasonable out-of-pocket costs and expenses
incurred by a Party or any of its Related Parties and included in Commercialization Costs pursuant
to Section [**], in each case with respect to [**] in the Field in the Profit-Share Territory, (e)
the reasonable out-of-pocket costs and expenses of maintaining Regulatory Approval for Licensed
Product, (f) except for those obligations to be paid fully by Alnylam under Section 7.7, [**] to
the extent reasonably allocable to the Profit-Share Territory, (g) the costs of product recalls,
withdrawals, insurance, [**] and returned product destruction, and (h) the cost of [**]. In
calculated Commercialization Costs, the costs of internal personnel engaged in Commercialization
efforts shall be based on the FTE Cost applicable to such efforts, unless another basis is
otherwise agreed by the Parties in writing. For sake of clarity, the FTE Cost of a sales
representative does not include [**] based on sales of Licensed Product in the Profit-Share
Territory, which such [**] shall be separately included as a Commercialization Costs budget item.
For purposes of clarity, costs and expenses included in the calculation of N.A. Pre-Tax Profit or
Loss, and the deductions specified in the definition of Net Sales or in Development Costs, shall
not be double-counted, and shall be determined from the books and records of the applicable Party
and its Affiliates maintained in accordance with GAAP, consistently applied.
Section 1.23
Confidential Information
. Confidential Information means any and all
information and data, including information regarding or included within Alnylam Technology and
Cubist Technology and all other scientific, pre-clinical, clinical, regulatory, manufacturing,
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marketing, financial or commercial information or data, whether communicated in writing or orally
or by any other method, which is provided by one Party to the other Party in connection with this
Agreement. Alnylam Technology and Alnylam Collaboration IP are Confidential Information of
Alnylam. Cubist Technology and Cubist Collaboration IP are Confidential Information of Cubist.
Joint Collaboration IP is the Confidential Information of both Parties.
Section 1.24
Control
or
Controlled
. Control or Controlled means, with
respect to any intellectual property right or other intangible property, the possession (whether by
license or ownership, or by control over an Affiliate having possession by license or ownership) by
a Party of the ability to grant to the other Party access or a license or sublicense as provided
herein without violating the terms of any agreement with any Third Party;
provided
that
with respect to Third Party Technology obtained by a Party during the Term, Control
shall be deemed not to exist unless such Third Party Technology is added to the Alnylam Technology
or the Cubist Technology (as the case may be) in accordance with Section 8.6.
Section 1.25
Cost of Goods Sold
. Cost of Goods Sold means, with respect to API
Bulk Drug Substance, Finished Product or placebo, as the case may be, Manufactured under this
Agreement, the reasonable internal and external costs of a Party or any of its Related Parties
incurred in Manufacturing such API Bulk Drug Substance, Finished Product or placebo, including:
(a) to the extent that such API Bulk Drug Substance, Finished Product or placebo is Manufactured by
a Party or any of its Related Parties, the Cost of Goods Sold of such API Bulk Drug Substance,
Finished Product or placebo, consisting of direct material and direct labor costs, [**] all
determined in accordance with the books and records of the applicable Party or its Related
Party(ies) maintained in accordance with United States GAAP, consistently applied, and (b) to the
extent that such API Bulk Drug Substance, Finished Product or placebo is Manufactured by a Third
Party manufacturer, the actual fees paid by a Party or any of its Related Parties to the Third
Party for the Manufacture, supply, packaging and labeling of such API Bulk Drug Substance, Finished
Product or placebo [**], determined in accordance with the books and records of the applicable
Party or its Related Party(ies) maintained in accordance with United States GAAP, consistently
applied. Cost of Goods Sold shall not include [**], except with respect to Licensed Product
Manufactured by Cubist for Alnylam to supply to its Asian Partner.
Section 1.26
Cover
,
Covering
or
Covered
. Cover, Covering or
Covered means that, with respect to Licensed Product, in the absence of a license granted under a
Valid Claim, the making, use, offering for sale, sale, or importation of Licensed Product would
infringe such Valid Claim or, with respect to a pending Valid Claim included in the Patent Rights
under which such license is granted, the making, use, offering for sale, sale, or importation of
Licensed Product would infringe such Valid Claim if such patent application were to issue as a
patent.
Section 1.27
CPI
. CPI means the Consumer Price Index Urban Wage Earners and
Clerical Workers, U.S. City Average, All Items, 1982-84 = 100, published by the United States
Department of Labor, Bureau of Labor Statistics (or its successor equivalent index) in the United
States.
Section 1.28
Cubist Collaboration IP
. Cubist Collaboration IP means (a) any
improvement, discovery or Know-How, patentable or otherwise, first identified, discovered or
developed solely by employees of Cubist or its Affiliates or other persons not employed by
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Alnylam or any of its Affiliates acting on behalf of Cubist or any of its Affiliates, in the conduct of the
Collaboration, and (b) any Patent Rights which claim or cover such improvements, discoveries or
Know-How and are owned or otherwise Controlled by Cubist or, subject to Section 13.8, any of its
Affiliates, at any time during the Term. Cubist Collaboration IP excludes Cubists interest in
Joint Collaboration IP.
Section 1.29
Cubist In-License
. Cubist In-License means any agreement between
Cubist and a Third Party executed during the Term pursuant to which Cubist has rights and
obligations with respect to, or which otherwise Cover, a Licensed Product and where (a) the
intellectual property that is the subject of such agreement is included within Cubist Technology,
and (b) such Cubist Technology is necessary or reasonably useful to Develop, Commercialize or
Manufacture Licensed Product in the Field.
Section 1.30
Cubist Know-How
. Cubist Know-How means Know-How Controlled by Cubist
or, subject to Section 13.8, any of its Affiliates, during the Term that is necessary or reasonably
useful for Alnylam and its Affiliates to perform their obligations or exploit their rights under
this Agreement (other than Cubists rights in Joint Collaboration IP and Cubist Collaboration IP).
Section 1.31
Cubist Patent Rights
. Cubist Patent Rights means those Patent Rights
that (a) claim (i) Cubist Know-How, or (ii) the Development, Manufacture or Commercialization of
Licensed Product, and that are necessary or reasonably useful to Develop, Manufacture or
Commercialize Licensed Product in the Field, and (b) are Controlled by Cubist or, subject to
Section 13.8, any of its Affiliates, at any time during the Term. Cubist Patent Rights shall not
include Patent Rights included in Cubist Collaboration IP or Cubists interest in Joint
Collaboration IP.
Section 1.32
Cubist Technology
. Cubist Technology means, collectively, Cubist
Know-How and Cubist Patent Rights, Cubist Collaboration IP and Cubists interest in Joint
Collaboration IP, and any Third Party Technology that is included in the definition of Cubist
Technology after the Effective Date in accordance with Section 8.6.
Section 1.33
Development
or
Develop
. Development or Develop means
non-clinical and clinical research and drug development activities, including research activities
directed at back-up compounds, toxicology, pharmacology and other discovery efforts, test method
development and stability testing, process development, formulation development, delivery system
development, quality assurance and quality control development, statistical analysis, clinical
studies (including pre- and post-approval studies and investigator sponsored clinical studies),
regulatory affairs, and regulatory approval and clinical study regulatory activities (excluding
regulatory activities directed to obtaining pricing and reimbursement approvals).
Section 1.34
Development Costs
. Development Costs means costs incurred by the
Parties or any of their Affiliates in Developing Licensed Product in the Field for the Profit-Share
Territory, in accordance with this Agreement and determined from the books and records of the
applicable Party and its Affiliates maintained in accordance with GAAP, consistently applied,
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whether incurred before or after Regulatory Approval, provided such activities and costs are
consistent with the Development Plan and related budget, including:
(a) all out-of-pocket costs and expenses incurred;
(b) the costs of internal scientific, medical or technical personnel engaged in such efforts,
which costs shall be determined based on the FTE Cost, unless another basis is otherwise agreed by
the Parties in writing;
(c) the costs and expenses for pre-clinical and clinical supplies needed for such efforts as
set forth in the Development Plan, consisting of (i) [**] for clinical supplies of Licensed Product
and placebo; (ii) cost of comparator or combination drugs or devices; and (iii) costs and expenses
of disposal of clinical samples;
(d) fees incurred in connection with filings for or relating to Regulatory Approvals or
pricing or reimbursement approval in the Field in the Profit-Share Territory;
(e) costs and expenses incurred in connection with (i) [**]; and (v) internal and Third Party
costs and expenses incurred in connection with (A) [**]; and
(f) any other costs incurred that are explicitly included in the budgets included in the
Development Plan.
For purposes of clarity, it is understood that costs and expenses included in the calculation
of N.A. Pre-Tax Profit or Loss, and the deductions specified in the definition of Net Sales or in
Development Costs, shall not be double-counted.
Section 1.35
Development Plan
. Development Plan means the written workplan,
timetable and budget for the Parties Licensed Product Development efforts in the Profit-Share
Territory, agreed upon by the Parties as of the Effective Date, as amended from time to time in
accordance with this Agreement. The initial Development Plan is attached as
Exhibit E
.
Section 1.36
Diligent Efforts
. Diligent Efforts means, with respect to each
Partys obligations relating to Licensed Product, the carrying out of such obligations in a
diligent and sustained manner using efforts substantially similar to the efforts a
biopharmaceutical company of comparable size and resources would typically devote to a product of
similar market potential, profit potential, similar stage in development or commercialization, or
strategic value resulting from its own research efforts, based on conditions then prevailing, and
taking into account other relevant factors, including technical, medical, clinical efficacy,
safety, manufacturing, and delivery considerations, product labeling or anticipated labeling, the
patent and other proprietary position of the product, the regulatory environment and competitive
market conditions. Diligent Efforts with respect to Alnylams obligations, as specified in
Sections 3.3, 4.3(b), 5.9, 6.1(b) and 9.6 related to the actions of its Related Parties or the
actions of any other Third Party with whom Alnylam has entered into an agreement related to
Licensed Product shall mean that (a) to the extent such obligation is not currently included in its
agreement with such Related Party or other Third Party, Alnylam shall [**], (b) in entering into
any new agreement with a Related Party or such other Third Party, Alnylam shall [**], and (c) in
each case, Alnylam shall take reasonable action to enforce such obligations.
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Section 1.37
Directly Competitive Product
. Directly Competitive Product
means any therapeutic or prophylactic product that specifically targets RSV. For avoidance of
doubt, Directly Competitive Product as to a Party shall not include a product with [**].
Section 1.38
Distribution Costs
. Distribution Costs means the costs, excluding
[**], incurred by a Party or any of its Related Parties or for its account, specifically
identifiable to the distribution of a Licensed Product to a Third Party in the Field intended for
commercial sale in the Profit-Share Territory, including (a) handling, transportation, customs
clearance, containers, freight, duties and insurance (including shipments from Third Party
logistics service providers to wholesalers, and excluding such costs, if any, treated as a
deduction in the definition of Net Sales), (b) customer services including order entry, billing and
adjustments, inquiry and credit and collection, and (c) direct cost of facilities utilized for the
storage and distribution of Licensed Product, determined from the books and records of the
applicable Party and its Affiliates maintained in accordance with GAAP, consistently applied.
Section 1.39
DMF
. DMF means a Drug Master File filed with the FDA, or an
equivalent filing with any other Regulatory Authority.
Section 1.40
Drug Regulation Laws
. Drug Regulation Laws means Laws regulating
drugs and pharmaceutical products, including the United States Federal Food, Drug, and Cosmetic
Act, 21 U.S.C. § 301
et seq.
, the Prescription Drug Marketing Act of 1987, the Federal Controlled
Substances Act, 21 U.S.C. § 801
et seq
., and policies issued by the FDA, and similar Laws of the
EMEA or other countries or jurisdictions in the Territory, each as in effect and as amended from
time to time.
Section 1.41
EMEA
. EMEA means the European Medicines Agency or any successor
agency thereto.
Section 1.42
European Union
or
EU
. European Union or EU means the
countries of the European Union, as it is constituted as of the Effective Date and as it may be
expanded from time to time, and Switzerland, Norway and Iceland.
Section 1.43
Executive Officers
. Executive Officers means the Chief Executive
Officer of Alnylam (or a senior executive officer of Alnylam designated by Alnylams Chief
Executive Officer) and the Chief Executive Officer of Cubist (or a senior executive officer of
Cubist designated by Cubists Chief Executive Officer).
Section 1.44
Existing Alnylam In-Licenses
. Existing Alnylam In-Licenses means the
Third Party agreements set forth on
Exhibit C
.
Section 1.45
FDA
. FDA means the United States Food and Drug Administration or any
successor agency thereto.
Section 1.46
Field
. Field means the treatment or prophylaxis of diseases in
humans.
Section 1.47
Finished Product
. Finished Product means the finished product
formulation of Licensed Product, containing API Bulk Drug Substance, filled into unit packages
-8-
for
final labeling and packaging, and as finally labeled and packaged in a form ready for
administration.
Section 1.48
First Commercial Sale
. First Commercial Sale means, with respect to
Licensed Product in a country, the first commercial sale of Licensed Product in such country.
Sales for clinical study purposes or compassionate, named patient or similar use shall not
constitute a First Commercial Sale.
Section 1.49
First Opt-Out Milestone
. First Opt-Out Milestone means the earlier
of: (a) each of the following conditions having been met: (i) [**], in each case with respect to
Licensed Product in the Field and with respect to the Profit-Share Territory; or (b) [**] with
respect to Licensed Product in the Field and with respect to the Profit-Share Territory. For
purposes of clause (a)(iii) above, the JSC shall make the determination whether to continue with
plans for [**].
Section 1.50
FTE
. FTE means the number of full-time-equivalent person-years (each
consisting of a total of [**] hours) of Development, Manufacturing or Commercialization work by
each Partys personnel on or directly related to the applicable activity conducted hereunder.
Section 1.51
FTE Cost
. FTE Cost means the amount obtained by multiplying (a) the
number of FTEs by (b) either (i) $[**] with respect to FTEs engaged in Development activities or
engaged in any scientific aspects of Commercialization including drug safety analysis, or (ii) with
respect to FTEs engaged in other Commercialization activities, such rate as shall be determined by
the JCT in connection with preparation of the first Commercialization Plan, which such amount shall
be based on [**], consistent with GAAP, in each case of clauses (i) or (ii) [**] annually by [**],
in the case of the FTE Cost under clause (i), and over the [**], in the case of the FTE Cost under
clause (ii) (
i.e.
, the first such [**] with respect to the FTE Cost for FTEs engaged in Development
would occur on [**]).
Section 1.52
GAAP
. GAAP means United States generally accepted accounting
principles applied on a consistent basis, or any successor accounting principles generally accepted
for public companies in the United States (such as International Financial Reporting Standards
(
IFRS
)). Unless otherwise defined or stated, financial terms shall be calculated by
the accrual method under GAAP.
Section 1.53
Generic Competition
. Generic Competition means, with respect to a
Licensed Product in any country in the Royalty Territory in a given Calendar Quarter, that, during
such Calendar Quarter, one or more Generic Products shall be commercially available in such country
and such Generic Products shall have a [**] (calculated on the basis of [**]) of [**] percent
([**]%) of the [**] of Licensed Products and Generic Products (based on [**], or if such data is
not available, such other reliable data source as reasonably determined by Cubist and agreed to by
Alnylam (such agreement not to be unreasonably withheld or delayed));
provided
,
however
, that, if [**] data (or data from another data source selected in accordance with
the foregoing) is unavailable to determine the percentage [**] for a country in the Royalty
Territory where a Generic Product is being sold, the average Generic Competition of the countries
in the EU for which such data is available will be deemed to be the Generic Competition for such
country in which such data is not available.
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Section 1.54
Generic Product
. Generic Product means any pharmaceutical product
sold by a Third Party not authorized by Cubist or its Related Parties that is (a) [**].
Section 1.55
Good Clinical Practice
. Good Clinical Practice means the current good
clinical practice applicable to the clinical Development of Licensed Product under applicable Law,
to the extent such standards are not less stringent than the U.S. current good clinical practice,
including the ICH guidelines.
Section 1.56
Good Laboratory Practice
. Good Laboratory Practice means the current
good laboratory practice applicable to the Development of Licensed Product under applicable Law, to
the extent such standards are not less stringent than the U.S. current good laboratory practice,
including 21 C.F.R. Part 58.
Section 1.57
Governmental Authority
. Governmental Authority means any United
States federal, state or local or any foreign government, or political subdivision thereof, or any
multinational organization or authority or any authority, agency or commission entitled to exercise
any administrative, executive, judicial, legislative, police, regulatory or taxing authority or
power, any court or tribunal (or any department, bureau or division thereof), or any governmental
arbitrator or arbitral body.
Section 1.58
Government Health Care Programs
. Government Health Care Programs
means the Medicare program (Title XVIII of the Social Security Act), the Medicaid program (Title
XIX of the Social Security Act), TRICARE, the Federal Employee Health Benefits Program, and other
foreign, federal, state and local governmental health care plans and programs.
Section 1.59
Government Order
. Government Order means any order, writ, judgment,
injunction, decree, stipulation, ruling, determination or award entered by or with any Governmental
Authority.
Section 1.60
Health Care Laws
. Health Care Laws means Laws relating to Government
Health Care Programs, Private Health Care Plans, privacy and confidentiality of patient health
information and human biological materials, including: federal and state Laws pertaining to the
federal Medicare and Medicaid programs (including the Medicaid rebate program); federal Laws
pertaining to the Federal Employees Health Benefit Program, the TRICARE program and other
Government Health Care Programs; federal and state Laws applicable to health care fraud and abuse,
kickbacks, physician self-referral and false claims (including 42 U.S.C. § 1320a-7a, 42 U.S.C. §
1320a-7b, 42 U.S.C. § 1395nn and the federal Civil False Claims Act, 31 U.S.C. § 3729
et seq.
); the
Health Insurance Portability and Accountability Act of 1996; and 45 C.F.R. Part 46, each as in
effect and as amended from time to time.
Section 1.61
ICH
. ICH means the International Conference on Harmonization of
Technical Requirements for Registration of Pharmaceuticals for Human Use.
Section 1.62
IND
. IND means an Investigational New Drug Application filed with FDA
or a similar application filed with an applicable Regulatory Authority outside of the United States
such as a clinical trial application (CTA) or a clinical trial exemption (CTX).
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Section 1.63
Investigator Sponsored Clinical Study
. Investigator Sponsored Clinical
Study means a human clinical study of Licensed Product that is sponsored and conducted by a Third
Party under an agreement with a Party pursuant to which such Party provides clinical supplies of
Licensed Product or funding for such clinical study.
Section 1.64
Joint Collaboration IP
. Joint Collaboration IP means, collectively,
(a) any improvement, discovery or Know-How, patentable or otherwise, first identified, discovered
or developed jointly by the Parties or their Affiliates or others acting on behalf of Cubist and
Alnylam or their Affiliates in the conduct of the Collaboration, and (b) any Patent Rights which
claim or cover such improvements, discoveries or Know-How during the Term.
Section 1.65
Know-How
. Know-How means all biological materials and other tangible
materials, inventions, practices, methods, protocols, formulas, knowledge, know-how, trade secrets,
processes, procedures, assays, skills, experience, techniques and results of experimentation and
testing, including pharmacological, toxicological and pre-clinical and clinical test data and
analytical and quality control data, patentable or otherwise.
Section 1.66
Knowledge of Alnylam
. Knowledge of Alnylam means the [**].
Section 1.67
Kyowa Agreement
. Kyowa Agreement means the License and Collaboration
Agreement entered into by and between Alnylam and Kyowa Hakko as of June 19, 2008, with respect to
the Development and Commercialization of Licensed Product in Asia.
Section 1.68
Kyowa Hakko
. Kyowa Hakko means Kyowa Hakko Kirin Co., Ltd. (formerly
known as Kyowa Hakko Kogyo Co., Ltd.), a corporation organized and existing under the laws of
Japan.
Section 1.69
Law
. Law means any United States federal, state or local or foreign
or multinational law, statute, standard, ordinance, code, rule, regulation, resolution or
promulgation, or any Government Order, or any license, franchise, permit or similar right granted
under any of the foregoing, or any similar provision having the force or effect of law.
Section 1.70
Legal Exclusivity Period
. Legal Exclusivity Period means, with
respect to a Licensed Product, the period beginning on the earlier of the commencement of the (a)
Patent-Based Exclusivity Period or (b) Regulatory-Based Exclusivity Period, and expiring on the
later of the expiration of the (i) Patent-Based Exclusivity Period or (ii) Regulatory-Based
Exclusivity Period.
Section 1.71
Licensed Product
. Licensed Products means any RNAi Product directed
to RSV.
Section 1.72
Major EU Country
. Major EU Country means any of the United Kingdom,
France, Germany, Italy or Spain.
Section 1.73
Manufacturing
or
Manufacture
. Manufacturing or Manufacture
means, as applicable, all activities associated with the production, manufacture, supply,
processing, filling, finishing, testing, packaging, labeling, shipping, and storage of Licensed
Product or placebo (including API Bulk Drug Substance and Finished Product), including process and
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formulation development, process validation, stability testing, manufacturing scale-up,
pre-clinical, clinical and commercial manufacture and analytical development, product
characterization, quality assurance and quality control development, testing and release.
Section 1.74
N.A. Pre-Tax Profit or Loss
. N.A. Pre-Tax Profit or Loss means Net
Sales of Licensed Product in North America by Cubist and its Affiliates (but not Sublicensees) plus
Sublicense Income minus (a) Cost of Goods Sold, (b) Distribution Costs and (c) Commercialization
Costs,
in each case determined from the books and records of the applicable Party or its Related
Parties, maintained in accordance GAAP, consistently applied.
Section 1.75
Necessary Third Party IP
. Necessary Third Party IP means, on a
country-by-country basis, Know-How or Patent Rights that are owned or controlled by a Third Party
and Cover or are otherwise necessary or reasonably useful for the Development, Manufacture or
Commercialization of Licensed Product in the Field in such country, and are the subject of an
Alnylam In-License or a Cubist In-License.
Section 1.76
Net Sales
. Net Sales shall mean the gross amount invoiced by Cubist,
and its Affiliates with respect to the Profit-Share Territory and shall mean the gross amount
invoiced by Cubist and its Related Parties with respect to the Royalty Territory, in each case on
sales or other dispositions (excluding sales or dispositions for use in clinical trials, other
scientific testing, or as samples, or as part of compassionate use, patient assistance, named
patient or test marketing program or any similar program or study, or other similar cases, in each
case for which Cubist or its Related Parties receive no revenue) of Licensed Product to Third
Parties, less the following deductions:
(a) Trade, cash and quantity discounts and allowances actually allowed and taken directly with
respect to such sales or other dispositions;
(b) Tariffs, duties, excises, sales taxes, value-added or other taxes or governmental charges
imposed upon and paid directly with respect to the delivery, sale or use of Licensed Product
(excluding national, state or local taxes based on income);
(c) Amounts repaid or credited by reason of rejections, defects, recalls or returns or because
of reasonable and customary chargebacks, refunds, rebates (including rebates to managed care
organizations, group purchasing organizations, pharmacy benefit management companies, health
maintenance organizations, healthcare institutions, other buying groups or providers of healthcare
or social and welfare systems, or in connection with patient assistance or similar programs) or
retroactive price reductions (including any discounts granted later than at the time of invoicing),
government mandated rebates and similar types of rebates (e.g., Pharmaceutical Price Regulation
Scheme and Medicaid, or wholesalers, distributors and other trade customers), or cash sales
incentives, or deductions for items of a nature or substance similar to that of the foregoing
deductions in this clause (c) that may become customary;
(d) [**];
(e) [**];
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(f) Postage charges, shipping materials, freight, insurance and other transportation charges
incurred in shipping such Licensed Product to Third Parties, included and separately stated in the
applicable invoice; and
(g) Any item substantially similar in character or substance to any of the foregoing and not
separately invoiced to the customer, to the extent consistent with then prevailing industry
standards.
Such amounts shall be determined from the books and records of Cubist or its Related Parties,
maintained in accordance with GAAP, consistently applied.
For purposes of clarity, it is understood that costs and expenses included in the above
deductions and in the calculation of N.A. Pre-Tax Profit or Loss or in Development Costs shall not
be double-counted. In the case of pharmacy incentive programs, hospital performance incentive
program chargebacks, disease management programs, similar programs or discounts on bundles of
products, all discounts and the like shall be allocated among products in proportion to the
respective list prices of such products or such other reasonable allocation method as the Parties
shall agree.
The transfer of Licensed Product by Cubist or any of its Affiliates to a Related Party in the
Royalty Territory for resale, and the transfer of Licensed Product by Cubist or any of its
Affiliates to an Affiliate in the Profit-Share Territory for resale shall not be considered a sale.
In the case where a Licensed Product is a Combination Product, royalties with respect to a
Combination Product in a country of the Royalty Territory shall be equal to the royalties
calculated in accordance with Article VII, multiplied by a fraction whose numerator is the average
published sales price in such country for an equivalent dosage of Licensed Product (sold separately
as a stand-alone product) contained in a given Combination Product, and whose denominator is the
sum of the average published sale prices in such country of the Royalty Territory for all
components (sold separately as a stand alone product) that are equivalent to all components
contained in the Combination Product. If the numerator or denominator cannot be determined in the
manner set forth above, the Parties shall negotiate in good faith and agree to an appropriate
adjustment to Net Sales to reflect the relative significance of the stand-alone Licensed Product
contained in the Combination Product and the other components contained in the Combination Product,
which agreement shall not be unreasonably withheld, conditioned or delayed. If the Parties are
unable to reach agreement regarding such issue within thirty (30) days after commencing good faith
negotiations, the issue shall be referred to dispute resolution in accordance with Article XII.
Notwithstanding the foregoing, with respect to Licensed Products that are Combination
Products, Net Sales in the Profit-Share Territory shall not be reduced as set forth in the
immediately preceding paragraph and the cost of acquiring any other clinically active therapeutic
or prophylactic ingredient or other significant component, mechanism or device shall be included in
the calculation of the Cost of Goods Sold for purposes of calculating N.A. Pre-Tax Profit or Loss
for such Licensed Product in the Profit-Share Territory.
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As used above, the term
Combination Product
means any pharmaceutical product that
consists of a Licensed Product and other active compounds or active ingredients or other
significant component, mechanism or device or any combination of Licensed Product sold together
with another pharmaceutical product or other significant component, mechanism or device for a
single invoiced price, and the phrases sold as part of a Combination Product, sold
separately, Net Sales of the Combination Product and average sale price refer to sales by
Cubist or its Related Parties in the applicable country. All references to Licensed Product in
this Agreement shall be deemed to include Combination Product, to the extent applicable.
Section 1.77
New Drug Application
or
NDA
. New Drug Application or NDA
means (a) an application submitted to FDA pursuant to 21 U.S.C. § 505(b), which contains complete
details of the manufacture and testing of a new drug, for purposes of obtaining Regulatory Approval
for such new drug in the United States, for a particular indication, and also includes any
Biologics License Application, or (b) a similar application, such as a Marketing Approval
Authorization (
MAA
) filed with the EMEA or other Regulatory Authority.
Section 1.78
North America
or
N.A
.. North America or N.A. means the
United States, Canada and Mexico.
Section 1.79
Parties
. Parties means Alnylam and Cubist.
Section 1.80
Party
. Party means either Alnylam or Cubist.
Section 1.81
Patent-Based Exclusivity Period
. Patent-Based Exclusivity Period
means, with respect to a country in the Royalty Territory, that period of time during which at
least one Valid Claim within the Alnylam Patent Rights Covers Licensed Product in such country.
Section 1.82
Patent Rights
. Patent Rights means patents and patent applications
and all substitutions, divisions, continuations, continuations-in-part, reissues, reexaminations,
supplemental protection certificates and extensions and the like thereof, and all counterparts
thereof in any country.
Section 1.83
Person
. Person means any natural person, corporation, firm, business
trust, joint venture, association, organization, company, partnership or other business entity, or
any government, or any agency or political subdivisions thereof.
Section 1.84
Phase I Clinical Study
. Phase I Clinical Study means a clinical study
of Licensed Product in human volunteers or patients with the endpoint of determining initial
tolerance, toxicity, safety or pharmacokinetic information, which shall be deemed commenced when
the third volunteer or patient in such study has received his or her initial dose of Licensed
Product.
Section 1.85
Phase II Clinical Study
. Phase II Clinical Study means a preliminary
efficacy and safety or dose ranging human clinical study of Licensed Product in the target patient
population, which shall be deemed commenced when the third patient in such study has received his
or her initial dose of Licensed Product.
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Section 1.86
Phase III Clinical Study
. Phase III Clinical Study means a human
clinical study to confirm with statistical significance the efficacy and safety of Licensed Product
performed to obtain Regulatory Approval for Licensed Product in any country, which shall be deemed
commenced when the third patient in such study has received his or her initial dose of Licensed
Product.
Section 1.87
Pivotal Clinical Study
. Pivotal Clinical Study means a human clinical
study, including any Phase III Clinical Study, the results of which, if the pre-defined endpoints
are met, are intended to be the data from a pivotal study necessary to support Regulatory Approval
for Licensed Product in any country.
Section 1.88
Post-Approval Study
. Post Approval Study means a clinical study of
Licensed Product that is initiated in a country in the Territory after receipt of Regulatory
Approval for such Licensed Product in such country.
Section 1.89
Private Health Care Plans
. Private Health Care Plans means
non-governmental Third Party health care payors and plans, including insurance companies, health
maintenance organizations and other managed care organizations, Blue Cross and Blue Shield plans
and self-funded employers.
Section 1.90
Post Approval Medical and Regulatory Activities
. Post Approval
Medical and Regulatory Activities means all medical and regulatory activities directed at support
of Licensed Product after Regulatory Approval, including medical education, use of medical science
liaisons, post approval regulatory activities, Post Approval Studies, and patient
safety/pharmacovigilance surveillance.
Section 1.91
Product Liability Costs
. Product Liability Costs means costs
associated with Third Party product liability claims or Actions resulting from the Development,
Manufacture or Commercialization of Licensed Product under this Agreement in the Field in the
Profit-Share Territory and product liability insurance premiums for policies covering the
Development, Manufacture or Commercialization of Licensed Product in the Field in the Profit-Share
Territory (other than Losses entitled to indemnification under Section 10.11(c)(i) or (ii)).
Section 1.92
Profit-Share Territory
. Profit-Share Territory means, subject to
Section 4.7, North America.
Section 1.93
Product Trademark
. Product Trademark means the trademark(s) and
service mark(s) for use in connection with the distribution, marketing, promotion and sale of
Licensed Product, or accompanying logos, trade dress or indicia of origin. Product Trademarks
specifically excludes the corporate names and logos of the Parties and their Affiliates.
Section 1.94
Regulatory Approval
. Regulatory Approval means the approval of the
applicable Regulatory Authority necessary for the marketing and sale of Licensed Product for a
particular indication in a country, excluding separate pricing or reimbursement approvals that may
be required, and including the expansion or modification of the label for such indication.
Section 1.95
Regulatory Authority
. Regulatory Authority means any federal,
national, multinational, state, provincial or local regulatory agency, department, bureau or other
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governmental entity with authority over the manufacturing, marketing, sale or use of a
pharmaceutical product in a country, including the FDA in the United States and the EMEA in the EU.
Section 1.96
Regulatory-Based Exclusivity Period
. Regulatory-Based Exclusivity
Period means, with respect to a Licensed Product in a country in the Royalty Territory, that period
of time during which Cubist or any of its Related Parties has been granted the exclusive legal
right by a Regulatory Authority (or is otherwise entitled to the exclusive legal right by operation
of applicable Law) in such country to market and sell the active ingredient contained in such
Licensed Product in such country.
Section 1.97
Related Party
. Related Party means (a) with respect to Cubist, any of
Cubists Affiliates or Sublicensees, and, (b) with respect to Alnylam, any of Alnylams Affiliates
or Sublicensees and Alnylams Asian Partner.
Section 1.98
RNAi Product
. RNAi Product means a double-stranded oligonucleotide
molecule designed to act primarily through an RNA interference mechanism that is not a microRNA,
microRNA antagonist or microRNA mimic and which consists of either (a) two separate oligomers of
native or chemically modified RNA that are hybridizable to one another along a substantial portion
of their lengths, or (b) a single oligomer of native or chemically modified RNA that is
hybridizable to itself by self-complementary base-pairing along a substantial portion of its length
to form a hairpin, in either case that inactivates, including inactivation resulting from cleavage,
a target mRNA, which encodes a protein product, via a double-stranded RNase, such as those involved
in the RNA interference mechanism.
Section 1.99
Royalty Territory
. Royalty Territory means, subject to Section 4.7,
the entire Territory other than North America.
Section 1.100
RSV
. RSV means all strains of the respiratory syncytial virus.
Section 1.101
RSV01 Product
. RSV01 Product means any product containing Alnylams
proprietary composition known as ALN-RSV01. ALN-RSV01 is described on
Exhibit B
.
Section 1.102
RSV02 Product
. RSV02 Product means any product containing Alnylams
proprietary composition designated by the JSC as ALN-RSV02.
Section 1.103
Safety Data
. Safety Data means adverse event information and other
information (if any) required by one (1) or more Regulatory Authorities to be collected or to be
reported to such Regulatory Authorities under applicable Laws.
Section 1.104
Sales Representative
. Sales Representative means an individual, who
engages in or manages sales calls and other promotional efforts with respect to Licensed Product
and who is employed by a Party or an Affiliate of a Party.
Section 1.105
Second Opt-Out Milestone
. Second Opt-Out Milestone means the earlier
to occur of: (a) [**]. For the avoidance of doubt, if there is a deadlock at the JSC with respect
to the determination in clause (b), then [**].
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Section 1.106
Sublicensee
. Sublicensee, as to a Licensed Product, means any Third
Party to whom a Party or any of its Affiliates grants a sublicense (a) in the case of Cubist or its
Affiliates, under any Alnylam Technology to Develop, Manufacture or Commercialize any Licensed
Product in the Field in the Territory, and (b) in the case of Alnylam or its Affiliates, under any
Cubist Technology licensed to Alnylam pursuant to Section 3.2 or Section 11.3;
provided
that
the term Sublicensee does not include [**].
Section 1.107
Sublicense Income
. Sublicense Income means (a) with respect to
Cubist, any payment Cubist or any of its Affiliates receives from a licensee or Sublicensee for the
grant to such licensee or Sublicensee of a sublicense to the rights to Alnylam Technology licensed
to Cubist under this Agreement or a license to the Cubist Technology with respect to Licensed
Product in the Field in the Profit-Share Territory, or, in the event Alnylam exercises the Opt-Out
Option, any payment Cubist or any of its Affiliates receives from a licensee or Sublicensee for the
grant to such licensee or Sublicensee of a sublicense to the rights to Alnylam Technology licensed
to Cubist under this Agreement or a license to the Cubist Technology with respect to Licensed
Product in North America, (b) with respect to Alnylam, any payment Alnylam or any of its Affiliates
receives from a licensee or Sublicensee for the grant to such licensee or Sublicensee of a
sublicense to the rights to Cubist Technology licensed to Alnylam or a license to Alnylam
Technology under this Agreement with respect to Licensed Product in the Field in the Profit-Share
Territory, in each case to the extent permitted by the JSC under this Agreement, and (c) with
respect to Alnylam, in the event Cubist terminates this Agreement after the Second Opt-Out
Milestone, any payment Alnylam or any of its Affiliates receives from a licensee or Sublicensee for
the grant to such licensee or Sublicensee of a sublicense to the rights to Cubist Technology or a
license under Alnylam Technology with respect to Licensed Product in the Field in North America, in
each case including [**]. As used in this Section 1.107, licensee does not include [**].
The foregoing provisions of this Section 1.107 notwithstanding, Sublicense Income shall not
include:
[**]
Section 1.108
Territory
. Territory means the entire world, except for Asia.
Section 1.109
Third Party
. Third Party means any Person other than a Party or any
of its Affiliates.
Section 1.110
United States
or
U.S.
. United States or U.S. means the
United States of America and its territories and possessions.
Section 1.111
Valid Claim
. Valid Claim means a claim (a) of any issued, unexpired
patent that has not been revoked or held unenforceable or invalid by a decision of a court or
governmental agency of competent jurisdiction from which no appeal can be taken, or with respect to
which an appeal is not taken within the time allowed for appeal, and that has not been disclaimed
or admitted to be invalid or unenforceable through reissue, disclaimer or otherwise or (b) of any
patent application that has been filed with a good faith belief that claims are reasonably likely
to issue that Cover Licensed Product and which such application has not been
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cancelled, withdrawn or abandoned or been pending for more than [**] as measured from the
earliest claimed priority date of such patent application.
Section 1.112
Additional Definitions
. Each of the following definitions is set forth
in the Section of this Agreement indicated below:
|
|
|
Definition
|
|
Section
|
|
|
|
1974 Convention
|
|
13.1(c)
|
AAA
|
|
12.1
|
Additional RSV Product
|
|
4.6
|
Agreement
|
|
Preamble
|
Alnylam
|
|
Preamble
|
Alnylam Indemnitees
|
|
10.11(a)
|
Alnylam Trademarks
|
|
8.8(b)
|
Asian Partner Payments
|
|
7.11
|
Bankruptcy Code
|
|
3.5
|
Challenging Party
|
|
11.2(c)
|
Collaboration Manager
|
|
2.2
|
Combination Product
|
|
1.76
|
Commercialization Plan
|
|
5.3(a)
|
Competitive Infringement
|
|
8.4(a)
|
Confidential Information
|
|
9.1
|
Cubist
|
|
Preamble
|
Cubist Indemnitees
|
|
10.11(b)
|
Cubist Trademarks
|
|
8.8(b)
|
Dispute
|
|
12.1
|
Effective Date
|
|
Preamble
|
Excluded Claim
|
|
12.1
|
IFRS
|
|
1.52
|
Indemnitee
|
|
10.11(d)
|
JCT
|
|
5.2
|
JSC
|
|
2.1(a)
|
JSC Chairperson
|
|
2.1(b)
|
Losses
|
|
10.11(a)
|
M&A Event
|
|
13.8
|
MAA
|
|
1.77
|
Negotiation Period
|
|
3.1(g)
|
Non-Challenging Party
|
|
11.2(c)
|
Option Period
|
|
3.1(g)
|
Opt-Out Option
|
|
4.7(a)
|
Patent Expenses
|
|
8.3(e)
|
Promotional Materials
|
|
5.5
|
ROFN Notice
|
|
3.1(g)
|
ROFN Right
|
|
3.1(g)
|
Royalty Term
|
|
7.5(d)
|
Safety Information Exchange Agreement
|
|
5.9
|
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|
|
|
Definition
|
|
Section
|
|
|
|
Severed Clause
|
|
13.3
|
Supply Agreement
|
|
6.3
|
Supply Agreement Term Sheet
|
|
6.3
|
Tax or Taxes
|
|
7.13(e)
|
Term
|
|
11.1
|
Third Party Technology
|
|
8.6
|
ARTICLE II
MANAGEMENT OF COLLABORATIVE ACTIVITIES
Section 2.1
Joint Steering Committee
. The Parties hereby establish a joint committee
to facilitate the Collaboration in the Profit-Share Territory as follows:
(a)
Composition of the Joint Steering Committee
. The Collaboration in the
Profit-Share Territory shall be conducted under the direction of a joint steering committee (the
JSC
) comprised of three (3) named representatives of Cubist and three (3) named
representatives of Alnylam or such other number of representatives as the Parties may from time to
time mutually agree. Each Party shall appoint its respective representatives to the JSC from time
to time, and may substitute one or more of its representatives, in its sole discretion, effective
upon notice to the other Party of such change. Each Party shall have at least one JSC
representative who is a senior employee (vice president level or above), and all JSC
representatives shall have appropriate expertise and ongoing familiarity with the Collaboration.
Additional representatives or consultants may from time to time, by mutual consent of the Parties,
be invited to attend JSC meetings, provided such representatives and consultants are subject to
written obligations that are no less stringent than the confidentiality obligations and
restrictions on use set forth in Article IX. All proceedings for the JSC shall take place in
English. Each Party shall bear its own expenses relating to attendance at such meetings by its
representatives.
(b)
JSC Chairperson
. The chairperson of the JSC (the
JSC Chairperson
) shall
rotate every twelve (12) months between Alnylam and Cubist. The initial JSC Chairperson shall be a
representative of Alnylam. The JSC Chairpersons responsibilities shall include (i) scheduling
meetings at least [**] per Calendar Quarter, but more frequently if the JSC determines it
necessary; (ii) setting agendas for meetings with solicited input from other members; and (iii)
confirming and delivering minutes to the JSC for review and final approval.
(c)
Meetings
. The first JSC meeting shall be held within [**] after the Effective
Date, and the JSC shall meet in accordance with a schedule established by mutual agreement of the
Parties, but no less frequently than [**] each Calendar Quarter, with the location for such
meetings alternating between Alnylam and Cubist facilities in Massachusetts (or such other
locations as are determined by the JSC). Alternatively, the JSC may meet by
means of teleconference, videoconference or other similar communications equipment, but at
least [**] meetings per Calendar Year shall be conducted in person.
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(d)
JSC Responsibilities
. The JSC shall have the following responsibilities with
respect to the Collaboration:
(i) providing updates regarding the Development of Licensed Product in the Territory;
(ii) monitoring, planning and coordinating the Development of Licensed Product in the
Profit-Share Territory and the Parties respective commitments relating to shared Development
Costs;
(iii) reviewing and approving (A) each annual update to the Development Plan, and (B) any
modifications to the Development Plan within [**] after each submission thereof to the JSC (or
sooner as circumstances warrant);
(iv) regularly assessing the progress of the Parties in their conduct of the Development Plan
against the timelines and budgets contained therein, reviewing relevant data, and considering
issues of priority;
(v) overseeing Manufacturing activities related to the Development of Licensed Product for the
Territory;
(vi) reviewing information and data relating to the Development of Licensed Products by
Alnylam and its Related Parties for Asia;
(vii) coordinating with the JCT regarding Commercialization matters related to the
Profit-Share Territory, as necessary or appropriate;
(viii) [**].
(ix) performing such other activities as the Parties agree in writing shall be the
responsibility of the JSC; and
(x) attempting to resolve any and all disputes relating to the conduct of the Collaboration in
the Profit-Share Territory by consensus.
For purposes of clarity, it is expected that with respect to the sharing of information
regarding Licensed Product, (A) each Party will, through the JSC and through regular communication
between each Partys designated Collaboration Manager, keep the other Party informed at a detailed
level about all activities related to the Development, Manufacture and Commercialization of
Licensed Product in the Field in the Profit-Share Territory, and will provide all information
requested of such Party by the other Party related to the Development, Manufacture and
Commercialization of Licensed Product in the Field in the Profit-Share Territory, (B) Cubist will
regularly share information with Alnylam through the JSC regarding its activities in the Royalty
Territory, consistent with keeping Alnylam reasonably informed of the progress and results of
Development, Manufacture and Commercialization in the Royalty Territory, and (C) Alnylam will
regularly share information with Cubist through the JSC regarding the activities of Alnylam and its
Related Parties with respect to Development, Manufacture and Commercialization of Licensed Product
for Asia consistent with keeping
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Cubist reasonably informed of the progress and results of Development, Manufacture and
Commercialization of Licensed Product for Asia.
For purposes of clarity, the JSC shall not have the authority to modify the terms of this
Agreement.
Section 2.2
Appointment of Subcommittees, Project Teams and Collaboration Managers
.
The JSC shall be empowered to create such subcommittees of itself and project teams as it may deem
appropriate or necessary. Each such subcommittee and project team shall report to the JSC, which
shall have authority to approve or reject recommendations or actions proposed thereby subject to
the terms of this Agreement. Each Party shall also designate a collaboration manager (each a
Collaboration Manager
), who shall be responsible for the day-to-day coordination of the
Collaboration and will serve to facilitate communication between the Parties with respect to both
the Profit-Share Territory and the Royalty Territory. Each Party may change its designated
Collaboration Manager from time to time upon written notice to the other Party.
Section 2.3
Reports and Minutes
. Each Party shall prepare and deliver to the JSC, by
no later than each [**] (for the period ending December 31 of the prior Calendar Year), written
reports summarizing such Partys Development activities for Licensed Product in the Field for the
Territory performed to date (or updating such report for activities performed since the last such
report submitted hereunder, as applicable). Such reports may be provided in any reasonable written
form determined by the reporting Party, including in a presentation slide format that reasonably
summarizes such activities. Alnylam shall also, at the same time it submits a written report under
this Section 2.3 regarding activities in the Territory, also provide a written report to the JSC
summarizing the status, progress and results of activities performed by Alnylam and its Asian
Partner with respect to Development, Manufacture or Commercialization of Licensed Product for Asia.
In addition, Cubist shall provide Alnylam with prompt written notice of the achievement by Cubist
of any milestone event set forth in Section 7.2. Each Party will provide the members of the JSC
with copies, which may be in electronic format, of all materials it intends to present at a JSC
meeting. The JSC may also request at any time specific data or information related to
Collaboration activities or any other data to which the JSC is entitled under this Agreement or
that a written report be prepared in advance of any meeting summarizing certain material data and
information arising out of the conduct of the Collaboration any other data to which the JSC is
entitled under this Agreement and the Party or appropriate committee to whom such request is made
shall promptly provide to the other Party or the JSC such report, data or information. A secretary
shall be appointed for each meeting and shall prepare minutes of the meeting, it being understood
that the secretary and the JSC Chairperson shall not be representatives of the same Party (that is,
if the JSC Chairperson is a representative of Cubist, the secretary shall be a representative of
Alnylam, and vice versa).
Section 2.4
Decision-Making
. Decisions within the purview of the JSC shall be made
by the JSC by consensus, with the representatives of each Party collectively having one vote on
behalf of such Party. For each meeting of the JSC, at least two (2) representatives of each Party
shall constitute a quorum. Action on any matter may be taken at a meeting, by teleconference,
videoconference or by written agreement.
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Section 2.5
Deadlocks
. The JSC shall attempt to resolve any and all disputes
relating to the Collaboration by consensus. If the JSC is unable to reach a consensus with respect
to a dispute, then the dispute shall be submitted to escalating levels of Alnylam and Cubist senior
management for review. If such dispute cannot be resolved despite escalation, then the Chief
Executive Officers of Alnylam and Cubist shall attempt to resolve such dispute. If the Chief
Executive Officers cannot reach an agreement regarding such dispute within [**] days after
submission to them for resolution, then if the dispute is one over which the JSC has authority
pursuant to Section 2.1(d) or if the dispute relates to the Royalty Territory, then Cubist shall
have the final decision-making authority subject to Sections 2.5(a) and (b). Notwithstanding
anything in this Agreement to the contrary, any decision within the purview of the JSC for which
Cubist has exercised its final decision-making authority shall be considered a decision or approval
of the JSC.
(a) Notwithstanding anything in this Agreement to the contrary, Cubist (i) has no final
decision-making authority over the Development or Commercialization of Licensed Product for Asia or
outside the Field, or the Manufacture of Licensed Product by Alnylam or its Related Parties for
such purposes, (ii) may not conduct, sponsor, fund or otherwise support a Clinical Study or
Post-Approval Study of Licensed Product that would [**] the Development or Commercialization of
Licensed Product in the Field in Asia without Alnylams prior written consent; (iii) may not effect
a transfer of responsibility for the Manufacture of API Bulk Drug Substance or Finished Product
from Alnylam to Cubist, it being understood that any such decisions shall be made by the Parties in
accordance with Article VI; (iv) may not exercise its final decision-making authority to resolve
any disputes between the Parties regarding the [**]; (v) may not exercise its final decision-making
authority to [**]; (vi) may not exercise its final decision-making authority with respect to
decisions about whether [**], (vii) may not exercise its final decision-making authority to resolve
any dispute regarding [**]; and (viii) may not exercise its final decision-making authority to (A)
require Alnylam to use other than Diligent Efforts to perform its obligations under the
Collaboration, (B) require Alnylam to perform any activities for which it is not responsible under
this Agreement, to amend the Development Plan or Commercialization Plan to impose additional
obligations on Alnylam without Alnylams consent, including for purposes of clarity, to approve any
change in the budgets for the Development Plan or the Commercialization Plan pursuant to Section
4.5 or Section 5.3(b), it being understood that Cubist shall have final decision-making authority
regarding implementation of the activities set forth in the Development Plan and the
Commercialization Plan, including pricing of Licensed Product in the Territory; (C) resolve any
dispute as to what level of effort constitutes Diligent Efforts, (D) require Alnylam to take any
action that would, or fail to take any action where the failure to take such action would, violate
any applicable Law, rule or regulation or any agreement with any Third Party (
provided
,
that
, in entering into any such agreement, Alnylam is not in breach of its obligation under
this Agreement) or infringe the intellectual property rights of Third Parties, or (E) expand or
narrow the responsibilities of the JSC or JCT; and
(b) with respect to all disputes between the Parties under this Agreement that are not subject
to Cubists final decision-making authority, the dispute resolution provisions of Article XII shall
apply.
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Section 2.6
Dissolution of JSC
. The JSC shall be dissolved upon the earlier to occur
of (a) [**];
provided
that
, after the [**] of the Effective Date, Alnylam shall
have the right, but shall not be obligated, to participate on the JSC. In the event the JSC is
dissolved or Alnylam elects not participate under the preceding sentence, (i) decisions within the
purview of the JSC shall be made by Cubist subject to the limits on Cubists decision-making
authority set forth in Section 2.5 (a) and subject to Section 2.5(b), and (ii) information sharing
shall continue as set forth in Section 4.8
Section 2.7
Collaboration Guidelines
.
(a) In conducting activities under this Agreement, neither Party shall prejudice the value of
Licensed Product by reason of such Partys activities outside of the Collaboration. Except as
specifically provided in Article III or Section 10.1, the foregoing shall not require either Party
to limit the development, manufacture or commercialization of products other than Licensed Product.
Without limiting the provisions of this Section 2.7(a), Alnylam agrees that it will not conduct,
sponsor, fund or otherwise support without Cubists prior written consent, and will use Diligent
Efforts to prevent any Related Party from, conducting, sponsoring, funding or otherwise supporting,
a clinical study of any Licensed Product for Asia that would [**] the Development or
Commercialization of Licensed Products in the Territory. In all matters relating to this
Agreement, the Parties shall seek to comply with good pharmaceutical and environmental practices.
(b) Subject to the terms of this Agreement, the activities and resources of each Party shall
be managed by such Party, acting independently and in its individual capacity.
ARTICLE III
LICENSE GRANTS
Section 3.1
Alnylam Grants
.
(a)
Development License
. Subject to the terms of this Agreement, Alnylam hereby
grants to Cubist (i) a co-exclusive (with Alnylam, to the extent of Alnylams rights and
obligations under this Agreement) right and license, with the right to grant sublicenses, under the
Alnylam Technology, to Develop Licensed Products in the Field for the Profit-Share Territory, and
(ii) an exclusive right and license, with the right to grant sublicenses, under the Alnylam
Technology, to Develop Licensed Products in the Field for the Royalty Territory. Such licenses
shall be (A) royalty-bearing for the Royalty Term of Licensed Product in each country of the
Royalty Territory, and (B) subject to the Parties rights and obligations with respect to N.A.
Pre-Tax Profit or Loss in the Profit-Share Territory for the Term in accordance with Section 7.4.
Upon expiration of the Royalty Term in the case of a country in the Royalty Territory, the license
granted under clause (ii) shall convert to an exclusive, perpetual, fully paid-up,
non-royalty-bearing licenses to Develop Licensed Products in the Field in the applicable
country(ies). Notwithstanding anything in this Agreement to the contrary, Alnylam shall not be
entitled to
multiple royalty or other payments by reason of the split of the license granted to Cubist
under this Article III into a Development, Commercialization and a Manufacturing license.
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(b)
Commercialization License
. Subject to the terms of this Agreement, Alnylam hereby
grants to Cubist an exclusive right and license, with the right to grant sublicenses, under the
Alnylam Technology to Commercialize Licensed Products in the Field in the Territory. Such license
shall be (i) royalty-bearing for the Royalty Term of Licensed Product in each country of the
Royalty Territory, and (ii) subject to the Parties rights and obligations with respect to N.A.
Pre-Tax Profit or Loss in the Profit-Share Territory for the Term. Upon expiration of the Royalty
Term in the case of a country in the Royalty Territory, the license granted under clause (i) shall
convert to an exclusive, perpetual, fully paid-up, non-royalty-bearing license to Commercialize
Licensed Products in the Field in such country(ies).
(c)
Manufacturing License
. Subject to the terms of this Agreement, including
Alnylams rights as set forth in Article VI, Alnylam hereby grants to Cubist a co-exclusive (with
Alnylam, to the extent of Alnylams rights and obligations under Article VI) right and license,
with the right to grant sublicenses, to the extent consistent with Article VI, under the Alnylam
Technology, to Manufacture or have Manufactured Licensed Products for Development and
Commercialization in the Field for the Territory.
(d)
Limitation on Exclusivity
. For purposes of clarity, notwithstanding anything to
the contrary in Section 3.1(a), 3.1(b) or 10.1, Alnylam has previously and retains the right after
the Effective Date to grant non-exclusive licenses to Third Parties to Develop, Manufacture and
Commercialize RNAi Products for the Territory under Alnylam Technology other than under the Alnylam
Sequence Specific Patent Rights or Alnylam Sequence Specific Know-How;
provided
,
that
, neither Alnylam nor any of its Affiliates (i) will license or will disclose Licensed
Product-specific data, sequence information or other Licensed Product-specific Know-How to any
Third Party other than to a Related Party for purposes of enabling Alnylam to fulfill its
obligations under this Agreement or with respect to the Development and Commercialization of
Licensed Products in Asia, (ii) has or will allow any Third Party to rely on Licensed
Product-specific regulatory filings or pre-clinical or clinical work, or, except as specified in a
Development Plan for purposes of the Collaboration, collaborate with any Third Party other than a
Related Party regarding Licensed Products in any manner, including in any manner that conflicts
with Section 3.1(a), 3.1(b) or 10.1, or (iii) will, after the Effective Date, grant a right or
license to any Third Party under any Patent Rights or Know-How that would allow such Third Party to
Develop, Manufacture and Commercialize Licensed Products other than pursuant to options or other
rights existing on the Effective Date under the agreements listed in
Exhibit D
.
(e)
Affiliates; Sublicenses
.
(i) Cubist shall have the right to grant sublicenses under the licenses granted to it pursuant
to Sections 3.1(a), (b) and (c), and the right to grant licenses of its rights under any Joint
Collaboration IP, to an entity that is its Affiliate for so long as such entity remains an
Affiliate of Cubist and complies in all material respects with the obligations of Cubist under this
Agreement. Cubist hereby guarantees the full payment and performance of its Affiliates under this
Agreement.
(ii) Subject to Sections 3.1(f), 3.3 and 10.1, and for the Profit-Share Territory [**], Cubist
has the right to grant sublicenses of its rights and the licenses granted to it
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under this Agreement (and the right to grant sublicenses under Alnylams interest in any Joint
Collaboration IP) to Third Parties to Develop and Commercialize Licensed Product in the Field in
the Territory (A) [**].
(iii) Subject to Sections 3.1(f) and 3.3 and Article VI, Cubist shall have the right to grant
sublicenses of its rights and the license granted under Section 3.1(c) (and the right to grant
sublicenses under Alnylams interest in any Joint Collaboration IP) to Third Parties to Manufacture
the RSV01 Product, the RSV02 Product, any Additional RSV Product, or a Licensed Product
sublicensed under Section 3.1(e)(ii) for Development and Commercialization in the Field for the
Territory.
(f)
Alnylam In-Licenses
. All licenses and other rights granted to Cubist hereunder
are subject to the rights and obligations of Alnylam under the Alnylam In-Licenses and the Kyowa
Agreement. Cubist shall comply with all terms and conditions of the Alnylam In-Licenses and the
Kyowa Agreement in the Territory applicable to a Sublicensee of Alnylam, and shall perform and take
such actions in the Territory as may be required of a Sublicensee (and, with respect to the Kyowa
Agreement and the [**], as may be required of Alnylam, with respect to Development, Manufacture and
Commercialization of Licensed Product for the Territory) to allow Alnylam to comply with its
obligations thereunder, including obligations relating to sublicensing, patent matters,
confidentiality, reporting, audit rights, indemnification and diligence;
provided
that
in no event shall Cubist be responsible for any payment obligations or other financial
obligations of any kind of Alnylam under such agreements except as otherwise specifically set forth
in Sections 4.7, 7.6, 7.7, 7.9 and 8.6. In order to facilitate Cubists compliance with this
Section 3.1(f), Alnylam will provide Cubist with reasonable notice in advance of any action or
information required of Cubist in respect of the Alnylam In-Licenses, including a description
regarding Alnylams interpretation of such requirements, and Cubist will, to the extent required
under this Section 3.1(f), perform such actions and provide such information in accordance with
such requirements as reasonably interpreted by Alnylam.
(g)
Right of First Negotiation for Asia.
Alnylam hereby grants to Cubist a right of
first negotiation to add Asia to the Royalty Territory hereunder (the
ROFN Right
) if,
during the Term, (i) the Kyowa Agreement terminates and (ii) Alnylam determines to seek an Asian
Partner other than Kyowa Hakko for Licensed Products in the Field in Asia. Prior to initiating
formal business discussions with one or more Third Parties other than Kyowa Hakko regarding such
opportunity, Alnylam shall notify Cubist of Alnylams determination to seek an Asian Partner other
than Kyowa Hakko (the
ROFN Notice
), and Cubist shall have [**] after receipt of the ROFN
Notice (the
Option Period
) to notify Alnylam in writing that either (A) Cubist is
exercising its ROFN Right and is interested in adding Asia to the Royalty Territory hereunder, or
(B) Cubist is not interested in adding Asia to the Royalty Territory hereunder and therefore waives
its ROFN Right. Failure by Cubist to provide written notice of its exercise of the ROFN Right
within the Option Period shall constitute a waiver by Cubist of its ROFN Right. If Cubist provides
written notice to Alnylam exercising its ROFN Right within the Option Period, the Parties shall
negotiate exclusively in good faith for a period of up to [**] from the date the ROFN Notice was
received by Cubist (or such longer period as the Parties may mutually agree) (the
Negotiation
Period
) regarding mutually agreeable terms and conditions, including mutually agreeable
financial terms and conditions, on which this Agreement would be amended to add Asia to the Royalty
Territory hereunder. If, despite such good faith negotiations, the
-25-
Parties do not execute such an amendment within the Negotiation Period, or if Cubist waives
its ROFN Right, then Alnylam shall thereafter be free to negotiate and execute agreement(s) with
one or more Third Parties with respect to such opportunity;
provided
that
for a
period of [**] after the earlier of Cubists waiver of its ROFN Right or the expiration of the
Negotiation Period, Alnylam shall not enter into an agreement regarding such opportunity on terms
that, in the aggregate, are materially more favorable to the Third Party than those last offered by
Alnylam to Cubist.
Section 3.2
Cubist Grants
.
(a)
Manufacturing License
. Subject to the terms and conditions of this Agreement,
Cubist hereby grants to Alnylam a non-exclusive, fully paid-up, non-royalty-bearing worldwide right
and license, with the right to grant sublicenses, subject to Section 3.2(c), under the Cubist
Technology, to Manufacture or have Manufactured Licensed Products, but solely to the extent
necessary (i) during the Term, to enable Alnylam to fulfill its obligations under this Agreement
with respect to the Collaboration, and (ii) during and after the Term, for the Development and
Commercialization of Licensed Products for Asia but only to the extent that such [**].
(b)
Cubist Technology License
. Subject to the terms and conditions of this Agreement,
Cubist hereby grants to Alnylam a non-exclusive, fully paid-up, non-royalty-bearing license, with
the right to grant sublicenses, subject to Section 3.2(c), under any Cubist Technology but solely
to the extent necessary (i) during the Term, to enable Alnylam to fulfill its obligations under
this Agreement with respect to the Collaboration, and (ii) during and after the Term, to Develop
and Commercialize Licensed Products for Asia but only to the extent that such [**].
(c)
Affiliates; Sublicenses
.
(i) Alnylam shall have the right to grant sublicenses under the licenses granted to it
pursuant to Sections 3.2(a) and (b), and, subject to the licenses granted to Cubist under Sections
3.1(a), (b) and (c), the right to grant licenses of its rights under any Joint Collaboration IP, to
an entity that is an Affiliate for so long as such entity remains an Affiliate of Alnylam and
complies in all material respects with the obligations of Alnylam under this Agreement. Alnylam
hereby guarantees the full payment and performance of its Affiliates under this Agreement.
(ii) Subject to Article VI, Alnylam shall have the right to grant sublicenses to Third Parties
under the licenses granted to it pursuant to Sections 3.2(a)(i).
(iii) Alnylam shall have the right to grant sublicenses to Third Parties under the licenses
granted to it under Section 3.2(b)(i);
provided
that
[**].
(iv) Alnylam shall have the right to grant sublicenses to Third Parties under the licenses
granted to it pursuant to Sections 3.2(a)(ii) and 3.2(b)(ii).
(d)
Payments Owed by Cubist
. Alnylam shall promptly reimburse Cubist for
any
amounts that Cubist or any of its Affiliates shall owe to any Third Party by reason of the
-26-
license granted by Cubist to Alnylam under this Section 3.2 or under Section 11.3(a) and any
sublicense granted by Alnylam or any of its Affiliates with respect to Development, Manufacture or
Commercialization of Licensed Product under any such license, if such Third Party Technology was
included in the definition of Cubist Technology in accordance with Section 8.6.
Section 3.3
Sublicensing Terms; Liability
.
(a) Each sublicense granted by a Party pursuant to this Article III shall be subject and
subordinate to the terms and conditions of this Agreement and shall contain terms and conditions
consistent with those in this Agreement. Each Party shall promptly provide the other Party with a
copy of the fully executed sublicense agreement covering any sublicense granted hereunder, and such
sublicense agreement shall contain the following provisions: (i) a requirement that such
Sublicensee submit applicable sales or other reports to the Party granting the sublicense to the
extent necessary or relevant to the reports required to be made or records required to be
maintained under this Agreement; (ii) the audit requirement set forth in Section 7.12; (iii) a
requirement that such Sublicensee comply with the confidentiality and non-use provisions of Article
IX with respect to both Parties Confidential Information; and (iv) any other provisions applicable
to a Sublicensee required under any Alnylam In-License or Cubist In-License, as the case may be, of
which the other Party is notified in writing. If a granting Party becomes aware of a material
breach of any sublicense by a Sublicensee of the rights granted to such Party under this Article
III, the granting Party shall promptly notify the other Party of the particulars of the same and
use Diligent Efforts to enforce the terms of such sublicense.
(b) Each Party shall at all times be responsible for the performance of its Sublicensees under
this Agreement.
Section 3.4
Joint Collaboration IP
. Subject to (i) the rights granted to each Party
under this Agreement, including the exclusive licenses granted to Cubist under Section 3.1, (ii)
the obligations of the Parties set forth in Section 10.1 and (iii) the payment obligations set
forth in Article VII, each Party shall have the right to use, sell, keep, license, sublicense or
assign its interest in Joint Collaboration IP and otherwise undertake all activities a sole owner
might undertake with respect to such Joint Collaboration IP without the consent of and without
accounting to the other Party.
Section 3.5
Section 365(n) of the Bankruptcy Code
. All rights and licenses granted
under or pursuant to any Section of this Agreement, including Sections 3.1 and 3.2 hereof, are
rights to intellectual property (as defined in Section 101(35A) of Title 11 of the United States
Code, as amended (such Title 11, the
Bankruptcy Code
)). Each Party hereby acknowledges
that (a) copies of research data, (b) laboratory samples, (c) product samples and inventory, (d)
formulas, (e) laboratory notes and notebooks, (f) data and results related to clinical trials, (g)
regulatory filings and approvals, (h) rights of reference in respect of regulatory filings and
approvals, (i) pre-clinical research data and results, and (j) marketing, advertising and
promotional materials, constitute embodiments of intellectual property pursuant to Section 365(n)
of the Bankruptcy Code. Each Party agrees not to interfere with the other Partys
exercise of rights and licenses to intellectual property licensed hereunder and embodiments
thereof in accordance with this Agreement and agrees to use reasonable efforts to assist the other
Party to obtain such intellectual property and embodiments thereof in the possession or control of
-27-
Third Parties as reasonably necessary for the other Party to exercise such rights and licenses in
accordance with this Agreement.
Section 3.6
Retained Rights
. Any rights of a Party not expressly granted under this
Agreement shall be retained by such Party.
ARTICLE IV
DEVELOPMENT OF LICENSED PRODUCTS;
ADDITIONAL RSV PRODUCTS; OPT-OUT RIGHTS
Section 4.1
Overview
. The Parties will collaborate in the further Development of
Licensed Product;
provided
,
however
, that the Parties will Develop Licensed Product
in the Field in the Profit-Share Territory in accordance with the allocations of Development
responsibilities set forth in the Development Plan as amended from time-to-time in accordance with
Section 4.2, and, subject to the obligation to update the JSC, Cubist will be solely responsible
for, and with respect to the Major EU Countries shall use Diligent Efforts with respect to, the
Development of Licensed Product in the Field in the Royalty Territory.
Section 4.2
Development Plan; Amendments; Development Responsibilities
.
(a) The Development of Licensed Product in the Profit-Share Territory shall be governed by the
Development Plan, and the Parties shall use Diligent Efforts to conduct all their Development
activities relating to Licensed Product in accordance with the Development Plan. As of the
Effective Date, the Development Plan includes an initial overall plan for the Development of
Licensed Product in the United States. The Development Plan as of the Effective Date also includes
the initial funding budgeted for each stage of Development in the United States.
(b) The JSC shall review the Development Plan not less frequently than annually and shall
develop detailed and specific Development Plan updates, which shall update or include annual
Development budgets for the Profit-Share Territory for each Calendar Year until the completion of
Licensed Product Development activities in the Profit-Share Territory. No later than [**] of each
Calendar Year, the JSC shall prepare a preliminary draft of the update to the Development Plan and
budget for the following Calendar Year. The JSC shall review and agree (subject to the final Board
approval of each Party) on a final version of each annual updated Development Plan and budget no
later than each [**] for the immediately following Calendar Year. The Parties may also develop and
submit to the JSC from time to time other proposed substantive amendments to the Development Plan.
The JSC shall review such proposed amendments and may approve such proposed amendments or any other
proposed amendments that the JSC may consider from time to time in its discretion and, upon such
approval by the JSC, the Development Plan shall be amended accordingly. Amendments and updates to
the Development Plan, including any budgets for the Profit-Share Territory contained
in the Development Plan, shall not be effective without the approval of the JSC. In
connection with each annual update to the Development Plan, the JSC shall review the FTE Cost, and
shall recommend to the Parties whether any amendment should be made to the prospective FTE Cost to
reflect updated benchmarking information or adjustments to account for FTE skill sets that
-28-
were not included in the original FTE Cost calculation. No change to the FTE Cost shall be
effective without the written agreement of both Parties.
(c) The Parties anticipate that responsibilities for Development activities for the
Profit-Share Territory will initially be allocated between the Parties substantially as set forth
in
Exhibit E
.
(d) Notwithstanding anything in this Agreement to the contrary, Cubist shall not have an
obligation to seek JSC approval of development plans and budgets in the Royalty Territory, but will
keep the JSC apprised of such plans.
Section 4.3
Development Efforts; Manner of Performance; Records and Reports
.
(a) Each of Alnylam and Cubist shall use Diligent Efforts to execute and to perform, or cause
to be performed, the activities assigned to it relating to the Development Plan and to cooperate
with the other in carrying out the Development Plan, in each case in good scientific manner and in
compliance with applicable Law, Good Clinical Practice and Good Laboratory Practice.
Notwithstanding anything in this Agreement to the contrary, neither Party will engage or use a
Third Party to perform any of the Development activities allocated to it under the Development Plan
or provide any Licensed Product to any Third Party in the Profit-Share Territory unless such
action, and the form of agreement with such Third Party, have been approved in advance by the JSC.
(b) Each Party will maintain scientific records, in sufficient detail and in good scientific
manner appropriate for patent and regulatory purposes, which will fully and properly reflect all
work done and results achieved in the performance of the Development activities with respect to
Licensed Product by such Party and its permitted contractors and permitted Sublicensees. Each
Party will have the right, during normal business hours and upon reasonable notice, to inspect and
copy (or request the other Party to copy) all records of the other Party maintained in connection
with the work done and results achieved in the performance of such Development activities, but
solely to the extent such records relate to Licensed Product or to the extent access to such
records is necessary for a Party to exercise its rights under this Agreement. All such records,
and the information disclosed therein, as well as all disclosures made pursuant to Sections 4.3(c)
and 4.8, will be maintained in confidence by the recipient in accordance with Article IX and will
only be used for purposes of the Collaboration;
provided
that
Alnylam shall be
permitted to disclose any such information obtained from Cubist to its Asian Partner for the
purpose of assisting such Asian Partner to Develop, Manufacture and Commercialize Licensed Products
for Asia, subject to the requirement that, to the extent permissible under Alnylams agreements
with its Asian Partner, the Asian Partner has an obligation to disclose to Alnylam, and to permit
Alnylam to disclose to Cubist, and permit Cubist to use for the purposes set forth in this
Agreement, information and records of all work done and results achieved by such Asian Partner in
the performance of Development, Manufacture or Commercialization of Licensed Products for Asia,
including the information specified in this Section 4.3(b) and the information specified in Section
4.3(c) and Section 4.8. Alnylam shall use Diligent Efforts to require its Asian Partner to permit
the disclosures of information and records to Cubist contemplated by the preceding sentence.
-29-
(c) In addition to the other disclosure obligations set forth in this Section 4.3, at times
and in a manner to be reasonably agreed by the Parties, each Party shall disclose to the other
Party a written summary, in a form mutually agreed by the Parties, of clinical data with respect to
Licensed Products generated by or under authority of such Party or any Related Party since the last
such disclosure. Upon the request of either Party, the other Party shall provide prompt and
complete access to, and the right to use for purposes of the activities for which such requesting
Party is licensed hereunder, any Clinical Regulatory Filings and Safety Data generated by such
Party or its Related Parties;
provided
that
in any such case the requesting Party
provides notice to the other Party reasonably in advance and reimburses the other Party for any
reasonably incurred copying costs of providing such access. Each Party must provide access to its
Related Partys Clinical Regulatory Filings and Safety Data on the same basis as if the Related
Parties were such Party. If requested by either Party or the JSC, the Parties shall discuss any
issues relating to such Clinical Regulatory Filings or Safety Data provided by a Party to the other
Party. In addition to the foregoing, if required by a Regulatory Authority(ies) or if it is
reasonably necessary for a Party or its Related Party(ies) to have access to the underlying raw
data, case report forms or other original documents (including laboratory notebooks) generated by
or on behalf of the other Party or its Related Party(ies), then such other Party shall provide, or
cause to be provided, access to the originals, of such items.
Section 4.4
Joint Development Costs
.
(a) The Parties shall share Development Costs as follows: (i) all Development Costs solely
for the Profit-Share Territory shall be shared equally by the Parties, and (ii) all Development
Costs incurred with respect to Development of Licensed Product for the Profit-Share Territory but
generating data or other Know-How that also has applicability in the Royalty Territory shall be
continue to be shared equally by the Parties except that any incremental costs associated
specifically with any Development activities not required for the Profit-Share Territory shall be
[**]. The Parties shall discuss and attempt to mutually determine in good faith how specific
Development Costs are allocated in accordance with the foregoing sentence. Except as otherwise set
forth in this Section 4.4(a), Cubist shall be responsible for its costs associated with Development
of Licensed Product for the Royalty Territory.
(b) Development Costs shall initially be borne by the Party incurring the cost or expense,
subject to reimbursement as provided in Section 4.5. Each Party shall calculate and maintain
records of Development Costs incurred by it in accordance with procedures to be established by the
JSC. Alnylam and Cubist shall report [**] to each other on their Development Costs, with such
reports to be submitted within [**] after the [**] of each Calendar Year. Notwithstanding the
foregoing, within [**] after the end of the [**], Alnylam and Cubist shall each provide to the
other an estimate of such Partys Development Costs for such [**]. The Parties shall seek to
resolve any questions related to such accounting statements within [**] after receipt.
Section 4.5
Reimbursement of Development Costs
.
(a) The Party that incurs more than its share of the total actual Development Costs for
Licensed Product, as allocated under Section 4.4(a), shall be paid by the other Party an amount of
cash sufficient to reconcile to its agreed percentage of actual Development Costs in
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each Calendar Quarter;
provided
that
, except as set forth in Section 4.5(b) total
actual Development Costs for a Party for a Calendar Year shall not exceed [**] percent ([**]%) of
the budgeted Development Costs for such Party for such Calendar Year, as shown in the then current
version of the Development Plan, except to the extent the JSC approves the increase over [**]
percent ([**]%) of the budgeted Development Costs for such Party before the additional costs are
incurred. Subject to Section 4.5(b), if actual Development Costs for a Calendar Year to date
incurred by either Party exceed budgeted Development Costs for such Party for such Calendar Year by
more than [**] percent ([**]%) and the JSC did not approve some or all of such increase before the
costs were incurred, the Development Costs deemed to have been incurred by such Party for purposes
of determining the balancing payment under the first sentence of this Section 4.5(a) shall be
limited to [**] percent ([**]%) of such Partys budgeted Development Costs plus any portion of the
increase over such amount that was approved in advance by the JSC or approved under Section 4.5(b).
Decisions of the JSC with respect to Development Cost overruns shall be made in accordance with
Section 2.5. Reconciling payments under this Section 4.5 for any Calendar Quarter shall be made
within [**] after the end of such Calendar Quarter.
(b) Notwithstanding anything in Section 4.5(a) to the contrary, the Parties agree to approve a
Partys actual Development Costs in excess of [**] percent ([**]%) of such Partys budgeted
Development Costs to the extent the overrun is attributable [**], provided that a contingency for
such issue is not already included in the budget for Development Costs for such Calendar Year.
Section 4.6
Additional RSV Products
. If, at any time during the Term, the JSC
determines to commence Development of a Licensed Product other than the RSV01 Product or the RSV02
Product (an
Additional RSV Product
), then the Additional RSV Product shall be included in
the Collaboration and the Parties will promptly update the Development Plan accordingly.
Section 4.7
Alnylam Opt-Out Option
.
(a)
Exercise of Option
. At any time after the First Opt-Out Milestone, Alnylam, by
written notice to Cubist, shall have the right, in its sole discretion, to opt-out of further
Development of all Licensed Products by providing written notice to Cubist citing this Section 4.7
(the
Opt-Out Option
), which Opt-Out Option shall, subject to Section 4.7(b), take effect
[**] after the date of such written notice. Upon the effective date of Alnylams exercise of its
Opt-Out Option, the following consequences shall occur:
(i) The Royalty Territory shall thereafter be expanded to comprise the entire Territory;
(ii) The Profit-Share Territory shall cease to exist;
(iii) The Parties shall cease to share in N.A. Pre-Tax Profit or Loss;
(iv) Except as set forth in 4.7(a)(v) and 4.7(a)(xii) and subject to Section 4.7(b), Alnylam
shall cease to share in Development Costs pursuant to Sections 4.4 and 4.5;
-31-
(v) For a period of [**] following the effective date of Alnylams Opt-Out Option, Alnylam
shall continue to be responsible for fifty percent (50%) of Development Costs incurred by Cubist
under the then current Development Plan;
provided
that
the cumulative Development
Costs paid by Alnylam for Licensed Product under this Section 4.7(a)(v) after Alnylam has exercised
the Opt-Out Option shall not exceed: (A) [**] Dollars ($[**]) if Alnylam exercised the Opt-Out
Option after the First Opt-Out Milestone and prior to the Second Opt-Out Milestone and (B) [**]
Dollars ($[**]) if Alnylam exercised the Opt-Out Option after the Second Opt-Out Milestone.
(vi) Without limiting Cubists obligations under Section 7.2, and subject to Sections
4.7(a)(ix) 4.7(a)(xii), Cubist shall make the non-refundable, non-creditable milestone payments set
forth below to Alnylam not later than [**] after the earliest date on which the corresponding
milestone event set forth below has been achieved:
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Payment if
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Alnylams
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Exercise of the
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Opt-Out Option
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Payment if
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Takes Effect
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Alnylams
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After the First
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Exercise of the
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Opt-Out
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Opt-Out Option
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Milestone and
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 4.7(a)(xii)
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Milestone Event
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Milestone
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Milestone
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Option I
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(A) Acceptance
for filing of an
application for
Regulatory Approval
for a Licensed
Product for any
indication in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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(B) First
Commercial Sale of
a Licensed Product
in any indication
in the United
States
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$
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[**]
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$
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[**]
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$
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[**]
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(C) Acceptance
for filing of an
application for
Regulatory Approval
for a Licensed
Product for any
indication other
than the indication
with respect to
which the milestone
event described in
Section
4.7(a)(vi)(A) above
was achieved in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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Payment if
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Alnylams
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Exercise of the
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Opt-Out Option
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Payment if
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Takes Effect
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Alnylams
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After the First
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Exercise of the
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Opt-Out
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Opt-Out Option
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Milestone and
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 4.7(a)(xii)
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Milestone Event
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Milestone
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Milestone
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Option I
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(D) Regulatory
Approval of a
Licensed Product
for any indication
other than the
indication with
respect to which
the milestone event
described in
Section
4.7(a)(vi)(A) above
was achieved in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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The milestone payments set forth in this Section 4.7(a)(vi) shall be paid only once, upon the
first achievement of the applicable milestone event by the first Licensed Product to achieve such
milestone event.
(vii) Without limiting Cubists obligations under Section 7.3 (which shall continue to apply
to Net Sales of Licensed Product in the Royalty Territory but only as the Royalty Territory was
defined immediately prior to Alnylams exercise of the Opt-Out Option), and subject to Sections
4.7(a)(ix) and 4.7(a)(xii), in addition to all other amounts payable under this Agreement, Cubist
shall make the non-refundable, non-creditable milestone payments set forth below to Alnylam upon
the achievement of the milestone events set forth below, such payment to be made as set forth
below:
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Payment if
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Alnylams
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Exercise of the
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Opt-Out Option
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Payment if
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Takes Effect
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Alnylams
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After the First
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Exercise of the
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Opt-Out
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Opt-Out Option
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Milestone and
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 4.7(a)(xii)
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Milestone Event
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Milestone
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Milestone
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Option I
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Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
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[**]
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$
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[**]
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Payment if
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Alnylams
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Exercise of the
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Opt-Out Option
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Payment if
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Takes Effect
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Alnylams
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After the First
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Exercise of the
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Opt-Out
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Opt-Out Option
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Milestone and
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
|
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Opt-Out
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Section 4.7(a)(xii)
|
Milestone Event
|
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Milestone
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Milestone
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Option I
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Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
|
[**]
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$
|
[**]
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Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
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[**]
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$
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[**]
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The milestone payments set forth in this Section 4.7(a)(vii) shall be paid only once, upon the
first achievement of the applicable milestone event. For purposes of determining whether a
milestone event set forth in this Section 4.7(a)(vii) has occurred (and without creating an
obligation to pay the milestone more than once as set forth in the preceding sentence), Calendar
Year Net Sales shall be aggregated for all Licensed Products sold in North America during the
relevant Calendar Year.
If more than one of such milestone events first occurs based on sales of Licensed Products in
the same Calendar Year, all of such milestone payments shall be paid for such Calendar Year. If a
milestone payment set forth above is earned based on Net Sales over a period that is shorter in
duration than a full Calendar Year, such payment shall become due and payable [**] after the end of
the Calendar Quarter in which the milestone event is achieved.
(viii) Without limiting Cubists obligations under Section 7.5 (which shall continue to apply
to Net Sales of Licensed Product in the Royalty Territory as the Royalty Territory was defined
immediately prior to Alnylams exercise of the Opt-Out Option), and subject to Sections 4.7(a)(ix),
4.7(a)(xii), 7.5(c), 7.5(d), 7.6 and 7.8 through 7.20 (inclusive) (which, for such purpose, shall
be modified as necessary to apply to the royalty obligations described in this Section
4.7(a)(viii)), Cubist shall pay to Alnylam royalties on the aggregate Net Sales of all Licensed
Products in North America by Cubist or its Related Parties as follows:
-34-
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Royalty Rate (as
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a Percentage of
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Net Sales) if
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Royalty Rate (as
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Alnylams
|
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a Percentage of
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Exercise of the
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Net Sales) if
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Opt-Out Option
|
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Alnylams
|
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Takes Effect
|
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Exercise
|
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After the First
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of the Opt-Out
|
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|
Opt-Out
|
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Option Takes
|
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Milestone and
|
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Effect
|
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Aggregate Calendar Year Net
|
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Prior to the
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After the Second
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Sales of Licensed Products in
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Second Opt-Out
|
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Opt-Out
|
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Section 4.7(a)(xii)
|
North America
|
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Milestone
|
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Milestone
|
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Option I
|
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$[**] $[**]
|
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[**]
|
%
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[**]
|
%
|
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|
[**]
|
%
|
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|
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|
|
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Greater than $[**]
and less than or
equal to $[**]
|
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[**]
|
%
|
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[**]
|
%
|
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|
[**]
|
%
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Greater than $[**]
and less than or
equal to $[**]
|
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|
[**]
|
%
|
|
|
[**]
|
%
|
|
|
[**]
|
%
|
|
|
|
|
|
|
|
|
|
|
|
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|
Greater than $[**]
and less than or
equal to $[**]
|
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|
[**]
|
%
|
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|
[**]
|
%
|
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|
[**]
|
%
|
|
|
|
|
|
|
|
|
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|
Greater than $[**]
|
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[**]
|
%
|
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[**]
|
%
|
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|
[**]
|
%
|
The foregoing provisions of this Section 4.7 and Section 7.6(a) notwithstanding, and in
addition to the amounts set forth above in this Section 4.7, Cubist shall pay to Alnylam (A) [**]
percent ([**]%) of the allocated milestone amounts under the Existing Alnylam In-Licenses that are
identified on
Exhibit H
, and (B) [**] percent ([**]%) of all royalties on the Net Sales of
Licensed Products in North America payable under the Existing Alnylam In-Licenses up to a maximum
of [**] percent ([**]%) of such Net Sales (i.e., Cubists maximum [**] percent ([**]%) share would
be [**] percent ([**]%) of such Net Sales).
(ix) The foregoing provisions of this Section 4.7(a) notwithstanding, if Alnylam has
exercised its Opt-Out Option and Cubist or any of its Affiliates, prior to or after Alnylams
exercise of its Opt-Out Option, granted or grants one or more Third Party licensees or
Sublicensees a sublicense under the Alnylam Technology or a license under the Cubist Technology to
Develop or Commercialize any Licensed Product in the Field in a country or countries in North
America, then Cubist shall have no payment obligations under Sections 4.7(a)(vi), 4.7(a)(vii) or
4.7(a)(viii) with respect to development or sales milestones achieved, or Net Sales of Licensed
Products, by such Cubist licensee or Sublicensee in such country(ies) in
-35-
North America, and, in lieu of such payments and subject to Section 7.9(c), Cubist shall instead
pay Alnylam a portion of Sublicense Income received from such Third Party licensee or Sublicensee
with respect to such country(ies) in North America in accordance with the following:
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Opt-Out Point
|
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Percentage of Sublicense Income
|
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After the First Opt-Out Milestone and
prior to the Second Opt-Out Milestone
|
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[**]
|
%
|
|
|
|
|
|
After the Second Opt-Out Milestone
|
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|
[**]
|
%
|
For purposes of clarity, if Alnylam exercises its Opt-Out Option Cubists payment obligations under
Sections 4.7(a)(vi), 4.7(a)(vii) and 4.7(a)(viii) shall apply with respect to development and sales
milestones achieved, and the Net Sales of Licensed Products sold, by Cubist and its Affiliates in
such country(ies) in North America.
(x) The JSC and JCT shall be dissolved, and, except as set forth in Article VI, all decisions
regarding Development, Commercialization and Manufacture of Licensed Product shall become subject
to Cubists final decision-making authority, except that: (A) Cubist may not conduct, sponsor,
fund or otherwise support a Clinical Study or Post-Approval Study of Licensed Product that would
[**] the Development or Commercialization of Licensed Product in the Field in Asia, without
Alnylams prior written consent, (B) Cubist may not resolve any dispute as to what constitutes
Diligent Efforts or as to whether the First Opt-Out Milestone or the Second Opt-Out Milestone has
been achieved, and (C) Cubist may not unilaterally amend this Agreement.
(xi) This Agreement shall otherwise remain in effect.
(xii) Notwithstanding the foregoing provisions of this Section 4.7(a), if (1) Alnylam
exercises the Opt-Out Option after the Second Opt-Out Milestone and (2) [**], then:
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A.
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Cubist shall promptly provide Alnylam with a
copy of such [**] and with a summary of all relevant information
relating to such [**];
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B.
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Additionally, Cubist shall provide Alnylam with
such additional information regarding such [**] and planned [**] as
Alnylam may reasonably request;
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C.
|
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Within [**] after receipt of the information
and documents provided by Cubist pursuant to clause (A); provided
however in no event shall such time period expire earlier than [**]
after delivery of any information requested by Alnylam pursuant to
clause (B), Alnylam shall make one of the following two elections and
notify Cubist of such election: (I) elect to accept the milestones and
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royalties set forth in the column entitled Section 4.7(a)(xii)
Option I in Sections 4.7(a)(vi), 4.7(a)(vii) and 4.7(a)(viii), in
lieu of the otherwise applicable opt-out economics set forth above in
Sections 4.7(a)(vi), 4.7(a)(vii) and 4.7(a)(viii) (provided that such
reduced economics shall remain subject to the applicable provisions
of Section 7.9 referenced in Section 4.7(a)(viii)) or (II) agree to
fund [**] percent ([**]%) of the [**], in which case there shall be
no reduction to the applicable opt-out economics set forth above in
Sections 4.7(a)(vi), 4.7(a)(vii) and 4.7(a)(viii);
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D.
|
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If Alnylam makes the election set forth in
clause (C)(I) above and Cubist subsequently achieves a [**] provided to
Alnylam by Cubist pursuant to clause (A) above, Cubist shall notify
Alnylam of such occurrence promptly after receipt of such [**] and
Alnylam shall thereafter have an option, exercisable by providing
Cubist with notice of such exercise within [**] after Alnylams receipt
of Cubists notification, to pay Cubist [**] percent ([**]%) of the
amount of the additional [**] actually incurred by Cubist in [**] and,
if Alnylam exercises such option and thereafter makes such payment
within [**] after Alnylams receipt of Cubists notification, the
reduction to Alnylams opt-out economics set forth in clause (C)(I)
above shall not apply; and
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E.
|
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If Alnylam makes the election set forth in
clause (C)(II) above, then the JSC shall be reconstituted and, [**],
all Development and Manufacture for the purposes of Development of
Licensed Product for the Profit-Share Territory shall [**]. For
purposes of clarity, (i) at the time [**], the JSC will be dissolved
again and Alnylam will, from that point forward, receive milestones and
royalties based upon the exercise of its Opt-Out Option after the
Second Opt-Out Milestone and (ii) at no time shall Alnylam resume
sharing in N.A. Pre-Tax Profit or Loss.
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(b)
Cubist Termination
. Notwithstanding anything in this Section 4.7 to the contrary,
Alnylams exercise of its Opt-Out Option shall not take effect if, prior to the effective date of
such Opt-Out Option under this Section 4.7, Cubist provides written notice to Alnylam of Cubists
decision to terminate this Agreement under Section 11.2(a).
Section 4.8
Technology Transfer and Exchange of Know-How
.
(a)
Exchange of Know-How
. Promptly following the Effective Date, Alnylam will make
available to Cubist, at no cost or expense to Cubist, such Alnylam Know-How as is requested by
Cubist in connection with Cubists Development efforts, including all data from any and all
clinical trials and preclinical studies and non-clinical development work for Licensed Products
that are in existence as of the Effective Date. During the Term, Alnylam shall promptly update
Cubist as to all Alnylam Know-How that has not previously been provided
-37-
under this Agreement, and shall provide to Cubist any such additional Alnylam Know-How
promptly upon Cubists request.
(b)
Updates if JSC Ceases to Exist
. In the event during the Term the JSC ceases to
exist, then no later than [**] of each Calendar Year thereafter (for the period ending December 31
of the prior Calendar Year), (i) Cubist shall prepare and deliver to Alnylam a written report
summarizing the status, progress and results of activities performed by Cubist and its Related
Parties with respect to the Development, Manufacture or Commercialization of Licensed Product in
the Field for the Territory performed since the last such report submitted under this Agreement,
and (ii) Alnylam shall submit to Cubist a written report summarizing the status, progress and
results of activities performed by Alnylam and its Related Parties with respect to Development,
Manufacture or Commercialization of Licensed Product for Asia since the last report submitted under
this Agreement. Such reports may be provided in any reasonable written form determined by the
Party making such report, including in a presentation slide format that reasonably summarizes such
activities.
ARTICLE V
COMMERCIALIZATION AND CERTAIN OTHER RESPONSIBILITIES
Section 5.1
Diligent Efforts
. Cubist shall have the sole right to Commercialize
Licensed Product in the Field in the Territory. The costs of Commercialization in the Royalty
Territory shall be borne one hundred percent (100%) by Cubist. The costs of Commercialization in
the Profit-Share Territory shall be shared equally by the Parties through the sharing of N.A.
Pre-Tax Profit or Loss under Section 7.4 even if there are no Net Sales. Cubist shall use Diligent
Efforts to Commercialize Licensed Products in those countries in the Territory in which Cubist has
obtained Regulatory Approval and where Commercialization is commercially reasonable, including by
providing appropriate incentives consistent with its normal business practices to Sales
Representatives involved in the Commercialization of Licensed Products in the Territory.
Section 5.2
Joint Commercialization Team
. Commencing with the earlier of (i) [**]
and (ii) the date [**] prior to the anticipated launch of the first Licensed Product in the
Territory, and provided Alnylam has not exercised its Opt-Out Option, the Parties will establish a
joint commercialization team (
JCT
) to coordinate the Commercialization of Licensed
Product in the Field in the Profit-Share Territory. The provisions of Sections 2.1(a), 2.1(b) and
2.1(c) relating to the operation of the JSC shall also apply to the JCT;
provided
,
however
, that Alnylam shall have the right, but not the obligation, to participate in the
JCT. The responsibilities of the JCT include:
(a) providing updates regarding the Commercialization of Licensed Product in the Profit-Share
Territory;
(b) reviewing, commenting on and approving the Commercialization Plan and all updates to the
Commercialization Plan;
(c) coordinating with the JSC regarding Development matters as necessary or appropriate to
Commercialization of Licensed Product in the Profit-Share Territory;
-38-
(d) overseeing Manufacturing activities related to the Commercialization of Licensed Product
in the Territory;
(e) receiving updates from Cubist on the status of Commercialization activities in the Royalty
Territory;
(f) performing such other activities as the Parties agree in writing shall be the
responsibility of the JCT; and
(g) attempting to resolve any and all disputes relating to the Commercialization of Licensed
Product in the Territory by consensus.
For purposes of clarity, the JCT shall not have the authority to modify the terms of this
Agreement.
Cubist shall have final decision-making authority with respect to all decisions related to
Commercialization in the Territory, including those decisions within the purview of the JCT,
subject in each case to the specific limitations set forth in Sections 2.5(a) and (b), but not
including the escalation procedures contained in Section 2.5, and subject to the limitations in
Section 5.3.
Section 5.3
Commercialization Plan
.
(a) Commencing no later than [**] prior to the anticipated launch of the first Licensed
Product, Cubist shall prepare and deliver to the JCT, by no later than [**] of each Calendar Year,
a written plan and budget that describes in detail the Commercialization activities (including
pre-launch and launch activities, if applicable) to be undertaken with respect to Licensed Product
in the Profit-Share Territory in the next Calendar Year and the dates by which such activities are
targeted to be accomplished (each, a
Commercialization Plan
). The Commercialization Plan
(including the budget) shall contain sufficient detail with respect to Commercialization tactics
and other matters to enable the JCT to conduct a meaningful review of the Commercialization Plan,
and the JCT shall approve the first Commercialization Plan for the Profit-Share Territory no later
than [**] prior to launch of the first Licensed Product in the Profit-Share Territory. Thereafter,
the JCT shall review the Commercialization Plan not less frequently than annually and shall develop
Commercialization Plan updates, which shall include updated budgets for the Profit-Share Territory,
for each Calendar Year. Cubist may also develop and submit to the JCT for review from time to time
other proposed substantive amendments to the Commercialization Plan. Amendments and updates to the
Commercialization Plan, including any budgets for the Profit-Share Territory contained in the
Commercialization Plan, shall not be effective without the approval of the JCT. Notwithstanding
anything in this Agreement to the contrary, if Cubist engages or uses a Third Party to perform any
Commercialization activities in the Profit-Share Territory under circumstances where such Third
Party will be granted a sublicense under Alnylam Technology or where there will be a material
penalty for early termination that is inconsistent with industry standards, [**].
(b) The amount by which the Commercialization Costs actually incurred by a Party in any
Calendar Year exceeds such Partys allocated share, under Section 7.4(a), of the total
Commercialization Costs for such period, as shown on the applicable Commercialization
-39-
Plan, shall be taken into account in the calculation of the balancing payment to be made under
Section 7.4(b) so as to reconcile each Party to its agreed percentage of actual Commercialization
Costs in accordance with Section 7.4(b);
provided
that
, except as set forth in
Section 5.3(c), the total actual Commercialization Costs for a Party for a Calendar Year shall not
exceed [**] percent ([**]%) of the budgeted Commercialization Costs for such Party for such
Calendar Year, as shown in the then current version of the Commercialization Plan, except to the
extent the JCT approves the increase over [**] percent ([**]%) of the budgeted Commercialization
Costs for such Party before the additional costs are incurred. Except as set forth in Section
5.3(c), if actual Commercialization Costs for the Calendar Year to date incurred by either Party
exceed budgeted Commercialization Costs for such Party for such Calendar Year by more than [**]
percent ([**]%) and the JCT did not approve some or all of such increase before the costs were
incurred, the Commercialization Costs deemed to have been incurred by such Party for purposes of
determining the balancing payments pursuant to Section 7.4(b) shall be limited to [**] percent
([**]%) of such Partys budgeted Commercialization Costs plus any portion of the increase over such
amount that was approved in advance by the JCT or that is approved or permitted under Section
5.3(c). Decisions of the JCT with respect to Commercialization Cost overruns shall be made in
accordance with Section 2.5. Alnylam and Cubist shall report [**] to each other on their
Commercialization Costs, with such reports to be submitted within [**] after the [**].
Notwithstanding the foregoing, within [**] after the end of the [**], Alnylam and Cubist shall each
provide to the other an estimate of such Partys Commercialization Costs for such [**]. The Parties
shall seek to resolve any questions related to such accounting statements within [**] after
receipt.
(c) Notwithstanding anything in Section 5.3(b) to the contrary, [**], reasonable out-of-pocket
costs of patent enforcement incurred by a Party or any of its Related Parties under Section [**] is
approved by the JSC and reasonable out-of-pocket costs incurred by a Party or any of its Related
Parties under Section [**], in each case with respect to Actions in the Field in the Profit-Share
Territory shall be included as Commercialization Costs regardless of whether such costs are
included in the Commercialization Plan, provided that the Parties shall use good faith efforts to
include estimates of such costs in the Commercialization Plan. In addition, the limitations in
Section 5.3(b) with respect to Commercialization Costs in excess of [**] percent ([**]%) of budget
shall not apply to [**], including [**], which such amounts shall be included in Commercialization
Costs in the amounts actually incurred in accordance with Cubists then-current [**], as
communicated by Cubist to Alnylam for the applicable Calendar Year. The Parties further agree that
the JCT shall approve a Partys Commercialization Costs in excess of [**] percent ([**]%) of such
Partys budgeted Commercialization Costs to the extent the overrun is attributable to [**],
provided that a contingency for such issue is not already included in the budget for
Commercialization Costs for such Calendar Year.
Section 5.4
Regulatory Filings
. Except as may be otherwise specified by the JSC or
set forth in
Exhibit E
or as otherwise required for Alnylam to perform its obligations
under this Agreement, Cubist (or its Related Parties) shall be the holder of all INDs and
Regulatory Approvals (including IND and NDA submissions) for Licensed Product in the Territory, and
Cubist shall have the right to (a) oversee, monitor and coordinate all regulatory actions,
communications and filings with, and submissions to, each Regulatory Authority, (b) be responsible
for interfacing, corresponding and meeting with each Regulatory Authority and (c) be responsible
for maintaining all regulatory filings. Alnylam or its Asian Partner shall have the
-40-
right to cross-reference all INDs, Regulatory Approvals and all other regulatory filings filed
by Alnylam or Cubist or their respective Related Parties in the Territory with respect to the
Development, Manufacture or Commercialization of Licensed Products for Asia.
Section 5.5
Advertising and Promotional Materials
. As between the Parties, Cubist
will be responsible for the creation, preparation, production, reproduction and filing with the
applicable Regulatory Authorities, of relevant written sales, promotion and advertising materials
relating to Licensed Product (
Promotional Materials
) for use in the Territory. All such
Promotional Materials will be compliant with all applicable Laws, and in the Profit Share Territory
shall be consistent with the Commercialization Plan. Subject to any limitations imposed by
applicable Law, all such Promotional Materials and all documentary information and oral
presentations (where practicable) regarding the marketing and promotion of Licensed Product in the
Field in the Territory shall (a) acknowledge the Parties license arrangement and collaboration on
Licensed Product, and (b) in the Profit-Share Territory, shall display the Cubist and Alnylam names
and logos with equal prominence. Copies of all Promotional Materials used in the Territory will be
archived by Cubist in accordance with applicable Law. Upon Alnylams reasonable request, copies of
the core Promotional Materials used by Cubist in the Profit-Share Territory shall be translated
into English (where applicable) and provided to Alnylam, and the costs of such translations shall
be Commercialization Costs. Upon Alnylams reasonable request and cost, copies of the core
Promotional Materials used by Cubist in the Royalty Territory shall be translated into English
(where applicable) and provided to Alnylam. Upon Cubists reasonable request and cost, copies of
the core Promotional Materials for Licensed Product used by Alnylam or any of its Related Parties
in the Field for Asia shall be translated into English (where applicable) and provided to Cubist.
Section 5.6
Sales and Distribution
. Cubist shall be responsible for booking sales
and shall warehouse and distribute Licensed Product in the Territory. If Alnylam receives any
orders for Licensed Product in the Field for the Territory, it shall refer such orders to Cubist.
Section 5.7
Reporting Obligations
.
(a)
Within Territory
. Cubist shall prepare and deliver to the JCT (or, if the JCT
does not exist, shall deliver to Alnylam), by no later than each [**] (for the period ending
December 31 of the prior Calendar Year), written reports summarizing Cubists Commercialization
activities for Licensed Product in the Field in the Territory performed to date (or updating such
report for activities performed since the last such report submitted hereunder, as applicable). In
addition, Cubist shall provide Alnylam with written notice of (i) all filings and submissions for
Regulatory Approval regarding Licensed Product in the Territory in a timely manner; (ii) all
Regulatory Approvals obtained or denied, the filing of any IND for Licensed Product, the First
Commercial Sale of Licensed Product in each country in the Territory and the achievement by Cubist
of any milestone event set forth in Section 7.2 or 7.3, within [**] after Cubist learns such event
has occurred;
provided
,
however
, that in all circumstances, Cubist shall inform
Alnylam of such event prior to public disclosure of such event by Cubist. Moreover, to the extent
consistent with the provisions of Section 3.1(f) and subject to Section 7.4, Cubist shall prepare
and deliver to Alnylam any additional reports required under the Alnylam In-Licenses, in each case
sufficiently in advance to enable Alnylam to comply with its obligations under the Alnylam
In-Licenses. Cubist shall also provide to the JCT such other information as Alnylam
-41-
may reasonably request related to Commercialization of Licensed Product in the Territory and
shall keep the JCT reasonably informed of Cubists Commercialization activities with respect to
Licensed Product in the Field in the Territory.
(b)
Asia
. Alnylam shall prepare and deliver to the JCT (or, if the JCT does not
exist, shall deliver to Cubist), by no later than each [**] (for the period ending December 31 of
the prior Calendar Year), written reports summarizing the Commercialization activities of Alnylam
and its Related Parties with respect to Licensed Product in the Field for Asia performed to date
(or updating such report for activities performed since the last such report submitted hereunder,
as applicable). In addition, Alnylam shall provide Cubist with written notice within [**] after
Alnylam becomes aware (but in any event prior to public disclosure by Alnylam) of (i) all filings
and submissions for Regulatory Approvals regarding Licensed Product in Asia; and (ii) all
Regulatory Approvals obtained or denied, the filing of any IND for Licensed Product or the First
Commercial Sale of Licensed Product, in each case in each country in Asia. Alnylam shall also
provide such other information to Cubist as Cubist may reasonably request and shall keep Cubist
reasonably informed of Commercialization activities of Alnylam and its Asian Partner with respect
to Licensed Product in the Field in Asia.
Section 5.8
Other Responsibilities
. Without intending to limit in any way Cubists
overall responsibility for Commercialization of Licensed Products in the Territory, the Parties
agree that Cubist shall be solely responsible for (a) handling all returns of Licensed Product, in
the Territory, it being understood that if Licensed Product is returned to Alnylam, it shall
promptly be shipped to a facility designated by Cubist; and (b) handling all aspects of Licensed
Product order processing, invoicing and collection, distribution, inventory and receivables in the
Territory;
provided
that
in the Profit-Share Territory, the costs of such
activities shall be included as Commercialization Costs or Distribution Costs, as the case may be,
in the calculation and reconciliation of N.A. Pre-Tax Profit or Loss in accordance with Section
7.4. All returns will be required to be made in accordance with Cubists standard return
procedures which require a return authorization to be issued by Cubist or its designee.
Section 5.9
Adverse Event and Licensed Product Complaint Reporting Procedures; Notice of
Information Affecting Marketability of Licensed Product
. Each Party will maintain a record of
any and all complaints it receives with respect to Licensed Products, and will use Diligent Efforts
to ensure that its Related Parties maintain such records. Each Party will notify the other Party
in reasonable detail of any complaint it receives with respect to Licensed Product within
sufficient time to allow the other Party and its Related Parties to comply with any and all
regulatory and other requirements imposed upon them in any jurisdiction in which Licensed Product
is being marketed or tested in Clinical Studies or Post-Approval Studies. Cubist will maintain a
global safety database for Licensed Product. The reasonable costs of implementing and maintaining
the global safety database shall be included as Commercialization Costs in the calculation and
reconciliation of N.A. Pre-Tax Profit or Loss in accordance with Section 7.4 even though the global
safety database will also be used with respect to the Royalty Territory. In the event Alnylam
elects to exercise its Opt-Out Option under Section 4.7, notwithstanding anything to the contrary
contained in Section 4.7 or otherwise in this Agreement, Alnylam shall continue to pay [**] of the
reasonable costs of maintaining the global safety database, and shall reimburse Cubist for such
costs on a monthly basis within [**] after receipt of an invoice from Cubist. Alnylam and the
Asian Partner will have access to all data in the global adverse event
-42-
database, subject to reasonable procedures to be mutually agreed upon by the Parties and such
Asian Partner and set forth in the Safety Information Exchange Agreement, as defined below. Cubist
will provide Alnylam and the Asian Partner with all adverse event information and safety data
relating to Licensed Product in its Control through access to the global adverse event database.
Alnylam will use Diligent Efforts to require that its Asian Partner will report to Alnylam or
directly to Cubist the details around any adverse events and serious adverse events relating to
Licensed Product in its Control within the time periods for such reporting as specified in the
Safety Information Exchange Agreement. Cubist shall be responsible for submitting adverse event
reports with respect to Licensed Products to the applicable Regulatory Authorities in the
Territory. Cubists reasonable costs associated with submitting adverse event reports in the
Royalty Territory shall be borne by Cubist. Cubists reasonable costs associated with submitting
adverse event reports in the Profit-Share Territory shall be included as Commercialization Costs in
the calculation and reconciliation of N.A. Pre-Tax Profit or Loss in accordance with Section 7.4.
In addition, each Party shall promptly notify the other Party if such Party becomes aware of any
information or circumstance that is likely to have a material adverse effect on the Development,
Manufacture or Commercialization of Licensed Products in the Territory. Within [**] after the
Effective Date, the Parties will develop and agree in writing upon a safety information exchange
agreement (the
Safety Information Exchange Agreement
) that will include safety data
exchange procedures governing the coordination of collection, investigation, reporting, and
exchange of information concerning any adverse experiences, and any product quality and product
complaints involving adverse experiences, related to Licensed Product, sufficient to enable each
Party to comply with its legal and regulatory obligations and consistent with the terms of this
Agreement. At Cubists request, Alnylam shall use Diligent Efforts to require that its Asian
Partner become a Party to the Safety Information Exchange Agreement.
Section 5.10
Recalls, Market Withdrawals or Corrective Actions
. If any Regulatory
Authority issues or requests a recall or takes a similar action in connection with Licensed Product
in the Territory, or if either Party determines that an event, incident or circumstance has
occurred that may result in the need for a recall or market withdrawal in the Territory, the Party
notified of such recall or similar action, or the Party that desires such recall, withdrawal or
similar action, shall, within [**], advise the other Party thereof by telephone or facsimile.
Cubist, in consultation with Alnylam, shall decide whether to conduct a recall or product
withdrawal in the Territory (except in the case of a government mandated recall, when Cubist may
act without such advance notice, but shall notify Alnylam as soon as possible) and the manner in
which any such recall or withdrawal shall be conducted. Alnylam will make available to Cubist,
upon request, all of Alnylams pertinent records that Cubist may reasonably request to assist
Cubist in effecting any recall.
Section 5.11
Medical Inquiries
. Cubist shall handle all medical questions or
inquiries from members of the medical profession in the Territory regarding Licensed Product in the
Field. Cubists reasonable costs associated with handling medical questions or inquiries from
members of the medical profession in the Profit-Share Territory shall be included as
Commercialization Costs in the calculation and reconciliation of N.A. Pre-Tax Profit or Loss in
accordance with Section 7.4.
-43-
Section 5.12
Export Monitoring
. Cubist and its Related Parties will use Diligent
Efforts to monitor and prevent exports of Licensed Product from the Territory to countries in Asia,
using methods commonly used in the industry for such purpose, and shall promptly inform Alnylam of
any such exports of Licensed Product from the Territory to countries in Asia, and the actions taken
to prevent such exports. Cubist agrees to take any actions reasonably requested in writing by
Alnylam that are consistent with applicable Law to prevent exports of Licensed Product from the
Territory to countries in Asia. Alnylam shall use Diligent Efforts to effect provisions with its
Asian Partner that require the Asian Partner to use efforts consistent with those required of
Cubist under this Section 5.12 to inform Cubist of, and to prevent, exports of Licensed Products
from countries in Asia into countries in the Territory.
ARTICLE VI
MANUFACTURE AND SUPPLY
Section 6.1
Supply Obligations; Alnylams Existing Manufacturing Arrangements
.
(a) Subject to Section 6.2, from and after the Effective Date, Alnylam will use Diligent
Efforts, either itself or through Third Parties, to Manufacture, in accordance with applicable cGMP
(as defined in the Supply Agreement Term Sheet), and supply to Cubist API Bulk Drug Substance and
Finished Product (as applicable) in quantities that are reasonably sufficient for the conduct of
Development and Commercialization by Cubist with respect to the Profit-Share Territory under the
Development Plan and Commercialization Plan, respectively, and for Development and
Commercialization in the Royalty Territory. Cubist shall pay Alnylam an amount equal to Alnylams
Cost of Goods Sold for API Bulk Drug Substance and Finished Product (as applicable) supplied by
Alnylam to Cubist pursuant to this Section 6.1 with respect to the Development and
Commercialization in the Royalty Territory, payable within [**] after receipt of an invoice
therefor in accordance with the Supply Agreement. Alnylams Cost of Goods Sold for API Bulk Drug
Substance and Finished Product (as applicable) supplied by Alnylam to Cubist pursuant to this
Section 6.1 for Development in the Profit-Share Territory shall be included as Development Costs.
Alnylams Cost of Goods Sold for API Bulk Drug Substance and Finished Product (as applicable)
supplied by Alnylam to Cubist pursuant to this Section 6.1 for Commercialization in the
Profit-Share Territory shall be shared by the Parties through the calculation of N.A. Pre-Tax
Profit or Loss.
(b) Prior to the Effective Date, Alnylam entered into the master services agreements
identified on
Exhibit F
with respect to the supply of API Bulk Drug Substance and Finished
Product for clinical trials, and such agreements are hereby deemed approved by Cubist. Subject to
Sections 6.2 and 6.3, Alnylam shall be responsible for the day-to-day management of such suppliers
on behalf of the Parties, under the direction of the JSC;
provided
that
in no event
shall Alnylam amend any of the agreements identified on
Exhibit F
with respect to any
Licensed Product without Cubists prior written approval of the form of the amendment, which
approval shall not be unreasonably withheld or delayed. After the Effective Date, Alnylam, in
consultation with Cubist, shall use Diligent Efforts to enter into such additional agreements (if
any, as determined by the Parties) with suppliers of API Bulk Drug Substance or Finished Product
(as applicable) to supply the Parties with API Bulk Drug Substance or Finished Product in
quantities that are reasonably sufficient for the conduct of Development and
-44-
Commercialization activities for the Territory pursuant to this Agreement. The selection of
such Third Party suppliers and the terms of the agreements with such Third Party suppliers with
respect to Licensed Products shall be subject to prior approval by both Parties, which approval
shall not be unreasonably withheld or delayed. The terms of any such agreements shall include the
right of both Parties to audit any such Third Party suppliers of API Bulk Drug Substance or
Finished Product being supplied for the Territory. In the case of the agreements identified on
Exhibit F
, to the extent permitted by such agreements and upon the reasonable request of
Cubist, Alnylam shall audit such existing Third Party suppliers with respect to activities related
to Licensed Products and, to the extent permitted by such agreements, shall permit Cubist
representatives to participate as part of the audit team. The results of any such audit shall be
reported to Alnylam as provided in such agreements and Alnylam shall report such results to Cubist
to the extent permitted by such agreements. Notwithstanding anything in this Agreement to the
contrary, Alnylam shall use Diligent Efforts to amend the agreements listed on
Exhibit F
to
the extent necessary to permit Cubist representatives to participate in audits of such Third
Parties with respect to Licensed Product and to have access to audit results.
(c) The JSC shall not take any action or direct Alnylam to take any action that would result
in the breach of any agreement set forth on
Exhibit F
, or of any subsequent agreement
between Alnylam and an API Bulk Drug Substance or Finished Product supplier, including any minimum
purchase obligation or non-cancelable order obligation contained in any such agreement.
Section 6.2
Transition of Manufacturing Responsibilities to Cubist.
(a) The Parties contemplate that, at a suitable time after the Effective Date, the Parties may
agree to transfer responsibility for Manufacturing API Bulk Drug Substance and Finished Product for
the Territory (as applicable) to Cubist or a designated Third Party manufacturer. The Supply
Agreement Term Sheet also contains provisions under which Cubist may assume responsibility for the
Manufacture of Licensed Product.
(b) If, and at such time as a transition of Manufacturing to Cubist is to occur under Section
6.2(a), Cubist will either (i) enter into agreement(s) with API Bulk Drug Substance supplier(s) or
Finished Product suppliers or (ii) supply API Bulk Drug Substance or Finished Product (after
completion of transfer of responsibilities), in either case to replace the agreement(s) referenced
in Section 6.1 or to provide a second source of supply for API Bulk Drug Substance or Finished
Product, the terms of any such agreements or arrangements involving Cubist shall be subject to both
Parties prior written approval, which approval shall not be unreasonably withheld or delayed.
After such transition, Cubists Cost of Goods Sold for API Bulk Drug Substance and Finished Product
(as applicable) supplied by Cubist for Development in the Profit-Share Territory shall be included
as Development Costs, and Cubists Cost of Goods Sold for API Bulk Drug Substance and Finished
Product (as applicable) supplied by Cubist for Commercialization in the Profit-Share Territory
shall be shared by the Parties through the calculation of N.A. Pre-Tax Profit or Loss.
(c) From and after such time, if any, as responsibility for Manufacturing API Bulk Drug
Substance or Finished Product is transitioned to Cubist, Cubist shall use Diligent Efforts to
Manufacture or have Manufactured and supply sufficient quantities of the API Bulk
-45-
Drug Substance or Finished Product (as applicable) to enable Cubist to respond on a timely
basis to customer demand for Licensed Products in the Field in the Territory.
(d) Cubist acknowledges that Alnylam has certain supply obligations to Kyowa Hakko under the
Kyowa Agreement, and that, if any such obligations to Kyowa Hakko or to another Asian Partner
remain at the time of any transition of responsibility for supply to Cubist pursuant to Section
6.2(a), the Parties shall use Diligent Efforts to structure such transition in a manner that
enables Alnylam to satisfy such supply obligations to Kyowa Hakko (or another Asian Partner, as
applicable) after such transition in a reasonable manner, provided in no event shall Cubist have
any obligation to supply Alnylam with any Licensed Product other than the Licensed Product Cubist
is Manufacturing for itself.
(e) Alnylam shall pay Cubist an amount equal to [**] for any API Bulk Drug Substance and
Finished Product (as applicable) supplied by Cubist to Alnylam (or its designee) pursuant to
Section 6.2(d) [**] to which Alnylam is entitled under its agreement with its Asian Partner, which
such amount shall be paid within [**] after receipt of an invoice therefor. Sale by Cubist of API
Bulk Drug Substance or Finished Product to Alnylam under this Agreement shall not be included in
the calculation of Net Sales.
Section 6.3
Supply Agreement
. The terms of
Exhibit G
hereof (the
Supply Agreement Term Sheet
) shall govern the Manufacture and supply of Licensed Product
hereunder until such time as the Parties enter into a supply agreement (the
Supply
Agreement
), after which time, the terms of the Supply Agreement shall govern. The Parties
will use their commercially reasonable efforts to enter into, within [**] after the Effective Date,
a Supply Agreement among Alnylam, Cubist and Kyowa Hakko, consistent with the terms set forth in
Exhibit G
, and containing such other terms as shall be consistent with this Agreement, the
Kyowa Agreement and industry standards for a contract manufacturing agreement in the context of a
collaborative effort. For purposes of clarity, if Cubist assumes responsibility for the
Manufacture and supply of License Product pursuant hereto or pursuant to the Supply Agreement Term
Sheet or the Supply Agreement, it is the intention of the Parties that Cubist will have the same
rights and obligations as the manufacturer and supplier that Alnylam held prior to such time under
the Supply Agreement Term Sheet or the Supply Agreement, as the case may be.
Section 6.4
Technology Transfer
. Promptly after a decision of the Parties or
election by Cubist under Section 6.2 to transfer Manufacture of the API Bulk Drug Substance or
Finished Product (as applicable) to Cubist or to a Third Party API Bulk Drug Substance supplier or
Finished Product supplier with whom Cubist enters into an agreement, as permitted under Section
6.2, Alnylam will transfer to Cubist or to such Third Party supplier all documents and
Manufacturing information and other Know-How necessary or reasonably useful to enable Cubist to
Manufacture or have Manufactured the API Bulk Drug Substance and Finished Product (as applicable).
Alnylams costs and expenses incurred in connection with any such transfer of technology under this
Section 6.4 shall [**], to the extent consistent with this Agreement.
-46-
ARTICLE VII
FINANCIAL PROVISIONS
Section 7.1
Upfront Fee
. Within five (5) Business Days after the Effective Date,
Cubist shall pay Alnylam a non-refundable, non-creditable initial payment of Twenty Million Dollars
($20,000,000).
Section 7.2
Development Milestones
. Cubist shall make the non-refundable,
non-creditable milestone payments set forth below to Alnylam not later than [**] after the earliest
date on which the corresponding milestone event set forth below has been achieved:
|
|
|
Milestone Event
|
|
Payment*
|
(a) Acceptance for filing of an application for
Regulatory Approval for a Licensed Product for any
indication in the EMEA or in a Major EU Country
|
|
$ [**]
|
(b) First Commercial Sale of a Licensed Product in
any indication in a Major EU Country
|
|
$ [**]
|
(c) Acceptance for filing of an application for
Regulatory Approval for a Licensed Product for any
indication other than the indication with respect to
which the milestone event described in Section 7.2(a)
above was achieved in the EMEA or in a Major EU Country
|
|
$[**]
|
(d) Regulatory Approval of a Licensed Product for
any indication other than the indication with respect
to which the milestone event described in Section
7.2(a) above was achieved in the EMEA or in a Major EU
Country
|
|
$ [**]
|
|
|
|
*
|
|
The milestone payments for RSV02 Products and Additional RSV Products shall be [**] percent
([**]%) of the amounts set forth in the chart above.
|
The milestone payments set forth in this Section 7.2 shall be paid only once, upon the first
achievement of the applicable milestone event by the first Licensed Product to achieve such
milestone event;
provided
that
if any such milestone event is first achieved by an
RSV02 Product or an Additional RSV Product such that Cubist pays [**] percent ([**]%) of the amount
set forth in the table above in connection with the achievement of such milestone, then [**]
percent ([**]%) of such milestone amount shall be paid by Cubist if such milestone event is
subsequently achieved by an RSV01 Product.
-47-
Section 7.3
Sales Milestones
. In addition to all other amounts payable under this
Agreement, Cubist shall make non-refundable, non-creditable milestone payments set forth below to
Alnylam upon the achievement of the milestone events set forth below, such payment to be made as
set forth below:
|
|
|
Milestone Event
|
|
Payment*
|
(a) Calendar Year Net Sales of Licensed Product in the
Royalty Territory greater than $[**]
|
|
$ [**]
|
(b) Calendar Year Net Sales of Licensed Product in the
Royalty Territory greater than $[**]
|
|
$[**]
|
(c) Calendar Year Net Sales of Licensed Product in the
Royalty Territory greater than $[**]
|
|
$ [**]
|
|
|
|
*
|
|
The milestone payments for RSV02 Products and Additional RSV Products shall be [**] percent
([**]%) of the amounts set forth in the chart above.
|
The milestone payments set forth in this Section 7.3 shall each be payable only once, upon the
first achievement of the applicable Net Sales threshold in a given Calendar Year;
provided
that
if any such success milestone is first achieved by an RSV02 Product or an Additional
RSV Product such that Cubist pays [**] percent ([**]%) of the amount set forth in the table above
in connection with the achievement of such milestone, then [**] percent ([**]%) of such milestone
amount shall be paid by Cubist if the milestone event is subsequently achieved by an RSV01 Product.
For purposes of determining whether a milestone event set forth in this Section 7.3 has
occurred (and without creating an obligation to pay the milestone more than once as set forth in
the preceding paragraph of this Section 7.3), Calendar Year Net Sales shall be calculated for each
Licensed Product separately.
If more than one of such milestone events first occurs based on sales of Licensed Product in
the same Calendar Year, all of such milestone payments shall be paid for such Calendar Year. If a
milestone payment set forth above is earned based on Net Sales over a period that is shorter in
duration than a full Calendar Year, such payment shall become due and payable [**] after the end of
the Calendar Quarter in which the milestone event is achieved.
Section 7.4
N.A. Pre-Tax Profit or Loss
.
(a)
Allocation of N.A. Pre-Tax Profit or Loss
. Subject to Section 5.3(b), the Parties
shall share in N.A. Pre-Tax Profit or Loss for the Profit-Share Territory as follows: fifty
percent (50%) to Alnylam and fifty percent (50%) to Cubist. N.A. Pre-Tax Profit or Loss shall be
calculated in accordance with Section 7.4(b). It is understood that costs and expenses included in
components of N.A. Pre-Tax Profit or Loss shall not be double counted and shall not also be
included in Development Costs.
-48-
(b)
Quarterly Reconciliation of N.A. Pre-Tax Profit or Loss
.
(i) Within [**] after the end of each Calendar Quarter after the Effective Date, Cubist shall
submit to Alnylam a written report setting forth (A) all Net Sales of Licensed Products in the
Profit-Share Territory made by Cubist or its Related Parties during such Calendar Quarter, together
with an accounting of the deductions from gross invoice price to Net Sales in accordance with
Section 1.76, (B) all Sublicense Income received during such Calendar Quarter, and (C) the Cost of
Goods Sold, Commercialization Costs and Distribution Costs incurred by Cubist with respect to
Licensed Products in the Field in the Profit-Share Territory.
(ii) Within [**] after the end of each Calendar Quarter after the Effective Date, Alnylam
shall submit to Cubist a written report setting forth the Cost of Goods Sold, Commercialization
Costs and Distribution Costs incurred by Alnylam with respect to Licensed Products in the Field in
the Profit-Share Territory.
(iii) In submitting the reports contemplated by Sections 7.4(b)(i) and 7.4(b)(ii), subject to
Section 5.3(c), the Parties shall submit costs and expenses for inclusion in the reconciliation of
N.A. Pre-Tax Profit or Loss only to the extent such costs and expenses were made or incurred by
such Party for activities described in the then current Commercialization Plan, or (B) as otherwise
approved by the JSC or JCT.
(iv) Within [**] after the receipt of Alnylams report pursuant to Section 7.4(b)(ii), Cubist
shall submit to Alnylam a written report setting forth in reasonable detail the calculation of N.A.
Pre-Tax Profit or Loss and the calculation of the net amount owed by Cubist to Alnylam, or by
Alnylam to Cubist, in order to ensure the sharing of N.A. Pre-Tax Profit or Loss set forth in
Section 7.4(a). The net amount payable shall be paid by Cubist or by Alnylam (as the case may be)
within [**] after the end of the applicable Calendar Quarter.
Section 7.5
Licensed Product Royalties in the Royalty Territory
.
(a)
Royalty Rates
. Subject to Sections 7.5(b), 7.5(c), 7.5(d), 7.6, 7.7, 7.8 and 7.9,
Cubist shall pay to Alnylam royalties on the aggregate Net Sales in the Royalty Territory of each
Licensed Product by Cubist or its Related Parties, determined on a Licensed Product-by-Licensed
Product basis, as follows:
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Royalty Rate for
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Licensed Products
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Royalty Rate for
|
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other than RSV01
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RSV01 Products
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Products (as a
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Calendar Year Net Sales
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(as a percentage
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percentage of
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of Licensed Product
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of such Net Sales)
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such Net Sales)
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$[**] $[**]
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[**]%
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[**]%
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Greater than $[**] and less than
or equal to $[**]
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[**]%
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[**]%
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Royalty Rate for
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Licensed Products
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Royalty Rate for
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other than RSV01
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RSV01 Products
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Products (as a
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Calendar Year Net Sales
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(as a percentage
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percentage of
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of Licensed Product
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of such Net Sales)
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such Net Sales)
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Greater than $[**] and less than
or equal to $[**]
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[**]%
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[**]%
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Greater than $[**] and less than
or equal to $[**]
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[**]%
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[**]%
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Greater than $[**]
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[**]%
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[**]%
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(b)
Applicability of Royalty Rates to Net Sales in the Royalty Territory
. Royalties
on aggregate Net Sales of Licensed Product in the Royalty Territory in a Calendar Year shall be
paid at the rate applicable to the portion of Net Sales within each of the Net Sales levels above
during such Calendar Year. For example, subject to Sections 7.5(c), 7.5(d), 7.6, 7.7, 7.8 and 7.9,
if, during a Calendar Year, Net Sales of an RSV01 Product were equal to $[**], the royalty payable
by Cubist would be calculated by [**].
(c)
Royalties in North America After Exercise of the Opt-Out Option
. In the event
Alnylam exercises its Opt-Out Option under Section 4.7, (i) the Royalty Territory shall be expanded
to include North America, and (ii) Net Sales of Licensed Products for purposes of calculating the
royalty tiers shall be determined separately for North America and the rest of the Territory in
accordance with Section 4.7(a), provided that the royalty rates applicable to North America shall
be those set forth in Section 4.7(a).
(d)
Royalty Term and Adjustments
. The obligations of Cubist to make royalty payments
at the full rates recited in Section 7.5(a) shall commence on the Effective Date and shall expire
on a Licensed Product-by-Licensed Product and country-by-country basis on the later of: (i) the
expiration of the Legal Exclusivity Period or (ii) the tenth (10th) anniversary of the date of the
First Commercial Sale of such Licensed Product in such country by Cubist or its Related Parties
(the
Royalty Term
). The foregoing provisions of this Section 7.5(d) notwithstanding, the
royalties payable with respect to Net Sales of a Licensed Product sold in any country in the
Royalty Territory shall be reduced to [**] percent ([**]%) of the amounts otherwise payable
pursuant to Section 7.5(a) (as further adjusted by the other provisions of this Article VII),
during any portion of the Royalty Term when there is not an applicable Legal Exclusivity Period in
effect with respect to such Licensed Product in such country.
Section 7.6
Adjustments for Necessary Third Party IP Payments in the Royalty
Territory
.
(a) With respect to Licensed Products in the Royalty Territory, (i) subject to Section 7.9,
Alnylam shall bear [**] percent ([**]%) of any royalties, upfront fees, milestones or other
payments owed under the Existing Alnylam In-Licenses with respect to the Development,
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Manufacture or Commercialization of a Licensed Product in the Field in the Royalty Territory;
(ii) subject to Sections 7.6(b) and 7.9, Cubist shall bear [**] percent ([**]%) of any royalties
upfront fees, milestones or other payments under the Alnylam In-Licenses, other than the Existing
Alnylam In-Licenses, to the extent reasonably allocable to Necessary Third Party IP for the
Development, Manufacture or Commercialization of a Licensed Product in the Field in the Royalty
Territory; and (iii) subject to Sections 7.6(b) and 7.9, Cubist shall bear [**] percent ([**]%) of
any royalties upfront fees, milestones or other payments under the Cubist In-Licenses, to the
extent reasonably allocable to Necessary Third Party IP for the Development, Manufacture or
Commercialization of a Licensed Product in the Field in the Royalty Territory. Any such amounts
shall be paid by Cubist or paid by Alnylam and reimbursed by Cubist;
provided
that
if such amounts are paid by Alnylam, Alnylam shall invoice Cubist for the amounts identified on a
Calendar Quarter basis, and Cubist shall pay such invoices within [**] after receipt of Alnylams
invoice.
(b) Subject to Section 7.9, [**] percent ([**]%) of all royalties, upfront fees, milestones or
other payments under the Alnylam In-Licenses and the Cubist In-Licenses actually paid by Cubist
pursuant to Section 7.6(a)(ii) or 7.6(a)(iii) shall be fully creditable against royalties payable
by Cubist to Alnylam pursuant to Section 7.5(a) or Section 4.7. [**].
Section 7.7
Necessary Third Party IP in the Profit-Share Territory
. With respect to
Licensed Product in the Profit-Share Territory, (a) [**] percent ([**]%) of any royalties, upfront
fees, milestones or other payments under the Alnylam In-Licenses (other than Existing Alnylam
In-Licenses), (b) [**] percent ([**]%) of royalties payable under Existing Alnylam In-Licenses up
to [**] percent ([**]%) of Net Sales, (c) [**] percent ([**]%) of the allocated milestones under
Existing Alnylam In-Licenses that are identified on
Exhibit H
, and (d) ([**]%) of any
royalties, upfront fees, milestones or other payments under the Cubist In-Licenses, in each case
under clauses (a), (b), (c) and (d), to the extent reasonably allocable to Necessary Third Party IP
for the Development, Manufacture or Commercialization of Licensed Products in the Field for the
Profit-Share Territory, shall be included in Commercialization Costs or Development Costs, as
applicable; provided that it is understood that [**] percent ([**]%) of the allocated milestones
identified on
Exhibit H
shall be included in Commercialization Costs or Development Costs,
as the case may be, with respect to Licensed Products for the Profit-Share Territory. Alnylam
shall bear [**] percent ([**]%) of any royalties, up-front fees, milestones or other payments owed
under the Existing Alnylam In-Licenses with respect to Development, Manufacture or
Commercialization of Licensed Product in the Field in the Profit-Share Territory to the extent not
covered under the preceding sentence.
Section 7.8
Royalty Adjustments for Generic Products
. If, during a given Calendar
Quarter, there is Generic Competition in a particular country of the Royalty Territory with respect
to a Licensed Product, then subject to Section 7.9, the royalties payable on the Net Sales of such
Licensed Product in such country during such Calendar Quarter shall be reduced to (a) [**] percent
([**]%) of the amounts otherwise payable pursuant to Section 7.5(a), as adjusted by the other
provisions of this Article VII, with respect to such Licensed Product in such country for such
Calendar Quarter, and (b) [**] percent ([**]%) of the amounts otherwise payable pursuant to Section
7.5(a), as adjusted by the other provisions of this Article VII, with respect to such Licensed
Product in such country for such Calendar Quarter where the market share in such
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country for the Generic Product (determined in accordance with Section 1.54) is greater than
[**] percent ([**]%).
Section 7.9
Minimum Payments in the Royalty Territory
.
(a) Unless the reductions in Section 7.8(b) apply, notwithstanding anything to the contrary in
Section 7.5, 7.6 or 7.8, with respect to any Licensed Product in any country in the Royalty
Territory in any Calendar Quarter, if the royalty payments (after all adjustments and reductions)
to be made to Alnylam by Cubist would otherwise be less than the royalty amounts payable by Alnylam
(and not reimbursed by Cubist) to Third Parties under the Alnylam In-Licenses with respect to such
Net Sales of Licensed Product in the Royalty Territory plus [**] percent ([**]%) of the Net Sales
of such Licensed Product in the Royalty Territory in such Calendar Quarter, then Alnylam shall
invoice Cubist for such shortfall amounts on a Calendar Quarter basis, and Cubist shall pay such
invoices within [**] after receipt of Alnylams invoice.
(b) If the reductions in Section 7.8(b) apply, notwithstanding anything to the contrary in
Section 7.5, 7.6 or 7.8, with respect to any Licensed Product in any country in the Royalty
Territory in any Calendar Quarter, if the royalty payments (after all adjustments and reductions)
to be made to Alnylam by Cubist would otherwise be less than the amounts payable by Alnylam to
Third Parties under the Alnylam In-Licenses plus [**] percent ([**]%) of the Net Sales of such
Licensed Product in such Calendar Quarter in the Royalty Territory, then Alnylam shall invoice
Cubist for such shortfall amounts on a Calendar Quarter basis, and Cubist shall pay such invoices
within [**] after receipt of Alnylams invoice.
(c) If the provisions of Section 4.7(a)(ix) apply, notwithstanding anything to the contrary in
Section 4.7(a)(ix) or this Article VII, if the portion of Sublicense Income attributable to the Net
Sales of Licensed Products by such Cubist Sublicensee in such country(ies) in North America in any
Calendar Quarter would otherwise be less than the royalty amounts payable by Alnylam to Third
Parties under the Alnylam In-Licenses with respect to such Net Sales of Licensed Product in such
country(ies) in North America in such Calendar Quarter plus [**] percent ([**]%) of such Net Sales,
then Alnylam shall invoice Cubist for such shortfall amounts on a Calendar Quarter basis, and
Cubist shall pay such invoices within [**] after receipt of Alnylams invoice.
Section 7.10
Royalty Reports; Payments
. Within [**] after the end of each Calendar
Quarter for which royalties are payable by Cubist to Alnylam with respect to Net Sales of Licensed
Products in the Royalty Territory pursuant to Section 7.5, Cubist shall submit to Alnylam a report,
on a country-by-country basis, providing in reasonable detail an accounting of all Net Sales
(including an accounting of all unit sales of Licensed Product and calculation of the deductions
from gross invoice price to Net Sales in accordance with Section 1.76) made during such Calendar
Quarter and the calculation of the applicable royalties under Section 7.5(a). Cubist shall pay to
Alnylam all amounts payable by it under Section 7.5 as indicated in the report at the time Cubist
submits the report.
Section 7.11
Payments from Alnylam to Cubist; Reports
. Alnylam will pay Cubist [**]
percent ([**]%) of any Asian Partner Payments received by Alnylam from its Asian Partner after the
Effective Date, in accordance with this Section 7.11. No sooner than [**] and no later than
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[**] after the end of each Calendar Quarter in which Alnylam receives Asian Partner Payments,
Alnylam shall submit to Cubist a report, providing in reasonable detail an accounting of all Asian
Partner Payments received by Alnylam during such Calendar Quarter and the calculation of the
applicable payment under this Section 7.11. Alnylam shall pay to Cubist all amounts payable by it
under this Section 7.11 as indicated in the report at the time Alnylam submits the report. As used
in this Section 7.11,
Asian Partner Payments
means any of the following received by
Alnylam from its Asian Partner: (a) [**]. For avoidance of doubt, this Section 7.11 survives any
termination of this Agreement as long as such termination occurs after NDA submission in the United
States.
Section 7.12
Audits
. Each Party shall keep complete and accurate records of the
items underlying Development Costs, Commercialization Costs, Distribution Costs, Net Sales, Cost of
Goods Sold, Necessary IP Rights, royalties, milestones, other license fees and other payments and
the elements required to calculate N.A. Pre-Tax Profit or Loss relating to the reports and payments
required by Sections 4.4, 4.5, 4.7, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10 and 7.11. Each
Party will have the right [**] at its own expense to have an independent, certified public
accountant, selected by such Party and reasonably acceptable to the other Party, review any such
records of the other Party in the location(s) where such records are maintained by the other Party
upon reasonable notice and during regular business hours and under obligations of confidence, for
the sole purpose of verifying the basis and accuracy of payments made under Sections 4.4, 4.5, 4.7,
7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10 and 7.11 within the prior [**] period. If the review
of such records reveals that the other Party has failed to accurately report information pursuant
to Sections 4.4, 4.5, 4.7, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10 and 7.11, then the other
Party shall promptly pay to the auditing Party any resulting amounts due under such Sections,
together with interest calculated in the manner provided in Section 7.17. If any such
discrepancies are greater than five percent (5%) of the amounts actually due for any Calendar
Quarter under Sections 4.4, 4.5, 4.7, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, 7.10 and 7.11, the
other Party shall pay all of the costs of such review.
Section 7.13
Tax Matters
.
(a) Cubist will make all payments to Alnylam under this Agreement without deduction or
withholding except to the extent that any such deduction or withholding is required by applicable
Law to be made on account of Taxes (as that term is defined in Section 7.13(e) below).
(b) Any Tax required to be withheld under applicable Law on amounts payable under this
Agreement will promptly be paid by Cubist on behalf of Alnylam to the appropriate Governmental
Authority, and Cubist will furnish Alnylam with proof of payment of such Tax. Any such Tax
required to be withheld will be an expense of and borne by Alnylam. Cubist will give notice of its
intention to begin withholding any such Tax in advance and cooperate to use reasonable and legal
efforts to reduce such Tax on payments made to Alnylam hereunder.
(c) Cubist and Alnylam will cooperate with respect to all documentation required by any
relevant Government Authority or reasonably requested by Cubist to secure a reduction in the rate
of applicable withholding Taxes.
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(d) If Cubist had a duty to withhold Taxes in connection with any payment it made to Alnylam
under this Agreement but Cubist failed to withhold, and such Taxes were assessed against and paid
by Cubist, then Alnylam will indemnify and hold harmless Cubist from and against such Taxes
(including interest). If Cubist makes a claim under this Section 7.13(d), it will comply with the
obligations imposed by Section 7.13(b) as if Cubist had withheld Taxes from a payment to Alnylam.
(e) Solely for purposes of this Section 7.13,
Tax
or
Taxes
means any
present or future taxes, levies, imposts, duties, charges, assessments or fees of any nature
(including interest, penalties and additions thereto) that are imposed by a Government Authority.
Section 7.14
United States Dollars
. All dollar ($) amounts specified in this
Agreement are United States dollar amounts.
Section 7.15
Currency Exchange
. All payments to be made by Cubist to Alnylam shall
be made in U.S. dollars, to an Alnylam bank account able to receive U.S. dollars. In the case of
sales outside the United States, royalty payments by Cubist to Alnylam shall be converted to U.S.
dollars in accordance with the following: the rate of currency conversion shall be calculated
using a simple average of mid-month and month-end spot rates as published by The Wall Street
Journal, Eastern Edition. This method of conversion is and shall be consistent with Cubists then
current methods. Cubist shall give Alnylam prompt written notice of any changes to Cubists
customary and usual procedures for currency conversion, which shall only apply after such notice
has been delivered and
provided
that
such changes continue to maintain a set
methodology for currency conversion.
Section 7.16
Blocked Payments
. If, by reason of applicable Law in any country, it
becomes impossible or illegal for Cubist or its Related Party(ies) to transfer, or have transferred
on its behalf, royalties or other payments to Alnylam, Cubist shall promptly notify Alnylam of the
conditions preventing such transfer and such royalties or other payments shall be deposited in
local currency in the relevant country to the credit of Alnylam in a recognized banking institution
designated by Alnylam or, if none is designated by Alnylam within a period of [**], in a recognized
banking institution selected by Cubist or its Related Party(ies), as the case may be, and
identified in a notice given to Alnylam.
Section 7.17
Late Payments
. The paying Party shall pay interest to the receiving
Party on the aggregate amount of any payments that are not paid on or before the date such payments
are due under this Agreement at a rate per annum equal to the lesser of one percent (1%) per month
or the highest rate permitted by applicable Law, calculated on the number of days such payments are
paid after the date such payments are due.
Section 7.18
No Overlapping Royalties
. Notwithstanding any other provision of this
Agreement, in no event shall any royalty payment provided for under any Section of this
Agreement be paid with respect to any sale of a specific Licensed Product to the extent a
royalty has been paid pursuant to any other Section of this Agreement with respect to such sale of
the same specific Licensed Product;
provided
that
the higher royalty amount is
paid, and
provided
further
that the foregoing shall not apply to the payment of
sales milestones under Sections 4.7, 7.3 and 11.4.
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Section 7.19
Reporting
. The Parties will use the Calendar Year to establish monthly,
quarterly and annual time periods for all of their financial budgeting and actual reporting
requirements, including N.A. Pre-Tax Profit or Loss reporting.
Section 7.20
Resolution of Disputes
. If there is a dispute, claim or controversy
relating to any financial obligation by one Party to the other Party pursuant to this Agreement,
such Party shall provide such other Party with written notice setting forth in reasonable detail
the nature and factual basis for such good-faith dispute and each Party agrees that it shall seek
to resolve such dispute within [**] after the date such written notice is received. If no such
resolution is reached by the Parties, the dispute shall be resolved through the procedures set
forth in Article XII. Notwithstanding any other provision of this Agreement to the contrary, the
obligation to pay any reasonably disputed amount shall not be deemed to have been triggered until
such dispute is resolved hereunder;
provided
that
all amounts that are not in
dispute shall be paid in accordance with this Agreement.
ARTICLE VIII
INTELLECTUAL PROPERTY OWNERSHIP, PROTECTION AND RELATED MATTERS
Section 8.1
Inventorship
. Inventorship for patentable inventions conceived or
reduced to practice during the course of the performance of activities pursuant to this Agreement
shall be determined in accordance with United States patent laws for determining inventorship.
Section 8.2
Ownership
. Subject to the licenses and rights granted to Cubist under
this Agreement, Alnylam shall own the entire right, title and interest in and to all inventions and
discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered
solely by employees or consultants of Alnylam or acquired solely by Alnylam in the course of
conducting the Collaboration. Subject to the licenses and rights granted to Alnylam under this
Agreement, Cubist shall own the entire right, title and interest in and to all inventions and
discoveries (and Patent Rights claiming patentable inventions therein) first made or discovered
solely by employees or consultants of Cubist or acquired solely by Cubist in the course of
conducting the Collaboration. The Parties shall jointly own any inventions and discoveries (and
Patent Rights claiming patentable inventions therein) first made or discovered jointly in the
course of conducting the Collaboration.
Section 8.3
Prosecution and Maintenance of Patent Rights
.
(a)
Cubist Technology
. Cubist shall have the sole right to, at Cubists discretion,
file, conduct prosecution, and maintain (including the defense of any interference or opposition
proceedings), all Patent Rights comprising Cubist Technology (other than Joint Collaboration IP),
in Cubists name.
(b)
Alnylam Technology
. Alnylam shall have the sole right to, at Alnylams
discretion, file, conduct prosecution, and maintain (including the defense of any interference or
opposition proceedings), all Patent Rights comprising Alnylam Technology (other than Joint
Collaboration IP), in Alnylams name. Alnylam shall provide to Cubist copies of all prosecution
filings related to Alnylam Sequence Specific Patent Rights sent to or received from patent offices
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in the Territory, unless otherwise directed by Cubist, and, with respect to patent applications
containing Alnylam Sequence Specific Patent Rights having information not previously filed that is
intended to be submitted to patent offices in the Territory, shall use reasonable efforts to
provide Cubist with a draft of each such filing reasonably in advance of submission and shall
consider in good faith any comments regarding such draft application that Cubist may timely
provide. In addition, Alnylam shall provide to Cubist such other information related to
prosecution of the Alnylam Patent Rights as Cubist may from time to time reasonably request to
allow Cubist to track prosecution and maintenance of Alnylam Patent Rights. In the event Alnylam
decides not to file a patent application on Alnylam Know-How that would contain Alnylam Sequence
Specific Patent Rights, or decides to abandon prosecution of any Alnylam Sequence Specific Patent
Rights or decides to not otherwise maintain or extend any Alnylam Sequence Specific Patent Rights,
Alnylam shall give Cubist written notice sufficiently in advance of any loss of rights to allow
Cubist to file, prosecute, maintain or extend, as the case may be, such Alnylam Sequence Specific
Patent Rights, in Alnylams name.
(c)
Joint Collaboration IP
.
(i) Alnylam shall have the first right to, at Alnylams discretion, file, conduct prosecution,
and maintain (including the defense of any interference or opposition proceedings), all Patent
Rights included in Joint Collaboration IP, in the names of both Alnylam and Cubist. Cubist shall
use Diligent Efforts to make available to Alnylam or its authorized attorneys, agents or
representatives, such of its employees as Alnylam in its reasonable judgment deems necessary in
order to assist it in obtaining patent protection for such Joint Collaboration IP. Each Party
shall sign, or use Diligent Efforts to have signed, all legal documents necessary to file and
prosecute patent applications or to obtain or maintain patents in respect of such Joint
Collaboration IP, at its own cost.
(ii) If Alnylam elects not to seek or continue to seek or maintain patent protection on any
Joint Collaboration IP in the Territory, Cubist shall have the right to, at Cubists discretion, to
seek, prosecute and maintain in any country in the Territory patent protection on such Joint
Collaboration IP in the names of both Alnylam and Cubist. Alnylam shall use Diligent Efforts to
make available to Cubist its authorized attorneys, agents or representatives, such of Alnylams
employees as are reasonably necessary to assist Cubist in
obtaining and maintaining the patent protection described under this Section 8.3(c)(ii).
Alnylam shall sign or use Diligent Efforts to have signed all legal documents necessary to file and
prosecute such patent applications or to obtain or maintain such patents.
(iii) With respect to Patent Rights included in the Joint Collaboration IP, the Party filing,
prosecuting and maintaining such Patent Rights shall provide the other Party, within [**] after
submitting or receiving such filings or correspondence, with copies of all filings and
correspondence submitted to and received from patent offices in the Territory and, with respect to
substantive filings and correspondence to be submitted to patent offices in the Territory, shall
use reasonable efforts to provide the other Party with drafts of such filings and correspondence
reasonably in advance of submission and shall consider in good faith any comments regarding such
filings and correspondence that the other Party may timely provide.
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(d)
Patent Term Extensions
. The Parties shall cooperate, if necessary and
appropriate, with each other in gaining patent term extensions (including those extensions
available under U.S. Drug Price Competition and Patent Term Restoration Act of 1984, the
Supplementary Certificate of Protection of Member States of the EU and other similar measures in
any other country) wherever applicable to Patent Rights Controlled by either Party that Cover
Licensed Product in the Territory. The Parties shall, if necessary and appropriate, use reasonable
efforts to agree upon a joint strategy relating to patent term extensions, but, in the absence of
mutual agreement with respect to any extension issue, the patent or the claims of the patent shall
be selected on the basis of the scope, enforceability and remaining term of the patent in the
relevant country or region. All filings for such extensions shall be made by the Party Controlling
such patent or, in the case of Patent Rights included in the Joint Collaboration IP, by the Party
responsible for filing, prosecuting and maintaining such Patent Rights in accordance with this
Section 8.3.
(e)
Patent Expenses
. The patent filing, prosecution and maintenance expenses incurred
after the Effective Date with respect to Patent Rights comprised of Alnylam Technology and Cubist
Technology (
Patent Expenses
) shall be borne by the Party responsible for filing,
prosecuting and maintaining such Patent Rights under this Section 8.3;
provided
that
[**].
Section 8.4
Third Party Infringement
.
(a)
Notices
. Each Party shall promptly report in writing to the other Party any (i)
known or suspected infringement of any Alnylam Technology or Cubist Technology being used in the
Collaboration, including any Joint Collaboration IP or (ii) unauthorized use or misappropriation of
any Confidential Information or Know-How of a Party by a Third Party of which it becomes aware, in
each case only to the extent relevant to the Development, Manufacture or Commercialization of
Licensed Product and involving a competing product (
Competitive Infringement
) in the
Territory, and shall provide the other Party with all available evidence supporting such
infringement, or unauthorized use or misappropriation.
(b)
Rights to Enforce
.
(i)
Cubists First Right
. Subject to the provisions of any Third Party agreement
under which Cubists rights in Cubist Technology are granted, Cubist shall have the sole and
exclusive right to initiate an infringement or other appropriate suit anywhere in the world against
any Third Party who at any time has infringed, or is suspected of infringing, any Patent Rights, or
of using without proper authorization any Know-How, comprising Cubist Patent Rights, Cubist
Know-How, or Cubist Collaboration IP.
(ii)
Alnylams First Right
. Subject to the provisions of any Third Party agreement
under which Alnylams rights in Alnylam Technology are granted and subject to Section 8.4(b)(iii)
below, Alnylam shall have the sole and exclusive right to initiate an infringement or other
appropriate suit anywhere in the world against any Third Party who at any time has infringed, or is
suspected of infringing, any Patent Rights, or of using without proper authorization any Know-How,
comprising Alnylam Patent Rights, Alnylam Know-How, Alnylam Collaboration IP or Joint Collaboration
IP.
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(iii)
Requests to Initiate Enforcement Action
. Alnylam will consider in good faith
any request from Cubist to initiate an infringement or other appropriate suit against any Third
Party with respect to a Competitive Infringement in the Territory of Alnylam Patent Rights, Alnylam
Know-How, Alnylam Collaboration IP or Joint Collaboration IP;
provided
,
however
,
that Alnylam shall not be required to initiate any such suit. If, however, Alnylam elects not to
initiate such suit with respect to Alnylam Sequence Specific Patent Rights or Alnylam Sequence
Specific Know-How, or otherwise does not commence suit with respect to Alnylam Sequence Specific
Patent Rights within [**] after Cubists request made under the preceding sentence, Cubist shall
have the right to initiate such suit with respect to the Alnylam Sequence Specific Patent Rights
and to join Alnylam as a party.
(c)
Procedures; Expenses and Recoveries
. The Party having the right to initiate any
infringement suit under Section 8.4(b) above shall have the sole and exclusive right to select
counsel for any such suit and shall pay all expenses of the suit, including attorneys fees and
court costs and reimbursement of the other Partys reasonable out-of-pocket expense in rendering
assistance requested by the initiating Party;
provided
that
with respect to any
such suit, the Parties may mutually agree to jointly bear such costs and expenses, in which case
the allocation of recoveries described below may be adjusted as mutually agreed by the Parties. If
required under applicable Law in order for the initiating Party to initiate or maintain such suit,
or if either Party is unable to initiate or prosecute such suit solely in its own name or it is
otherwise advisable to obtain an effective legal remedy, in each case, the other Party shall join
as a party to the suit and will execute and cause its Affiliates to execute all documents necessary
for the initiating Party to initiate litigation to prosecute and maintain such action. In
addition, at the initiating Partys request, the other Party shall provide reasonable assistance to
the initiating Party in connection with an infringement suit at no charge to the initiating Party
except for reimbursement by the initiating Party of reasonable out-of-pocket expenses incurred in
rendering such assistance. The non-initiating Party shall have the right to participate and be
represented in any such suit by its own counsel at its own expense. If the Parties obtain from a
Third Party, in connection with such suit, any damages, license fees, royalties or other
compensation (including any amount received in settlement of such litigation) in respect of a
Competitive Infringement in the Royalty Territory, such amounts shall be allocated, subject to any
adjustment to such
allocation agreed by the Parties in connection with an agreement to jointly bear the costs and
expenses of the infringement action as described above, as follows:
(i) first, to reimburse each Party for all expenses of the suit incurred by such Party,
including attorneys fees and disbursements, court costs and other litigation expenses;
(ii) second, [**] percent ([**]%) of the balance to be paid to the Party initiating the suit;
and
(iii) third, the remainder to be paid to the other Party.
With respect to any such suit in the Profit-Share Territory, any damages, license fees,
royalties or other compensation (including any amount received in settlement of such litigation) in
respect of a Competitive Infringement in the Profit-Share Territory, shall [**].
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Section 8.5
Claimed Infringement; Third Party Challenges to Patent Rights
. If a
Party (a) becomes aware of any claim that the Development, Manufacture or Commercialization of
Licensed Product in the Territory infringes the Patent Rights of any Third Party or (b) receives
any notices regarding or becomes party to any Action in which a Third Party challenges or denies
the validity or enforceability of any Patent Rights licensed to the other Party hereunder, or any
claim thereof (i) Controlled by such Party in the Profit-Share Territory, (ii) Covering Licensed
Product, (iii) specific to Licensed Product in the Field and (iv) not broadly applicable to RNAi
Products, such Party shall promptly notify the other Party. With respect to any matter described
in the foregoing clause (a), in any such instance, the Parties shall cooperate and shall mutually
agree upon an appropriate course of action, which may include settlement of such claim. Each Party
shall have an equal right to participate in any settlement discussions that are held with such
Third Parties. If there is a dispute between the Parties as to whether or not Third Party Patent
Rights at issue in such matter described in the foregoing clause (a) Cover Licensed Product, the
Parties agree to select an independent patent counsel to decide whether or not the subject Third
Party Patent Rights Cover Licensed Product. The Parties agree that if such patent counsel
determines that such Third Party Patent Rights Cover Licensed Product, they will accept such
determination for purposes of Sections 7.6 and 7.7. If the decision is that such Third Party
Patent Rights do not Cover Licensed Product, either Party may still obtain a license, but shall be
solely responsible for any payment obligations to the Third Party. With respect to any matter
described in the foregoing clause (b), the Parties shall cooperate and shall mutually agree upon an
appropriate course of action, and the Party responsible for filing, prosecuting and maintaining
such Patent Rights pursuant to Section 8.3 shall have responsibility for defending the
patentability, validity and/or enforceability of such Patent Rights in such Action. The reasonable
out-of-pocket costs incurred by the defending Party or any of its Related Parties with respect to
such Action described in the foregoing clause (b) [**]. For the avoidance of doubt, the costs
incurred by a defending Party or any of its Related Parties with respect to an Action of the kind
described in the foregoing clause (b), but with respect to Patent Rights outside the Profit-Share
Territory, [**];
provided
that
, if such matter arises in the context of an Action
brought by a Party pursuant to Section 8.4, the costs of such Action shall be borne as provided in
Section 8.4. Each Party shall also provide to the other Party copies of any other notices it
receives or has received
from Third Parties regarding any patent nullity actions, any declaratory judgment actions and
any alleged infringement or misappropriation of Third Party intellectual property relating to the
Development, Manufacture or Commercialization of Licensed Product in the Territory. Such notices
shall be provided promptly, but in no event after more than [**] after receipt thereof.
Section 8.6
Third Party Technology
.
(a) If after the Effective Date, (i) Alnylam or any of its Affiliates acquires from a Third
Party Know-How or Patent Rights that would fall within the definition of Alnylam Technology but for
the proviso of Section 1.24 and that is subject to payment obligations to such Third Party, or (ii)
Cubist or any of its Affiliates acquires from a Third Party Know-How or Patent Rights within the
definition of Cubist Technology but for the proviso of Section 1.24 and that is subject to payment
obligations to such Third Party (collectively,
Third Party Technology
) then the Party
acquiring the Third Party Technology shall promptly so notify the other Party and provide to such
other Party a copy of the agreement and a written description of the payment obligations that would
be allocated to [**] in the Royalty Territory, or [**], or paid by Alnylam under Section 3.2(d)
with respect to the Development, Manufacture or
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Commercialization of Licensed Product for Asia (as
the case may be), in each case which allocation shall be determined [**].
(b) Cubist may elect to include Third Party Technology acquired by Alnylam or any of its
Affiliates in the rights and licenses granted to Cubist under Section 3.1 with respect to the
Development, Manufacture or Commercialization of Licensed Products in the Royalty Territory by
providing written notice to Alnylam of such election prior to Commercialization of such Licensed
Product in the Royalty Territory, and, in such event, such Third Party Technology shall be deemed
included within the definition of Alnylam Patent Rights, Alnylam Know-How and Alnylam Technology,
as applicable, and the agreement with the Third Party under which such Third Party Technology was
acquired shall be included in the definition of Alnylam In-License, in each case solely with
respect to the Royalty Territory. Notwithstanding anything in this Agreement to the contrary,
neither Alnylam nor any of its Affiliates shall enter into any agreement with any Third Party or
take any other action that would prevent such Third Party Technology acquired by Alnylam or any of
its Affiliates from becoming Alnylam Technology upon Cubists election in accordance with this
Section 8.6(b) or the election of the JSC or JCT under Section 8.6(c).
(c) The JSC or JCT may elect to include Third Party Technology acquired by Alnylam or any of
its Affiliates within the rights and licenses granted to Cubist pursuant to Section 3.1, or by
Cubist or any of its Affiliates within the rights and licenses granted to Alnylam pursuant to
Section 3.2, in each case with respect to Development, Manufacture or Commercialization of Licensed
Products in the Profit-Share Territory by providing written notice to Alnylam or Cubist (as the
case may be) of such election prior to the Commercialization of such Licensed Product in the
Profit-Share Territory, and, in such event, such Third Party Technology shall be deemed included in
the definition of Alnylam Patent Rights, Alnylam Know-How and Alnylam Technology, or Cubist Patent
Rights, Cubist Know-How and Cubist Technology, as the case may be, and the agreement with the Third
Party under which such Third
Party Technology was acquired shall be included in the definition of Alnylam In-License or
Cubist In-License (as applicable), in each case solely with respect to the Profit-Share Territory.
(d) Alnylam may elect to include Third Party Technology acquired by Cubist or any of its
Affiliates in the rights and licenses granted to Alnylam pursuant to Section 3.2 with respect to
(i) the Development, Manufacture or Commercialization of Licensed Products for Asia, (ii) the
fulfillment of its obligations under this Agreement with respect to the Collaboration, and (iii)
the Manufacture of Licensed Products for the Royalty Territory by providing written notice to
Cubist of such election prior to the Commercialization of such Licensed Product in Asia, and, in
such event, such Third Party Technology shall be deemed included within the definition of Cubist
Patent Rights, Cubist Know-How and Cubist Technology, as the case may be, and the agreement with
the Third Party under which such Third Party Technology was acquired shall be included in the
definition of Cubist In-License. Neither Cubist nor any of its Affiliates shall enter into any
agreement with any Third Party or take any other action that would prevent Third Party Technology
acquired by Cubist or any of its Affiliates from becoming Cubist Technology, upon Alnylams
election in accordance with this Section 8.6(d) or the election of the JSC or JCT under Section
8.6(c).
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Section 8.7
Patent Marking
. Each Party agrees to comply with the patent marking
statutes in each country in which Licensed Product is sold by such Party or its Related Parties.
Section 8.8
Trademarks
.
(a) Each Party and its Affiliates shall retain all right, title and interest in and to its and
their respective corporate names and logos.
(b) Cubist will develop and propose, and the JCT shall review and comment on, one or more
Product Trademark(s) for use by Cubist and its Related Parties throughout the Territory. Such
Product Trademark(s) considered by the JCT may, with Alnylams consent, not to be unreasonably
withheld or delayed, include the Product Trademark(s) developed or used by Alnylam with respect to
Licensed Product in Asia (the
Alnylam Trademarks
). Any Product Trademark(s) (other than
the Alnylam Trademarks) that are used by Cubist to promote and sell Licensed Product in the
Territory are hereinafter referred to as the
Cubist Trademarks
. Alnylam (or its Related
Parties, as appropriate) shall own all rights to Alnylam Trademarks, and all goodwill associated
therewith, throughout the world. Cubist (or its Related Parties, as appropriate) shall own all
rights to Cubist Trademarks and all goodwill associated therewith, throughout the world. Alnylam
shall also own rights to any Internet domain names incorporating the applicable Alnylam Trademarks
or any variation or part of such Alnylam Trademarks used as its URL address or any part of such
address; and Cubist shall also own rights to any Internet domain names incorporating the applicable
Cubist Trademarks or any variation or part of such Cubist Trademarks used as its URL address or any
part of such address.
(c) If Alnylam Trademarks are used to promote and sell Licensed Product in the Territory, then
the following provisions shall apply: Alnylam shall grant Cubist an exclusive license to use such
Alnylam Trademarks to Commercialize Licensed Product in the Territory.
Cubist agrees that the quality of Licensed Product and the Manufacture and Commercialization
thereof shall be consistent with the quality standards applied by Alnylam thereto. In addition,
Cubist shall comply strictly with Alnylams trademark style and usage standards that Alnylam
communicates to Cubist from time to time with respect to the Alnylam Trademarks. Cubist shall, at
[**] expense in the Royalty Territory and subject to [**] for the Profit-Share Territory, at the
request of Alnylam from time to time, submit to Alnylam for approval a reasonable number of
production samples of Licensed Product and related packaging materials. If Alnylam reasonably
objects to the quality of Licensed Product or the usage of the Alnylam Trademarks in connection
with any sample, it shall give written notice of such objection to Cubist within [**] after receipt
by Alnylam of the sample, specifying the way in which such usage of the Alnylam Trademarks fails to
meet the style, usage or quality standards for Licensed Product set forth in the second and third
sentences of this Section 8.8(c), and Cubist shall [**] cease sale and distribution of Licensed
Product. If Cubist wishes to continue to distribute and sell Licensed Product, it must remedy the
failure and submit further samples to Alnylam for approval.
(d) If Alnylam Trademarks are used to promote and sell Licensed Product in the Territory, then
Alnylam will use Diligent Efforts to establish, maintain and enforce such Alnylam Trademarks in the
applicable countries in the Territory. Cubist shall be responsible for [**] percent ([**]%) of the
costs of such efforts in the Royalty Territory and Cubist shall reimburse Alnylam for [**] such
costs incurred by Alnylam within [**] after receiving any
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invoice from Alnylam for such costs.
[**] in the costs of such efforts in the Profit-Share Territory and Cubist shall reimburse Alnylam
for [**] percent ([**]%) of such costs incurred
by Alnylam within [**] after receiving any invoice
from Alnylam for such share of such costs. Cubist will use Diligent Efforts to establish, maintain
and enforce the Cubist Trademarks in the Territory, at its expense, subject to the applicable cost
sharing provisions for the Profit-Share Territory.
(e) If either Party becomes aware of any infringement of any Product Trademark by a Third
Party, such Party shall promptly notify the other Party and the Parties shall consult with each
other and jointly determine the best way to prevent such infringement, including by the institution
of legal proceedings against such Third Party.
ARTICLE IX
CONFIDENTIALITY AND PUBLICITY
Section 9.1
Confidential Information
. During the Term and for a period of [**] after
any termination or expiration hereof, each Party agrees to keep in confidence and not to disclose
to any Third Party, or use for any purpose, except pursuant to, and in order to carry out, the
terms and objectives of this Agreement, any Confidential Information of the other Party. The terms
of this Agreement shall be considered Confidential Information of both Parties hereunder. The
restrictions on the disclosure and use of Confidential Information set forth in the first sentence
of this Section 9.1 shall not apply to any Confidential Information that:
(a) was known by the receiving Party prior to disclosure by the disclosing Party hereunder (as
evidenced by the receiving Partys written records or other competent evidence);
(b) is or becomes part of the public domain through no fault of the receiving Party;
(c) is disclosed to the receiving Party by a Third Party having a legal right to make such
disclosure without violating any confidentiality or non-use obligation that such Third Party has to
the disclosing Party and provided such Third Party is not disclosing such information on behalf of
the disclosing Party; or
(d) is independently developed by personnel of the receiving Party who did not have access to
the Confidential Information (as evidenced by the receiving Partys written records or other
competent evidence).
In addition, if either Party is required to disclose Confidential Information of the other
Party by regulation, law or legal process, including by the rules or regulations of the United
States Securities and Exchange Commission or similar regulatory agency in a country other than the
United States or of any stock exchange or Nasdaq, such Party shall provide prior written notice and
a copy of such intended disclosure to such other Party if possible under the circumstances, shall
consider in good faith the other Partys comments, and shall disclose only such Confidential
Information of such other Party as is required to be disclosed. In addition, either Party may
disclose to bona fide potential investors, lenders, potential acquirors/acquirees,
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and potential
and existing collaborators, and to such Partys consultants and advisors, the existence and terms
of this Agreement to the extent necessary in connection with a proposed equity or debt financing of
such Party, or a proposed acquisition or business combination or transaction, so long as such
recipients are bound in writing to maintain the confidentiality of such information in accordance
with the terms of this Agreement.
Section 9.2
Employee, Consultant and Advisor Obligations and Disclosure to Regulatory
Authorities
. Each Party agrees that it and its Affiliates shall provide or permit access to
Confidential Information received from the other Party and such Partys Affiliates and
representatives only to the receiving Partys employees, consultants, advisors and permitted
subcontractors, Sublicensees, Alnylams Asian Partner and sub-distributors, and to the employees,
consultants, advisors and permitted subcontractors, Sublicensees and sub-distributors of the
receiving Partys Affiliates, who in such Partys reasonable judgment have a need to know such
Confidential Information to assist the receiving Party with the activities contemplated by this
Agreement and who are subject to obligations of confidentiality and non-use with respect to such
Confidential Information similar to the obligations of confidentiality and non-use of the receiving
Party pursuant to Section 9.1;
provided
that
Alnylam and Cubist shall each remain
responsible for any failure by its Affiliates, and its and its Affiliates respective employees,
consultants, advisors and permitted subcontractors, Sublicensees and sub-distributors, and, in the
case of Alnylam, Alnylams Asian Partner, to treat such Confidential Information as required under
Section 9.1 (as if such Affiliates, employees, consultants, advisors and permitted subcontractors,
Sublicensees and sub-
distributors were Parties directly bound to the requirements of Section 9.1). Each Party may
also disclose Confidential Information of the other Party to Regulatory Authorities, but solely in
connection with the activities contemplated by this Agreement, including activities by Alnylam or
its Asian Partner with respect to the Development, Manufacture or Commercialization of Licensed
Products for Asia.
Section 9.3
Certain Disclosures by Alnylam or Cubist
. Notwithstanding anything in
this Agreement to the contrary, but subject to the last paragraph of Section 9.1, Alnylam and
Cubist agree that, except as contemplated by the Development Plan or as otherwise directed by the
JSC, neither Alnylam or any of its Affiliates nor Cubist or any of its Affiliates shall disclose
their own Confidential Information that is specific to Licensed Product other than to any of their
respective Related Parties;,
provided
that either Party or any of its Affiliates may
disclose its own Confidential Information that is specific to Licensed Product (a) to the same
extent as it is allowed to disclose the other Partys Confidential Information under Section 9.2 or
(b) in connection with Development, Manufacture or Commercialization of Licensed Product in the
Territory or Asia.
Section 9.4
Publicity
. Upon the execution of this Agreement, the Parties shall issue
a joint press release regarding the subject matter of this Agreement in the form attached as
Exhibit I
. After such initial joint press release, neither Party shall issue a press
release or make a public announcement relating to Licensed Product or this Agreement without the
prior written approval of the other Party, which approval shall not be unreasonably withheld or
delayed, except that (a) a Party may issue such press release or public announcement if the
contents of such press release or public announcement have previously been made public other than
through a breach of this Agreement by the issuing Party and (b) a Party may issue such a press
release or public announcement if required by applicable Law, including by the rules or regulations
of the United
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States Securities and Exchange Commission or similar regulatory agency in a country
other than the United States or of any stock exchange or Nasdaq, in each case under clause (a) or
(b) after first notifying the other Party of such planned press release or public announcement at
least [**] Business Days in advance of issuing such press release or making such public
announcement (or, with respect to press releases and public announcements made pursuant to the
foregoing clause (b), with as much advance notice as possible under the circumstances if it is not
possible to provide notice at least [**] Business Days in advance) for the sole purpose of allowing
the other Party to review the proposed press release or public announcement for the inclusion of
Confidential Information or the use of its name;
provided
that
the Party subject to
the requirement shall include in such press release or public announcement made pursuant to the
foregoing clause (b) only such information relating to Licensed Product or this Agreement as is
required by such applicable Law.
Section 9.5
Publications
. Subject to the restrictions provided below, the JSC shall
determine the publication strategy for the Territory. In the event either Party is permitted by
the JSC to publish or present the results of Development carried out on Licensed Product, such
publication or presentation shall be subject to the prior review by the other Party for
patentability and protection of such other Partys Confidential Information. Each Party shall
provide to the other
Party the opportunity to review any proposed abstracts, manuscripts or summaries of
presentations that cover the results of Development of the Product. Each Party shall designate a
person or persons who shall be responsible for reviewing such publications. Such designated person
shall respond in writing promptly and in no event later than [**] days after receipt of the
proposed material with either approval of the proposed material or a specific statement of concern,
based upon either the need to seek patent protection or concern regarding competitive disadvantage
arising from the proposal. In the event of concern, the submitting Party agrees not to submit such
publication or to make such presentation that contains such information until the other Party is
given a reasonable period of time (not to exceed [**] days) to seek patent protection for any
material in such publication or presentation that it believes is patentable or to resolve any other
issues, and the submitting Party shall remove from such proposed publication any Confidential
Information of the other Party as requested by such other Party. With respect to any proposed
abstracts, manuscripts or summaries of presentations by investigators or other Third Parties,
including Related Parties such materials shall be subject to review under this Section 9.5 to the
extent that Alnylam or Cubist, as the case may be, has the right to do so.
Section 9.6
Asian Partner
. Alnylam shall use Diligent Efforts to amend its agreement
with its Asian Partner such that any press releases and publications related to Licensed Product by
such Asian Partner are subject to the review and approval procedures set forth in Sections 9.4 and
9.5.
Section 9.7
Coordination with Alnylams Asian Partner
. Alnylam and Cubist shall use
Diligent Efforts to meet (in-person or via video conference or teleconference) with representatives
of Alnylams Asian Partner to discuss and coordinate their respective activities with respect to
Licensed Products, including: (a) adverse event reporting, (b) publications and press releases,
(c) sharing of data and Confidential Information, (d) Manufacturing and (e) review of Development
activities.
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ARTICLE X
REPRESENTATIONS AND WARRANTIES; CERTAIN COVENANTS;
INDEMNIFICATION
Section 10.1
Exclusivity Covenant
. During the Term, neither Party nor its Affiliates
shall, outside this Agreement, directly or indirectly, conduct Development of, Manufacture or
Commercialize a Directly Competitive Product, anywhere in the Territory or grant rights to an Third
Party to do any of the foregoing. If either Party or its Affiliates would violate the provisions
of this Section 10.1 as a result of a merger, acquisition or combination with a Third Party, (a)
[**] with the understanding that the foregoing right shall in no way diminish a Partys obligations
to use Diligent Efforts to Develop, Manufacture or Commercialize Licensed Product under this
Agreement.
Section 10.2
Representations of Authority
. Alnylam and Cubist each represents and
warrants to the other Party that, as of the Effective Date, it has full right, power
and authority to enter into this Agreement and to perform its respective obligations under
this Agreement and that it has the right to grant to the other the licenses and sublicenses granted
pursuant to this Agreement.
Section 10.3
Consents
. Alnylam and Cubist each represents and warrants to the other
Party that, except for any Regulatory Approvals, pricing or reimbursement approvals, manufacturing
approvals or similar approvals necessary for the Development, Manufacture or Commercialization of
the Licensed Product, all necessary consents, approvals and authorizations of all Government
Authorities and other Persons required to be obtained by it as of the Effective Date in connection
with the execution, delivery and performance of this Agreement have been obtained by the Effective
Date.
Section 10.4
No Conflict
. Alnylam and Cubist each represents and warrants to the
other Party that, notwithstanding anything to the contrary in this Agreement, the execution and
delivery of this Agreement by such Party, the performance of such Partys obligations hereunder and
the licenses and sublicenses to be granted by such Party pursuant to this Agreement (a) do not
conflict with or violate any requirement of applicable Laws existing as of the Effective Date and
applicable to such Party and (b) do not conflict with, violate, breach or constitute a default
under any contractual obligations of such Party or any of its Affiliates existing as of the
Effective Date. Each Party shall comply with all Laws applicable to the Development, Manufacture
and Commercialization of the Product, including applicable Drug Regulation Laws, Clinical
Investigation Laws and Health Care Laws.
Section 10.5
Enforceability
. Alnylam and Cubist each represents and warrants to the
other Party that, as of the Effective Date, this Agreement is a legal and valid obligation binding
upon it and is enforceable against it in accordance with its terms.
Section 10.6
Sales Representatives
.
(a) Cubist represents and warrants to Alnylam that it will use Diligent Efforts to cause its
Sales Representatives in the Territory not to make statements, claims or undertakings
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to any Person
with whom they discuss or promote Licensed Product that are not consistent with, and not to provide
or use any labeling, literature, or other materials other than those consistent with, Promotional
Materials provided to the JCT for review and comment in advance of use in the Territory. Cubist
shall not, and shall use Diligent Efforts to cause its Sales Representatives not to, make any
representation, statement, warranty or guaranty with respect to Licensed Product that is not
consistent with the applicable, current package insert of prescribing information or other
documentation accompanying or describing Licensed Product, including Cubists standard limited
warranty and disclaimers, if any.
(b) Cubist represents and warrants to Alnylam that it shall use Diligent Efforts to cause its
Sales Representatives to comply with the applicable Laws and guidelines and related to the
performance of its obligations hereunder, including the Federal Food, Drug and Cosmetics
Act, the Prescription Drug Marketing Act of 1987, the Federal and State Anti-Kickback Statutes
and all applicable regulations thereunder, and AMA Guidelines on Gifts to Physicians from Industry
and PhRMA Guidelines, and all relevant EMEA regulations, authorizations and local laws regarding
advertisement, sale and promotion of pharmaceutical products as well as any relevant code of
practice, in each case as amended from time to time, and to comply with the policies in Cubists
compliance training materials for the Territory.
Section 10.7
Additional Representations and Warranties of Alnylam
. Alnylam
represents and warrants to Cubist that, except as set forth on
Schedule 10.7
, as of the
Effective Date:
(a)
Exhibit A
sets forth a complete and accurate list of (i) the Alnylam Patent Rights
owned by Alnylam, and (ii) to the Knowledge of Alnylam after due inquiry, the Alnylam Patent
Rights in-licensed by Alnylam, in each case as of the Effective Date.
(b) Alnylam has not granted, and during the Term will not grant, rights to any Third Party
under the Alnylam Technology that conflict with the rights granted to Cubist hereunder and such
Alnylam Technology is held free and clear of any liens, security interests and other similar
encumbrances.
(c) Alnylam has not received any written notice of (i) any claim that any patent or trade
secret right owned or controlled by a Third Party would be infringed or misappropriated by the
manufacture, use, sale, offer for sale or importation of Licensed Products in the Field in the
Territory, or (ii) any threatened claims or litigation seeking to invalidate or otherwise challenge
the Alnylam Patent Rights owned by Alnylam or Alnylams rights therein.
(d) To the Knowledge of Alnylam after due inquiry, none of the Alnylam Patent Rights owned by
Alnylam are subject to any pending re-examination, opposition, interference or litigation
proceedings.
(e) Alnylam has provided Cubist with access to (i) all documents requested by Cubist and in
Alnylams possession or control relating to the Alnylam Patent Rights and Alnylam Know-How and (ii)
all other information in Alnylams possession or control that, in Alnylams reasonable judgment, is
materially adverse to Cubists freedom to operate under the Alnylam Patent Rights or to use Alnylam
Know-How in the Field in the Territory.
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(f) To the Knowledge of Alnylam after due inquiry, there have been (i) no material
inventorship or ownership challenges with respect to any of the Alnylam Patent Rights or Alnylam
Know-How and (ii) no inventorship or ownership challenges of any kind with respect to the Alnylam
Sequence Specific Patent Rights.
(g)
Exhibit F
sets forth a true and complete list of all material agreements,
including license agreements, clinical trial agreements and manufacturing or supply agreements, to
which Alnylam is a party and which relate to Licensed Product in the Territory. Alnylam is not in
breach under any of the agreements listed on
Exhibit F
, nor, to the Knowledge of Alnylam,
is any other party thereto. Alnylam has not received any notice of breach under any of the
agreements listed in
Exhibit F
. Alnylam has previously provided Cubist with access to true
and
complete copies (or, in the case of clinical trial agreements, a representative form of
clinical trial agreement) of each of the agreements listed on
Exhibit F
. The Alnylam
In-License Agreements are in full force and effect and Alnylam will maintain the Alnylam In-License
Agreements in full force and effect during the Term, will perform all of its obligations thereunder
and will not amend any such agreement in a manner that would adversely affect the rights and
obligations of Cubist under this Agreement. Alnylam will notify Cubist promptly upon receiving any
notice of material breach from a party thereunder.
(h) To the Knowledge of Alnylam, no Third Party is infringing any claims of any issued patents
encompassed within the Alnylam Patent Rights by offering for sale or selling any Directly
Competitive Product in the Territory.
(i) The Alnylam Patent Rights in the Territory that are pending patent applications as of the
Effective Date are being diligently prosecuted at the respective patent offices, and, to the
Knowledge of Alnylam after due inquiry, the Alnylam Patent Rights in the Territory that are granted
have been maintained properly and correctly and all applicable fees have been paid on or before the
due date for payment, in each case subject to Alnylams reasonable business judgment regarding the
management of such patent portfolio.
(j) To the Knowledge of Alnylam after due inquiry, the Development and Manufacture of Licensed
Product in the Territory to date has been conducted by Alnylam and its Affiliates and its
subcontractors, in compliance (in all material respects) with all applicable Laws. To the
Knowledge of Alnylam after due inquiry, neither Alnylam nor any of its Affiliates, nor any of their
respective officers, employees or agents, has made an untrue statement of a material fact or
fraudulent statement to any Regulatory Authority or failed to disclose a material fact required to
be disclosed to any Regulatory Authority.
(k) Except as would not have a material adverse effect on the Development, Manufacture or
Commercialization of Licensed Products or Cubists rights under this Agreement, all testing and
research of Licensed Products (excluding the manufacture of materials used in clinical trials) by
Alnylam and its Affiliates have been conducted in compliance with Good Clinical Practices and Good
Laboratory Practices applicable and required at the time such activity was performed and all
materials used in clinical trials of Licensed Products by Alnylam and its Affiliates have been
Manufactured in compliance with Good Manufacturing Practices applicable at the time such activity
was performed.
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(l) To the Knowledge of Alnylam after due inquiry, there is no material matter concerning the
safety or efficacy of any Licensed Product as to which Alnylam has not provided Cubist with access
to all material information. Alnylam has disclosed to Cubist or made available to Cubist for
review all relevant data and documentation in its control that is material in order to assess the
safety and efficacy of Licensed Product.
(m) There are no inquiries, actions or other proceedings pending before or, to the Knowledge
of Alnylam, threatened by any Regulatory Authority with respect to Licensed Product or any facility
where a Licensed Product is Manufactured, and neither Alnylam nor its Affiliates have received
written notice threatening any such inquiry, action or other proceeding.
(n) Except for disclosures (i) to Third Parties for evaluation purposes subject to
confidentiality obligations, (ii) to Alnylams Asian Partner, (iii) to Third Party contractors
providing research or development services to Alnylam and subject to confidentiality obligations,
or (iv) made in Alnylam Patent Rights, Alnylam represents that it has not licensed or disclosed
Alnylam Sequence Specific Know-How to any Third Party.
(o) Alnylam has not granted any right or license to Isis Pharmaceuticals, Inc. to Develop or
Commercialize Licensed Products.
Section 10.8
Cubist Representation Regarding Cubist In-Licenses
. Cubist represents
that there are no Cubist In-Licenses as of the Effective Date.
Section 10.9
No Warranties
. EXCEPT AS OTHERWISE EXPRESSLY SET FORTH HEREIN, NEITHER
PARTY MAKES ANY REPRESENTATION OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, TO
THE OTHER PARTY, AND EACH PARTY HEREBY DISCLAIMS ALL IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS
FOR A PARTICULAR PURPOSE AND NONINFRINGEMENT WITH RESPECT TO LICENSED PRODUCT. EACH PARTY HEREBY
DISCLAIMS ANY REPRESENTATION OR WARRANTY THAT THE DEVELOPMENT, MANUFACTURE AND COMMERCIALIZATION OF
THE LICENSED PRODUCT PURSUANT TO THIS AGREEMENT WILL BE SUCCESSFUL OR THAT ANY PARTICULAR SALES
LEVEL WITH RESPECT TO THE LICENSED PRODUCT WILL BE ACHIEVED.
Section 10.10
No Debarment
. Neither Party nor any of its Affiliates has been
debarred or is subject to debarment and neither Party nor any of its Affiliates will use in any
capacity, in connection with the Development, Manufacture or Commercialization of the Product, any
Person who has been debarred pursuant to Section 306 of the United States Federal Food, Drug, and
Cosmetic Act, or who is the subject of a conviction described in such section. Each Party agrees
to inform the other Party in writing immediately upon becoming aware that any Person who is
performing services hereunder is debarred or is the subject of a conviction described in Section
306, or if any action, suit, claim, investigation or legal or administrative proceeding is pending
or, to the best of such Partys knowledge, is threatened, relating to the debarment or conviction
of such Party or any Person used in any capacity by such Party or any of its Affiliates in
connection with the Development, Manufacture or Commercialization of Licensed Product.
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Section 10.11
Indemnification
.
(a)
General Indemnification by Cubist
. Cubist shall indemnify, hold harmless, and
defend Alnylam, its Affiliates, and their respective directors, officers, employees and agents (the
Alnylam Indemnitees
) from and against any and all Third Party claims, suits, losses,
liabilities, damages, costs, fees and expenses (including reasonable attorneys fees)
(collectively,
Losses
) arising out of or resulting from, directly or indirectly, (i) any
breach of, or inaccuracy in, any representation or warranty made by Cubist in this Agreement, or
any breach or violation of any covenant or agreement of Cubist in or pursuant to this Agreement, or
(ii) the negligence or willful misconduct by or of Cubist, its Affiliates and their respective
Sublicensees, and their respective directors, officers, employees and agents in the performance of
Cubists obligations under this Agreement. Cubist shall have no obligation to indemnify the Alnylam
Indemnitees to the extent that the Losses in the Territory that arise out of or result from,
directly or indirectly, any breach of, or inaccuracy in, any representation or warranty made by
Alnylam in this Agreement, any breach or violation of any covenant or agreement of Alnylam in or
pursuant to this Agreement, the negligence or willful misconduct by or of any of the Alnylam
Indemnitees or any Loss to the extent arising from or related to the Development, Manufacture,
Commercialization, or use of Licensed Products outside the Field or for Asia by Alnylam or any of
its Related Parties.
(b)
General Indemnification by Alnylam
. Alnylam shall indemnify, hold harmless, and
defend Cubist, its Affiliates and their respective directors, officers, employees and agents (the
Cubist Indemnitees
) from and against any and all Losses arising out of or resulting from,
directly or indirectly, (i) any breach of, or inaccuracy in, any representation or warranty made by
Alnylam in this Agreement, or any breach or violation of any covenant or agreement of Alnylam in or
pursuant to this Agreement, (ii) the negligence or willful misconduct by or of Alnylam, its
Affiliates and their respective Sublicensees, and their respective directors, officers, employees
and agents in the performance of Alnylams obligations under this Agreement or (iii) the
Development, Manufacture, Commercialization, or use of Licensed Products outside the Field or for
Asia by Alnylam or any of its Related Parties. Alnylam shall have no obligation to indemnify the
Cubist Indemnitees to the extent that the Losses arise out of or result from, directly or
indirectly, any breach of, or inaccuracy in, any representation or warranty made by Cubist in this
Agreement, or any breach or violation of any covenant or agreement of Cubist in or pursuant to this
Agreement, or the negligence or willful misconduct by or of any of the Cubist Indemnitees.
(c)
Product Liability
.
(i) Cubist shall indemnify and hold harmless the Alnylam Indemnitees from, against and in
respect of any and all Losses arising out of Third Party product liability claims incurred or
suffered by the Alnylam Indemnitees, or any of them, directly or indirectly relating to Licensed
Product used or sold in the Territory under this Agreement and resulting from or arising out of the
negligence, willful misconduct, or breach of this Agreement of or by Cubist or any of the other
Cubist Indemnitees, except to the extent caused by the negligence, willful misconduct or breach of
this Agreement of or by Alnylam or any of the other Alnylam Indemnitees.
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(ii) Alnylam shall indemnify and hold harmless the Cubist Indemnitees from, against and in
respect of any and all Losses arising out of Third Party product liability claims incurred or
suffered by the Cubist Indemnitees, or any of them, directly or indirectly relating to Licensed
Product and resulting from or arising out of the negligence, willful misconduct, breach of this
Agreement of or by Alnylam or any of the other Alnylam Indemnitees, or the Development,
Manufacture, Commercialization, or use of Licensed Products outside the Field or for Asia by
Alnylam or any of its Related Parties, except to the extent caused by the negligence, willful
misconduct or breach of this Agreement of or by Cubist or any of the other Cubist Indemnitees and
related to the Territory.
(iii) Any Losses arising out of Third Party product liability claims (other than such claims
entitled to indemnification under Section 10.10(c)(i) or 10.10(c)(ii)) shall be (A) [**].
(d)
Indemnification Procedure
. In the event of any such claim against any Cubist
Indemnitee or Alnylam Indemnitee (individually, an
Indemnitee
), the indemnified Party
shall promptly notify the other Party in writing of the claim and the indemnifying Party shall
manage and control, at its sole expense, the defense of the claim and its settlement. The
Indemnitee shall cooperate with the indemnifying Party and may, at its option and expense, be
represented in any such action or proceeding. The indemnifying Party shall not be liable for any
settlements, litigation costs or expenses incurred by any Indemnitee without the indemnifying
Partys written authorization. Notwithstanding the foregoing, if the indemnifying Party believes
that any of the exceptions to its obligation of indemnification of the Indemnitees set forth in
Section 10.11(a), 10.11(b) or 10.11(c) may apply, the indemnifying Party shall promptly notify the
Indemnitees, which shall then have the right to be represented in any such action or proceeding by
separate counsel at their expense;
provided
that
the indemnifying Party shall be
responsible for payment of such expenses if the Indemnitees are ultimately determined to be
entitled to indemnification from the indemnifying Party.
Section 10.12
Limitation of Liability
. NEITHER PARTY HERETO WILL BE LIABLE FOR
SPECIAL, INCIDENTAL, CONSEQUENTIAL OR PUNITIVE DAMAGES ARISING OUT OF THIS AGREEMENT OR THE
EXERCISE OF ITS RIGHTS HEREUNDER, INCLUDING LOST PROFITS ARISING FROM OR RELATING TO ANY BREACH OF
THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES, EXCEPT AS A RESULT OF A PARTYS WILLFUL
MISCONDUCT OR A MATERIAL BREACH OF THE CONFIDENTIALITY AND NON-USE OBLIGATIONS IN ARTICLE IX.
NOTHING IN THIS SECTION 10.12 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR
OBLIGATIONS OF EITHER PARTY.
Section 10.13
Insurance
. Each Party shall maintain insurance during the Term and
for a period of at least [**] years after the last commercial sale of a Licensed Product in the
Field in the Territory under this Agreement, with a reputable, solvent insurer in an amount
appropriate for its business and products of the type that are the subject of this Agreement, and
for its obligations under this Agreement. Specifically, each Party shall maintain product and
clinical trial liability insurance of at least $[**] per occurrence on a worldwide basis. Each
Party will further ensure compliance with all foreign local clinical trial liability insurance
requirements that
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may apply with respect to Licensed Product. Upon request, each Party shall provide the other
Party with evidence of the existence and maintenance of such insurance coverage.
ARTICLE XI
TERM AND TERMINATION
Section 11.1
Term
. Unless terminated earlier in accordance with this Article XI,
this Agreement shall remain in force for the period commencing on the Effective Date and expiring,
on a Licensed Product-by-Licensed Product and country-by-country basis either (a) with respect to
any country in the Royalty Territory, upon expiration of the applicable Royalty Term, or (b) with
respect to the Profit-Share Territory until this Agreement is terminated in accordance with
Section 11.2(a), (the
Term
). Upon expiration of the Term, the licenses granted to Cubist
under Article III in the Royalty Territory shall convert to perpetual, exclusive fully paid-up,
non-royalty-bearing licenses.
Section 11.2
Termination Rights
.
(a)
Termination for Convenience
. Cubist shall have the right to terminate this
Agreement at any time after the Effective Date (i) on three (3) months prior written notice to
Alnylam if such notice is given prior to the acceptance for filing of the first application for
Regulatory Approval of a Licensed Product in a country or regulatory jurisdiction in the Territory,
or (ii) on nine (9) months prior written notice if such notice is given after the acceptance for
filing of the first application for Regulatory Approval of a Licensed Product in a country or
regulatory jurisdiction in the Territory.
(b)
Termination for Cause
. This Agreement may be terminated at any time during the
Term upon written notice by either Party if the other Party is in material breach of a material
obligation hereunder and has not cured such breach within [**] in the case of a payment breach or
[**] in the case of all other material breaches of material obligations, after written notice of
the breach.
(c)
Challenges of Patent Rights
. If a Party or any of its Related Parties (the
Challenging Party
) (i) commences or participates in any action or proceeding (including
any patent opposition or re-examination proceeding), or otherwise asserts any claim, challenging or
denying the validity or enforceability of any of the Patent Rights of the other Party (i.e., the
Patent Rights included in the Alnylam Technology or the Patent Rights included in the Cubist
Technology, as the case may be), or any claim thereof, or (ii) actively assists any other Person
bringing or prosecuting any action or proceeding (including any patent opposition or re-examination
proceeding) challenging or denying the validity or enforceability of any of such other Partys
Patent Rights or any claim thereof, then the other Party (the
Non-Challenging Party
) will
have the right, in its sole discretion, to give notice to the Challenging Party that the licenses
granted to the Challenging Party with respect to all or any portion of the Non-Challenging Partys
Patent Rights included in the Alnylam Technology or the Cubist Technology (as the case may be) will
terminate [**] after such notice (or such longer period as the Non-Challenging Party may designate
in such notice), and, unless the Challenging Party withdraws or causes to be withdrawn all such
challenge(s) within such [**] period (or such longer period as is
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designated by the Non-Challenging Party), such license rights will so terminate. The
foregoing provisions of this Section 11.2(c) notwithstanding, if (x) Alnylam is the Non-Challenging
Party, (y) Alnylam does not elect to terminate this Agreement pursuant to this Section 11.2(c), and
(z) the patent challenge is unsuccessful, then (1) [**]. Notwithstanding anything in this Section
11.2(c) to the contrary, a challenge by Cubist as to whether a patent application was filed by
Alnylam in good faith for purposes of the definition of Valid Claim shall not be considered a
challenge for which Alnylam can exercise its rights under this Section 11.2(c).
Section 11.3
Effect of Termination
.
(a)
Termination by Alnylam
. Without limiting any other legal or equitable remedies
that Alnylam may have, if Alnylam terminates this Agreement in accordance with Section 11.2(b) or
11.2(c), then (i) Cubists obligations under Section [**] shall survive for a period of [**] after
the effective date of termination, (ii) Cubist shall, for a period of [**] following the date of
notice of termination, continue to pay [**] percent ([**]%) of [**] and
provided
that
the [**] by Cubist under this clause shall not exceed (A) [**] Dollars ($[**]) if
Alnylam terminated this Agreement after the First Opt-Out Milestone and prior to the Second Opt-Out
Milestone and (B) [**] Dollars ($[**]) if Alnylam terminated this Agreement after the Second
Opt-Out Milestone; (iii) the licenses granted to Alnylam in Section 3.2 shall survive and any
restrictions on sublicensing shall no longer apply, (iv) Cubist shall as promptly as practicable
transfer to Alnylam or Alnylams designee (A) possession and ownership of all governmental or
regulatory correspondence, conversation logs, filings and approvals (including all Regulatory
Approvals and pricing and reimbursement approvals) relating to the Development, Manufacture or
Commercialization of Licensed Product and all Cubist Trademarks then being used in connection with
Licensed Product, other than Cubists corporate trademarks (B) copies of all data, reports, records
and materials, Commercialization Plans, marketing plans, Promotional Materials, and other sales and
marketing related information in Cubists possession or Control to the extent that such data,
reports, records, materials or other information relate to the Development, Manufacture or
Commercialization of Licensed Product, including all non-clinical and clinical data relating to
Licensed Product, and customer lists and customer contact information and all Safety Data and other
adverse event data in Cubists possession or Control;
provided
that
(I) Cubist
shall not be required by this provision to provide any confidential information to Alnylam and (II)
Cubist shall use Diligent Efforts to obtain for Alnylam the right to access all such data, reports,
records, materials, and other sales and marketing related information, and (C) all records and
materials in Cubists possession or Control containing Confidential Information of Alnylam, (v) if
requested by Alnylam, appoint Alnylam as Cubists or Cubists Related Parties agent for all
Licensed Product-related matters involving Regulatory Authorities in the Territory until all
Regulatory Approvals and other regulatory filings have been transferred to Alnylam or its designee,
(vi) if the effective date of termination is after First Commercial Sale in any country in the
Territory, then, if requested by Alnylam, Cubist shall appoint Alnylam as its exclusive distributor
of Licensed Product in the Territory and grant Alnylam the right to appoint sub-distributors, until
such time as all Regulatory Approvals in the Territory have been transferred to Alnylam or its
designee, (vii) if Cubist or its Related Parties are Manufacturing Finished Product, [**], provided
such period of time shall not exceed [**], unless otherwise agreed by Cubist, (viii) if Alnylam so
requests, Cubist shall transfer to Alnylam any Third Party agreements relating to the Development,
Manufacture or Commercialization of Licensed Product to which Cubist is a party, subject to any
required consents of such Third
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Party, which Cubist shall use Diligent Efforts to obtain promptly, and (ix) [**]. Cubist
shall execute all documents and take all such further actions, including, where applicable, the
prompt assignment of Regulatory Approvals and Third Party agreements, as may be reasonably
requested by Alnylam in order to give effect to the foregoing clauses (i) through (ix) as soon as
practicable and in order to enable Alnylam to continue to Develop, Manufacture and Commercialize
Licensed Products in the Field in the Territory in the same manner as was being conducted by Cubist
prior to any such termination.
(b)
Termination by Cubist for Convenience
. If Cubist terminates this Agreement in
accordance with Section 11.2(a), then the provisions of Section 11.3(a)(i)-(ix) shall apply, except
that the period during which Cubist shall be required to continue to pay [**] under Section
11.3(a)(ii) shall be [**] (following the three month notice period) rather than the [**] specified
in Section 11.3(a)(ii). In addition, during the applicable termination notice period pursuant to
Section 11.2(a), Cubist shall continue to perform [**] all Development, Manufacture and
Commercialization activities with respect to Licensed Products in accordance with the plans for
such activities reviewed and approved by the JSC and JCT prior to Cubists determination to
terminate;
provided
that
Alnylam may, in its discretion, elect to shorten such
termination notice period in order to facilitate a more rapid reversion of all Licensed Product
rights back to Alnylam by providing Cubist reasonable written notice of such election, in which
case Cubist shall use Diligent Efforts to facilitate such more rapid reversion. Cubist shall
execute all documents and take all such further actions as may be reasonably requested by Alnylam
in order to give effect to the foregoing provisions of this Section 11.3(b).
(c)
Termination by Cubist for Cause or for Patent Challenge by Alnylam
. Without
limiting any other legal or equitable remedies that Cubist may have, if Cubist terminates this
Agreement in accordance with Section 11.2(b) or 11.2(c), then the provisions of Section
11.3(a)(iii)-(viii) shall apply;
provided
that
if Cubist has the right to terminate
this Agreement in accordance with Section 11.2(b) or 11.2(c), then in lieu of exercising such
termination right, Cubist may elect not to terminate this Agreement and to convert the Parties
profit-sharing arrangement with respect to Licensed Product in the Profit-Share Territory to a
royalty arrangement, in which case the consequences of such conversion shall be the same as those
set forth in Section 4.7 (i.e., as if Alnylam had opted out of the profit-sharing arrangement) as
of the time of such conversion, except that, if such termination occurs before the First Opt-Out
Milestone, in lieu of any and all of the payments otherwise due to Alnylam under such Section and
under Article VII of this Agreement, Cubist shall pay to Alnylam (i) royalties on Net Sales of
Licensed Product by Cubist and its Related Parties equal to (A) in North America, [**] percent
([**]%) of the royalty amounts payable under Section 4.7(a)(viii) applicable after an exercise by
Alnylam of the Opt-Out Option after the First Opt-Out Milestone but prior to the Second Opt-Out
Milestone, subject to the adjustment provisions set forth in such Section and subject to Section
4.7(a)(ix), and (B) in the Territory outside of North America, [**] percent ([**]%) of the royalty
amounts payable under Section 7.5(a), subject to the adjustment provisions set forth in Sections
7.5(d), 7.6, 7.8, 7.9(b) (with respect to Section 7.9(b), as if the reductions in Section 7.8(b)
apply, whether or not the conditions set forth in Section 7.8(b) for such reductions have been
satisfied) and 7.10 through 7.20 (inclusive) (which, for such purpose, shall be modified as
necessary to apply to the royalty obligations described in this Section 11.3(c)(i)(B) and (ii)
milestone payments on milestones achieved by Cubist and its Related Parties with respect to
Licensed Product equal to (A) in North America, [**] percent ([**]%) of
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the milestone payment amounts payable under Sections 4.7(a)(vi) and 4.7(a)(vii) applicable
after an exercise by Alnylam of the Opt-Out Option after the First Opt-Out Milestone but prior to
the Second Opt-Out Milestone, subject to Section 4.7(a)(ix), and (B) in the Territory outside of
North America, [**] percent ([**]%) of the milestone payment amounts payable under Sections 7.2 and
7.3. If Cubist terminates this Agreement pursuant to Section 11.2(a) or 11.2(b), Cubist may
offset any unpaid amounts owed to Alnylam pursuant to Section 4.7 or Article VII by the amount of
Cubists damages determined by any court having jurisdiction over such matter to have resulted from
Alnylams breach of this Agreement.
Section 11.4
Payments to Cubist
. In the event Cubist terminates this Agreement
under Section 11.2, and such termination occurs after the First Opt-Out Milestone, Alnylam shall
thereafter make the following payments to Cubist:
(a) Subject to Sections 11.4(f) and 11.4(g), Alnylam shall make the non-refundable,
non-creditable milestone payments set forth below to Cubist not later than [**] after the earliest
date on which the corresponding milestone event set forth below has been achieved:
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Payment if
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Cubists
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Termination
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Takes Effect
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Payment if
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After the First
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Cubists
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Opt-Out
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Termination
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Milestone but
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 11.4(g)
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Milestone Event
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Milestone
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Milestone
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Option I
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(A) Acceptance
for filing of an
application for
Regulatory Approval
for a Licensed
Product for any
indication in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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(B) First
Commercial Sale of
a Licensed Product
in any indication
in the United
States
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$
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[**]
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$
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[**]
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$
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[**]
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(C) Acceptance
for filing of an
application for
Regulatory Approval
for a Licensed
Product for any
indication other
than the indication
with respect to
which the milestone
event described in
paragraph (A) above
was achieved in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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Payment if
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Cubists
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Termination
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Takes Effect
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Payment if
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After the First
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Cubists
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Opt-Out
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Termination
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Milestone but
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 11.4(g)
|
Milestone Event
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Milestone
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Milestone
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Option I
|
(D) Regulatory
Approval of a
Licensed Product
for any indication
other than the
indication with
respect to which
the milestone event
described in
paragraph (A) above
was achieved in the
United States
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$
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[**]
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$
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[**]
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$
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[**]
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The milestone payments set forth in this Section 11.4(a) shall be paid only once, upon the
first achievement of the applicable milestone event by the first Licensed Product to achieve such
milestone event.
(b) Subject to Sections 11.4(f) and 11.4(g), Alnylam shall make the non-refundable,
non-creditable milestone payments set forth below to Cubist upon the achievement of the milestone
events set forth below, such payment to be made as set forth below:
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Payment if
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Cubists
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Termination
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Takes Effect
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Payment if
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After the First
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Cubists
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Opt-Out
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Termination
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Milestone but
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Takes Effect
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Prior to the
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After the Second
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Second Opt-Out
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Opt-Out
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Section 11.4(g)
|
Milestone Event
|
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Milestone
|
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Milestone
|
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Option I
|
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(A) Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
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[**]
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$
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[**]
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(B) Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
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[**]
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$
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[**]
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(C) Aggregate
Calendar Year Net
Sales of Licensed
Products in North
America greater
than $[**]
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$
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[**]
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$
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[**]
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$
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[**]
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Subject to Section 11.4(c), the milestone payments set forth in this Section 11.4(b) shall be
paid only once, upon the first achievement of the applicable milestone event. For purposes of
determining whether a milestone event set forth in this Section 11.4(b) has occurred (and without
creating an obligation to pay the milestone more than once as set forth in the preceding sentence),
Calendar Year Net Sales shall be aggregated for all Licensed Products sold in North America during
the relevant Calendar Year.
If more than one of the milestone events set forth in this Section 11.4(b) first occurs based
on sales of Licensed Product in North America in the same Calendar Year, all of such milestone
payments shall be paid for such Calendar Year. If a milestone payment set forth above is earned
based on Net Sales over a period that is shorter in duration than a full Calendar Year, such
payment shall become due and payable [**] after the Calendar Quarter in which the milestone event
is achieved.
(c) Alnylam shall pay additional milestones upon each of the events listed in paragraphs (a)
and (b) having been met in the Territory outside North America;
provided
that
the
payment amounts set forth above shall be reduced to [**] percent ([**]%) of the amounts specified
above.
(d) Alnylam shall, subject to Sections 7.5(d), 7.6(b), 7.8, Sections 7.10 through 7.20
(inclusive) (which for such purpose, shall be modified as necessary to apply to the royalty
obligations described in this Section 11.4 and to reflect the fact that Alnylam is the
royalty-paying Party and Cubist is the royalty-receiving Party), Section 11.4(f) and Section
11.4(g), pay to Cubist royalties on the aggregate Net Sales (with such definition modified
accordingly for this purpose) of Licensed Products in the Territory by Alnylam and its
Sublicensees, as follows:
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Aggregate Calendar
Year Net
Sales
of Licensed Products
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Royalty Rate (as
a
Percentage of
Such
Aggregate
Net
Sales) if
Cubists
Termination
Takes
Effect
After the
First
Opt-Out
Milestone But
Prior
to the
Second
Opt-Out
Milestone
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Royalty Rate (as
a
Percentage of
Such
Aggregate
Net
Sales) if
Cubists
Termination
Takes
Effect
After the
Second
Opt-Out
Milestone
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Section 11.4(g)
Option I
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$[**] $[**]
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[**]%
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[**]%
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[**]%
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Greater than $[**]
and less than or
equal to $[**]
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[**]%
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[**]%
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[**]%
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Greater than $[**]
and less than or
equal to $[**]
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[**]%
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[**]%
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[**]%
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Greater than $[**]
and less than or
equal to $[**]
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[**]%
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[**]%
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[**]%
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Greater than $[**]
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[**]%
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[**]%
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[**]%
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(e) In addition to the reductions and offsets otherwise provided for under this Section 11.4,
(i) [**] percent ([**]%) of the allocated milestone amounts under the Existing Alnylam In-Licenses
that are identified on
Exhibit H
, and (ii) [**] percent ([**]%) of all royalties on the Net
Sales in North America of Licensed Products paid by Alnylam under the Existing Alnylam In-Licenses
up to a maximum of [**] percent ([**]%) of such Net Sales shall be creditable by Alnylam against
all amounts payable by Alnylam to Cubist pursuant to this Section 11.4 (i.e. Alnylams maximum [**]
percent ([**]%) creditable share would be [**] percent ([**]%) of such Net Sales).
(f) The foregoing provisions of this Section 11.4 notwithstanding, if Alnylam granted or
grants a sublicense under the Cubist Technology or a license under the Alnylam Technology to
Develop or Commercialize Licensed Product in the Field in a country or countries in North America,
then Alnylam shall have no payment obligations under Sections 11.4(a), (b), (c) or (d) with respect
to development or sales milestones achieved, or Net Sales of Licensed Products sold, by such
Alnylam Sublicensee or licensee in such country in North America, and, in lieu of such payments,
Alnylam shall instead pay Cubist a portion of Sublicense Income received from such Third Party
Sublicensee or licensee with respect to such country(ies) in North America in accordance with the
following;
provided
that in no event shall the amount paid to
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Cubist be less than the amounts owed by Cubist or any of its Affiliates under any Cubist
In-License with respect to such Licensed Product in such country(ies):
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Effective
Date of Cubists Termination
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Percentage of Sublicense Income
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After the First Opt-Out Milestone and
prior to the Third Opt-Out Milestone
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[**]%
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After the Second Opt-Out Milestone
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[**]%
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For purposes of clarity, (A) if this Agreement is terminated by Cubist pursuant to Section 11.2 and
such termination occurs prior to the First Opt-Out Milestone, Alnylam shall have no payment
obligations to Cubist pursuant to this Section 11.4, and (B) if this Agreement is terminated by
Cubist pursuant to Section 11.2 and such termination occurs after the First Opt-Out Milestone,
Alnylams payment obligations under Sections 11.4(a), 11.4(b), 11.4(c) and 11.4(d), in each case
subject to Section 11.4(e), shall apply with respect to development and sales milestones achieved,
and the Net Sales of Licensed Products sold, by Alnylam and its Affiliates in such country(ies) in
North America.
(g) Notwithstanding the foregoing provisions of this Section 11.4, if Cubist (i) terminates
this Agreement pursuant to Section 11.2 after the Second Opt-Out Milestone and (ii) [**], then:
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A.
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Alnylam shall promptly provide Cubist with a
copy of such [**] and with a summary of all relevant information
relating to such [**] for such Licensed Product for a pediatric
clinical indication;
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B.
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Additionally, Alnylam shall provide Cubist with
such additional information regarding such [**] and planned [**] as
Alnylam may reasonably request;
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C.
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Within [**] after receipt of the information
and documents provided by Alnylam pursuant to clause (A);
provided
however
in no event shall such time period
expire earlier than [**] after delivery of any information requested by
Cubist pursuant to clause (B), Cubist shall make one of the following
two elections and notify Alnylam of such election: (I) elect to accept
the milestones and royalties set forth in the column entitled Section
11.4(g) Option I in Sections 11.4(a), 11.4(b) and 11.4(d), in lieu of
the otherwise applicable post-termination economics set forth above in
Sections 11.4(a), 11.4(b) and 11.4(d) or (II) agree to fund [**]
percent ([**]%) of the [**] for such subsequent additional [**], in
which case there shall be no reduction to the applicable
post-termination economics set forth above in Sections 11.4(a), 11.4(b)
and 11.4(d);
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D.
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If Cubist makes the election set forth in
clause (C)(I) above and Alnylam subsequently achieves a [**] provided
to Cubist by Alnylam pursuant to clause (A) above, Alnylam shall notify
Cubist of such occurrence promptly after receipt of such [**] and
Cubist shall thereafter have an option, exercisable by providing
Alnylam with notice of such exercise within [**] after Cubists receipt
of Alnylams notification, to pay Alnylam [**] percent ([**]%) of the
amount of the additional [**] actually incurred by Alnylam in [**] and,
if Cubist exercises such option and thereafter makes such payment
within [**] after Cubists receipt of Alnylams notification, the
reduction to Cubists post-termination economics set forth in clause
(C)(I) above shall not apply; and
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E.
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If Cubist makes the election set forth in
clause (C)(II) above, then the JSC shall be reconstituted and, [**],
all Development and Manufacture for the purposes of Development of
Licensed Product for the Profit-Share Territory shall again be subject
to the provisions of this Agreement as if Cubist had not terminated the
Agreement pursuant to Section 11.2. For purposes of clarity, (i) [**],
the JSC will be dissolved again and Cubist will, from that point
forward, receive milestones and royalties based upon the termination of
this Agreement pursuant to Section 11.2 after the Second Opt-Out
Milestone and (ii) at no time shall Cubist resume sharing in N.A.
Pre-Tax Profit or Loss.
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Section 11.5
Effect of Expiration or Termination; Survival
. Expiration or
termination of this Agreement shall not relieve the Parties of any obligation accruing prior to
such expiration or termination. Any expiration or termination of this Agreement shall be without
prejudice to the rights of either Party against the other accrued or accruing under this Agreement
prior to expiration or termination, including payment obligations arising prior to such expiration
or termination. The provisions of Sections 3.2(a)(ii), 3.2(b)(ii), 3.2(c)(iv), 3.2(d), 3.3, 3.4,
3.5, 4.3(b), 4.3(c), 9.1, 9.2, 9.3, 10.11, 10.12, 10.13, 11.3 and 11.4, this Section 11.5 and
Articles XII and XIII shall survive any expiration or termination of this Agreement and all other
provisions contained in this Agreement that by their explicit terms survive expiration or
termination of this Agreement, shall survive. Except as set forth in this Article XI, upon
termination or expiration of this Agreement all other rights and obligations of the Parties under
this Agreement terminate.
ARTICLE XII
FINAL DECISION-MAKING; DISPUTE RESOLUTION
Section 12.1
Disputes
. Except as otherwise provided in Section 2.5, the Parties
shall negotiate in good faith and use reasonable efforts to settle any dispute, controversy or
claim arising from, or related to, this Agreement or to the breach, termination or validity hereof
(collectively,
Dispute
). In particular, the Chief Executive Officer of Alnylam and the
Executive Officer of Cubist shall attempt to resolve all Disputes. If the Chief Executive Officers
cannot reach an agreement regarding a Dispute, and a Party wishes to pursue the matter, each
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such Dispute that is not an Excluded Claim shall be finally resolved by binding arbitration
under the then-current Commercial Arbitration Rules of the American Arbitration Association
(
AAA
) by one or more arbitrators appointed in accordance with Section 12.2, and judgment
on the arbitration award may be entered in any court having jurisdiction thereof or of the relevant
Party or its assets. As used in this Section 12.1, the term
Excluded Claim
means a
dispute that concerns (a) [**].
Section 12.2
Arbitration
.
(a) The arbitration provided for in Section 12.1 shall be conducted by a panel of three (3)
persons experienced in the pharmaceutical business who are independent of both Parties and neutral
with respect to the Dispute presented for arbitration. Within thirty (30) days after initiation of
arbitration, each Party shall select one person to act as arbitrator and the two Party-selected
arbitrators shall select a third arbitrator within thirty (30) days after their appointment. If
the arbitrators selected by the Parties are unable or fail to agree upon the third arbitrator, the
third arbitrator shall be appointed by the AAA. The place of arbitration shall be Boston,
Massachusetts, and all proceedings and communications shall be in English.
(b) Either Party may apply to the arbitrators for interim injunctive relief until the
arbitration award is rendered or the controversy is otherwise resolved. Either Party also may,
without waiving any remedy under this Agreement, seek from any court having jurisdiction any
injunctive or provisional relief necessary to protect the rights or property of that Party pending
the arbitration award. The arbitrators shall have no authority to award punitive or any other type
of damages not measured by a Partys compensatory damages. Each Party shall bear its own costs and
expenses and attorneys fees, and the Party that does not prevail in the arbitration proceeding
shall pay the arbitrators and any administrative fees of arbitration. Except to the extent
necessary to confirm an award or as may be required by law, neither a Party nor an arbitrator may
disclose the existence, content, or results of an arbitration without the prior written consent of
both Parties. In no event shall an arbitration be initiated after the date on which commencement
of a legal or equitable proceeding based on the dispute, controversy or claim would be barred by
the applicable Massachusetts statute of limitations. Any dispute concerning the application of the
statute of limitations shall be resolved by the arbitrators.
(c) The Parties agree that, in the event of a Dispute over the nature or quality of
performance under this Agreement, neither Party may terminate this Agreement until final resolution
of the Dispute through arbitration or other judicial determination, and this Agreement shall be
terminated only if arbitrators determine that the termination of this Agreement is an appropriate
remedy. The Parties further agree that any payments made pursuant to this Agreement pending
resolution of the Dispute shall be refunded promptly if an arbitrator or court determines that such
payments are not due.
(d) The Parties hereby agree that any disputed performance or suspended performances pending
the resolution of the arbitration that the arbitrators determine to be required to be performed by
a Party must be completed within a reasonable time period following the final decision of the
arbitrators.
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(e) The Parties hereby agree that any monetary payment to be made by a Party pursuant to a
decision of the arbitrators shall be made in United States dollars, free of any tax or other
deduction. The Parties further agree that the decision of the arbitrators shall be the sole,
exclusive and binding remedy between them regarding the matters presented to the arbitrators.
ARTICLE XIII
MISCELLANEOUS
Section 13.1
Choice of Law
. This Agreement shall be governed by and interpreted
under, and any court action in accordance with Section 13.7 shall apply, the laws of the
Commonwealth of Massachusetts excluding: (a) its conflicts of laws principles; (b) the United
Nations Conventions on Contracts for the International Sale of Goods; (c) the 1974 Convention on
the Limitation Period in the International Sale of Goods (the
1974 Convention
); and (d)
the Protocol amending the 1974 Convention, done at Vienna April 11, 1980.
Section 13.2
Notices
. Any notice or report required or
permitted to be
given or made under this Agreement by one of the Parties to the other shall be in writing and shall
be deemed to have been delivered upon personal delivery or (a) in the case of notices provided
between Parties in the continental United States, four days after deposit in the mail or the
Business Day next following deposit with a reputable overnight courier and (b) in the case of
notices provided by telecopy (which notice shall be followed immediately by an additional notice
pursuant to clause (a) above if the notice is of a default hereunder), upon completion of
transmissions to the addressees telecopier, as follows (or at such other addresses or facsimile
numbers as may have been furnished in writing by one of the Parties to the other as provided in
this Section 13.2):
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If to Alnylam:
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Alnylam Pharmaceuticals, Inc.
300 Third Street
Cambridge, Massachusetts 02142
U.S.A.
Attention: Chief Executive Officer
Facsimile No.: (617) 551-8101
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With a copy to:
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Alnylam Pharmaceuticals, Inc.
300 Third Street
Cambridge, Massachusetts 02142
U.S.A.
Attention: Vice President Legal
Facsimile No.: (617) 575-7315
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If to Cubist:
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Cubist Pharmaceuticals, Inc.
65 Hayden Avenue
Lexington, Massachusetts 02421
U.S.A.
Attention: President, Chief Executive Officer
Facsimile No.: (781) 861-1412
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With a copy to:
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Cubist Pharmaceuticals, Inc.
65 Hayden Avenue
Lexington, Massachusetts 02421
U.S.A.
Attention: General Counsel
Facsimile No.: (781) 860-1407
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Section 13.3
Severability
. If, under applicable Law, any provision of this
Agreement is invalid or unenforceable, or otherwise directly or indirectly affects the validity of
any other material provision(s) of this Agreement (such invalid or unenforceable provision, a
Severed Clause
), this Agreement shall endure except for the Severed Clause. The Parties
shall consult one another and use reasonable efforts to agree upon a valid and enforceable
provision that is a reasonable substitute for the Severed Clause in view of the intent of this
Agreement.
Section 13.4
Captions
. All captions herein are for convenience only and shall not
be interpreted as having any substantive meaning.
Section 13.5
Integration
. This Agreement constitutes the entire agreement between
the Parties hereto with respect to the subject matter of this Agreement and supersedes all previous
agreements, whether written or oral. Notwithstanding the authority granted to the JSC under this
Agreement, this Agreement may be amended only in writing signed by properly authorized
representatives of each of Alnylam and Cubist. If a conflict arises between the Development Plan,
the Global Strategic Commercialization Plan and the Commercialization plans and budgets, on the one
hand, and this Agreement, on the other hand, the terms of this Agreement shall govern.
Section 13.6
Independent Contractors; No Agency
. Neither Party shall have any
responsibility for the hiring, firing or compensation of the other Partys employees or for any
employee benefits. No employee or representative of a Party shall have any authority to bind or
obligate the other Party to this Agreement for any sum or in any manner whatsoever, or to create or
impose any contractual or other liability on the other Party without said Partys written approval.
For all purposes, and notwithstanding any other provision of this Agreement to the
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contrary, Cubists legal relationship under this Agreement to Alnylam shall be that of
independent contractor.
Section 13.7
Submission to Jurisdiction
. Each Party submits to the exclusive
jurisdiction of the state and federal courts sitting in Boston, Massachusetts, with respect to
actions or proceedings arising out of or relating to this Agreement in which a Party brings an
action in aid of arbitration or an action on a claim that is not subject to arbitration by the
terms of Section 12.1 of this Agreement. Each Party further agrees that the jurisdiction of such
courts shall be exclusive and that all claims in respect of such action or proceeding may be heard
and determined only in such courts, and agrees not to bring any action or proceeding arising out of
or relating to this Agreement in any other court, except that an action or proceeding seeking
injunctive relief or brought to enforce an arbitration decision issued pursuant to Section 12.2 may
be brought in any court of competent jurisdiction. Each Party waives any defense of lack of
personal jurisdiction, improper venue or inconvenient forum to the maintenance of any action or
proceeding in a state or federal court sitting in Boston, Massachusetts and waives any bond, surety
or other security that might be required of the other Party with respect thereto. Each Party may
make service on the other Party by sending or delivering a copy of the process to the Party to be
served at the address and in the manner provided for the giving of notices in Section 13.2.
Nothing in this Section 13.7, however, shall affect the right of any Party to serve legal process
in any other manner permitted by law.
Section 13.8
Assignment; Successors
. Neither Alnylam nor Cubist may assign this
Agreement in whole or in part, nor any rights hereunder, without the prior written consent of the
other Party;
provided
that
(a) either Party may assign this Agreement in whole or
in part to an Affiliate on the condition that the assigning Party shall remain liable hereunder for
the prompt payment and performance of all obligations of the assignee, which right to assign shall
include the right to assign rights to receive any payments required under this Agreement consistent
with license grants, sublicenses and other rights referenced in Sections 3.1, 3.2 and 3.4 upon
reasonable written notice to the other Party of such assignment, and (b) this Agreement may be
assigned by a Party if such Party merges with, or all or substantially all of such Partys business
or assets to which this Agreement relates are acquired by another Person (whether by merger, sale
of assets, sale of stock or otherwise) (an
M&A Event
), to such Partys merger partner or
acquirer. Each Party agrees that, notwithstanding any other provisions of this Agreement to the
contrary, if an M&A Event occurs with respect to a Party, such M&A Event [**]. In the event the
intellectual property or technology of such merger partner or acquirer of such Party, or of any
Third Party that becomes an Affiliate of such Party by virtue of such M&A Event is the subject of
an Alnylam In-license or Cubist In-license as of the date of the M&A Event, the terms of Section
8.6 shall continue to apply with respect to such intellectual property and technology. Any
assignment made other than in accordance with the immediately preceding sentence shall be wholly
void and invalid, and the assignee in any such assignment shall acquire no rights whatsoever, and
the non-assigning Party shall not recognize, nor shall it be required to recognize, such
assignment. This Section 13.8 limits both the right and the power to assign this Agreement or
rights under this Agreement. This Agreement shall be binding upon, and shall inure to the benefit
of, all permitted successors and assigns.
Section 13.9
No Consequential or Punitive Damages
. NEITHER PARTY HERETO WILL BE
LIABLE FOR INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL,
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EXEMPLARY, PUNITIVE OR MULTIPLE DAMAGES ARISING OUT OF THIS AGREEMENT OR THE EXERCISE OF ITS
RIGHTS HEREUNDER, OR FOR ANY LOSS OR INJURY TO A PARTYS PROFITS OR GOODWILL ARISING FROM OR
RELATING TO ANY BREACH OF THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF SUCH DAMAGES. NOTHING IN
THIS SECTION 13.9 IS INTENDED TO LIMIT OR RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF
EITHER PARTY WITH RESPECT TO THIRD PARTY CLAIMS.
Section 13.10
Performance by Affiliates
. To the extent that this Agreement imposes
obligations on Affiliates of a Party, such Party agrees to cause its Affiliates to perform such
obligations. Either Party may use one or more of its Affiliates to perform its obligations and
duties hereunder;
provided
that
the Parties shall remain liable hereunder for the
prompt payment and performance of all their respective obligations hereunder.
Section 13.11
Force Majeure
. Neither Party shall be held liable to the other Party
nor be deemed to have defaulted under or breached this Agreement for failure or delay in performing
any obligation under this Agreement to the extent that such failure or delay is caused by or
results from causes beyond the reasonable control of the affected Party, potentially including
embargoes, war, acts of war (whether war be declared or not), insurrections, riots, civil
commotions, strikes, lockouts or other labor disturbances, fire, floods, locusts or other acts of
God, or acts, omissions or delays in acting by any Governmental Authority or the other Party. The
affected Party shall notify the other Party of such
force majeure
circumstances as soon as
reasonably practical, and shall promptly undertake all reasonable efforts necessary to cure such
force majeure
circumstances.
Section 13.12
Construction
. Each Party acknowledges that it has been advised by
counsel during the course of negotiation of this Agreement, and, therefore, that this Agreement
shall be interpreted without regard to any presumption or rule requiring construction against the
Party causing this Agreement to be drafted. Whenever the context may require, any pronoun shall
include the corresponding masculine, feminine and neuter forms. The words include, includes
and including shall be deemed to be followed by the phrase without limitation. The word will
shall be construed to have the same meaning and effect as the word shall. Unless the context
requires otherwise, (a) any definition of or reference to any agreement, instrument or other
document herein shall be construed as referring to such agreement, instrument or other document as
from time to time amended, supplemented or otherwise modified (subject to any restrictions on such
amendments, supplements or modifications set forth herein or therein), (b) any reference to any
Laws herein shall be construed as referring to such Laws as they from time to time may be enacted,
repealed or amended, (c) any reference herein to any Person shall be construed to include the
Persons successors and assigns, (d) the words herein, hereof and hereunder, and words of
similar import, shall be construed to refer to this Agreement in its entirety and not to any
particular provision hereof, (e) any reference herein to the words mutually agree or mutual
written agreement shall not impose any obligation on either Party to agree to any terms relating
thereto or to engage in discussions relating to such terms except as such Party may determine in
such Partys sole discretion; (f) all references herein
to Articles, Sections, Exhibits and Schedules shall be construed to refer to Articles,
Sections, Exhibits and Schedules of this Agreement; and (g) the word or is used in the inclusive
sense (and/or).
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Section 13.13
Execution in Counterparts; Facsimile Signatures
. This Agreement may be
executed in counterparts, each of which counterparts, when so executed and delivered, shall be
deemed to be an original, and all of which counterparts, taken together, shall constitute one and
the same instrument even if both Parties have not executed the same counterpart. Signatures
provided by facsimile transmission or by electronic PDF transmission shall be deemed to be original
signatures.
[
Remainder of page intentionally left blank
]
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IN WITNESS WHEREOF, Alnylam and Cubist have caused this Agreement to be duly executed by their
authorized representatives under seal, in duplicate on the dates written herein below.
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ALNYLAM PHARMACEUTICALS, INC.
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By:
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/s/ John M. Maraganore
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Title: Chief Executive Officer
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Date: January 9, 2009
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CUBIST PHARMACEUTICALS, INC.
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By:
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/s/ Michael W. Bonney
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Title: President, Chief Executive Officer
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Date: January 8, 2009
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EXHIBIT A
Alnylam Patent Rights
Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A
total of 118 pages were omitted pursuant to a request for confidential treatment.
[**]
A-1
EXHIBIT B
ALN-RSV01
[**]
B-1
EXHIBIT C
Existing Alnylam In-Licenses
As of the Effective Date, Existing Alnylam In-Licenses includes the following Third Party
agreements:
[**]
C-1
EXHIBIT D
Existing Alnylam Out-Licenses That Include Rights or Options to Licensed Products
[**]
D-1
EXHIBIT E
Development Plan Overview
Confidential Materials omitted and filed separately with the Securities and Exchange Commission. A
total of 5 pages were omitted pursuant to a request for confidential treatment.
[**]
E-1
EXHIBIT F
Material Agreements Related to Licensed Products in the Territory
A.
Alnylam Master Services Agreements
As of the Effective Date, Alnylam has entered into the following Third Party master services
agreements related to the Manufacture of API Bulk Drug Substance. Product.
[**]
B
.
Alnylam Active Clinical Trial Agreements
[**]
C. The Existing Alnylam In-Licenses identified on
EXHIBIT C
.
F-1
EXHIBIT G
Supply Agreement Term Sheet
1.
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Alnylam and Cubist shall use their commercially reasonable efforts to enter into a
supply agreement (the
Supply Agreement
) among Alnylam, Cubist and Kyowa Hakko,
which Supply Agreement will be consistent with the terms of this supply agreement term
sheet (the
Supply Agreement Term Sheet
). From the Effective Date until the
effective date of the Supply Agreement, the terms of the Agreement and this Supply
Agreement Term Sheet shall govern the Manufacture and supply of Licensed Product under the
Agreement;
provided
,
however
, that in the event of conflict between this
Supply Agreement Term Sheet and the Agreement, the terms of the Agreement shall apply.
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2.
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The Parties shall be responsible for establishing the specifications (the
Specifications
) and approving the master batch record, including the necessary
documentation, certificates of analysis and test results, for the API Bulk Drug Substance
and Finished Product to be supplied under the Supply Agreement.
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3.
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Until Regulatory Approval of a Licensed Product in the Territory, Alnylam shall
supply API Bulk Drug Substance and Finished Product to Cubist for use in the Profit-Share
Territory consistent with the Development Plan and for use in the Royalty Territory. The
costs for such API Bulk Drug Substance and Finished Product shall be determined in
accordance with the Agreement. Cubist shall use the API Bulk Drug Substance and Finished
Product supplied by Alnylam solely for purposes contemplated under this Agreement and
shall not transfer any such API Bulk Drug Substance or Finished Product to any Third Party
for any other purpose.
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4.
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Unless agreed otherwise in writing by the Parties, [**] before the commencement of
each Calendar Quarter, Cubist will give to Alnylam a forecast of the estimated quarterly
requirements of API Bulk Drug Substance and Finished Product for the Royalty Territory for
the [**] period commencing with such Calendar Quarter (the
Royalty Territory
Forecast
). Such Royalty Territory Forecast will include quantity and unit
requirements for API Bulk Drug Substance and Finished Product on a country-by-country
basis. With respect to the Royalty Territory, [**] percent ([**]%) of the forecasted
requirements of API Bulk Drug Substance and Finished Product during the [**] Calendar
Quarters of such Royalty Territory Forecast, and [**] percent ([**]%) of the forecasted
requirements of API Bulk Drug Substance and Finished Product during the [**] Calendar
Quarters of such Royalty Territory Forecast, shall be considered binding on Cubist, and
Alnylam shall supply such forecasted amounts. The forecasted requirements of API Bulk
Drug Substance and Finished Product during the [**] Calendar Quarters of such Royalty
Territory Forecast will be non-binding. Cubist will provide Alnylam with binding purchase
orders for API Bulk Drug Substance and Finished Product at least [**] in advance of the
delivery date for such API Bulk Drug Substance or Finished Product, as the case may be. In
the event that Cubist requests any
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G-1
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changes to forecast, Alnylam shall (i) use its commercially reasonable efforts to
accommodate such requests and (ii) use its commercially reasonable efforts to minimize any
costs incurred as a result of such changes.
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5.
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Unless agreed otherwise in writing by the Parties, [**] before the commencement of
each Calendar Quarter, the JSC or the JCT, as the case may be, will give to Alnylam a
forecast of the estimated quarterly requirements of API Bulk Drug Substance and Finished
Product for the Profit-Share Territory for the [**] period commencing with such Calendar
Quarter (the
Profit-Share Forecast
and together with the Royalty Territory
Forecast, the
Forecast
). Such Profit-Share Forecast will include quantity and
unit requirements for API Bulk Drug Substance and Finished Product on a country-by-country
basis. With respect to the Profit-Share Territory, the JSC or the JCT, as the case may
be, shall approve any changes in the amounts of Licensed Product to be Manufactured for
the Profit-Share Forecast;
provided
,
however
, that Alnylam shall use its
commercially reasonable efforts to minimize any costs incurred as a result of such
changes, and for purposes of clarity, any such minimized costs shall be considered
Development Costs or Commercialization Costs, as the case may be, for purposes of the
Agreement.
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6.
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In the event of an actual or anticipated shortage of supply of API Bulk Drug
Substance or Finished Product, Alnylam shall promptly notify Cubist and, unless otherwise
agreed by the Parties, available supply shall be allocated between the Royalty Territory,
the Profit-Share Territory and Asia on a pro-rata basis based on good faith forecasts of
requirements. In addition, Alnylam will use commercially reasonable efforts to resolve
all failure to supply issues as promptly as possible in consultation with Cubist and Kyowa
Hakko.
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7.
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If and to the extent that a Failure to Supply (as hereinafter defined) occurs, Cubist
shall have the right to assume control of the Manufacture of Licensed Product;
provided
,
however
, that (a) the Parties, working through the JSC or JCT,
as appropriate, will conduct an orderly transfer of the technology necessary to so
Manufacture Licensed Product and (b) the Parties shall use Diligent Efforts to structure
such transition in a manner that enables Alnylam to satisfy its supply obligations to
Kyowa Hakko. For purposes of this Supply Agreement Term Sheet, a
Failure to
Supply
will be deemed to have occurred only after Alnylam has failed to deliver [**]
percent ([**]%) of the aggregate requirements for Licensed Product for a given Calendar
Quarter in the Royalty Territory and the Profit-Share Territory, respectively, as
described in the Forecast, in two out of any four consecutive Calendar Quarters.
Similarly, if Cubist suffers a Failure to Supply, Alnylam shall have the right to reassume
control of the Manufacture of Licensed Product.
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8.
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Alnylam agrees that all API Bulk Drug Substance and Finished Product supplied to
Cubist will, at the time of delivery to Cubist, have been Manufactured in
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G-2
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accordance with the Specifications and the master batch record, and except for batches not
intended for human use, with current Good Manufacturing Practices and equivalent Laws
outside the United States (cGMP). Alnylam will be solely responsible for all costs and
expenses caused by failed batches, including batches which fail to meet the requirements of
the previous sentence, as a result of the negligence or intentional misconduct of any
Alnylam employee.
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9.
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In addition to more detailed terms regarding the matters specified above in this
Supply Agreement Term Sheet, the Supply Agreement shall contain other customary supply
agreement provisions, including indemnification provisions appropriate for a Supply
Agreement. Furthermore, Alnylam and Cubist will enter into a Technical and Quality
Agreement with respect to the Licensed Product governing, among other things, quality
assurance requirements, documentation and procedures, audit and inspection rights and
similar matters.
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G-3
EXHIBIT H
Milestone
Payments Under the Existing Alnylam In-Licenses
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Existing Alnylam In
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Alnylam Payment
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Allocable Share of
Milestone to be
split in Profit-Share
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license
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Milestone
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Obligation
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Territory
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H-1
EXHIBIT I
Press Release
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Contacts:
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Cubist Pharmaceuticals, Inc.
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Alnylam Pharmaceuticals, Inc.
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Eileen C. McIntyre
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Cynthia Clayton (Investors)
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781-860-8533
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617-551-8207
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eileen.mcintyre@cubist.com
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Tara Murphy
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Adriana Jenkins (Media)
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Weber Shandwick
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Yates Public Relations
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617-520-7045
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617-744-1713
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TMurphy@WeberShandwick.com
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Alnylam and Cubist Form Strategic Collaboration to Develop and Commercialize
RNAi Therapeutics Targeting Respiratory Syncytial Virus (RSV) Infection
Lexington, Mass. and Cambridge, Mass., January 9, 2009
Cubist Pharmaceuticals, Inc., (Nasdaq:
CBST), a leading acute care biopharmaceutical company, and Alnylam Pharmaceuticals, Inc. (Nasdaq:
ALNY), a leading RNAi therapeutics company, announced today that they have formed a strategic
collaboration to develop and commercialize Alnylams ALN-RSV program. The RSV-specific RNAi
therapeutic program includes ALN-RSV01, which is currently in Phase II clinical development for the
treatment of respiratory syncytial virus (RSV) infection in adult lung transplant patients, as well
as several other potent and specific second-generation RNAi-based RSV inhibitors in pre-clinical
studies.
The collaboration is structured as a 50/50 co-development and profit share arrangement in North
America, and a milestone- and royalty-bearing license arrangement in the rest of the world outside
of Asia, where ALN-RSV is partnered with Kyowa Hakko Kirin Co., Ltd. Alnylam will receive an
upfront payment of $20 million. In addition, Alnylam is eligible to receive development and sales
milestone payments from Cubist that could total $82.5 million, for a total in upfront and potential
milestone payments of $102.5 million,
I-1
as well as double digit royalties on net sales outside of
North America and Asia. After achieving certain development milestones, Alnylam could convert the
North American co-development and profit share to a royalty-bearing license with development and
sales milestones. Cubist will have sole rights for commercialization of the ALN-RSV program
worldwide outside of Asia, subject to the cost and profit sharing in North America.
Cubist is pleased to be working with Alnylam and to be involved in the development and potential
commercialization of a therapy for this significant infectious disease, said Michael W. Bonney,
President and Chief Executive Officer of Cubist. We expect that this collaboration will leverage
the development expertise and commercial success we have achieved in the area of infectious
disease. There is significant need for novel therapeutics to effectively treat patients with RSV
infection, a leading cause of pediatric hospitalization and a prevalent infection in certain adult
populations. We are convinced that developing a treatment for RSV infection is an important
therapeutic and commercial opportunity, and, like Alnylam, are committed to addressing this need.
We are excited to have formed this new alliance with Cubist a like-minded organization that
shares our commitment to bringing a novel RNAi therapeutic to patients infected with RSV. We have
tremendous respect for the Cubist team, and have been impressed with the development and ongoing
commercial success they have had with their lead anti-infective program, CUBICIN
®
(daptomycin for
injection), said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. Partnering this
program brings additional critical mass to the advancement of ALN-RSV01 and/or second-generation
RSV-specific RNAi therapeutics in our broader program which we aim to advance through ongoing
pre-clinical studies toward potential clinical studies as early as 2010. The partnership also
provides Alnylam with yet additional financial flexibility to invest beyond RSV in the multiple
product opportunities represented by our growing pipeline of novel RNAi therapeutics.
In 2008, Alnylam conducted the GEMINI study in which ALN-RSV01 was evaluated in a double-blind,
randomized, placebo-controlled Phase II clinical trial. Data from this study showed that
intranasally administered ALN-RSV01 demonstrated statistically significant anti-viral efficacy with
an approximately 40% relative reduction in RSV infection rate and a 95% increase in the number of
infection-free subjects, as compared with placebo. The RNAi therapeutic is currently being studied
in a double-blind, randomized, placebo-controlled Phase II clinical trial to assess the safety and
tolerability of aerosolized ALN-RSV01 in adult lung transplant patients naturally infected with
RSV. As a secondary objective, this trial will evaluate the anti-viral activity of ALN-RSV01 in
patients with a naturally acquired RSV lower respiratory tract infection. Based on these and other
data, Cubist and Alnylam will aim to maximize the value of the entire RSV program for advancement
in pediatric and adult RSV-infected patients.
About Respiratory Syncytial Virus (RSV)
RSV is a highly contagious virus that causes infections in both the upper and lower respiratory
tract. RSV infects nearly every child at least once by the age of two years and is a major cause
of hospitalization due to respiratory infection in children and people with
I-2
compromised immune
systems, and others. RSV infection typically results in cold-like symptoms but can lead to more
serious respiratory illnesses such as croup, pneumonia, bronchiolitis, and in extreme cases, death.
RSV infection in the pediatric and adult populations account for more than 300,000
hospitalizations per year in the U.S. In addition, RSV infection in infants has been linked to the
development of childhood
asthma. As a result, there is a significant need for novel therapeutics to treat patients who
become infected with RSV.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding
how genes are turned on and off in cells, and a completely new approach to drug discovery and
development. Its discovery has been heralded as a major scientific breakthrough that happens once
every decade or so, and represents one of the most promising and rapidly advancing frontiers in
biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine.
RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to
mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation
of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi
therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs),
thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential
to treat disease and help patients in a fundamentally new way.
About Cubist Pharmaceuticals
Cubist Pharmaceuticals, Inc. is a biopharmaceutical company focused on the research, development,
and commercialization of pharmaceutical products that address unmet medical needs in the acute care
environment. In the U.S., Cubist markets CUBICIN
®
(daptomycin for injection), the first
antibiotic in a new class of anti-infectives called lipopeptides. Cubist has an agreement with
AstraZeneca to handle U.S. hospital sales for their established broad spectrum antibiotic,
MERREM
®
I.V. (meropenem for injection). In addition to the collaboration with Alnylam
on RSV announced today, the Cubist product pipeline includes ecallantide, a recombinant human
protein in Phase 2 clinical trials for the prevention of blood loss during cardiothoracic surgery;
and two programs with recently submitted INDs that address unmet medical needs to treat
Gram-negative infections and CDAD (
Clostridium difficile
-associated diarrhea). Cubist is
headquartered in Lexington, MA. Additional information can be found at Cubists web site at
www.cubist.com
I-3
About Alnylam Pharmaceuticals
Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or
RNAi. The company is applying its therapeutic expertise in RNAi to address significant medical
needs, many of which cannot effectively be addressed with small molecules or antibodies, the
current major classes of drugs. Alnylam is leading the translation of RNAi as a new class of
innovative medicines with peer-reviewed research efforts published in the worlds top scientific
journals including
Nature
,
Nature Medicine
, and
Cell
. The company is leveraging these capabilities
to build a broad pipeline of RNAi therapeutics; its most advanced program is in Phase II human
clinical trials for the treatment of respiratory syncytial virus (RSV) infection and is partnered
with Cubist and Kyowa Hakko. In addition, the company is developing RNAi therapeutics for the
treatment of a wide range of disease areas, including liver cancers, hypercholesterolemia,
Huntingtons disease, and TTR amyloidosis. The companys leadership position in fundamental
patents, technology, and know-how relating to RNAi has enabled it to form major alliances with
leading companies including Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko, and
Cubist. To reflect its outlook for key scientific, clinical, and business initiatives, Alnylam
established
RNAi 2010
in January 2008 which includes the companys plan to significantly expand
the scope of delivery solutions for RNAi therapeutics, have four or more programs in clinical
development, and to form four or more new major business collaborations, all by the end of 2010.
Alnylam is a joint owner of Regulus Therapeutics LLC, a joint venture focused on the discovery,
development, and commercialization of microRNA therapeutics. Founded in 2002, Alnylam maintains
headquarters in Cambridge, Massachusetts. For more information, please visit
http://www.alnylam.com.
Cubist Forward-Looking Statement
This press release contains forward-looking statements, including statements regarding ALN-RSV01
and the ALN-RSV program as a potential treatment for RSV. There are many factors that could cause
actual results to differ materially from those in these forward-looking statements. These factors
include the following: (i) Cubist and Alnylams ability to develop, manufacture and achieve
commercial success for ALN-RSV01 or other RNAi therapeutics that are the subject of this
collaboration; (ii) whether the FDA accepts proposed clinical trial protocols that may be achieved
in a timely manner for ALN-RSV01 or other RNAi therapeutics that are the subject of this
collaboration; (iii) Cubists ability to conduct successful clinical trials in a timely manner;
(iv) the demonstrated clinical efficacy and safety of ALN-RSV01 or other RNAi therapeutics that are
the subject of this collaboration as they relate to standards for regulatory approval and in
comparison to competitive products; (v) ALN-RSV01 and other RNAi therapeutics that are the subject
of this collaboration could take a significantly longer time to gain regulatory approval and market
acceptance than Cubist or Alnylam expects or may never gain such approval or acceptance in RSV;
(vi) others may develop RSV technologies or products superior to, and/or which reach the market
before ALN-RSV01 or other RNAi therapeutics that are the subject of this collaboration; (vii)
technical difficulties or excessive costs relating to the manufacture of ALN-RSV01 or other RNAi
therapeutics that are the subject of this collaboration; (viii) a smaller market for ALN-RSV01 or
other RNAi therapeutics that are the subject of this
I-4
collaboration in RSV than Cubist or Alnylam currently anticipates; (ix) Cubists and Alnylams
ability to adequately develop and maintain adequate protection for the intellectual property
related to ALN-RSV01 or other RNAi therapeutics that are the subject of this collaboration; and (x)
a variety of other risks common to our industry that may be encountered with respect to the
development, manufacture or commercialization of ALN-RSV, including ongoing regulatory review,
public and investment community perception of the industry, legislative or regulatory changes, and
Cubists ability to attract and retain talented employees. Drug development involves a very high
degree of risk. Success of a product candidate in early stage clinical trials or pre-clinical
trials does not mean that subsequent trials will also be successful or that the candidate will be
successfully commercialized. Additional factors that could cause actual results to differ
materially from those projected or suggested in any forward-looking statements are contained in
Cubists most recent 10-K and 10-Q filings with the Securities and Exchange Commission, including
those factors discussed under the caption Risk Factors in such filings. These statements speak
only as of the date of this release, and Cubist undertakes no obligation to update or revise these
statements, except as may be required by law.
Alnylam Forward-Looking Statement
Various statements in this release concerning Alnylams future expectations, plans and prospects,
constitute forward-looking statements for the purposes of the safe harbor provisions under The
Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those
indicated by these forward-looking statements as a result of various important factors, including
statements concerning the timing and scope of clinical trials and studies for ALN-RSV therapeutics,
the potential to achieve certain results which could trigger milestone payments and royalties to
Alnylam, and the potential market for novel RSV therapeutics, as well as those risks more fully
discussed in the Risk Factors section of its most recent quarterly report on Form 10-Q on file
with the Securities and Exchange Commission. In addition, any forward-looking statements represent
Alnylams views only as of today and should not be relied upon as representing its views as of any
subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.
Cubist and CUBICIN are registered trademarks of Cubist Pharmaceuticals, Inc.
AstraZeneca and MERREM are registered trademarks of the AstraZeneca group of companies.
I-5
Schedule 10.7
Disclosure Schedule
This Disclosure Schedule is provided in connection with Section 10.7 of that certain Collaboration
and License Agreement (the Agreement), dated January 9, 2009 between Alnylam Pharmaceuticals,
Inc. (Alnylam) and Cubist Pharmaceuticals, Inc. (
Cubist
). Capitalized terms used
herein and not otherwise defined shall have the meanings given such terms in the Agreement, unless
the context indicates otherwise.
The section numbers below correspond to the section numbers of the representations and warranties
in the Agreement. An item of disclosure in any section or subsection of this Disclosure Schedule
shall qualify other sections and subsections of the Agreement to the extent it is reasonably clear
from a reading of the disclosure that such disclosure is applicable to such other sections and
subsections. Inclusion of an item in this Disclosure Schedule does not necessarily indicate that an
item is material or called for by a representation in the Agreement.
10.7-1
10.7(b)
[**]
10.7(c)
[**]
10.7-2
10.7 (d)
OPPOSITIONS & APPEALS
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Patent #
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# of Opponents
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Opponents/Appellants
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Status
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10.7-3
Exhibit 10.3
Execution
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
AMENDED AND RESTATED LICENSE AND COLLABORATION AGREEMENT
This Amended and Restated License and Collaboration Agreement (the
Agreement
) is entered
into as of the 1st day of January, 2009 (the
Amendment Effective Date
) by and among
Alnylam
Pharmaceuticals, Inc.
, a Delaware corporation, with its principal place of business at 300
Third Street, Cambridge, Massachusetts 02142 (
Alnylam
),
Isis Pharmaceuticals, Inc.
, a
Delaware corporation, with its principal place of business at 1896 Rutherford Road, Carlsbad,
California 92008 (
Isis
, and each of Alnylam and Isis, a
Licensor
and together, the
Licensors
), and
Regulus Therapeutics Inc.
(formerly Regulus Therapeutics LLC), a
Delaware corporation, with its principal place of business at 1896 Rutherford Road, Carlsbad,
California 92008 (
Regulus
).
RECITALS
Whereas,
Isis and Alnylam each granted a license to Regulus in accordance with that
certain License and Collaboration Agreement dated September 6, 2007 (the
Original License
Agreement
);
Whereas
, as of the Amendment Effective Date, Alnylam, Isis and Regulus converted
Regulus from a Delaware limited liability company into a Delaware corporation; and
Whereas
, as a result of this corporate conversion, Isis, Alnylam, and Regulus now
desire to amend and restate the Original License Agreement, as provided herein.
AGREEMENT
Now, Therefore,
in consideration of the mutual covenants contained herein, and other
good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, Isis,
Alnylam and Regulus each agrees as follows:
1.
DEFINITIONS
Capitalized terms used herein and not defined elsewhere herein have the meanings set forth in
Exhibit 1
.
2.
ASSIGNMENT; LICENSES
2.1
Assignments to Regulus.
(a) Isis hereby grants, sells, conveys, transfers, assigns, releases and delivers to Regulus
all right, title and interest in and to the Patent Rights and contracts listed on
Schedule
2.1(a)
attached hereto, to have and hold the same unto itself, its successors and assigns
forever, and Regulus hereby accepts such grant, sale, conveyance, etc.
(b) Alnylam hereby grants, sells, conveys, transfers, assigns, releases and delivers to
Regulus all right, title and interest in and to the Patent Rights and contracts listed on
Schedule 2.1(b)
attached hereto, to have and hold the same unto itself, its successors and
assigns forever, and Regulus hereby accepts such grant, sale, conveyance, etc.
(c) Notwithstanding the foregoing, to the extent any contract for which assignment is provided
for herein is not assignable pursuant to such contract without the written consent of another party
or requires novation, if assigned, this Agreement will not constitute an assignment or an attempted
assignment thereof if such assignment or attempted assignment would constitute a breach thereof.
To the extent a contract is not assigned pursuant to this provision, the applicable Licensor will
cooperate with the other Parties and will use its Commercially Reasonable Efforts to provide
Regulus the economic and other benefits intended to be assigned to Regulus under the relevant
contract.
2.2
Licenses Granted to Regulus
.
(a)
Grants
. Subject to the terms and conditions of this Agreement (including but not
limited to Section 2.4), each Licensor hereby grants to Regulus a worldwide, royalty-bearing,
sublicenseable (in accordance with Section 2.5) license in the Field, under such Licensors
Licensed IP,
|
(i)
|
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to Develop miRNA Compounds and miRNA
Therapeutics,
|
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(ii)
|
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to Manufacture miRNA Compounds and miRNA
Therapeutics, and
|
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(iii)
|
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to Commercialize miRNA Therapeutics.
|
Subject to Section 2.4, the rights granted under clauses (i), (ii) and (iii) will be (y) exclusive
with respect to miRNA Compounds which are miRNA Antagonists and miRNA Therapeutics containing such
miRNA Compounds, and (z) non-exclusive with respect to miRNA Compounds which are Approved Precursor
Antagonists and miRNA Therapeutics containing such miRNA Compounds.
(b)
Request to License miRNA Mimics and Additional miRNA Precursor Antagonists
.
Regulus may request a worldwide, royalty-bearing, sublicenseable (in accordance with Section 2.5),
non-exclusive license in the Field, under each Licensors Licensed IP, to Develop, Manufacture and
Commercialize a specific miRNA Mimic or a specific miRNA Precursor Antagonist that is not then an
Approved Precursor Antagonist, and miRNA Therapeutics containing such miRNA Mimic or miRNA
Precursor Antagonist, by providing written notice to Licensors thereof on a miRNA Mimic-by-miRNA
Mimic or miRNA Precursor Antagonist-by-miRNA Precursor Antagonist basis. Such license is subject
to (i) review and affirmative approval by the Licensors, which approval may be withheld by a
Licensor in such Partys sole discretion, and (ii) compliance with relevant Third Party Rights
([***]). For the avoidance of doubt, Regulus will have no rights to such miRNA Mimic or miRNA
Precursor Antagonist hereunder unless and until the affirmative approval of the relevant
Licensor(s) and any required consents or approvals from Third Parties have been obtained and
Regulus agrees to comply with all Third Party Rights, even to the extent inconsistent with the
terms of this
2
Agreement, following which such miRNA Mimic or miRNA Precursor Antagonist will be deemed to be
an Approved Mimic or Approved Precursor Antagonist, respectively.
(c)
Retained Rights
. The exclusive license granted to Regulus by Alnylam pursuant to
Section 2.2(a) is subject to Alnylams retained right to (i) use and exploit its Licensed IP solely
to support its own internal Research in the Alnylam Field
,
and (ii) grant Permitted Licenses. The
exclusive license granted to Regulus by Isis pursuant to Section 2.2(a) is subject to Isis
retained right to (i) use and exploit its Licensed IP solely to support its own internal Research
in the Isis Field
,
and (ii) grant Permitted Licenses. All rights in and to each Licensors
Licensed IP not expressly licensed pursuant to Sections 2.2(a) and (b), and any other Patent Rights
or Know-How of such Licensor, are hereby retained by such Licensor.
2.3
Licenses Granted to Licensors Under Regulus IP
. Subject to the terms and
conditions of this Agreement and to Third Party Rights:
(a) Regulus hereby grants to Alnylam a worldwide, exclusive, royalty-free, perpetual and
irrevocable license, with the right to grant sublicenses, under the Regulus IP solely to the extent
necessary or useful to research, discover, develop, make, have made, use, sell, offer to sell
and/or otherwise commercialize double-stranded oligonucleotides (other than Approved Mimics) and
any product containing double-stranded oligonucleotides (other than Approved Mimics) (the
Alnylam
Field
).
(b) Regulus hereby grants to Isis a worldwide, exclusive, royalty-free, perpetual and
irrevocable license, with the right to grant sublicenses, under the Regulus IP solely to the extent
necessary or useful to research, discover, develop, make, have made, use, sell, offer to sell
and/or otherwise commercialize single-stranded oligonucleotides (other than miRNA Antagonists,
Approved Precursor Antagonists, or Approved Mimics) and any product containing single-stranded
oligonucleotides (other than miRNA Antagonists, Approved Precursor Antagonists or Approved Mimics)
(the
Isis Field
).
2.4
Third Party Rights; Additional Rights
.
(a)
Existing Out-License Agreements.
The licenses granted under Section 2.2 and 2.3 are
subject to and limited by the licenses granted, and other obligations owed, by each Licensor to a
Third Party prior to the Effective Date under a Licensed Patent Right Controlled by such Licensor,
pursuant to agreements described on (i)
Part 1 of Schedule 2.4(a)
in the case of Licensed
Patent Rights Controlled by Isis, and (ii)
Part 2 of Schedule 2.4(a)
in the case of
Licensed Patent Rights Controlled by Alnylam, and (iii) in an addendum transmittal instrument
delivered by each Licensor within 30 days after the Effective Date. The schedules and instruments
provided under this Section 2.4(a) will be collectively referred to as the
Out-License Summary
,
and the agreements described therein will be collectively referred to as the
Out-License
Agreements
).
(b)
Existing In-Licenses from Third Parties
.
(i) Certain of the Licensed Patent Rights as of the Effective Date that are licensed to
Regulus under Section 2.2 are in-licensed or were acquired by the applicable Licensor under
agreements with Third Party licensors or sellers that may contain restrictions on the scope of the
licenses or trigger payment or other material obligations or restrictions (such
3
license or purchase agreements in effect as of the Effective Date being the
In-License
Agreements
). The licenses and other rights (including sublicense and disclosure rights) granted
to a Party pursuant to this Agreement are subject to, and are limited to the extent of the terms of
any (i) In-License Agreements between Isis and any Third Party licensor, as specifically described
on
Part 1 of Schedule 2.4(b)
and (ii) any In-License Agreement between Alnylam and any
Third Party, as specifically described on
Part 2 of Schedule 2.4(b).
The schedules
provided under this Section 2.4(b) will be collectively referred to as
In-License Summary
. Each
Part of the In-License Summary summarizes all material restrictions on the scope of the licenses,
and all material payment obligations owed, under the In-License Agreements (other than the Previous
Agreements) which the applicable Licensor reasonably believes apply to the licenses granted to
Regulus hereunder as of the Effective Date. Except as provided in Section 5.6(d), Regulus will
assume all financial and other obligations to the relevant Third Party, and be subject to all
restrictions, set forth on the In-License Summary and arising from the grant to Regulus of the
licenses pursuant to Section 2.2(a) as of the Effective Date.
(ii) In addition to the financial obligations and scope limitations set forth on the
In-License Summary and the Out-License Summary, and to the extent access to such terms have been
made available to such licensed Party in unredacted form (
provided
,
however
, that
such licensed Party has not failed to request such access in accordance with Section 2.4(e)), a
Party receiving a license or sublicense under Licensed IP hereunder will comply, and will cause its
Affiliates and Sublicensees to comply, with all other terms of the In-License Agreements and
Out-License Agreements, including without limitation diligence requirements, applicable to the
licenses granted to such Party hereunder.
(c)
Optional In-Licenses
. Notwithstanding anything to the contrary herein, the licenses to
Isis Licensed IP hereunder initially shall not include licenses to Patent Rights or Know-How
licensed by Isis under the agreements listed and described on
Part 1 of Schedule 2.4(c)
and the licenses to Alnylams Licensed IP hereunder initially shall not include licenses to Patent
Rights or Know-How licensed by Alnylam under the agreements listed and described on
Part 2 of
Schedule 2.4(c)
(such agreements on
Schedule 2.4(C)
referred to as the
Optional
In-Licenses
). Regulus is hereby granted the option of expanding its licenses under Section 2.2 to
include Patent Rights and Know-How licensed to the relevant Licensor pursuant to [***] Optional
In-Licenses, with respect to [***] miRNA Compounds and related miRNA Therapeutics, by notifying the
Parties in writing of the relevant Optional In-License, and each miRNA Compound with respect
thereto, for which such option is exercised. Upon such exercise and Regulus written agreement to
assume all financial and other obligations and restrictions imposed by the desired Optional
In-License (including, to the extent access to such terms have been made available to Regulus in
unredacted form (
provided
,
however
, that Regulus has not failed to request such
access in accordance with Section 2.4(e)), all other terms of such Optional In-License applicable
to the licenses granted to Regulus hereunder), the Patent Rights and Know-How licensed to the
relevant Licensor pursuant to the specified Optional In-License shall be deemed included in such
Licensors Licensed IP solely with respect to the relevant miRNA Compounds and related miRNA
Therapeutics.
(d)
Additional Rights after Effective Date
. If after the Effective Date, a Party (the
Controlling Party
) invents or acquires rights or title to an invention claimed by a Patent Right
that would be included in the Licensed Patent Rights or Regulus Patent Rights (the
Additional
Rights
), then, on the anniversary of the Effective Date following such invention or
4
acquisition of such Additional Right, or as otherwise reasonably requested by a Party, the
Controlling Party must notify each other Party (each, a
Non-Controlling Party
) of such
acquisition or invention. If a Non-Controlling Party wishes to include such Additional Rights
under the licenses granted pursuant to Sections 2.2, 2.3 or 5.6 (as the case may be), such
Non-Controlling Party will notify the Controlling Party of its desire to do so, the Controlling
Party will provide the Non-Controlling Party a summary of all material restrictions on the scope of
the licenses granted, and all material payment obligations owed, under any Third Party Agreement
applicable to such Additional Rights and the Non-Controlling Party may, upon written notice to the
Controlling Party, obtain a license under such Additional Rights and will assume all financial and
other obligations to, and be subject to all restrictions imposed by, the Controlling Partys
licensors or collaborators, if any, arising from the grant to such Non-Controlling Party of such
license (including, to the extent access to such terms have been made available to such
Non-Controlling Party in unredacted form (
provided
,
however
, that such
Non-Controlling Party has not failed to request such access in accordance with Section 2.4(e)), all
other terms of such Third Party Agreements applicable to the licenses granted to such
Non-Controlling Party hereunder). Notwithstanding the foregoing, any Additional Rights that do not
carry financial or other obligations or restrictions will be automatically included under the
licenses granted pursuant to Section 2.2, 2.3 or 5.6. If the Controlling Party pays any upfront
payments or similar acquisition costs to access Additional Rights, the Controlling Party and
relevant Non-Controlling Party(ies) will negotiate in good faith regarding sharing such acquisition
costs and payments. When acquiring or creating such Additional Rights pursuant to any agreement
entered into after the Effective Date, each Party will endeavor in good faith to secure the right
to sublicense such Additional Rights to the other Parties.
(e)
Applicable Agreements
. Each Party agrees to provide, upon the request of a Party, access
to each Third Party Agreement that is the subject of any provision of this Section 2.4;
provided
,
however
, that the Parties agree and acknowledge that (i) the Third Party
Agreements so provided may, to the extent necessary to protect confidential information of the
relevant Third Party or financial information of the relevant Party, be redacted, and (ii) if so
redacted, the Party assuming any obligations or accepting any limitations under a Third Party
Agreement pursuant to this Section 2.4, will only be liable to the extent access to such terms have
been made available to such licensed Party in unredacted form.
2.5
Sublicenses
.
(a) Subject to Third Party Rights, Regulus will have the right to grant to its Affiliates and
Third Parties sublicenses under the licenses granted in Sections 2.2(a) and (b).
(b) Subject to Third Party Rights, the Opt-In Party will have the right to grant to its
Affiliates and Third Parties sublicenses under the rights granted to such Licensor in Section
5.6(a).
(c) Each such sublicense will be subject and subordinate to, and consistent with, the terms
and conditions of this Agreement, and will provide that any such Affiliate and Sublicensee will
not further sublicense except on terms consistent with this Section 2.5. Regulus or the Opt-In
Party, as applicable, will provide the other Parties with a copy of any sublicense granted
pursuant to this Section 2.5 within 30 days after the execution thereof. Such copy may be
redacted to exclude confidential scientific information and other information
5
required by a Sublicensee to be kept confidential;
provided
that all relevant
financial terms and information will be retained. Regulus or the Opt-In Party, as applicable,
will remain responsible for the performance of its Affiliates and Sublicensees, and will ensure
that all such Affiliates and Sublicensees comply with the relevant provisions of this Agreement.
In the event of a material default by any of its Affiliates or Sublicensees under a sublicense
agreement, Regulus or the Opt-In Party, as applicable, will inform the other Parties and will take
such action, after consultation with such other Parties, which, in Regulus or the Opt-in Partys
(as applicable) reasonable business judgment, will address such default.
3.
TECHNOLOGY TRANSFER
3.1
Technology Transfer to Regulus.
At each meeting of the Collaboration Working
Group the representatives will discuss new Know-How and Patent Rights of Isis and Alnylam that are
included in such Licensors Licensed Patents and Licensed Know-How hereunder at the level of detail
necessary to enable Regulus to effectively practice such Patent Rights and Know-How.
3.2
Technology Transfer from Regulus; Identification and Improvements.
At each
Collaboration Working Group meeting Regulus will present a description of all Regulus IP developed
by it or on its behalf, or over which Regulus otherwise acquired Control, since the last meeting.
The description will be at a level of detail necessary to enable Isis, Alnylam or both, as
appropriate, to effectively practice such Regulus IP in accordance with their respective licenses
under Section 2.3.
4.
DILIGENCE
4.1
General Diligence
. Except to the extent a Licensor receives a license from
Regulus pursuant to this Agreement to Develop, Manufacture and Commercialize miRNA Therapeutics,
Regulus will use Commercially Reasonable Efforts to Develop, and Commercialize miRNA Compounds and
miRNA Therapeutics in the Field.
4.2
Compliance with Laws
. Each Party will, and will ensure that its Affiliates and
Sublicensees will, comply with all relevant Laws in exercising their rights and fulfilling their
obligations under this Agreement.
4.3
Reporting
. By January 31
st
of each year, Regulus will prepare and
furnish each Licensor with a written report summarizing Regulus activities conducted during the
prior calendar year to Develop, Manufacture and Commercialize miRNA Therapeutics in the Field and
identifying the results obtained or benchmarks achieved since the last report to the Licensors.
4.4
Designation of Research Programs and Development Projects
. Regulus officers will
be responsible for reviewing the results of Research and Development activities under the Operating
Plan and designating (subject to the approval of the Managing Board) from time to time Research
Programs and Development Projects. A
Research Program
will begin upon the commencement of
discovery or characterization activities focused on one or more specific miRNA(s) after preliminary
validation of the biological function of such miRNA(s) has been identified (i.e., compound
discovery, not target validation) and will include all activities with respect to the Development,
Manufacturing and Commercialization of miRNA Compounds and
6
miRNA Therapeutics directed to such miRNA(s). A Research Program will become a
Development
Project
(and thereafter will no longer be a Research Program) when Regulus officers recommend,
and the Managing Board agrees, that a sufficient portfolio of data exists to support the initiation
of a [***] on a miRNA Compound drug candidate targeting such miRNA(s). Regulus will maintain a
written list of the then-current Research Programs and Development Projects (each, a
Program/Project List
).
5.
RIGHT TO OPT-IN
5.1
Notice of Development Project Status
. Concurrently with the conversion of a
Research Program into a Development Project, Regulus will notify each Licensor of such conversion
and whether or not Regulus will continue to pursue the Development and Commercialization of such
newly designated Development Project.
5.2
Continued Development by Regulus of Development Projects
. If Regulus notifies
Licensors pursuant to Section 5.1 that Regulus will continue to pursue the Development and
Commercialization of such Development Project, then, without limiting the generality of Section
4.1, Regulus will use Commercially Reasonable Efforts to Develop and Commercialize the relevant
Development Compounds and Development Therapeutics in the Field. Regulus will also (a) pay to each
Licensor a royalty of [***]% of Net Sales of such Development Therapeutics which are
Royalty-Bearing Products, during the relevant Royalty Term (
provided
,
however
,
that, for the remainder of the relevant Royalty Term following the end of the relevant Exclusivity
Period, the royalty rate will be [***]%) and (b) be responsible for all milestones, royalties and
other payments payable to Third Parties in respect of the Development, Manufacture and
Commercialization of such Development Therapeutics in the Field, by Regulus, its Affiliates and
Sublicensees, including any amounts payable by either Licensor to Third Parties under the Third
Party Rights. The Parties will use reasonable efforts to [***]. Regulus agrees that the royalty
described in clause (a) of this Section 5.2 is payable to each Licensor, regardless of whether a
particular Royalty-Bearing Product is covered by such Licensors Licensed IP. Each Party agrees
and acknowledges that such royalty structure (i) is freely entered into by such Party, (ii) is a
fair reflection of the value received by Regulus from the licenses granted by the Licensors, and
(iii) is a reasonable allocation of the value received by Regulus from each Licensor, due to the
difficulty of determining the extent to which Licensors Licensed IP covers or has enabled each
Royalty-Bearing Product.
5.3
Opt-In Election
. If Regulus notifies Licensors pursuant to Section 5.1 that it
will not continue to pursue the Development and Commercialization of such Development Project, each
Licensor will have the right, exercisable by providing written notice to Regulus and the other
Licensor within [***] days following receipt of such notice (
Initial Opt-In Election Period
), to
elect to continue to pursue the Development and Commercialization of such Development Project
(
Opt-In Election
).
(a)
Opt-In by One Licensor
. If only one, but not both, of the Licensors (the
Opt-In
Party
) makes an Opt-In Election with respect to such Development Project within the Initial Opt-In
Election Period, the High Terms set forth in Section 5.4 and the terms of Section 5.6 will apply
following the end of such Initial Opt-In Election Period and the Licensor who did not elect to
opt-in will waive its right to opt-in with respect to such Development Project.
7
(b)
No Opt-In; Second Opt-In Election
. If, within the Initial Opt-In Election Period,
neither Licensor makes an Opt-In Election (or both Licensors fail to submit any response), then
Regulus will use diligent efforts to negotiate and finalize, within [***] months following the end
of the Initial Opt-In Election Period, a term sheet with a Third Party pursuant to which such Third
Party will Develop and Commercialize, either by itself or with or on behalf of Regulus, such
Development Project in the Field.
|
(i)
|
|
If, despite diligent efforts, Regulus is unable
to finalize such term sheet with a Third Party with respect to the
Development Project within such [***] month period, or Regulus is able
to finalize such term sheet with a Third Party with respect to the
Development Project within such [***] month period, but Regulus is
unable to execute a definitive agreement substantially in conformance
with such term sheet within [***] months after finalizing such term
sheet, Regulus will notify Licensors thereof and each Licensor will
again have the right, exercisable by providing written notice to
Regulus and the other Licensor, within [***] days following Regulus
notice (
Second Opt-In Election Period
), to elect to continue to
pursue the Development and Commercialization of such Development
Project on the Low Terms set forth in Section 5.5.
|
|
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(ii)
|
|
If only one, but not both, of the Licensors,
makes an Opt-In Election within the Second Opt-In Election Period (the
Opt-In Party
), the Low Terms set forth in Section 5.5 and the terms
of Section 5.6 will apply following the end of such Second Opt-In
Election Period and the Licensor who did not make an Opt-In Election,
within such Second Opt-In Election Period, will have waived its right
to opt-in with respect to such Development Project.
|
|
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(iii)
|
|
If, within the Second Opt-In Election Period,
neither Licensor makes an Opt-In Election (or both Licensors fail to
submit any response), then Regulus will retain all rights to such
Development Project.
|
(c)
Opt-In by Both Licensors
. If, within the Initial Opt-In Election Period or Second
Opt-In Election Period, both Licensors submit an Opt-In Election with respect to such Development
Project, then the Parties will, to the extent mutually agreed, work together to amend the Operating
Plan to support Regulus in Developing and Commercializing the Development Project, including, as
applicable, creating a funding and early development plan, and the designation of roles and
responsibilities of each Party in the execution of such Operating Plan.
5.4
Opt-In on High Terms
. In the event that an Opt-In Election is made by only one of
the Licensors during the Initial Opt-In Election Period pursuant to Section 5.3(a), the following
terms will apply (
High Terms
):
8
(a)
Upfront Payment
. The Opt-In Party will pay to Regulus, within 15 days following
the end of the Initial Opt-In Election Period, a one-time payment of [***] Dollars ($[***]).
(b)
Royalties
. During the relevant Royalty Term, the Opt-In Party will pay to Regulus
the following royalties on Net Sales (aggregated from all relevant countries) of each
Royalty-Bearing Product in a calendar year:
|
|
|
|
|
|
|
|
|
|
|
Royalty Rate
|
|
Royalty Rate
|
On the portion of Net Sales
|
|
on Net Sales During
|
|
on Net Sales After
|
during the calendar year:
|
|
Exclusivity Period
|
|
Exclusivity Period
|
Less than or equal to $[***]:
|
|
|
[***]
|
%
|
|
|
[***]
|
%
|
Greater than $[***]:
|
|
|
[***]
|
%
|
|
|
[***]
|
%
|
The Opt-In Partys obligation to pay royalties under this Section 5.4(b) is imposed only once with
respect to the same unit of Royalty-Bearing Product.
(c)
Milestone Payments
. Subject to Section 5.6(f), the Opt-In Party will pay to
Regulus the following payments upon the achievement of the events set forth below by a
Royalty-Bearing Product for the relevant Development Project:
|
|
|
|
|
|
|
Payment
|
Milestone Event:
|
|
([***]):
|
(i) Filing of IND for first Royalty-Bearing Product
|
|
$
|
[***]
|
|
(ii) Upon Completion of the first Phase IIa Clinical Trial
|
|
$
|
[***]
|
|
(iii) Initiation (i.e., dosing of first patient) of the first
Phase III Clinical Trial
|
|
$
|
[***]
|
|
(iv) Filing of NDA in U.S. for first Royalty-Bearing Product
|
|
$
|
[***]
|
|
(v) Filing of NDA in the European Union for first Royalty-Bearing
Product
|
|
$
|
[***]
|
|
(vi) Regulatory Approval in U.S. for the first Royalty-Bearing
Product
|
|
$
|
[***]
|
|
(vii) Regulatory Approval in any Major Country in the European
Union for the first Royalty-Bearing Product
|
|
$
|
[***]
|
|
The Opt-In Party will notify the other Parties within 15 days following achievement or occurrence
of a milestone event. Each milestone payment under this Section 5.4(c) will be payable only once
with respect to the first Royalty-Bearing Product under the relevant
9
Development Project to achieve the milestone event. If an event in clause (ii), (iii), (iv) or (v)
occurs before an event in a preceding clause (i), (ii) or (iii), the milestone payment described in
such clause (i), (ii) or (iii) will be paid when the milestone payment described in such clause
(ii), (iii), (iv) or (v) is paid.
Milestone payments will continue to be due for milestone events occurring after any grant by the
Opt-In Party or its Affiliates to a Third Party of a sublicense of the Regulus IP or Licensed IP
licensed to the Opt-In Party under Section 5.6(a) with respect to the relevant Development Project.
(d)
Sublicense Income
. Subject to Section 5.6(f), the Opt-In Party will pay to
Regulus a portion of the Sublicense Income received by the Opt-In Party or its Affiliates, in
accordance with the following table:
|
|
|
|
|
Sublicense agreement initially entered into
|
|
Percentage of
|
during this timeframe:
|
|
Sublicense Income
|
Prior to Completion of first Phase IIa Clinical Trial
|
|
|
[***]
|
%
|
After Completion of first Phase IIa Clinical Trial, but
prior to completion of first Phase III Clinical Trial
|
|
|
[***]
|
%
|
After Completion of first Phase III Clinical Trial
|
|
|
[***]
|
%
|
5.5
Opt-In on Low Terms
. In the event that an Opt-In Election is made by only one,
but not both, of the Licensors during the Second Opt-In Election Period pursuant to Section
5.3(b)(ii), the following terms will apply (
Low Terms
):
(a)
Upfront Payment
. The Opt-In Party will pay to Regulus, within 15 days following
the end of the Second Opt-In Election Period, a one-time payment of [***] Dollars ($[***]).
(b)
Royalties
. During the relevant Royalty Term, the Opt-In Party will pay to Regulus
the following royalties on Net Sales (aggregated from all relevant countries) of each
Royalty-Bearing Product in a calendar year:
|
|
|
|
|
|
|
|
|
|
|
Royalty Rate
|
|
Royalty Rate
|
On the portion of Net Sales
|
|
on Net Sales During
|
|
on Net Sales After
|
during the calendar year:
|
|
Exclusivity Period
|
|
Exclusivity Period
|
Less than or equal to $[***]:
|
|
|
[***]
|
%
|
|
|
[***]
|
%
|
Greater than $[***]:
|
|
|
[***]
|
%
|
|
|
[***]
|
%
|
The Opt-In Partys obligation to pay royalties under this Section 5.5(b) is imposed only once with
respect to the same unit of Royalty-Bearing Product.
10
(c)
Milestone Payments
. Subject to Section 5.6(f), the Opt-In Party will pay to
Regulus the following payments upon the achievement of the events set forth below by a
Royalty-Bearing Product for the relevant Development Project:
|
|
|
|
|
|
|
Payment for
|
|
|
Royalty-Bearing
|
|
|
Product
|
|
|
([***]):
|
Milestone Event:
|
|
|
|
|
(i) Filing of IND for first Royalty-Bearing Product
|
|
$
|
[***]
|
|
(ii) Upon Completion of the first Phase IIa Clinical Trial
|
|
$
|
[***]
|
|
(iii) Initiation (i.e., dosing of first patient) of the
first Phase III Clinical Trial
|
|
$
|
[***]
|
|
(iv) Filing of NDA in U.S. for first Royalty-Bearing
Product
|
|
$
|
[***]
|
|
(v) Regulatory Approval in U.S. for the first
Royalty-Bearing Product
|
|
$
|
[***]
|
|
The Opt-In Party will notify the other Parties within 15 days following achievement or occurrence
of a milestone event. Each milestone payment under this Section 5.4(c) will be payable only once
with respect to the first Royalty-Bearing Product under the relevant Development Project to achieve
the milestone event. If an event in clause (ii), (iii), (iv) or (v) occurs before an event in a
preceding clause (i), (ii) or (iii), the milestone payment described in such clause (i), (ii) or
(iii) will be paid when the milestone payment described in such clause (ii), (iii), (iv) or (v) is
paid.
Milestone payments will continue to be due for milestone events occurring after any grant by the
Opt-In Party or its Affiliates to a Third Party of a sublicense of the Regulus IP or Licensed IP
licensed to the Opt-In Party under Section 5.6(a) with respect to the relevant Development Project.
(d)
Sublicense Income
. Subject to Section 5.6(f), the Opt-In Party will pay to
Regulus a portion of the Sublicense Income received by the Opt-In Party or its Affiliates, in
accordance with the following table:
|
|
|
|
|
Sublicense agreement initially entered into
|
|
Percentage of
|
during this timeframe:
|
|
Sublicense Income
|
Prior to Completion of first Phase IIa Clinical Trial
|
|
|
[***]
|
%
|
After Completion of first Phase IIa Clinical Trial,
but prior to completion of first Phase III Clinical
Trial
|
|
|
[***]
|
%
|
After Completion of first Phase III Clinical Trial
|
|
|
[***]
|
%
|
11
5.6
Other Terms Applicable to Opt-In Party
.
(a)
License Grant
.
|
(i)
|
|
Regulus will, and hereby does, grant to the
Opt-In Party, subject to and limited by the Third Party Rights, a
worldwide, royalty-bearing, sublicenseable (in accordance with Section
2.5), (x) license under all Regulus IP, and (y) sublicense under all
Licensed IP (within the scope of the license granted to Regulus under
such Licensed IP pursuant to Sections 2.2(a) and 2.2(b)), solely for
purposes of Developing, Manufacturing and Commercializing the relevant
Development Projects Development Compounds and Development
Therapeutics in the Field on the terms set forth in this Section 5.6.
Regulus shall comply with the provisions of Section 2.4 with respect to
the disclosure of information with respect to the relevant Third Party
Rights.
|
|
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(ii)
|
|
Subject to Third Party Rights, the rights
granted under Section 5.6(a)(i) to the Opt-In Party will be exclusive,
to the fullest extent possible, under Regulus IP and under Licensed IP.
For the sake of clarity, this means that Regulus IP will be
exclusively licensed by Regulus to the Opt-In Party with respect to the
relevant Development Project, and Regulus rights under the Licensed IP
will be exclusively sublicensed by Regulus to the Opt-In Party with
respect to the relevant Development Project, but any non-exclusive
licenses grant by the relevant Licensor to Regulus with respect to
Licensed IP shall not be deemed to have been expanded to exclusive
licenses to Regulus.
|
(b)
Diligence
. The Opt-In Party will use Commercially Reasonable Efforts to Develop,
Manufacture and Commercialize the relevant Development Compounds and Development Therapeutics, at
such Opt-In Partys own expense, in the Field, either by itself or with or through its Affiliates
or Sublicensees.
(c)
Non-Compete
. The non-Opt-In Party with respect to a Development Project will not,
itself or through its Affiliates or with Third Parties, Develop, Manufacture or Commercialize
Development Compounds or Development Therapeutics with respect to such Development Project during
the period (i) [***] of a Royalty-Bearing Product with respect to such Development Project anywhere
in the world as long as such Opt-In Party reasonably believes that a Development Therapeutic would
be a Royalty-Bearing Product upon first commercial sale, and (ii) [***] of a Royalty-Bearing
Product with respect to such Development Project anywhere in the world, until the expiration of
[***] for such Development Project;
provided
,
however
that each Party will be
entitled to grant Permitted Licenses.
(d)
Third Party and Inter-Licensor Payments
. In addition to the royalties and
milestones payable under Section 5.4 or 5.5 above, the Opt-In Party will be responsible for all
12
milestones, royalties and other payments payable to Third Party Licensors and assumed under
Section 2.4. The Parties will use reasonable efforts to [***]. In addition, the Opt-In Party will
be responsible for any other payments to the Third Parties in respect of the Development,
Manufacture and Commercialization of such Development Compounds and Development Therapeutics in the
Field. In addition, the Licensors agree that any amounts otherwise owed by one Licensor to another
pursuant to a Previous Agreement is hereby waived with respect to such Development Project.
(e)
No Longer a Development Project
. If one, but not both, Licensors make an Opt-In
Election with respect to a Development Project, such Development Project will be permanently
removed from the Program/Project List.
(f)
Credit for Prepaid Amounts
. The Parties agree that, with respect to any
Development Project, the relevant Opt-In Party should pay the greater of the cumulative Guaranteed
Payments and the cumulative Sublicense Income Payments as of the end of each calendar quarter, and,
because the timing of the Guaranteed Payments and the Sublicense Income Payments with respect to
any given Development Project may not align, the Parties agree that the relevant Opt-In Party will
not, with respect to any calendar quarter, be required to pay more than the amount necessary to
bring the cumulative payments made by such Opt-In Party with respect to such Development Project up
to the greater of the cumulative Guaranteed Payments and the cumulative Sublicense Income Payments
with respect to such calendar quarter. Therefore, with respect to any calendar quarter, the
relevant Opt-In Party shall pay the difference (if positive) between (i) the Cumulative Amount Owed
as of the end of such calendar quarter, minus (ii) the Cumulative Amount Owed (if any) as of the
end of the immediately prior calendar quarter. Several examples are provided in
Schedule
5.6(f)
.
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(A)
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Cumulative Amount Owed
means, with respect to
a Development Project and a calendar quarter, the greater of (1) the
cumulative Guaranteed Payments as of the end of such calendar quarter,
and (2) the cumulative Sublicense Income Payments as of the end of such
calendar quarter.
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(B)
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Guaranteed Payments
means, with respect to a
Development Project and a calendar quarter, (1) if High Terms apply,
the payments paid or payable pursuant to Sections 5.4(a) and 5.4(c)
with respect to such calendar quarter, and (2) if Low Terms apply, the
payments paid or payable pursuant to Section 5.5(a) and 5.5(c) with
respect to such calendar quarter.
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5.7
Payment of Royalties
. Following any dissolution or winding-up of Regulus that
results in no successor entity to Regulus, any royalties, milestones and/or sublicense fees due to
Regulus by a Licensor in connection with an Opt-In Election under this Agreement, will be reduced
by [***] percent ([***]%) and this amount will instead be payable by the Licensor required to pay
such fee directly to the other Licensor (the
Receiving Licensor
);
provided, however
, if the
Receiving Licensor has pass-through obligations with respect to a royalty
13
payment, milestone or sublicense fee, the payment to the Receiving Licensor will not be
reduced to an amount less than the amount of the pass-through obligation.
1
6.
[Intentionally Deleted]
7.
[Intentionally Deleted]
8.
PAYMENT TERMS; REPORTS; RECORD-KEEPING AND AUDIT RIGHTS
8.1
Reports and Payments
. The Party paying any royalties, milestones or Sublicense
Income Payments hereunder (the
Paying Party
) to another Party (each, a
Payee Party
) will
deliver to such Payee Party(ies), within 15 days after the end of each calendar quarter, a report
with a reasonably detailed written accounting of Net Sales of Royalty-Bearing Products that are
subject to royalty payments due to the Payee Party(ies) for such calendar quarter, milestones
payable and Sublicense Income received or accrued during such period. Such quarterly reports will
indicate gross sales on a country-by-country and Royalty-Bearing Product-by-Royalty-Bearing Product
basis, the deductions from gross sales used in calculating Net Sales and the resulting calculation
of the royalties due to the Payee Party(ies). Royalties or other payments accrued for the period
covered by each such quarterly report will be due and payable 45 days after the end of each
relevant calendar quarter. All amounts in this Agreement are expressed in U.S. Dollars and all
payments due to the Payee Party(ies) hereunder will be paid in U.S. Dollars. If any conversion of
foreign currency to U.S. Dollars is required in connection with any such payments, such conversion
will be made by using the conversion rate existing in the United States (as reported in
The Wall
Street Journal
) on the last Business Day of the reporting period to which such payments relate, or
such other publication as the Parties agree.
8.2
Tax Withholding
. The Paying Party will use all reasonable and legal efforts to
reduce tax withholding with respect to payments to be made to the Payee Party(ies).
Notwithstanding such efforts, if the Paying Party concludes that tax withholdings are required with
respect to payments to the Payee Party(ies), the Paying Party will withhold the required amount and
pay it to the appropriate governmental authority. In any such case, the Paying Party will promptly
provide the Payee Party(ies) with original receipts or other evidence reasonably sufficient to
allow the Payee Party(ies) to document such tax withholdings for purposes of claiming foreign tax
credits and similar benefits.
8.3
Late Payments
. Any payments that are not made on or before the due date will bear
interest at the lesser of (a) 1.5% per month or (b) the maximum permissible rate under applicable
law, for the period from the date on which such payment was due through the date on which payment
is actually made.
8.4
Financial Records
. Unless otherwise required by the Investor Rights Agreement,
the Paying Party will maintain, and will require its Affiliates and Sublicensees to maintain, for 3
years after the relevant reporting period all financial records relating to the transactions and
activities contemplated by this Agreement in sufficient detail to verify compliance with the terms
of this Agreement.
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1
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This Section 5.7 was taken from Section 10.7 of the LLC
Agreement.
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14
8.5
Audit Right
. Once during each calendar year, each Payee Party may retain an
independent certified public accountant reasonably acceptable to the Paying Party to audit the
financial records described in Section 8.4, upon reasonable notice to the Paying Party, during
regular business hours and under an obligation of confidentiality to the Paying Party. Such Payee
Party will bear all of the costs of such audit, except as provided below. The results of such
audit will be made available to all Parties;
provided
,
that
, such results will be
deemed the Confidential Information of the Paying Party hereunder. If the audit demonstrates that
the payments owed under this Agreement have been understated, the Paying Party will pay the balance
to the Payee Party, together with interest in accordance with Section 8.3. Further, if the amount
of the understatement is greater than 5% of the amount owed to such Payee Party with respect to the
audited period, then the Paying Party will reimburse the Payee Party for the reasonable cost of the
audit. If the audit demonstrates that the payments owed under this Agreement have been overstated,
the Payee Party will refund to the Paying Party the amount of such overpayment. All payments owed
by the Paying Party or Payee Party under this Section 8.5 will be made within 30 days after the
results of the audit are delivered to the Parties unless the Paying Party is disputing in good
faith the results of the audit in which case the payment will be made within 30 days after
resolution of such dispute.
9.
INTELLECTUAL PROPERTY
9.1
Ownership
.
(a) As among the Parties, (i) all of Alnylams Licensed IP will be owned solely by Alnylam,
(ii) all of Isis Licensed IP will be owned solely by Isis, and (iii) subject to the Buy-Out
process, all Work Product, and the Intellectual Property therein, will be owned by Regulus, and
each Licensor hereby assigns, and will cause its Affiliates to assign, to Regulus all Work Product
and the Intellectual Property therein.
(b) If Regulus enters into an agreement (other than the Services Agreement) with one of its
Affiliates, a Licensor, an Affiliate of a Licensor or a Third Party pursuant to which Regulus IP
could be developed, Regulus will use Commercially Reasonable Efforts to require such Person to
assign to Regulus all right, title and interest to Regulus IP developed by such Person, or
otherwise ensure that Regulus Controls all such Regulus IP.
9.2
Prosecution and Maintenance of Patent Rights
.
(a)
Regulus IP
. As among the Parties, Regulus will have the sole right to file,
prosecute and maintain Patent Rights covering any Regulus IP, at Regulus own expense.
(b)
Licensor IP
.
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(i)
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As among the Parties, each Licensor will have
the initial right to file, prosecute and maintain such Licensors
Licensed Patent Rights. Such activities will be at such Licensors
expense.
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(ii)
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Subject to any Third Party Rights, in the event
that a Licensor declines to file, prosecute or maintain such Licensors
Licensed Patent Rights, elects to allow any such Patent Rights to
lapse, or
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15
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elects to abandon any such Patent Rights before all appeals within
the respective patent office have been exhausted, then:
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(A)
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Such Licensor will provide
Regulus with reasonable notice of its decision to decline to
file, prosecute or maintain any such Patent Rights or its
election to allow any such Patent Rights to lapse, or its
election to abandon any such Patent Rights, so as to permit
Regulus to decide whether to file, prosecute or maintain the
same, and to take any necessary action.
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(B)
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Regulus may assume control of the
filing, prosecution and/or maintenance of such Patent Rights in
the name of such Licensor, at Regulus expense.
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(C)
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Such Licensor will, at Regulus
expense and reasonable request, assist and cooperate in the
filing, prosecution and maintenance of such Patent Rights.
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(D)
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Regulus will provide such
Licensor, sufficiently in advance for such Licensor to comment,
with copies of all patent applications and other material
submissions and correspondence with any patent counsel or patent
authorities pertaining to such Patent Rights.
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(E)
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Regulus will give due
consideration to the comments of such Licensor, but will have
the final say in determining whether or not to incorporate such
comments.
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(F)
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Regulus and such Licensor will
promptly provide the other with copies of all material
correspondence received from any patent counsel or patent
authorities pertaining to such Patent Rights.
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9.3
Enforcement
.
(a)
Competitive Infringement
. Subject to any Third Party Rights, the terms of this
Section 9.3(a) will apply with respect to any actual or suspected infringement of a Licensors
Licensed Patent Rights or Regulus Patent Rights by a Third Party making, using or selling a
therapeutic product that contains or consists of (y) a miRNA Compound as an active ingredient [***]
or (z) if clause (y) does not apply, an oligonucleotide(s) that falls within the field of a
Partys exclusive license under Section 2.3 of this Agreement. In the case of (z) above, the Party
with the exclusive license in the field where the infringing product most reasonably falls will be
considered the relevant Commercializing Party for purposes of this Section 9.3(a).
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(i)
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Each Party will promptly report in writing to
the other Parties any such infringement of which it becomes aware,
including, without limitation, receipt of any certification received
under the United States Drug Price Competition and Patent Term
Restoration Act of
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16
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1984 (Pub. Law 98-471), as amended (the
Hatch-Waxman Act
), claiming
that any of the Licensed Patent Rights or Regulus Patent Rights is
invalid, unenforceable or that no infringement will arise from the
manufacture, use or sale of such product (a
Paragraph IV
Certification
).
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(ii)
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The relevant Commercializing Party will have
the initial right, at such Commercializing Partys expense, to initiate
a legal action against such Third Party with respect to such
infringement of the Regulus Patent Rights and, if such Commercializing
Party is a Licensor, such Commercializing Partys Licensed Patent
Rights. At the Commercializing Partys reasonable request and expense,
the relevant Licensor(s) (if Regulus is the Commercializing Party) or
the other Licensor (if a Licensor is the Commercializing Party) will
use Commercially Reasonable Efforts to initiate a legal action against
such Third Party with respect to an infringement described in clause
(y) of this Section 9.3(a) of such other Licensor(s) Licensed Patent
Rights. Each other Party will join in any such action(s) as a party at
the Commercializing Partys request and at the Commercializing Partys
expense in the event that an adverse party asserts, the court rules or
other Laws then applicable provide, or the Commercializing Party
determines in good faith, that a court would lack jurisdiction based on
such other Partys absence as a party in such suit. Each other Party
may also at any time join in the Commercializing Partys action and may
be represented by counsel of its choice, at such Partys expense; but
in any event control of such action will remain with the
Commercializing Party. At the Commercializing Partys or enforcing
Licensors reasonable request and expense, the other Parties will
provide reasonable assistance to the Commercializing Party or enforcing
Licensor, as the case may be, in connection with any such action.
Without the prior written consent of the relevant other Party(ies), the
Commercializing Party or enforcing Licensor, as the case may be, will
not enter into any settlement admitting the invalidity of, impacting
the scope or interpretation of or otherwise impairing such other
Party(ies) rights, as the case may be, in any such Patent Rights.
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(iii)
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Any recoveries resulting from an action
brought under Section 9.3(a)(ii) in connection with an infringement
described in clause (y) of Section 9.3(a) (whether undertaken by the
Commercializing Party or the enforcing Licensor) will be applied as
follows:
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(A)
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First, to reimburse each Party
for all litigation costs in connection with such proceeding paid
by such Party (on a pro rata basis, based on each Partys
respective litigation costs, to the extent the recovery was less
than all such litigation costs); and
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17
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(B)
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The remainder of the recovery
will be retained by the Commercializing Party and [***].
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Any recoveries resulting from an action brought under Section
9.3(a)(ii) in connection with an infringement described in clause (z)
of Section 9.3(a) will be retained by the Commercializing Party.
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(iv)
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If the Commercializing Party does not, within 6
months of written notice from another Party or otherwise becoming aware
of such infringement (or within 30 days of the Commercializing Partys
receipt of a Paragraph IV Certification), commence and reasonably
pursue a legal action to prevent such infringement with respect to the
Regulus Patent Rights, Regulus will be entitled, at its expense, to
commence the action in its name. Each Licensor will join in such
action as a party at Regulus request and expense in the event that an
adverse party asserts, the court rules or other Laws then applicable
provide, or Regulus determines in good faith, that a court would lack
jurisdiction based on such Licensors absence as a party in such suit,
but control of such action will remain with Regulus. Any recoveries
resulting from such an action will be retained by Regulus.
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(b)
Non-Competitive Infringement
.
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(i)
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As among the Parties, except as provided in
Sections 9.3(a), Regulus will have the sole right to protect Regulus
Patent Rights from any actual or suspected infringement or
misappropriation, at Regulus own expense. Any recoveries resulting
from such an action will be retained by Regulus [***].
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(ii)
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As among the Parties, except as provided in
Section 9.3(a), each Licensor will have the sole right to protect such
Licensors Licensed Patent Rights from any actual or suspected
infringement or misappropriation. Such activities will be at such
Licensors expense. Any recoveries resulting from such an action will
be retained by such Licensor.
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9.4
Invalidity Claims
. Subject to any Third Party Rights, if a Third Party at any
time asserts a claim that a Licensors Licensed IP or the Regulus IP is invalid or otherwise
unenforceable (an
Invalidity Claim
), whether as a defense in an infringement action brought by a
Party pursuant to Section 9.3 or in an action brought against a Party under Section 9.5, the
general concepts of Section 9.3 will apply to such Invalidity Claim (i.e., each Party has the right
to defend its own intellectual property, except that the Commercializing Party will have the
initial right, to the extent provided in Section 9.3(a), to defend such Invalidity Claim, and
Regulus will have a step-in right, to the extent provided in Section 9.3(a), to defend such
Invalidity Claim).
18
9.5
Claimed Infringement
.
(a) Regulus will promptly notify the Licensors of the receipt of any claim that the
Development or Manufacture of miRNA Compounds or miRNA Therapeutics or Commercialization of miRNA
Therapeutics infringes the Patent Rights or misappropriates Know-How of any Third Party or the
commencement of any action, suit or proceeding with respect thereto, enclosing a copy of the claim
and all papers served.
(b) If a Party becomes aware that the Development or Manufacture of miRNA Compounds or miRNA
Therapeutics or the Commercialization of miRNA Therapeutics in the Field, by a Commercializing
Party, its Affiliates or Sublicensees, infringes or misappropriates, or is likely to or is alleged
to infringe or misappropriate, the Patent Rights or Know-How of any Third Party, such Party will
promptly notify intellectual property counsel to the other Parties, and such Commercializing Party
will have the sole right and responsibility to take any action it deems appropriate with respect
thereto;
provided
,
however
,
that
, to the extent that any action would
involve the enforcement of another Partys Licensed IP or the Regulus IP (if the Commercializing
Party is a Licensor), or the defense of an Invalidity Claim with respect to such other Partys
Licensed IP or the Regulus IP, the general concepts of Section 9.3 will apply to the enforcement of
such other Partys Licensed IP or the Regulus IP or the defense of such Invalidity Claim (i.e.,
each Party has the right to enforce its own intellectual property, except that the relevant
Commercializing Party will have the initial right, to the extent provided in Section 9.3(a), to
enforce such Licensed IP or Regulus IP or defend such Invalidity Claim, and Regulus will have a
step-in right, to the extent provided in Section 9.3(a), to enforce such Patent Right or defend
such Invalidity Claim).
9.6
Additional Right
. Notwithstanding any provision of Section 9, Isis will actively
participate in the planning and conduct of any enforcement of Regulus IP or Isis IP and will take
the lead of such enforcement to the extent that the scope or validity of any Licensed Patent Right
Controlled by Isis [***].
10.
CONFIDENTIAL INFORMATION
10.1
Permitted Disclosures
. Each Party may make Permitted Disclosures of another
Partys Confidential Information.
10.2
Scientific Publications
. No Party will publish, present or otherwise disclose to
the public the results of any Research Program or Development Project (
Research Results
), except
as specifically approved by the Collaboration Working Group or as provided in this Section 10.2
below or in Section 10.3. The Collaboration Working Group will agree upon the form and timing of
any publication or presentation or other disclosure (such as an abstract, manuscript or
presentation) to the public of the Research Results subject to the Collaboration Working Groups
approval. For clarification, this Section 10.2 and Section 10.3 will not apply with respect to the
use and disclosure of another Partys Confidential Information as specifically provided for in the
Investor Rights Agreement or Section 10.1 of this Agreement or for disclosure of any Partys own
information to comply with Law.
10.3
Disclosures Regarding Royalty-Bearing Products
. In addition, each
Commercializing Party may, without the Collaboration Working Groups approval, make
19
disclosures pertaining solely to its Royalty-Bearing Products;
provided
,
however
, that, (i) Regulus will immediately notify (and provide as much advance notice as
possible to) the other Parties of any event materially related to its Royalty-Bearing Products
(including any regulatory approval) so that the Parties may analyze the need to or desirability of
publicly disclosing or reporting such event and (ii) any press release or other similar public
communication by any Party related to efficacy or safety data and/or results of a Royalty-Bearing
Product will be submitted to the other Parties for review at least [***] Business Days (to the
extent permitted by Law) in advance of such proposed public disclosure, the other Parties shall
have the right to expeditiously review and recommend changes to such communication and the Party
whose communication has been reviewed shall in good faith consider any changes that are timely
recommended by the reviewing Parties. Notwithstanding the foregoing, in each case such right of
review and recommendation shall only apply for the first time that specific information is to be
disclosed, and shall not apply to the subsequent disclosure of information that (A) is
substantially similar to a previously reviewed disclosure and (B) in the context of the subsequent
disclosure, does not carry a substantially different qualitative message than that carried by the
previously reviewed disclosure.
11.
INDEMNIFICATION
11.1
Indemnification by Regulus
. Regulus agrees to defend each Licensor, the
Affiliates of each Licensor, and their respective agents, directors, officers and employees (the
Licensor Indemnitees
), at Regulus cost and expense, and will indemnify and hold harmless the
Licensor Indemnitees from and against any and all losses, costs, damages, fees or expenses
(
Losses
) relating to or in connection with a Third Party claim arising out of (a) any actual or
alleged death, personal bodily injury or damage to real or tangible personal property claimed to
result, directly or indirectly, from the manufacture, storage, possession, use or consumption of,
treatment with or sale, any miRNA Compound or miRNA Therapeutic (other than as set forth in Section
11.2(a) or in the Investor Rights Agreement), regardless of the form in which any such claim is
made or whether actual negligence is found, (b) any actual or alleged infringement or unauthorized
use or misappropriation of any Patent Right or other intellectual property right of a Third Party
with respect to the activities of Regulus, its Affiliates or Sublicensees under this Agreement or
the Services Agreement, (c) breach by Regulus of its representations, warranties or covenants made
under this Agreement or the Services Agreement, or (d) any negligent act or omission or willful
misconduct of Regulus, its Affiliates or Sublicensees or any of their employees, contractors or
agents, in performing its obligations or exercising its rights under this Agreement or the Services
Agreement;
provided
,
however
, that, with respect to each Licensor and its related
Licensor Indemnitees, the foregoing indemnity will not apply to the extent that any such Losses (i)
are attributable to the gross negligence or willful misconduct of such Licensor or its related
Licensor Indemnitees, or (ii) are otherwise subject to an obligation by such Licensor to indemnify
the Superset Indemnitees under Section 11.2(a)-(d).
11.2
Indemnification by Licensor(s)
. Each Licensor agrees to defend Regulus and its
Affiliates, and their respective agents, directors, officers and employees (the
Regulus
Indemnitees
) and the other Licensor, and its related Licensor Indemnitees (the Regulus
Indemnitees, such other Licensor and its related Licensor Indemnitees, collectively, the
Superset
Indemnitees
), at such Licensors cost and expense, and will indemnify and hold harmless the
Superset Indemnitees from and against any and all Losses, relating to or in connection with a Third
Party claim arising out of (a) any actual or alleged death, personal
20
bodily injury or damage to real or tangible personal property claimed to result, directly or
indirectly, from the manufacture, storage, possession, use or consumption of, treatment with or
sale, any miRNA Compound or miRNA Therapeutic Developed, Manufactured and/or Commercialized by such
Licensor, its Affiliates or Sublicensees pursuant to Section 5, regardless of the form in which any
such claim is made or whether actual negligence is found, (b) any actual or alleged infringement or
unauthorized use or misappropriation of any Patent Right or other intellectual property right of a
Third Party with respect to the activities of such Licensor, its Affiliates or Sublicensees under
this Agreement or the Services Agreement, (c) any breach by such Licensor of its representations,
warranties or covenants under this Agreement or the Services Agreement given to the other Party
seeking indemnification hereunder, or (d) any negligent act or omission or willful misconduct of
such Licensor or its Affiliates, or any of their employees, contractors or agents, in performing
its obligations or exercising its rights under this Agreement or the Services Agreement;
provided
,
however
, that with respect to Regulus or the indemnified Licensor, and
the relevant Superset Indemnitees, the foregoing indemnity will not apply to the extent that any
such Losses (i) are attributable to the gross negligence or willful misconduct of such Party or its
Superset Indemnitees, or (ii) are otherwise subject to an obligation by such Party to indemnify the
Licensor Indemnitees under Section 11.1(a)-(d).
11.3
Notification of Claims; Conditions to Indemnification Obligations
. A Party
entitled to indemnification under this Section 11 will (a) promptly notify the indemnifying Party
as soon as it becomes aware of a claim or action for which indemnification may be sought pursuant
hereto, (b) cooperate with the indemnifying Party in the defense of such claim or suit, and (c)
permit the indemnifying Party to control the defense of such claim or suit, including without
limitation the right to select defense counsel;
provided
that
if the Party entitled
to indemnification fails to promptly notify the indemnifying Party pursuant to the foregoing clause
(a), the indemnifying Party will only be relieved of its indemnification obligation to the extent
prejudiced by such failure. In no event, however, may the indemnifying Party compromise or settle
any claim or suit in a manner which admits fault or negligence on the part of the indemnified
Party, or which imposes obligations on the indemnified Party, other than financial obligations that
are covered by the indemnifying Partys indemnification obligation, without the prior written
consent of the indemnified Party. The indemnifying Party will have no liability under this Section
11 with respect to claims or suits settled or compromised without its prior written consent and the
indemnified Party may not, without the prior written consent of the indemnifying Party, compromise
or settle any claim or suit in a manner which admits fault or negligence on the part of the
indemnifying Party, or which imposes obligations on the indemnified Party.
11.4
Allocation
. In the event a claim is based partially on an indemnified claim
under this Agreement or the Investor Rights Agreement and partially on a non-indemnified claim or
based partially on a claim indemnified by one Party under this Agreement or the Investor Rights
Agreement and partially on a claim indemnified by another Party(ies) under this Agreement or the
Investor Rights Agreement, any payments in connection with such claims are to be apportioned
between the Parties in accordance with the degree of cause attributable to each Party.
21
12.
INSURANCE
12.1 Without limiting a Partys undertaking to defend, indemnify, and hold the other Parties
harmless as set forth in Section 11, to the extent available on commercially reasonable terms each
Party will obtain and maintain a commercial general liability policy, including coverage for
commercial general liability claims and coverage for products liability claims, taking into account
the stage of development of the miRNA Compound or miRNA Therapeutic to which such Party has rights
under this Agreement, in amounts reasonably sufficient to protect against liability under Section
11. The foregoing coverage will continue during the term of this Agreement and for a period of 3
years thereafter. The Parties have the right to ascertain from time to time that such coverage
exists, such right to be exercised in a reasonable manner.
13.
WARRANTIES
13.1
Mutual Warranties
. Each Party warrants that as of the Amendment Effective Date:
(a) it is a corporation duly organized and in good standing under the laws of the jurisdiction of
its incorporation or organization, and it has full power and authority and the legal right to own
and operate its property and assets and to carry on its business as it is now being conducted and
as it is contemplated to be conducted under this Agreement and the Services Agreement; (b) it has
the full right, power and authority to enter into this Agreement and the Services Agreement and to
grant the rights and licenses granted by it under this Agreement and the Services Agreement; (c)
there are no existing or, to its knowledge, threatened actions, suits or claims pending with
respect to the subject matter hereof or its right to enter into and perform its obligations under
this Agreement and the Services Agreement; (d) it has taken all necessary action on its part to
authorize the execution and delivery of this Agreement and the Services Agreement and the
performance of its obligations under this Agreement and the Services Agreement; (e) this Agreement
and the Services Agreement have been duly executed and delivered on behalf of it, and each
constitutes a legal, valid, binding obligation, enforceable against it in accordance with the terms
hereof, subject to the general principles of equity and to bankruptcy, insolvency, moratorium and
other similar laws affecting the enforcement of creditors rights generally; (f) all necessary
consents, approvals and authorizations of all regulatory and governmental authorities and other
persons required to be obtained by it in connection with the execution and delivery of this
Agreement and the Services Agreement and the performance of its obligations under this Agreement
and the Services Agreement have been obtained; and (g) the execution and delivery of this Agreement
and the Services Agreement and the performance of its obligations under this Agreement and the
Services Agreement do not conflict with, or constitute a default under, any of its existing
contractual obligations.
13.2
Additional Licensor Warranties
.
(a) Each Licensor warrants to Regulus that, as of the Effective Date, except as set forth on
Schedule 2.4(A)
or in accordance with Section 2.4: (i) such Licensor has the right to
grant to Regulus the rights granted to Regulus under such Licensors Licensed IP hereunder; and
(ii) no written claim has been made against such Licensor alleging that such Licensors Licensed
Patent Rights are invalid or unenforceable.
(b) Each Licensor further warrants to each other Party that such Licensor has prepared, or
will prepare, as applicable, its respective In-License Summary, Out-License
22
Summary and descriptions of Optional In-Licenses, in good faith and having used reasonable and
diligent efforts to disclose, in summary form, all material issues relating to the scope of the
license granted to Regulus and all material pass-through payment obligations. The Parties agree
and acknowledge that a Licensor shall be deemed to be in breach of the warranty in this Section
13.2(b) if such Licensor knowingly omitted from, or knowingly misrepresented in, its In-License
Summary, Out-License Summary or Optional In-License description any material issues relating to the
scope of the license granted to Regulus or any material pass-through payment obligations. For the
sake of clarity, the Parties agree and acknowledge, by way of example and not limitation, that a
Licensor shall not be deemed to be in breach of the warranty in this Section 13.2(b) if its
In-License Summary, Out-License Summary or Optional In-License description is incorrect or
misleading in light of facts, issues or technology changes which occur or become known after the
date such In-License Summary, Out-License Summary or Optional In-License description is provided to
the other Licensor.
(c) Each Licensor further warrants to each other Party that such Licensor has set forth on
Schedule 2.2(A)
, in good faith and having used reasonable and diligent efforts to identify,
all Patent Rights Controlled by such Licensor on the Effective Date that (1) are reasonably
necessary or useful to the research, development and commercialization of miRNA Compounds or miRNA
Therapeutics as contemplated by the current Operating Plan and (2) claim (a) miRNA Compounds or
miRNA Therapeutics in general, (b) specific miRNA Compounds or miRNA Therapeutics, (c) chemistry or
delivery of miRNA Compounds or miRNA Therapeutics, (d) mechanism(s) of action by which a miRNA
Antagonist directly prevents the production of the specific miRNA, or (e) methods of treating an
Indication by modulating one or more miRNAs;
except
, in each case for manufacturing
technology (including but not limited to analytical methods). In the event a Licensor is in breach
of this warranty, the Parties will work in good faith to amend
Schedule 2.2(A)
such that
the Patent Right that is the subject of the breach is including as a Licensed Patent Right under
this Agreement.
13.3
Disclaimer
. EXCEPT AS OTHERWISE EXPRESSLY SET FORTH IN THIS SECTION 13, NEITHER
PARTY MAKES ANY REPRESENTATIONS OR EXTENDS ANY WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED,
INCLUDING, BUT NOT LIMITED TO, WARRANTIES OF MERCHANTABILITY, QUALITY, FITNESS FOR A PARTICULAR
PURPOSE, NONINFRINGEMENT, OR VALIDITY OF PATENT CLAIMS, WHETHER ISSUED OR PENDING.
14.
LIMITATION OF LIABILITY
14.1 UNLESS RESULTING FROM A PARTYS WILLFUL MISCONDUCT OR FROM A PARTYS WILLFUL BREACH OF
SECTION 10, NO PARTY HERETO WILL BE LIABLE TO ANY OTHER PARTY OR ITS AFFILIATES FOR SPECIAL,
INCIDENTAL, CONSEQUENTIAL, EXEMPLARY, PUNITIVE, MULTIPLE OR OTHER INDIRECT DAMAGES ARISING OUT OF
THIS AGREEMENT OR THE EXERCISE OF ITS RIGHTS HEREUNDER, OR FOR LOSS OF PROFITS, LOSS OF DATA, LOSS
OF REVENUE, OR LOSS OF USE DAMAGES ARISING FROM OR RELATING TO ANY BREACH OF THIS AGREEMENT WHETHER
BASED UPON WARRANTY, CONTRACT, TORT, NEGLIGENCE, STRICT LIABILITY OR OTHERWISE, REGARDLESS OF ANY
NOTICE OF SUCH DAMAGES. NOTHING IN THIS SECTION 14 IS INTENDED TO LIMIT OR
23
RESTRICT THE INDEMNIFICATION RIGHTS OR OBLIGATIONS OF ANY PARTY UNDER THIS AGREEMENT.
15.
TERMINATION
15.1
Term
. This Agreement will become effective as of the Amendment Effective Date,
and will remain in effect until the earlier of (a) the termination of this Agreement in accordance
with Section 15.2, (b) the cessation of all Development of potential Royalty-Bearing Products prior
to the first commercial sale of a Royalty-Bearing Product anywhere in the world, or (c) following
the first commercial sale of a Royalty-Bearing Product anywhere in the world, the expiration of the
Royalty Terms for Royalty-Bearing Products on a country-by-country and a Royalty-Bearing
Product-by-Royalty-Bearing Product basis.
15.2
Termination for Breach
.
(a) If Regulus breaches any material provision of this Agreement (including any representation
or warranty), and fails to remedy such breach within sixty (60) days after written notice from the
Licensors, acting jointly, then the Licensors, acting jointly, shall have the right, but not the
obligation, to initiate the Buy-Out. In such event, the Licensors will determine which Licensor
will be considered the
Initiating Founding Investor
(as defined in the Investor Rights Agreement)
for purposes of the Buy-Out.
(b) If an Opt-In Party breaches any material provision of this Agreement with respect to the
relevant Development Project, and fails to remedy such breach within 60 days after written notice
from Regulus, then Regulus will have the right, but not the obligation, to terminate such Opt-In
Partys rights and licenses with respect to such Development Project and the breaching Opt-In Party
will promptly return to the aggrieved Party(ies) all related tangible Know-How and Confidential
Information of such aggrieved Party(ies).
(c) Except as provided in Section 15.2(b), if a Licensor breaches any material provision of
this Agreement (including any representation or warranty), and fails to remedy such breach within
sixty (60) days after written notice from any other Party, then (i) if such other Party is a
Licensor, such Licensor may initiate the Buy-Out, (ii) if such other Party is Regulus, Regulus may
not terminate this Agreement, and (iii) whether such other Party is Regulus or a Licensor, such
other Party has the right to seek other legal or equitable remedies with respect to such breach.
(d) Notwithstanding Section 15.2(b) or 15.2(c)(i), if a non-breaching Party gives the
allegedly-breaching Party a notice pursuant to this Section 15.2 of a material breach by such
alleged-breaching Party, and, as of the end of the cure period specified above, two or more Parties
are engaged in an arbitration pursuant to Section 16.7 in which such allegedly-breaching Party is
in good faith disputing the occurrence of the alleged material breach or the sufficiency of the
cure with respect thereto, then the non-breaching Parties may not (i) initiate the Buy-Out in the
case of Section 15.2(c)(i) or (ii) terminate the applicable license in the case of Section 15.2(b),
as a result of such breach unless and until the arbitrator issues an award that such breach
occurred (if that issue was in dispute) and/or that the cure was insufficient (if that issue was in
dispute), following which the breaching Party shall have 60 days to cure such breach (or unless
24
and until such allegedly-breaching Party is no longer disputing such issues in good faith, if
earlier).
15.3
Effects of Termination
.
(a) Any of Regulus direct Sublicensees may, by providing written notice to the Licensors
within the 60 day period immediately following termination of this Agreement with respect to
Regulus, in whole or in part, obtain from each Licensor a direct license from such Licensor, on the
same terms as the sublicense granted by Regulus to such Sublicensee with respect to such Licensors
Licensed IP, except to the extent that any such terms are inconsistent with the rights granted by
such Licensor to Regulus under this Agreement, in which case any terms in this Agreement which are
more protective of such Licensors rights will instead apply. If a Sublicensee provides such
notice, the Licensors will negotiate in good faith with such Sublicensee a written agreement to
reflect such terms;
provided
, that, (i) such Sublicensee is, at the time of termination of
this Agreement, in compliance with its sublicense agreement with Regulus, and (ii) such Sublicensee
cures any payment default of Regulus hereunder, with respect to any royalties or Sublicense Income
Payments due to the Licensors with respect to the sublicense granted by Regulus to such Sublicensee
hereunder.
15.4
Survival
. Upon termination of this Agreement, the following sections of this
Agreement will survive: Sections 2.1, 2.3, 8, 9.1(a), 9.3, 10, 11, 12, 14, 15.2, 15.3, 15.4 and 16,
and, to the extent related to Section 9.3, Sections 9.4, 9.5 and 9.6. In addition, if this
Agreement is terminated pursuant to a Buy-Out, then, with respect to each Development Project for
which an Opt-In Party has obtained a license under Section 5.6 before the initiation of the
Buy-Out, the following sections of this Agreement will survive with respect to such Development
Project: Sections 5.4 or 5.5 (as applicable), and Section 5.6, unless and until terminated
pursuant to Section 15.2(b), subject to Section 15.2(d) (with Regulus role in such termination
sections being played by the other Founding Investor following the dissolution of Regulus). Upon
any expiration of this Agreement with respect to a Royalty-Bearing Product under Section 15.1(c),
the license granted under any Know-How that is part of the Licensed IP and/or Regulus IP to a Party
with respect to such Royalty-Bearing Product will become a fully paid-up and perpetual license to
Manufacture, import, use, sell or otherwise Commercialize such Royalty-Bearing Product.
16.
MISCELLANEOUS
16.1
Assignment
. Neither this Agreement nor any of the rights or obligations
hereunder may be assigned by a Party without the prior written consent of the other Parties, except
(a) Regulus shall assign both this Agreement and the Services Agreement to a Person that acquires,
by merger, sale of assets or otherwise, all or substantially all of the business of Regulus to
which the subject matter of this Agreement relates, (b) each Licensor shall assign both this
Agreement and the Services Agreement along with the Transfer (as defined in the Investor Rights
Agreement) of such Licensors Shares (as defined in the Investor Rights Agreement) and
registerable securities, if any, and (c) each Party may assign or transfer its rights to receive
royalties, milestones and Sublicense Income Payments under this Agreement (but no liabilities) to a
Third Party in connection with [***]. Notwithstanding the foregoing, each Party will have the
right to assign this Agreement, in whole or in part, to an Affiliate of such Party without the
prior written consent of the other Parties;
provided
that
such assignee assumes in
writing all
25
obligations of the assigning Party hereunder. Any assignment not in accordance with the
foregoing will be void. This Agreement will be binding upon, and will inure to the benefit of, all
permitted successors and assigns. Each Party agrees that, notwithstanding any provisions of this
Agreement to the contrary, (y) in the event that this Agreement is assigned by a Party in
connection with the sale or transfer of all or substantially all of the business of such Party to
which the subject matter of this Agreement relates, such assignment will not provide the
non-assigning Parties with rights or access to the Know-How or Patent Rights of the acquirer of
such assigning Party, and (z) in the event of a Change of Control of a Party, the other Parties
shall not acquire rights or access to the Know-How or Patent Rights of the acquirer of such
acquired Party.
16.2
Force Majeure
. No Party will be held liable or responsible to any other Party
nor be deemed to have defaulted under or breached this Agreement for failure or reasonable delay in
fulfilling or performing any term of this Agreement (except any obligation to pay upfront payments,
milestones, royalties or Sublicense Income Payments) when such failure or delay is caused by or
results from causes beyond the reasonable control of the affected Party, which may include, without
limitation, embargoes, acts of war (whether war be declared or not), insurrections, riots, civil
commotions, acts of terrorism, strikes, lockouts or other labor disturbances, or acts of God. The
affected Party will notify the other Parties of such force majeure circumstances as soon as
reasonably practical and will make every reasonable effort to mitigate the effects of such force
majeure circumstances.
16.3
Section 365(n) of the Bankruptcy Code
. All rights and licenses granted under or
pursuant to any section of this Agreement are and will otherwise be deemed to be for purposes of
Section 365(n) of the United States Bankruptcy Code (Title 11, U.S. Code), as amended (the
Bankruptcy Code
), licenses of rights to intellectual property as defined in Section
101(35A) of the Bankruptcy Code. The Parties will retain and may fully exercise all of their
respective rights and elections under the Bankruptcy Code. The Parties agree that each Party, as
licensee of such rights under this Agreement, will retain and may fully exercise all of its rights
and elections under the Bankruptcy Code or any other provisions of Applicable Law outside the
United States that provide similar protection for intellectual property. The Parties further
agree that, in the event of the commencement of a bankruptcy proceeding by or against a Party under
the U.S. Bankruptcy Code or analogous provisions of applicable Law outside the United States, the
Party that is not subject to such proceeding will be entitled to a complete duplicate of (or
complete access to, as appropriate) such intellectual property and all embodiments of such
intellectual property, which, if not already in the non subject Partys possession, will be
promptly delivered to it upon the non subject Partys written request thereof. Any agreements
supplemental hereto will be deemed to be agreements supplementary to this Agreement for purposes
of Section 365(n) of the Bankruptcy Code.
16.4
Notices
. Any notice required or provided for by the terms of this Agreement or
the Services Agreement shall be delivered in accordance with Section 13.9 of the Investor Rights
Agreement.
16.5
Relationship of the Parties
. It is expressly agreed that the Parties will be
independent contractors hereunder and that the relationship among the Parties under this Agreement
will not constitute a partnership, joint venture or agency. No Party will have the authority under
this Agreement to make any statements, representations or commitments of any
26
kind, or to take any action, which will be binding on any other Party, without the prior
consent of such other Party. This Agreement will be understood to be a joint research agreement to
discover miRNA Compounds and associated uses and to develop Royalty-Bearing Products in accordance
with 35 U.S.C. § 103(c)(3).
16.6
Governing Law
. This Agreement will be governed and interpreted in accordance
with the substantive laws of the State of Delaware, excluding its conflicts of law rules;
provided
that
matters of intellectual property law concerning the existence,
validity, ownership, infringement or enforcement of intellectual property will be determined in
accordance with the national intellectual property laws relevant to the intellectual property in
question.
16.7
Dispute Resolution
. Except (a) for matters of intellectual property law
concerning the existence, validity, ownership, infringement or enforcement of intellectual
property, which matters will not be subject to the terms of this Section 16.7, and (b) as other
dispute resolution procedures are expressly provided herein, in the event of any dispute,
controversy or claim arising out of or relating to this Agreement, the Parties will try to settle
such dispute, controversy or claim amicably between themselves, including referring such dispute,
controversy or claim to the Executive Officers of the Parties. If the Parties are unable to so
settle such dispute, controversy or claim within a period of 60 days from the date of such
referral, then upon notice by any Party to the other Parties, any such dispute, controversy or
claim arising out of or relating to any provision of this Agreement, or the interpretation,
enforceability, performance, breach, termination or validity hereof, will be finally resolved under
the Commercial Arbitration Rules of the American Arbitration Association by a single arbitrator
appointed in accordance with such rules. The Parties will be entitled to the same discovery as
permitted under the U.S. Federal Rules of Civil Procedure;
provided
that
the
arbitrator will be entitled in its discretion to grant a request from a Party for expanded or more
limited discovery. The place of arbitration will be New York, New York. The language of the
arbitration will be English. At any time, a Party may seek or obtain preliminary, interim or
conservatory measures from the arbitrators or from a court.
16.8
Severability
. In the event any one or more of the provisions contained in this
Agreement should be held invalid, illegal or unenforceable in any respect, the validity, legality
and enforceability of the remaining provisions contained herein will not in any way be affected or
impaired thereby, unless the absence of the invalidated provision(s) adversely affect the
substantive rights of the Parties. The Parties will in such an instance use their best efforts to
replace the invalid, illegal or unenforceable provision(s) with valid, legal and enforceable
provision(s) which, insofar as practical, maintains the balance of the rights and obligations of
the Parties under this Agreement.
16.9
Entire Agreement
. This Agreement (including all schedules and exhibits hereto),
the Investor Rights Agreement and the Services Agreement constitute the entire agreement among the
Parties with respect to the subject matter herein and supersedes all previous agreements (other
than those listed in
Schedule A
(the
Previous Agreements
)), whether written or oral, with
respect to such subject matter, including without limitation the Original License Agreement. For
clarity, the Parties acknowledge and agree that the Original License Agreement remains in effect in
accordance with its terms with respect to the period between September 6, 2007 and the Amendment
Effective Date. Unless otherwise expressly indicated, references herein to sections, subsections,
paragraphs and the like are to such items within this
27
Agreement. The Parties acknowledge that this Agreement is being executed and delivered
simultaneously with the execution and delivery by the Parties and/or their Affiliates of the
Investor Rights Agreement and the Services Agreement. For purposes of clarity, nothing in this
Agreement (other than Section 5.6(d)) will be deemed to modify or amend any provision of any of the
Previous Agreements.
16.10
Amendment and Waiver
. This Agreement may not be amended, nor any rights
hereunder waived, except in a writing signed by the properly authorized representatives of each
Party.
16.11
No Implied Waivers
. The waiver by a Party of a breach or default of any
provision of this Agreement by any other Party will not be construed as a waiver of any succeeding
breach of the same or any other provision, nor will any delay or omission on the part of a Party to
exercise or avail itself of any right, power or privilege that it has or may have hereunder operate
as a waiver of any right, power or privilege by such Party.
16.12
Export Compliance
. The Parties acknowledge that the exportation from the United
States of materials, products and related technical data (and the re-export from elsewhere of
United States origin items) may be subject to compliance with United States export Laws, including,
without limitation, the United States Bureau of Export Administrations Export Administration
Regulations, the Federal Food, Drug and Cosmetic Act and regulations of the FDA issued thereunder,
and the United States Department of States International Traffic and Arms Regulations which
restrict export, re-export, and release of materials, products and their related technical data,
and the direct products of such technical data. The Parties agree to comply with all exports Laws
and to commit no act that, directly or indirectly, would violate any United States Law, or any
other international treaty or agreement, relating to the export, re-export, or release of any
materials, products or their related technical data to which the United States adheres or with
which the United States complies.
16.13
Counterparts
. This Agreement may be executed in any number of counterparts,
each of which will be deemed an original, and all of which together will constitute one and the
same instrument.
[Remainder of Page Intentionally Left Blank]
28
IN WITNESS WHEREOF, the Parties hereby execute this Agreement as of the date first written
above.
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ALNYLAM PHARMACEUTICALS, INC.
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By:
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/s/ Barry Greene
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Name:
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Barry Greene
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Title:
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President & COO
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ISIS PHARMACEUTICALS, INC.
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By:
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/s/ B. Lynne Parshall
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Name:
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B. Lynne Parshall
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Title:
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Chief Operating Officer & Chief Financial Officer
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REGULUS THERAPEUTICS INC.
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By:
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/s/ K.G. Xanthopoulos
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Name:
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K.G. Xanthopoulos
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Title:
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President & CEO
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Exhibit 1
Defined Terms
1.1
Additional Rights
will have the meaning set forth in Section 2.4(d).
1.2
Affiliate
of an entity means any other entity that, directly or indirectly, through one
or more intermediaries, controls, is controlled by, or is under common control with such first
entity. For purposes of this definition only, control (and, with correlative meanings, the terms
controlled by and under common control with) means the possession, directly or indirectly, of
the power to direct the management or policies of an entity, whether through the ownership of
voting securities or by contract relating to voting rights or corporate governance. For purposes
of this Agreement (a) Regulus will not be deemed to be an Affiliate of any Licensor and (b) a
Licensor and its Affiliates will not be considered an Affiliate of Regulus.
1.3
Agreement
will have the meaning set forth in the Preamble.
1.4
Alnylam
will have the meaning set forth in the Preamble.
1.5
Alnylam Field
will have the meaning set forth in Section 2.3(a).
1.6
Amendment Effective Date
has the meaning set forth in the Preamble.
1.7
Approved Mimic
will have the meaning set forth in Section 1.61.
1.8
Approved Precursor Antagonist
will have the meaning set forth in Section 1.61.
1.9
Bankruptcy Code
will have the meaning set forth in Section 16.3.
1.10
Business Day
means a day on which the banks in New York, New York are open for
business.
1.11
Buy-Out
will have the meaning set forth in the Investor Rights Agreement.
1.12
Change of Control
means, with respect to a Licensor, the earlier of (x) the public
announcement of or (y) the closing of: (a) a merger, reorganization or consolidation involving
such Licensor in which its shareholders immediately prior to such transaction would hold less than
50% of the securities or other ownership or voting interests representing the equity of the
surviving entity immediately after such merger, reorganization or consolidation, or (b) a sale to a
Third Party of all or substantially all of such Licensors assets or business relating to this
Agreement.
1.13
Collaboration Working Group
means a group having equal representation from Isis,
Alnylam and Regulus which will meet on a regular basis to share information about Know-How and
Patent Rights relevant to the joint venture and to conduct the business necessary under this
Agreement. Each Party will designate two Collaboration Working Group members within 30 days of the
Effective Date.
1.14
Combination Product
will have the meaning set forth in Section 1.67.
1.15
Commercialization
or
Commercialize
means any and all activities directed to
marketing, promoting, detailing, distributing, importing, having imported, exporting, having
exported, selling or offering to sell a miRNA Therapeutic following receipt of Regulatory Approval
for such miRNA Therapeutic.
1.16
Commercializing Party
means the Party Manufacturing, Developing or Commercializing a
miRNA Therapeutic under this Agreement pursuant to licenses granted under Sections 2.2 or 5.6.
1.17
Commercially Reasonable Efforts
means, reasonable, diligent, good faith efforts to
accomplish an objective as such Party would normally use to accomplish a similar objective, under
similar circumstances exercising reasonable business judgment. With respect to the Development,
Manufacturing or Commercialization of a miRNA Therapeutic, such efforts will be substantially
equivalent to the efforts used by such Party with respect to other products at similar stages in
their development or product life and of similar market potential, taking into account the profile
of the miRNA Therapeutic, the competitive landscape and other relevant factors commonly considered
in similar circumstances. For all Parties the level of effort will be at least that of a typical
medium sized biopharmaceutical company.
1.18
Completion
means, with respect to any clinical trial, the locking of the database
pertaining to such clinical trial.
1.19
Confidential Information
will have the meaning set forth in the Investor Rights
Agreement.
1.20
Control
or
Controlled
means the possession of the right (whether by ownership,
license or otherwise) to assign, or grant a license, sublicense or other right as provided for
herein without violating the terms of any agreement or other arrangement with any Third Party;
provided
,
however
, that neither Licensor will be deemed to Control Regulus IP and
no Party other than the relevant Licensor shall be deemed to Control such Licensors Licensed IP.
1.21
Controlling Party
will have the meaning set forth in Section 2.4(d).
1.22
Cover
,
Covered
or
Covering
means, (a) with respect to a patent, that, in the
absence of a license granted to a Person under a Valid Claim included in such patent, the practice
by such Person of an invention claimed in such patent would infringe such Valid Claim, or (b) with
respect to a patent application, that, in the absence of a license granted to a Person under a
Valid Claim included in such patent application, the practice by such Person of an invention
claimed in such patent application would infringe such Valid Claim if it were to issue as a patent.
1.23
Develop
or
Development
means, with respect to a miRNA Compound or miRNA Therapeutic,
any discovery, characterization, preclinical or clinical activity with respect to such miRNA
Compound or miRNA Therapeutic, including human clinical trials conducted after Regulatory Approval
of such miRNA Therapeutic to seek Regulatory Approval for additional Indications for such miRNA
Therapeutic.
2
1.24
Development Compound
means, with respect to a Development Project, any miRNA Compound
directed to the miRNA(s) which is the focus of such Development Project.
1.25
Development Project
will have the meaning set forth in Section 4.4.
1.26
Development Therapeutic
means, with respect to a Development Project, any miRNA
Therapeutic containing an miRNA Compound(s) directed to the miRNA(s) which is the focus of such
Development Project.
1.27
Disclosing Party
will have the meaning set forth in the Investor Rights Agreement.
1.28
Effective Date
means September 6, 2007, the date on which the Parties entered into the
Original License Agreement.
1.29
Exclusivity Period
means, with respect to a Royalty-Bearing Product in a country, that
period of time beginning with the first commercial sale of such Royalty-Bearing Product in such
country and ending on the later to expire of (a) the time during which the applicable Regulatory
Authority in such country is not permitted to grant Regulatory Approval for a generic equivalent of
such Royalty-Bearing Product and (b):
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with respect to a Royalty-Bearing Product being Commercialized by Regulus, the
last Valid Claim of the Patent Rights licensed to Regulus pursuant to this
Agreement or the Regulus Patent Rights Covering (i) the Manufacture of such
Royalty-Bearing Product in such country or (ii) the use, sale or other
Commercialization of such Royalty-Bearing Product in such country; or
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with respect to a Royalty-Bearing Product being Commercialized by a Licensor,
the last Valid Claim of the Patent Rights licensed to such Licensor pursuant to
this Agreement Covering (i) the Manufacture of such Royalty-Bearing Product in such
country or (ii) the use, sale or other Commercialization of such Royalty-Bearing
Product in such country.
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1.30
Executive Officer
means, with respect to a Party, the Chief Executive Officer of such
Party (or the officer or employee of such Party then serving in a substantially equivalent
capacity) or his/her designee of substantially equivalent rank.
1.31
FDA
means the United States Food and Drug Administration or any successor agency
thereto.
1.32
Field
means treatment and/or prophylaxis of any or all Indications.
1.33
GAAP
means United States Generally Accepted Accounting Principles, consistently
applied.
1.34
GLP
means the then-current good laboratory practice standards promulgated or endorsed
by the FDA as defined in 21 C.F.R. Part 58, and comparable foreign regulatory standards.
3
1.35
[***]
means a [***].
1.36
Hatch-Waxman Act
will have the meaning set forth in Section 9.3(a)(i)(A).
1.37
High Terms
will have the meaning set forth in Section 5.4.
1.38
In-License Agreement
will have the meaning set forth in Section 2.4(b).
1.39
In-License Summary
will have the meaning set forth in Section 2.4(b).
1.40
IND
means an Investigational New Drug Application or similar foreign application or
submission for approval to conduct human clinical investigations.
1.41
Indication
means any disease or condition, or sign or symptom of a disease or
condition, or symptom associated with a disease or syndrome.
1.42
Initial Opt-In Election Period
will have the meaning set forth in Section 5.3.
1.43
Intellectual Property
will have the meaning set forth in the Investor Rights Agreement.
1.44
Invalidity Claim
will have the meaning set forth in Section 9.4.
1.45
Investor Rights Agreement
means the Founding Investor Rights Agreement of Regulus among
the Parties, dated as of the Amendment Effective Date, as the same may be amended from time to time
after the Amendment Effective Date.
1.46
Isis
will have the meaning set forth in the Preamble.
1.47
Isis Field
will have the meaning set forth in Section 2.3(b).
1.48
Know-How
means any information, inventions, trade secrets or technology (excluding
Patent Rights), whether or not proprietary or patentable and whether stored or transmitted in oral,
documentary, electronic or other form. Know-How includes ideas, concepts, formulas, methods,
procedures, designs, compositions, plans, documents, data, discoveries, developments, techniques,
protocols, specifications, works of authorship, biological materials, and any information relating
to research and development plans, experiments, results, compounds, therapeutic leads, candidates
and products, clinical and preclinical data, clinical trial results, and Manufacturing information
and plans.
1.49
Law
means any law, statute, rule, regulation, ordinance or other pronouncement having
the effect of law of any federal, national, multinational, state, provincial, county, city or other
political subdivision, domestic or foreign.
1.50
Licensed IP
means, with respect to a Licensor, such Licensors Licensed Know-How and
Licensed Patent Rights.
1.51
Licensed Know-How
means, with respect to a Licensor, all Know-How Controlled by such
Licensor on the Effective Date or during the term of this Agreement (except
4
as otherwise expressly provided herein) that relates to (a) miRNA Compounds or miRNA
Therapeutics in general, (b) specific miRNA Compounds or miRNA Therapeutics, (c) chemistry or
delivery of miRNA Compounds or miRNA Therapeutics, (d) mechanism(s) of action by which a miRNA
Antagonist directly prevents the production of a specific miRNA, or (e) methods of treating an
Indication by modulating one or more miRNAs;
provided
,
however
, that in each case,
(i) for any such Know-How that include financial or other obligations to a Third Party, the
provisions of Section 2.4 will govern whether such Know-How will be included as Licensed Know-How
and (ii) Licensed Know How does not include manufacturing technology (including but not limited to
analytical methods).
1.52
Licensed Patent Rights
means, with respect to a Licensor, (A) all Patent Rights
Controlled by such Licensor on the Effective Date and listed on
Schedule 2.2(A)
, and (B)
all Patent Rights Controlled by such Licensor during the term of this Agreement (except as
otherwise expressly provided herein) that claim (a) miRNA Compounds or miRNA Therapeutics in
general, (b) specific miRNA Compounds or miRNA Therapeutics, (c) chemistry or delivery of miRNA
Compounds or miRNA Therapeutics, (d) mechanism(s) of action by which a miRNA Antagonist directly
prevents the production of the specific miRNA, or (e) methods of treating an Indication by
modulating one or more miRNAs;
provided
,
however
, that in each case, (i) for any
such Patent Rights that include financial or other obligations to a Third Party, the provisions of
Section 2.4 will govern whether such Patent Right will be included as a Licensed Patent Right and
(ii) Licensed Patent Rights do not include manufacturing technology (including but not limited to
analytical methods).
1.53
Licensor
will have the meaning set forth in the Preamble.
1.54
Licensor Indemnitees
will have the meaning set forth in Section 11.1.
1.55
Losses
will have the meaning set forth in Section 11.1.
1.56
Low Terms
will have the meaning set forth in Section 5.5.
1.57
Major Country
means France, Germany, Italy, Spain and the United Kingdom.
1.58
Manufacture
or
Manufacturing
means any activity involved in or relating to the
manufacturing, quality control testing (including in-process, release and stability testing),
releasing or packaging, for pre-clinical, clinical or commercial purposes, of a miRNA Compound or a
miRNA Therapeutic.
1.59
miRNA
means a structurally defined functional RNA molecule usually between 21 and 25
nucleotides in length, which is derived from genetically-encoded non-coding RNA which is predicted
to be processed into a hairpin RNA structure that is a substrate for the double-stranded
RNA-specific ribonuclease Drosha and subsequently is predicted to serve as a substrate for the
enzyme Dicer, a member of the RNase III enzyme family; including, without limitation, those miRNAs
exemplified in miRBase (http://microrna.sanger.ac.uk/). To the extent that [***] for purposes of
this Agreement;
provided
,
however
, that nothing contained herein shall require any
Party hereto to [***].
5
1.60
miRNA Antagonist
means a single-stranded oligonucleotide (or a single stranded analog
thereof) that is designed to interfere with or inhibit a particular miRNA. For purposes of
clarity, the definition of miRNA Antagonist is not intended to include oligonucleotides that
function predominantly through the RNAi mechanism of action or the RNase H mechanism of action.
1.61
miRNA Compound
means a compound consisting of (a) a miRNA Antagonist, (b) to the extent
listed in
Schedule 1.61
or otherwise agreed upon by Regulus and the relevant Licensor(s)
pursuant to Section 2.2(b), a miRNA Precursor Antagonist (an
Approved Precursor Antagonist
), or
(c) to the extent agreed upon by Regulus and the relevant Licensor(s) pursuant to Section 2.2(b), a
miRNA Mimic (an
Approved Mimic
).
1.62
miRNA Mimic
means a double-stranded or single-stranded oligonucleotide or analog
thereof with a substantially similar base composition as a particular miRNA and which is designed
to mimic the activity of such miRNA.
1.63
miRNA Precursor
means a transcript that originates from a genomic DNA and that
contains, but not necessarily exclusively, a non-coding, structured RNA comprising one or more
mature miRNA sequences, including, without limitation, (a) polycistronic transcripts comprising
more than one miRNA sequence, (b) miRNA clusters comprising more than one miRNA sequence, (c)
pri-miRNAs, and/or (d) pre-miRNAs.
1.64
miRNA Precursor Antagonist
means a single-stranded oligonucleotide (or a single
stranded analog thereof) that is designed to bind to a miRNA Precursor to prevent the production of
one or more miRNAs. For purposes of clarity, the definition of miRNA Precursor Antagonist is not
intended to include oligonucleotides that function predominantly through the RNAi mechanism of
action or the RNase H mechanism of action.
1.65
miRNA Therapeutic
means a therapeutic product having one or more miRNA Compounds as an
active ingredient(s).
1.66
NDA
means a New Drug Application or similar application or submission for approval to
market and sell a new pharmaceutical product filed with or submitted to a Regulatory Authority.
1.67
Net Sales
means, with respect to a Royalty-Bearing Product, the gross invoice price of
all units of such Royalty-Bearing Products sold by the relevant Commercializing Party, its
Affiliates and/or their direct Sublicensees to any Third Party, less the following items: (a)
trade discounts, credits or allowances, (b) credits or allowances additionally granted upon
returns, rejections or recalls, (c) freight, shipping and insurance charges, (d) taxes, duties or
other governmental tariffs (other than income taxes), (e) government-mandated rebates, and (f) a
reasonable reserve for bad debts. Net Sales under the following circumstances will mean the fair
market value of such Royalty-Bearing Product: (i) Royalty-Bearing Products which are used by such
Commercializing Party, its Affiliates or direct Sublicensees for any commercial purpose without
charge or provision of invoice, (ii) Royalty-Bearing Products which are sold or disposed of in
whole or in part for non cash consideration, or (iii) Royalty-Bearing Products which are provided
to a Third Party by such Commercializing Party, its Affiliates or direct Sublicensees
6
without charge or provision of invoice and used by such Third Party except in the cases of
Royalty-Bearing Products used to conduct clinical trials, reasonable amounts of Royalty-Bearing
Products used as marketing samples and Royalty-Bearing Product provided without charge for
compassionate or similar uses.
Net Sales will not include any transfer between or among a Party and any of its Affiliates or
direct Sublicensees for resale.
In the event a Royalty-Bearing Product is sold as part of a Combination Product (as defined below),
the Net Sales from the Combination Product, for the purposes of determining royalty payments, will
be determined by multiplying the Net Sales (as determined without reference to this paragraph) of
the Combination Product, by the fraction, A/A+B, where A is the average sale price of the
Royalty-Bearing Product when sold separately in finished form and B is the average sale price of
the other therapeutically active pharmaceutical compound(s) included in the Combination Product
when sold separately in finished form, each during the applicable royalty period or, if sales of
all compounds did not occur in such period, then in the most recent royalty reporting period in
which sales of all occurred. In the event that such average sale price cannot be determined for
both the Royalty-Bearing Product and all other therapeutically active pharmaceutical compounds
included in the Combination Product, Net Sales for the purposes of determining royalty payments
will be calculated as above, but the average sales price in the above equation will be replaced by
a good faith estimate of the fair market value of the compound(s) for which no such price exists.
As used above, the term
Combination Product
means any pharmaceutical product which consists of a
Royalty-Bearing Product and other therapeutically active pharmaceutical compound(s).
1.68
Non-Controlling Party
will have the meaning set forth in Section 2.4(d).
1.69
[***]
means [***].
1.70
[***]
means the [***].
1.71
Operating Plan
has the meaning ascribed to it in the Investor Rights Agreement.
1.72
Opt-In Election
will have the meaning set forth in Section 5.3.
1.73
Opt-In Party
will have the meaning set forth in Section 5.3(a) and 5.3(c).
1.74
Opt-In Product
means any miRNA Therapeutic that is Developed, Manufactured or
Commercialized pursuant to a Development Project for which one and only one Licensor has exercised
an Opt-In Election and which the relevant Opt-In Party subsequently licensed.
1.75
Optional In-License
will have the meaning set forth in Section 2.4(c).
1.76
Out-License Agreement
will have the meaning set forth in Section 2.4(a).
1.77
Out-License Summary
will have the meaning set forth in Section 2.4(a).
7
1.78
Paragraph IV Certification
will have the meaning set forth in Section 9.3(a)(i)(A).
1.79
Party
means Alnylam, Isis and/or Regulus;
Parties
means Alnylam, Isis and Regulus, or
any combination thereof.
1.80
Patent Rights
means (a) patent applications (including provisional applications and for
certificates of invention); (b) any patents issuing from such patent applications (including
certificates of invention); (c) all patents and patent applications based on, corresponding to, or
claiming the priority date(s) of any of the foregoing; and (d) any substitutions, extensions
(including supplemental protection certificates), registrations, confirmations, reissues,
divisionals, continuations, continuations-in-part, re-examinations, renewals and foreign
counterparts thereof.
1.81
Payee Party
will have the meaning set forth in Section 8.1.
1.82
Paying Party
will have the meaning set forth in Section 8.1.
1.83
Permitted Disclosures
The following are Permitted Disclosures:
(a) To the extent that a Recipient has been granted the right to sublicense under the terms
of this Agreement, such Party will have the right to provide a Disclosing Partys Confidential
Information to the employees, consultants and advisors of such Recipients Affiliate and Third
Party sublicensees and potential sublicensees who have a need to know the Confidential
Information for purposes of exercising such sublicense and are bound by an obligation to
maintain in confidence the Confidential Information of the Disclosing Party;
provided
,
that such Persons are bound to maintain the confidentiality of such information to the same
extent as if they were parties hereto.
(b) Each Recipient will have the right to provide a Disclosing Partys Confidential
Information:
|
(i)
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to governmental or other regulatory agencies in
order to seek or obtain patents, to seek or obtain approval to conduct
clinical trials, or to gain Regulatory Approval, as contemplated by
this Agreement;
provided
that
such disclosure may be
made only to the extent reasonably necessary to seek or obtain such
patents or approvals; and
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(ii)
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as necessary, if embodied in products, to
develop and commercialize such products as contemplated by this
Agreement.
|
1.84
Permitted License
means a license granted by a Licensor to a Third Party to enable such
Third Party to broadly manufacture or formulate oligonucleotides, where such Third Party is
primarily engaged in [***];
provided
,
however
, that any such license will not grant
rights to research, manufacture or formulate miRNA Compounds or miRNA Therapeutics for which the
other Licensor has obtained or later obtains a license pursuant to Section 5 or pursuant to the
Buy-Out process in the Investor Rights Agreement.
8
1.85
Person
means any corporation, limited or general partnership, limited liability
company, joint venture, trust, unincorporated association, governmental body, authority, bureau or
agency, any other entity or body, or an individual.
1.86
Phase IIa Clinical Trial
means, with respect to a Royalty-Bearing Product, any human
clinical trial conducted in patients with a particular Indication for the purpose of studying the
pharmacokinetic or pharmacodynamic properties and preliminary assessment of safety and efficacy of
such Royalty-Bearing Product over a measured dose response, as described in 21 C.F.R. §312.21(b) or
its foreign counterpart.
1.87
Phase III Clinical Trial
means, with respect to a Royalty-Bearing Product, a controlled
pivotal clinical study of such Royalty-Bearing Product that is prospectively designed to
demonstrate statistically whether such Royalty-Bearing Product is safe and effective to treat a
particular Indication in a manner sufficient to obtain Regulatory Approval to market such
Royalty-Bearing Product, as described in 21 CFR 312.21(c) or its foreign counterpart.
1.88
Previous Agreements
will have the meaning set forth in Section 16.9.
1.89
Program/Project List
will have the meaning set forth in Section 4.4.
1.90
Recipient
will have the meaning set forth in the Investor Rights Agreement.
1.91
Regulatory Approval
means the act of a Regulatory Authority necessary for the marketing
and sale (including, if required for marketing and sales, pricing) of such product in a country or
regulatory jurisdiction, including, without limitation, the approval of an NDA by the FDA.
1.92
Regulatory Authority
means any applicable government regulatory authority involved in
granting approvals for the marketing and/or pricing of a product in a country or regulatory
jurisdiction including, without limitation, the FDA.
1.93
Regulus
will have the meaning set forth in the Preamble.
1.94
Regulus Indemnitees
will have the meaning set forth in Section 11.2.
1.95
Regulus IP
means all Regulus Know-How and Regulus Patent Rights.
1.96
Regulus Know-How
means all Know-How conceived and/or developed by or on behalf of
Regulus (including by employees of a Licensor or its Affiliates in performance of the Services
Agreement), or over which Regulus otherwise acquires Control, including but not limited to any
Know-How assigned to Regulus by a Licensor under Section 9.1, but specifically excluding Licensed
IP.
1.97
Regulus Patent Rights
means any Patent Right claiming an invention conceived and/or
developed by or on behalf of Regulus (including by employees of a Licensor or its Affiliates in
performance of the Services Agreement), or over which Regulus otherwise acquires Control, including
but not limited to any Patent Right assigned to Regulus by a Licensor under Sections 2.1 or 9.1,
but specifically excluding Licensed IP.
9
1.98
Research
means pre-clinical research including gene function, gene expression and
target validation research, which may include small pilot toxicology studies but excludes the
pharmacokinetic and toxicology studies required to meet the regulations for filing an IND, clinical
development and commercialization.
1.99
Research Program
will have the meaning set forth in Section 4.4.
1.100
Royalty-Bearing Product
means
|
(a)
|
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a miRNA Therapeutic being Developed, Manufactured or
Commercialized by Regulus that, on a country-by-country basis, is, or Regulus
reasonably believes will be, at the time of first commercial sale of such miRNA
Therapeutic, Covered in such country by a Valid Claim of a Patent Right or
covered by Know-How of (i) a Licensed Patent Right licensed to it hereunder, or
(ii) any Regulus IP (except any Regulus IP solely in-licensed or acquired by
Regulus from a Third Party); or
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(b)
|
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an Opt-In Product that, on a country-by-country basis, is, or
the relevant Opt-In Party reasonably believes will be, at the time of first
commercial sale of such Opt-In Product, Covered in such country by a Valid
Claim of a Patent Right or covered by Know-How, which Patent Right or Know-How
is licensed to the applicable Opt-In Party hereunder.
|
1.101
Royalty Term
means, with respect to each Royalty-Bearing Product in a country, the
period commencing upon first commercial sale of such Royalty-Bearing Product in such country and
ending upon the later of (a) the expiration of the Exclusivity Period, or (b) 10 years following
first commercial sale of such Royalty-Bearing Product.
1.102
Second Opt-In Election Period
will have the meaning set forth in Section 5.3(c)(i).
1.103
Services Agreement
means that certain Amended and Restated Services Agreement by and
between Regulus, Alnylam and Isis dated the Amendment Effective Date, as the same may be amended
from time to time after the Amendment Effective Date.
1.104
Sublicense Income
means all amounts received by the Opt-In Party or its Affiliates
with respect to any sublicense granted to a Third Party by the Opt-In Party or its Affiliates of
the Regulus IP or Licensed IP licensed to the Opt-In Party under Section 5.6(a), including, without
limitation, upfront payments and milestones, but excluding:
(a) amounts received by the Opt-In Party or its Affiliates as payments for actual direct costs
for performing future Development, Manufacturing or Commercialization activities undertaken by the
Opt-In Party or its Affiliates for, or in collaboration with, such Sublicensee or its Affiliates
with respect to the relevant Opt-In Products;
(b) amounts received by the Opt-In Party and/or its Affiliates from such Sublicensee or its
Affiliates as the purchase price for the Opt-In Partys or any of its Affiliates
10
debt or equity securities,
except
that amounts which exceed the fair market value of such debt
or equity securities will be considered Sublicense Income;
(c) royalties paid by such Sublicensee or its Affiliates with respect to Net Sales of
Royalty-Bearing Products; and
(d) amounts paid by such Sublicensee or its Affiliates to the Opt-In Party or its Affiliates
to purchase Royalty-Bearing Products;
except
that any amount greater than the actual cost of goods
(with no profit added) of such Royalty-Bearing Products, determined in accordance with GAAP, will
be considered Sublicense Income.
1.105
Sublicense Income Payments
means, with respect to a Development Project and a calendar
quarter, the Sublicense Income received by the relevant Opt-In Party or its Affiliates in such
calendar quarter with respect to such Development Project, multiplied by the relevant percentage
determined pursuant to Section 5.4(d) or 5.5(d), as applicable.
1.106
Sublicensee
means a Third Party to whom a Party, or its Affiliates or Sublicensees,
has granted a sublicense in accordance with the terms of this Agreement.
1.107
Superset Indemnitees
will have the meaning set forth in Section 11.2.
1.108
Third Party
means any Person other than the Parties or any of their Affiliates.
1.109
Third Party Agreement
means either (i) an out-license agreement described in the
Out-License Summary, (ii) an In-License Agreement described on the In-License Summary, (iii) an
Optional In-License or (iv) an agreement pursuant to which a Controlling Party obtained Control
over an Additional Right.
1.110
Third Party Rights
means, with respect to a Party, any rights of, and any limitations,
restrictions or obligations imposed by, Third Parties pursuant to Third Party Agreements.
1.111
Valid Claim
means a claim (a) of any issued, unexpired patent that has not been
revoked or held unenforceable or invalid by a decision of a court or governmental agency of
competent jurisdiction from which no appeal can be taken, or with respect to which an appeal is not
taken within the time allowed for appeal, and that has not been disclaimed or admitted to be
invalid or unenforceable through reissue, disclaimer or otherwise; or (b) of any patent application
that has not been cancelled, withdrawn or abandoned, or been pending
for more than [**] years.
1.112
Work Product
means any data, documentation, inventions and other Know-How arising from
or made in the performance of the Services (as defined in the Services Agreement) by a Licensor.
11
SCHEDULE A
Previous Agreements
Strategic Collaboration & License Agreement between Isis Pharmaceuticals, Inc. and Alnylam
Pharmaceuticals, Inc., dated March 11, 2004, as supplemented or amended by letter agreements dated
March 9, 2004 (as amended by letter agreement dated October 28, 2005), March 11, 2004, and June 10,
2005
License Agreement between Max Plank Innovation GmbH (formerly Garching Innovation GmbH), Isis
Pharmaceuticals, Inc. and Alnylam Pharmaceuticals, Inc., dated October 18, 2004
Co-Exclusive License Agreement among The Board of Trustees of the Leland Stanford Junior
University, Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc., dated August 31, 2005
Schedule 1.61
Initial miRNA Precursor Antagonists
[***]
[***]
Schedule 2.1(A)
Patents and License Agreements Assigned to Regulus by Isis
Isis Patent Applications to be Assigned to Regulus
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IsisDocket
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Filing
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Priority
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Number
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Country
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Serial Number
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Date
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Date
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Title
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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Isis License Agreements to be Assigned to Regulus
[***][***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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2
Schedule 2.1(B)
Patents and License Agreements Assigned to Regulus by Alnylam
Alnylam Patent Applications to be Assigned to Regulus
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CaseNumber
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InvTitle
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Country
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CaseType
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AppNumber
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FilDate
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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Alnylam License Agreements to be Assigned to Regulus
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc. effective
August 15, 2005
[summary is attached as
Exhibit 2
]
3
Schedule 2.2(A)
Patents and Patent Applications Licensed to Regulus by Isis on the Effective Date
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Isis Docket
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Serial
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Priority
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Patent
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Number
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Country
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Number
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Filing Date
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Date
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Title
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Number
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4
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5
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6
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Isis Docket
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Patent
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Number
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7
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Isis Docket
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Serial
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Priority
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Patent
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Number
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Number
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Filing Date
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Date
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Number
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8
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Isis Docket
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Serial
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Priority
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Patent
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Number
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Number
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Filing Date
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Date
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Title
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Number
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[***]
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[***]
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[***]
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9
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Isis Docket
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Serial
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Priority
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Patent
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Number
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Country
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Number
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Filing Date
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Date
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Title
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Number
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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10
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11
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12
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13
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14
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Isis Docket
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Number
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Title
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Number
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17
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18
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19
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20
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21
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22
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23
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24
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25
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28
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29
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30
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38
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40
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42
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44
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45
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51
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[***]
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52
Patents and Patent Applications Licensed to Regulus by Alnylam on the Effective Date
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AppNumber
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
|
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[***]
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[***]
|
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
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[***]
|
|
[***]
|
57
Schedule 2.4(A)
Part 1
Isis Existing Out-License Agreements
This Appendix 2.4(A) contains a list and summary of certain agreements in effect as of the
Effective Date between Isis and certain Third Parties that may, as applicable, place certain
encumbrances or limitations on the licenses or sublicenses granted to Regulus and the
representations and warranties, where specified in the Agreement. Copies of the listed agreements
will be provided at Regulus request for a complete disclosure of the encumbrances and limitations
in each agreement.
As set forth in the Agreement, the information and disclosures contained in this Appendix are
intended only to qualify and limit the licenses granted by Isis to Regulus, the exclusivity
covenants, and the representations and warranties given by Isis under the Agreement and do not
expand in any way the scope or effect of any such licenses, representations or warranties.
Nothing herein constitutes an admission of any liability or obligation of Isis nor an admission
against any interest of Isis. The inclusion of this Appendix or the information contained in this
Appendix does not
indicate that Isis has determined that this Appendix or the information contained in this Appendix
when considered individually or in the aggregate, is necessarily material to Isis.
Regulus acknowledges that certain information contained in this Appendix may constitute material
Confidential Information relating to Isis which may not be used for any other purpose other than
that contemplated by the Agreement.
Capitalized terms used herein below, but not otherwise defined herein below, have the meanings
given to such terms in the applicable agreement listed below, unless it is clear from the context
that the term has the meaning set forth in the Agreement.
[***]
58
Schedule 2.4(A)
Part 2
Alnylams Existing Out-License Agreements
License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (formerly INEX
Pharmaceuticals Corporation) and Alnylam, dated January 8, 2007
License and Collaboration Agreement dated July 8, 2007, by and among Alnylam Pharmaceuticals, Inc.,
F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., effective on August 9, 2007
Research Collaboration and License Agreement between Novartis Institutes for BioMedical Research,
Inc. and Alnylam Pharmaceuticals, Inc., effective October 12, 2005, as amended by the Addendum Re:
Influenza Program effective as of December 13, 2005, Amendment No. 1 to such Addendum effective as
of March 14, 2006, and Amendment No. 2 to such Addendum effective as of May 5, 2006
[summaries are attached as
Exhibit 2
]
59
Schedule 2.4(B)
Part 1
Isis Existing In-License Agreements
This Appendix 2.4(B) contains a list and summary of certain agreements in effect as of the
Effective Date between Isis and certain Third Parties that may, as applicable, place certain
encumbrances or limitations on the licenses or sublicenses granted to Regulus and the
representations and warranties, where specified in the Agreement. Copies of the listed agreements
will be provided at Regulus request for a complete disclosure of the encumbrances and limitations
in each agreement.
As set forth in the Agreement, the information and disclosures contained in this Appendix are
intended only to qualify and limit the licenses granted by Isis to Regulus, the exclusivity
covenants, and the representations and warranties given by Isis under the Agreement and do not
expand in any way the scope or effect of any such licenses, representations or warranties.
Nothing herein constitutes an admission of any liability or obligation of Isis nor an admission
against any interest of Isis. The inclusion of this Appendix or the information contained in this
Appendix does not indicate that Isis has determined that this Appendix or the information contained
in this Appendix when considered individually or in the aggregate, is necessarily material to Isis.
Regulus acknowledges that certain information contained in this Appendix may constitute material
Confidential Information relating to Isis which may not be used for any other purpose other than
that contemplated by the Agreement.
Capitalized terms used herein below, but not otherwise defined herein below, have the meanings
given to such terms in the applicable agreement listed below, unless it is clear from the context
that the term has the meaning set forth in the Agreement.
[***]
Schedule 2.4(B)
Part 2
Alnylams Existing In-License Agreements
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc. effective
May 8, 2006 (the
Tuschl Agreement
)
Co-Exclusive License Agreement among The Board of Trustees of the Leland Stanford Junior
University, Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc. effective August 31, 2005
License Agreement among Garching Innovation GmbH, Alnylam Pharmaceuticals, Inc. and Isis
Pharmaceuticals, Inc. effective October 18, 2004
[summaries are attached as
Exhibit 2
]
2
Schedule 2.4(C)
Part 1
Isis Optional In-Licenses
This Appendix 2.4(C) contains a list and summary of certain agreements in effect as of the
Effective Date between Isis and certain Third Parties that may, as applicable, place certain
encumbrances or limitations on the licenses or sublicenses granted to Regulus and the
representations and warranties, where specified in the Agreement. Copies of the listed agreements
will be provided at Regulus request for a complete disclosure of the encumbrances and limitations
in each agreement.
As set forth in the Agreement, the information and disclosures contained in this Appendix are
intended only to qualify and limit the licenses granted by Isis to Regulus, the exclusivity
covenants, and the representations and warranties given by Isis under the Agreement and do not
expand in any way the scope or effect of any such licenses, representations or warranties.
Nothing herein constitutes an admission of any liability or obligation of Isis nor an admission
against any interest of Isis. The inclusion of this Appendix or the information contained in this
Appendix does not indicate that Isis has determined that this Appendix or the information contained
in this Appendix when considered individually or in the aggregate, is necessarily material to Isis.
Regulus acknowledges that certain information contained in this Appendix may constitute material
Confidential Information relating to Isis which may not be used for any other purpose other than
that contemplated by the Agreement.
Capitalized terms used herein below, but not otherwise defined herein below, have the meanings
given to such terms in the applicable agreement listed below, unless it is clear from the context
that the term has the meaning set forth in the Agreement.
[***]
Schedule 2.4(C)
Part 2
Alnylams Optional In-Licenses
[***]Amended and Restated Exclusive Patent License Agreement between Massachusetts Institute of
Technology (
MIT
) and Alnylam, dated May 9, 2007
License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (formerly INEX
Pharmaceuticals Corporation) (
Tekmira
) and Alnylam, dated January 8, 2007
The Sublicense Agreement between Tekmira and Alnylam, dated January 8, 2007
[summaries are attached as
Exhibit 2
]
2
Schedule 5.6(f)
Examples regarding Payments Due
Example 1: [***]
Party opts-in at [***]
Party responsible for High Terms
Party sublicenses product mid Phase IIb at terms below
|
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Cumulative
|
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Guaranteed
|
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Cumulative
|
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Sublicense
|
|
Sublicense
|
|
|
|
|
|
|
Payments
|
|
|
|
Guaranteed
|
|
|
|
|
|
Income
|
|
Income
|
|
Cumulative
|
|
Payments
|
|
|
Due Under
|
|
Paid Before
|
|
Payments
|
|
Sublicense
|
|
Sublicense
|
|
Payments
|
|
Payments
|
|
Amount
|
|
Payable By
|
Milestones
|
|
High Terms
|
|
Sublicense
|
|
Payable
|
|
Milestones
|
|
Income
|
|
Due ([***]%)
|
|
Due
|
|
Owed
|
|
Opt-in Party
|
Upfont
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
IND filing
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
Completion of Phase
IIa
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
Phase III start
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
Total
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
Example 2: [***]
Party opts-in at [***]
Party responsible for Low Terms
Party sublicenses product after IND at terms below
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cumulative
|
|
|
|
|
|
|
Guaranteed
|
|
|
|
Cumulative
|
|
|
|
|
|
Sublicense
|
|
Sublicense
|
|
|
|
|
|
|
Payments
|
|
|
|
Guaranteed
|
|
|
|
|
|
Income
|
|
Income
|
|
Cumulative
|
|
Payments
|
|
|
Due Under
|
|
Paid Before
|
|
Payments
|
|
Sublicense
|
|
Sublicense
|
|
Payments
|
|
Payments
|
|
Amount
|
|
Payable By
|
Milestones
|
|
Low Terms
|
|
Sublicense
|
|
Payable
|
|
Milestones
|
|
Income
|
|
Due ([***]%)
|
|
Due
|
|
Owed
|
|
Opt-in Party
|
Upfont
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
IND filing
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
Upfront sublicense
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
Completion of Phase
IIa
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
Phase III start
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
P3 end
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
Japan approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
Total
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
2
Example 3: [***]
Party opts-in at [***]
Party responsible for High Terms
Party sublicenses product mid Phase III at terms below
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Guaranteed
|
|
|
|
Cumulative
|
|
|
|
|
|
Sublicense
|
|
|
|
|
|
|
|
|
Payments
|
|
|
|
Guaranteed
|
|
|
|
|
|
Income
|
|
Cumulative
|
|
|
|
|
|
|
Due Under
|
|
Paid Before
|
|
Payments
|
|
Sublicense
|
|
Sublicense
|
|
Payments Due
|
|
Sublicense Income
|
|
Cumulative Amount
|
|
Payments Payable By
|
Milestones
|
|
High Terms
|
|
Sublicense
|
|
Payable
|
|
Milestones
|
|
Income
|
|
([***]%)
|
|
Payments Due
|
|
Owed
|
|
Opt-in Party
|
Upfont
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
IND filing
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
Completion of Phase
IIa
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
Phase III start
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU filing
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
FDA approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
EU approval
|
|
[***]
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
|
|
|
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
Total
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
[***]
|
|
3
Exhibit 2
Alnylam Summaries
Attachments to Schedules 2.1(B), 2.4(A) Part 2, 2.4(B) Part 2 and 2.4(C) Part 2
Copies of the following agreements, some in redacted form, have been, or shall be, made available
to Licensee as of the Effective Date:
Schedule 2.1(B)
:
Patents and License Agreements Assigned to Regulus by Alnylam
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc.
effective August 15, 2005
Schedule 2.4(A) Part 2
:
Alnylams Existing Out-License Agreements
License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (formerly
INEX Pharmaceuticals Corporation) and Alnylam Pharmaceuticals, Inc., dated January 8, 2007.
License and Collaboration Agreement dated July 8, 2007, by and among Alnylam
Pharmaceuticals, Inc., F. Hoffmann-La Roche Ltd and Hoffmann-La Roche Inc., effective on August 9,
2007
Research Collaboration and License Agreement between Novartis Institutes for BioMedical
Research, Inc. and Alnylam Pharmaceuticals, Inc., effective October 12, 2005, as amended by the
Addendum Re: Influenza Program effective as of December 13, 2005, Amendment No. 1 to such Addendum
effective as of March 14, 2006, and Amendment No. 2 to such Addendum effective as of May 5, 2006
Schedule 2.4(B) Part 2
:
Alnylams Existing In-License Agreements
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc.
effective May 8, 2006
Co-Exclusive License Agreement among The Board of Trustees of the Leland Stanford Junior
University, Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc. effective August 31, 2005
License Agreement among Garching Innovation GmbH, Alnylam Pharmaceuticals, Inc. and Isis
Pharmaceuticals, Inc. effective October 18, 2004
Schedule 2.4(C) Part 2
:
Alnylams Optional In-Licenses
Amended and Restated Exclusive Patent License Agreement between Alnylam Pharmaceuticals,
Inc. and Massachusetts Institute of Technology, dated May 9, 2007.
Page 1 of 61
The Sublicense Agreement between Tekmira Pharmaceuticals Corporation (formerly INEX
Pharmaceuticals Corporation) and Alnylam Pharmaceuticals, Inc., dated January 8, 2007.
This
In-License Summary
,
Out-License Summary
and summary of assigned contracts
and Optional In-Licenses highlights certain obligations of, or restrictions on, Alnylam and/or its
assignees or sublicensees of Licensed IP under In-License Agreements, Out-License Agreements,
assigned contracts and Optional In-Licenses, including without limitation In-License Agreement
payment obligations, which are applicable to Regulus under the Agreement, in each case subject to
the terms and conditions of such In-License Agreements. The summaries set forth in these summaries
are not intended to be comprehensive or inclusive of all obligations or restrictions which may be
applicable to assignees of such assigned contracts or sublicensees of Licensed IP under such
In-License Agreements, Out-License Agreements or Optional In-Licenses.
Unless otherwise expressly stated, capitalized terms not otherwise defined in these summaries
shall have the meanings ascribed to them in the applicable In-License Agreement, Out-License
Agreement, assigned contract or Optional In-License and references to sections, articles, schedules
or exhibits made in these summaries shall be to sections, articles, schedules or exhibits, as the
case may be, in or to such applicable In-License Agreement, Out-License Agreement, assigned
contract or Optional In-License.
Page 2 of 61
ROCKEFELLER (Stoffel)
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc. effective
August 15, 2005 (
Stoffel Agreement
)
Brief Summary of Technology Covered by License
:
Alnylam and The Rockefeller University jointly own intellectual property relating to
chemically modified oligonucleotides as therapeutic agents for reduction or elimination of microRNA
expression. These oligonucleotides or antagomirs target a miRNA by complimentary base pairing to
a miRNA or pre-miRNA nucleotide sequence. Antagomirs may be chemically modified to resist
nucleolytic degradation, or to enhance delivery into cells (e.g. by conjugation to cholesterol).
Scope of License (Section 1.1)
Alnylams worldwide, exclusive, sublicensable license is limited to a license to make, have
made, use, have used, import, have imported, sell, offer for sale and have sold Licensed Products
for all uses.
Rockefeller reserves the right to use, and to permit other non-commercial entities to use
the Rockefeller Patent Rights for educational and non-commercial research purposes.
Rockefeller Patent Rights were developed with funding from the U.S. National Institutes of
Health. The United States government retains rights in such intellectual property, including, but
not limited to, requirements that products, which result from such intellectual property and are
sold in the United States, must be substantially manufactured in the United States.
Certain Sublicense Terms
(Section 1.5)
|
|
|
Alnylam will prohibit the sublicensee from further sublicensing and require the
sublicensee to comply with the terms and conditions of the Stoffel Agreement.
|
|
|
■
|
|
Within thirty (30) days after Alnylam enters into a sublicense agreement, Alnylam will
deliver to Rockefeller a copy of the sublicense agreement which may be redacted with
respect to content that is not relevant to Alnylams obligations under the Stoffel
Agreement.
|
|
|
■
|
|
Alnylam is primarily liable to Rockefeller for any act or omission of a sublicensee
that would be a breach of the Stoffel Agreement if performed or omitted by Alnylam, and
Alnylam will be deemed to be in breach of the Stoffel Agreement as a result of such act or
omission.
|
Page 3 of 61
Diligence (Section 2)
|
|
|
By end of the year 2007, Alnylam (or sublicensees) will select the method of delivery.
|
|
|
|
|
By the end of the year 2008, Alnylam (or sublicensees) will optimize the lead compound.
|
|
|
|
|
By the end of the year 2010, Alnylam (or sublicensees) will conclude preclinical
development
|
Payment Obligations (Sections 3 and 4)
The following milestones are payable:
|
|
|
|
|
|
|
|
|
First issuance in the U.S. of a patent under the
Rockefeller Patent Rights covering a Licensed Product
|
|
|
|
|
|
$
|
[***]
|
|
|
|
|
|
|
|
|
|
|
First dosing of a subject in a Phase II clinical
trial for the first Licensed Product
|
|
|
|
|
|
$
|
[***]
|
|
|
|
|
|
|
|
|
|
|
Approval by the U.S. FDA of a New Drug Application
for the first Licensed Product
|
|
|
|
|
|
$
|
[***]
|
|
A [***]% royalty is payable to Rockefeller on Net Sales of Licensed Products by Alnylam,
its Affiliates and its sublicensees (no offsets).
If Alnylam grants a sublicense under the Stoffel Agreement and receives payment in
connection with such grant in the form of upfront fees, maintenance fees and milestone payments
(net of any sums due to Rockefeller under this Agreement for the same milestone event), Alnylam
will pay Rockefeller [***]% of such payments, excluding payments for costs incurred by Alnylam,
Payments to Alnylam in the form of royalties paid by a sublicensee, equity investments in Alnylam
by a sublicensee, loan proceeds paid to Alnylam by a sublicensee in an arms length transaction,
full recourse debt financing and research and development funding paid to Alnylam in a bona fide
transaction are also excluded from the sublicense income calculation.
Payments are due to Rockefeller within 60 days after the end of the quarter in which the
royalties or fees accrue.
Books and Records (Sections 4.3 and 4.4)
Sub-licensees are required to keep complete and accurate books and records to verify Net
Sales, and all of the royalties, fees, and other payments payable under the
Page 4 of 61
Stoffel Agreement. The
records for each quarter will be maintained for at least three (3) years after submission of the
applicable report required under the Stoffel Agreement.
Upon reasonable prior written notice to Alnylam, sublicensees will provide an independent,
reputable CPA appointed by Rockefeller and reasonably acceptable to Alnylam with access to all of
the books and records required by the Stoffel Agreement to conduct a review or audit of Net Sales,
and all of the royalties, fees, and other payments payable under the Stoffel Agreement. If the
audit determines that Alnylam has underpaid any royalty payment by 5% or more, Alnylam will also
promptly pay the costs of the review or audit.
Non-Use of Name (Section 5.4)
Sublicensees may not use the name, logo, seal, trademark, or service mark (including any
adaptation of them) of Rockefeller or any Rockefeller school, organization, employee, student or
representative, without the prior written consent of Rockefeller, except for purposes of compliance
with securities regulations.
Termination (Section 6.2)
Alnylam may terminate for convenience
Sublicenses will survive for 90 days following termination and Rockefeller agrees to enter
into license agreement(s) directly with sublicensees upon the same terms as the terms of the
Stoffel Agreement
Alnylam must promptly inventory all finished product and works-in-product of Licensed
Products of its sublicensees. Inventory may be sold off unless Rockefeller terminates for a breach
by Alnylam or its sublicensees or Alnylams bankruptcy.
Prosecution and Enforcement
(Section 7)
Alnylam will prepare the Rockefeller Patent Rights, but Rockefeller will prosecute and
maintain the Rockefeller Patent Rights with Alnylams input. Alnylam has a right to manage the
prosecution and enforcement. Alnylam will reimburse Rockefellers prosecution and maintenance
costs.
Alnylam must inform Rockefeller promptly, but no later than 30 days, after learning of
infringement of the Rockefeller Patent Rights. Alnylam and Rockefeller will consult each other
concerning response to infringement. Alnylam may enforce the Rockefeller Patent Rights;
recoveries, after the parties expenses are reimbursed, are treated as Net Sales subject to
royalties. Rockefeller has step-in enforcement rights.
Definitions
Licensed Products
means products that are made, made for, used, used for, imported,
imported for, sold, sold for or offered for sale by Alnylam or its Affiliates or
Page 5 of 61
sublicensees and
that either (i) in the absence of this Agreement, would infringe at least one Valid Claim of the
Rockefeller Patent Rights, or (ii) use a process or machine covered by a Valid Claim of Rockefeller
Patent Rights.
Net Sales
means with respect to each Licensed Product the gross amount invoiced by
Alnylam or its Affiliates or sublicensees on sales or other dispositions of such product to third
parties less Qualifying Costs directly attributable to a sale and actually taken and/or identified
on the invoice and borne by Company, or its Affiliates or sublicensees.
Qualifying Costs
means: (a) customary discounts in the trade for quantity purchased, prompt payment or wholesalers
and distributors; (b) credits, allowances or refunds for claims or returns or retroactive price
reductions (including government healthcare programs and similar types of rebates) that do not
exceed the original invoice amount; (c) prepaid outbound transportation expenses and transportation
insurance premiums; and (d) sales, transfer, excise and use taxes and other fees imposed by a
governmental agency. Sales for clinical study purposes or compassionate, named patient or similar
use shall not constitute Net Sales
Rockefeller Patent Rights
means Rockefellers interests in a specified patent
application ([***]) and related patent family relating to reduction or elimination of miRNA
expression.
Page 6 of 61
TEKMIRA
License and Collaboration Agreement between Tekmira Pharmaceuticals Corporation (formerly INEX
Pharmaceuticals Corporation) (
Tekmira
) and Alnylam, dated January 8, 2007 (
Effective
Date
) (
Tekmira Agreement
)
Brief Summary of Technology Covered by License
:
|
|
Tekmira (f.k.a. Inex Pharmaceuticals Corp.) granted Alnylam a license relating to liposomal
delivery of siRNA and miRNA products. Alnylam granted Tekmira (i) an option to obtain
exclusive, royalty-bearing, worldwide licenses under its fundamental siRNA intellectual
property for 3 genetic targets and (ii) an exclusive, royalty bearing license to certain
intellectual property relating to immunostimulatory RNA oligonucleotide compositions (IOC
Technology). Alnylam retained certain rights to participate with Tekmira in
commercialization of IOC Technology. In addition, Alnylam provided funding for a 2-year
formulation development collaboration with Tekmira, a multi-year loan for capital expenditure
purposes, and Tekmira will provide exclusive manufacturing services for Alnylams development
programs up until completion of Phase 2 clinical studies.
|
Limitations on Scope of License (Sections 6.1 and 6.4)
The license granted to Alnylam is limited to an exclusive, royalty-bearing, worldwide
license under Inex Technology, Inex Collaboration IP and Tekmiras interest in Joint Collaboration
IP to Develop, Manufacture and Commercialize Alnylam Royalty Products in the Alnylam Field, subject
to (a) Tekmiras non-exclusive license under Alnylams rights in Inex Technology and Collaboration
IP for purposes of performing Tekmiras obligations under the Collaboration with respect to Alnylam
Royalty Products, and the Manufacturing Activities, and (b) Tekmiras exclusive, worldwide license
under Alnylams rights in Inex Technology and Collaboration IP to Develop, Manufacture and
Commercialize Inex Development Products (as defined below) in the Alnylam Field.
Any license granted by Alnylam to a Third Party under Alnylam RNAi Technology and Alnylam
Collaboration IP would be subject to a non-exclusive, worldwide license granted to Tekmira for
purposes of performing Tekmiras obligations under the Collaboration with respect to Alnylam
Royalty Products, and the Manufacturing Activities.
Any license granted by Alnylam to a Third Party under Alnylam Core Patent Rights, Alnylam
Lipidoid Patent Rights, Alnylam Collaboration IP and Alnylams interest in Joint Collaboration IP
would be subject to an exclusive, worldwide license granted to Tekmira to Develop, Manufacture and
Commercialize RNAi Products directed to up to three (3) Targets (each such Target, an
Inex
Development Target
, and such RNAi Products, the
Inex Development Products
) which
Tekmira may select (as described below) in the Alnylam Field. During the Selection Term, Tekmira
has the right to nominate a Target, subject to (a) Alnylams contractual obligation to a Third
Party that would be breached by the inclusion of such Target as an Inex Development Target under
Page 7 of 61
the Tekmira Agreement, and (b) Alnylams determination after good faith review of its ongoing or
planned scientific and/or business activities that such Target is a Target of interest to Alnylam.
If neither of these criteria apply, the Target is deemed to have been successfully nominated as an
Inex Development Target
and Alnylam is obligated to use Commercially Reasonable Efforts
consistent with the terms of the Novartis Agreement to obtain Novartis consent to such selection.
If an Inex Development Target is not available for license, then Tekmira may nominate an additional
Target, until an aggregate of 3 Inex Development Targets have been identified and approved for
selection. If all 3 Inex Development Targets have not been approved for selection by the
expiration of the Selection Term, the Selection Term will be extended until the earlier of (i) the
date on which an aggregate of 3 such Inex Development Targets have been identified and approved for
selection, and (ii) January 8, 2014.
Any license granted by Alnylam to a Third Party under Alnylam IOC Technology, Alnylam
Collaboration IP and Alnylams interest in Joint Collaboration IP would be subject to an exclusive
license granted to Develop, Manufacture and Commercialize IOC Products in the Inex IOC Field in and
for the United States.
Restrictions on Sublicensing by Alnylam (Sections 6.2 and 6.4)
Alnylam may grant sublicenses to Third Parties to Develop, Manufacture and Commercialize
Alnylam Royalty Products;
provided
,
that
(i) with respect to any sublicense of
Alnylams rights under Section 6.1.1(a) (i.e., the exclusive license under Inex Technology to
develop and commercialize Alnylam Royalty Products in the Alnylam Field) of the Tekmira Agreement
in respect of any Alnylam Royalty Product for which Tekmira has not initiated Manufacturing of
batches of finished dosage form for GLP toxicology studies, Alnylam is required to use Commercially
Reasonable Efforts to facilitate a business discussion between Tekmira and Alnylams Sublicensee
(other than Tekmira or its Affiliates) with respect to the provision of manufacturing services by
Tekmira to such Sublicensee; and (ii) with respect to any sublicense of Alnylams rights under
Section 6.1.1(a) of the Tekmira Agreement in respect of any Alnylam Royalty Product for which
Tekmira has initiated Manufacturing of batches of finished dosage form for GLP toxicology studies,
Alnylams Sublicensee (other than Tekmira or its Affiliates) will be required to obtain its
requirements of the bulk finished dosage form of such Alnylam Royalty Product from Tekmira on the
terms set forth in Article 5 of the Tekmira Agreement. However, Tekmira agrees to negotiate in
good faith with Alnylam and/or Alnylams Sublicensee either an alternate or modified supply
arrangement or the release of such Sublicensee from such exclusive supply obligation in return for
reasonable compensation to Tekmira.
Each license and/or sublicense granted by Alnylam under the Tekmira Agreement to develop,
manufacture and commercialize Alnylam Royalty Products must be subject and subordinate to the terms
and conditions of the Tekmira Agreement and must contain terms and conditions consistent with those
in the Tekmira Agreement, including, without limitation, the requirements of Section 6.4 of the
Tekmira Agreement (see below). Commercializing Sublicensees are also required to: (i) submit
applicable sales or other reports consistent with those required under the Tekmira Agreement; (ii)
comply with an
Page 8 of 61
audit requirement similar to the requirement set forth in Section 7.6 of the Tekmira Agreement; and
(iii) comply with the confidentiality and non-use provisions of Article 8 of the Tekmira Agreement
with respect to both Parties Confidential Information. If Alnylam becomes aware of a material
breach of any sublicense by a Third Party Sublicensee, Alnylam is required to promptly notify
Tekmira of the particulars of same and take all Commercially Reasonable Efforts to enforce the
terms of such sublicense.
Section 6.4 of the Tekmira Agreement states that all licenses and other rights granted to
Alnylam with respect to Inex Technology under Article 6 of the Tekmira Agreement are subject to (i)
the rights granted to Tekmira, and to Tekmiras ability to grant rights to Alnylam under the Inex
In-Licenses, and (ii) the provisions of the UBC Sublicense Documents governing or relating to the
rights sublicensed to Alnylam.
Diligence and Annual Reports (Section 6.7
)
Alnylam is required to use Commercially Reasonable Efforts to Develop and Commercialize an
Alnylam Royalty Product.
Alnylam is required to deliver to Tekmira an annual report, due no later than December 31
of each Contract Year during the Agreement Term, which summarizes the major activities undertaken
by Alnylam during the preceding 12 months to Develop and Commercialize its Royalty Products in the
applicable field. The report will include an outline of the status of any such Royalty Products in
clinical trials and the existence of any sublicenses with respect to such Royalty Products which
have not been previously disclosed.
Financial Obligations (Sections 7.2-7.4 and 6.1.3)
Milestone Payments
:
(a) Alnylam will make milestone payments to Tekmira as set forth below on a
Target-by-Target basis, no later than 30 calendar days after the earliest date on which the
corresponding milestone event has been achieved with respect to the first Alnylam Royalty Product
directed to a Target (other than a Biodefense Target) to achieve such milestone event:
|
|
|
|
|
Milestone Event
|
|
Payment
|
Initiation of first Phase I Study
|
|
$
|
[***]
|
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Initiation of first Phase II Study
|
|
$
|
[***]
|
|
Acceptance by a Regulatory Authority in a Major Market of the first NDA for filing
|
|
$
|
[***]
|
|
First NDA Regulatory Approval in a Major Market
|
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$
|
[***]
|
|
Aggregate worldwide cumulative Net Sales equals or exceeds $[***]
|
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$
|
[***]
|
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Page 9 of 61
(b) If, however, the Target is a Biodefense Target, in lieu of the milestone payments set
forth above, the following milestone payments will be payable, on a Target-by-Target basis, no
later than 30 calendar days after the later of (i) the earliest date on which the corresponding
milestone event has been achieved with respect to the first Alnylam Royalty Product directed to a
Biodefense Target to achieve such milestone event and (ii) receipt by Alnylam of all funding from a
Funding Authority that Alnylam is eligible to receive for the achievement of such milestone event:
|
|
|
Milestone Event
|
|
Payment
|
Approval of the first IND filed by Alnylam
|
|
$ [***]
|
Positive safety data from the first Phase I Study to be completed
|
|
$ [***]
|
First Commercial Sale
|
|
$ [***]
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Notwithstanding the foregoing: (i) if the first Alnylam Royalty Product directed to a
Target to achieve a milestone event as set forth in clause (a) or (b) above is comprised of a
formulation Covered by or employing any Third Party Liposome Patent Rights, then only [***]% of the
corresponding milestone payment will be payable to Tekmira; and (ii) notwithstanding that a Target
is a Biodefense Target, if Alnylam or its Related Parties Commercialize or sell an Alnylam Royalty
Product directed to such Target other than to a Funding Authority, the milestone payment amounts
set forth in clause (a) will then apply in lieu of the amounts set forth in clause (b).
Each milestone payment by Alnylam to Tekmira hereunder will be payable only once for each
Target, regardless of the number of times the milestone is achieved with respect to one or more
Alnylam Royalty Products directed to such Target.
On and after [***], Alnylam will be entitled to reduce each milestone payment payable by
Alnylam under the Tekmira Agreement (after application of appropriate deductions by [***]% of such
milestone payment, until such time as the aggregate amount of all such reductions hereunder equals
$[***]. For clarity, Alnylam may offset (i) its obligation to pay the resulting milestone payment
against (ii) certain obligations of Tekmira owed to Alnylam pursuant to the Loan Agreement, as
provided in the Loan Agreement.
Royalty Payments
:
Royalties are payable to Tekmira on Net Sales of Alnylam Royalty Products worldwide as
follows:
Page 10 of 61
|
|
|
Aggregate Calendar Year Net Sales of the
|
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Royalty
|
Alnylam Royalty Product
|
|
(as a percentage of Net Sales)
|
on the first $[***] $[***]
|
|
[***]%
|
On the subsequent $[***] $[***]
|
|
[***]%
|
Greater than $[***]
|
|
[***]%
|
Notwithstanding the foregoing, if an Alnylam Royalty Product is comprised of a formulation
Covered by or employing any Third Party Liposome Patent Rights then royalties on Net Sales of
Alnylam Royalty Products will be calculated as follows:
|
|
|
Aggregate Calendar Year Net Sales of the
|
|
Royalty
|
Alnylam Royalty Product
|
|
(as a percentage of Net Sales)
|
on the first $[***] $[***]
|
|
[***]%
|
On the subsequent $[***] $[***]
|
|
[***]%
|
Greater than $[***]
|
|
[***]%
|
If the Development, Manufacture or Commercialization of an Alnylam Royalty Product in
accordance with the Tekmira Agreement infringes Necessary Third Party IP, the applicable royalties
in each country payable to Tekmira will be reduced by [***]% of the amount paid by Alnylam of any
royalties under all licenses of such Necessary Third Party IP that are reasonably allocable to the
Development, Manufacture and Commercialization of the Alnylam Royalty Product in or for such
country in the Alnylam Field;
provided
,
however
, that, on a country-by-country
basis, in no event will the royalties payable to Tekmira with respect to Net Sales in a country for
any Calendar Quarter be reduced below the greater of: (i) [***]% of the royalties otherwise payable
to Tekmira for such Calendar Quarter, and (ii) the amount of any royalties payable under the
In-licenses of Alnylam that are reasonably allocable to the Commercialization or Manufacture of the
Alnylam Royalty Product in or for such country in the Field (where the royalties are calculated by
adding one percentage point to the applicable royalty rate(s) in the applicable In-License(s)).
If Alnylam is required to make any payments to UBC in respect of the Inex Technology or
Inex Collaboration IP licensed to Alnylam pursuant to the UBC Sublicense Agreement, then Alnylam
will be entitled to offset any amounts payable by Alnylam to Tekmira under the Tekmira Agreement by
the amount of Alnylams payments to UBC until such amounts have been credited in full.
Royalty Reports; Payment and Audit Rights (Sections 7.3.4 and 7.6)
Commencing upon the First Commercial Sale of an Alnylam Royalty Product, Alnylam is
required to provide to Tekmira a quarterly written report showing the quantity of Alnylam Royalty
Products sold in each country (as measured in saleable units of product), the gross sales of such
Alnylam Royalty Product in each country, total deductions for such Alnylam Royalty Product for each
country included in the calculation of Net Sales, the Net Sales in each country of such Alnylam
Royalty Product subject to royalty payments and the royalties payable with respect to such Alnylam
Royalty
Page 11 of 61
Product. Quarterly reports are due no later than the 25th day following the close of each Calendar
Quarter. Royalties shown to have accrued by each royalty report are due and payable on the date
such royalty report is due.
Complete and accurate records must be kept in sufficient detail to enable the royalties and
other payments payable under the Tekmira Agreement to be determined.
Upon the written request of Tekmira and not more than once in each Calendar Year, a
Sublicensee must permit an independent certified public accounting firm of nationally recognized
standing selected by Tekmira and reasonably acceptable to such Sublicensee to have access during
normal business hours to such of the records of Sublicensee as may be reasonably necessary to
verify the accuracy of the royalty and other financial reports required to be delivered under the
Tekmira Agreement for any Calendar Year ending not more than [***] months prior to the date of such
request, for the sole purpose of verifying the basis and accuracy of payments made under Article 7
of the Tekmira Agreement.
Prosecution and Enforcement (Sections 10.2, 10.3 and 10.4)
Alnylam is solely responsible, at Alnylams discretion, for filing, prosecuting, conducting
ex parte
and
inter partes
proceedings (including the defense of any interference or opposition
proceedings) and maintaining all Patent Rights comprising Alnylam RNAi Technology, Alnylam IOC
Technology or Alnylam Collaboration IP, in Alnylams name.
Tekmira, at Tekmiras discretion, for filing, prosecuting, conducting
ex parte
and
inter
partes
proceedings, (including the defense of any interference or opposition proceedings), and
maintaining all Patent Rights comprising Inex Technology or Inex IOC Technology, in Tekmiras name,
or Inex Collaboration IP, in UBCs name.
Subject to Tekmiras continuing right to the prior review of, comment on, revision to and
approval of material documents, which will not be unreasonably delayed or withheld, Alnylam is
solely responsible, at Alnylams discretion, for filing, conducting
ex parte
and
inter partes
prosecution, and maintaining (including the defense of any interference or opposition proceedings)
all Patent Rights comprising Joint Collaboration IP, in the names of both Tekmira and Alnylam.
If Alnylam elects not to seek or continue to seek or maintain patent protection on any
Alnylam IOC Technology or Alnylam Collaboration IP which is subject to Tekmiras licensed rights
under the Tekmira Agreement, or Joint Collaboration IP, then Tekmira will have step-in rights. If
Alnylam declines to file, prosecute and/or maintain Valid Claims at Tekmiras request in Joint
Collaboration IP, then Tekmira will have step-in rights.
If Tekmira elects not to seek or continue to seek or maintain patent protection on any Inex
Technology or Inex Collaboration IP, which is subject to Alnylams licensed rights under the
Tekmira Agreement, then subject to the provisions of the UBC
Page 12 of 61
Sublicense Documents, Alnylam will have rights (but not the obligation), at its expense, to
prosecute and maintain in any country patent protection on such Inex Technology in the name of
Tekmira or Inex Collaboration IP in the name of UBC.
Each Party agrees: (a) to make its employees, agents and consultants reasonably available
to the other Party (or to the other Partys authorized attorneys, agents or representatives), to
the extent reasonably necessary to enable such Party to undertake patent prosecution; (b) to
provide the other Party with copies of all material correspondence pertaining to prosecution with
the patent offices; (c) to cooperate, if necessary and appropriate, with the other Party in gaining
patent term extensions wherever applicable to Patent Rights; and (d) to endeavor in good faith to
coordinate its efforts with the other Party to minimize or avoid interference with the prosecution
and maintenance of the other Partys patent applications.
The patent filing, prosecution and maintenance expenses incurred after the Effective Date
with respect to Patent Rights comprised of Alnylam Core Patent Rights, Alnylam IOC Technology,
Alnylam Lipidoid Patent Rights, Inex Technology, Inex IOC Technology and Collaboration IP will be
borne by each Party having the right to file, prosecute and maintain such Patent Rights under the
Tekmira Agreement.
Subject to the provisions of any Inex In-License and the provisions of the UBC Sublicense
Documents, in respect of the Alnylam Royalty Products in the Alnylam Field, Alnylam will have the
sole and exclusive right to initiate an infringement or other appropriate suit anywhere in the
world against any Third Party who at any time has infringed, or is suspected of infringing, any
Patent Rights, or of using without proper authorization, any Know-How, comprising any Inex
Technology or Collaboration IP that is licensed to Alnylam under the Tekmira Agreement.
Alnylam will have the sole and exclusive right to initiate an infringement or other
appropriate suit anywhere in the world against any Third Party who at any time has infringed, or is
suspected of infringing, any Patent Rights, or of using without proper authorization any Know-How,
comprising Alnylam RNAi Technology, Alnylam IOC Technology or Alnylam Collaboration IP; provided,
that if Alnylam fails to initiate a suit or take other appropriate action with respect to Alnylam
IOC Technology in the United States with respect to an IOC Product that it has the initial right to
initiate or take pursuant thereto within 90 days after becoming aware of the basis for such suit or
action, then Tekmira may, in its discretion, provide Alnylam with written notice of Tekmiras
intent to initiate a suit or take other appropriate action with respect to such IOC Product. If
Alnylam fails to initiate a suit or take such other appropriate action within 30 days after receipt
of such notice from Tekmira, then Tekmira will have the right to initiate a suit or take other
appropriate action that it believes is reasonably required to protect its licensed interests under
the Alnylam IOC Technology and Alnylam Collaboration IP with respect to such IOC Product.
Alnylam may defend any Infringement Claim brought against either Party or its Affiliates or
Sublicensees arising out of the Development, Manufacture or Commercialization of any Alnylam
Royalty Product in the Alnylam Field. Tekmira may
Page 13 of 61
defend any Infringement Claim brought against either Party or its Affiliates or Sublicensees
arising out of the Development, Manufacture or Commercialization of any Inex Royalty Product and in
(a) the Alnylam Field, in the case of Inex Development Products or (b) the Inex IOC Field, in the
case of Inex IOC Products.
As the responsible party, Alnylam must keep Tekmira informed, and from time to time consult
with Tekmira regarding the status of any such claims and provide Tekmira with copies of all
documents filed in, and all written communications relating to, any suit brought in connection with
such claims. Tekmira also has the right to participate and to be presented in any such claim or
related suit. If Alnylam fails to exercise its right to assume such defense within 30 days
following written notice of such Infringement Claim, Tekmira has the sole and exclusive right to
control the defense of such Infringement Claim.
Termination for Patent Challenge (Section 11.5)
If any Sublicensee asserts in any court or other governmental agency of competent
jurisdiction that an Inex Patent Right or a Patent Right Controlled by Tekmira by virtue of the
Inex-UBC License Agreement and sublicensed to Alnylam pursuant to the UBC Sublicense (in either
case, an
Inex Patent
) is invalid, unenforceable, or that no issued Valid Claim embodied
in such Inex Patent excludes a Third Party from making, having made, using, selling, offering for
sale, importing or having imported an Alnylam Royalty Product in such jurisdiction, then Tekmira
may, upon written notice to Alnylam, terminate all licenses granted to Alnylam for such Alnylam
Royalty Product(s) covered by such Inex Patent that is under challenge in the applicable
jurisdiction; provided, however, that Tekmira will not terminate such license if within 30 days of
Alnylams receipt of Tekmiras notification under the Tekmira Agreement (a) it is confirmed by
written notice to Tekmira that Sublicensee no longer intends to challenge the validity or
enforceability of such Inex Patent; or (b) documentation is provided to Tekmira to confirm
Sublicensees withdrawal of its filing, submission, or other process commenced in any court or
other governmental agency of competent jurisdiction to challenge the validity or enforceability of
any such Inex Patent.
Definitions
Alnylam Collaboration IP
means, generally (a) any improvement, invention, or Know-How
first discovered or developed by employees of Alnylam or its Affiliates or other persons not
employed by Tekmira acting on behalf of Alnylam, in the performance of the Collaboration, the
Manufacturing Activities, and/or Alnylams obligations under the Original Agreements, and (b) any
Patent Rights which claim, cover or relate to such Know-How. Alnylam Collaboration IP excludes
Alnylams interest in Joint Collaboration IP.
Alnylam Core Patent Rights
means those Patent Rights set forth in Schedule 1.3 of the
Tekmira Agreement, including various Tuschl I and Tuschl II patents and patent applications, as
such Schedule is supplemented from time to time pursuant to Section 6.5.1 of the Tekmira Agreement.
Page 14 of 61
Alnylam Field
means the treatment, prophylaxis and diagnosis of diseases in humans using
an RNAi Product or miRNA Product.
Alnylam IOC Technology
mean, generally (a) Know-How Controlled by Alnylam as of the
Effective Date that is useful or necessary to Develop, Commercialize and/or Manufacture an IOC
Product in the Inex IOC Field (excluding any Alnylam Collaboration IP and Alnylams interest in
Joint Collaboration IP), and (b) those Patent Rights set forth in Schedule 1.5 of the Tekmira
Agreement, including USSN [***].
Alnylam Lipidoid Patent Rights
means those Patent Rights Controlled by Alnylam under a
license from the Massachusetts Institute of Technology pursuant to the MIT License Agreement and
that are set forth in Schedule 1.6 of the Tekmira Agreement, including USSN [***].
Alnylam RNAi Know-How
means, generally, Know-How Controlled by Alnylam that Alnylam
determines in its reasonable judgment to be useful or necessary to Develop, Commercialize and/or
Manufacture an Alnylam Royalty Product in the Alnylam Field (excluding any Alnylam Collaboration IP
and Alnylams interest in Joint Collaboration IP).
Alnylam RNAi Patent Rights
means, generally, Patent Rights Controlled by Alnylam that
claim (a) Alnylam RNAi Know-How, or (b) the identification, characterization, optimization,
construction, expression, formulation, use or production of an Alnylam Royalty Product, as the case
may be, and which Alnylam determines in its reasonable judgment to be useful or necessary to
Develop, Commercialize and/or Manufacture an Alnylam Royalty Product in the Alnylam Field
(including, without limitation, the Alnylam Core Patent Rights and the Alnylam Lipidoid Patent
Rights, but specifically excluding Alnylam IOC Technology and any Patent Rights included in Alnylam
Collaboration IP or Alnylams interest in Joint Collaboration IP).
Alnylam RNAi Technology
means, collectively, Alnylam RNAi Know-How and Alnylam RNAi
Patent Rights.
Alnylam Royalty Product
means any RNAi Product or a miRNA Product that, but for the
licenses granted hereunder, would be Covered by one or more Valid Claims of the Inex Patent Rights.
Biodefense Target
means (a) a Target within the genome of one or more Category A, B and C
pathogens, as defined by the National Institute of Allergy and Infectious Diseases, including
without limitation, pathogens listed on Schedule 1.12 of the Tekmira Agreement, but specifically
excluding influenza virus, or (b) an endogenous cellular Target against which Alnylam Develops
and/or Commercializes an Alnylam Royalty Product for commercial supply to one or more Funding
Authorities.
Collaboration IP
means, collectively, Alnylam Collaboration IP, Inex Collaboration IP and
Joint Collaboration IP.
Page 15 of 61
Existing Inex In-Licenses
means the Third Party agreements listed on Schedule 1.30 to the
Tekmira Agreement.
IOC
or
Immunostimulatory Oligonucleotide Composition
means a single-stranded or
double-stranded ribonucleic acid (
RNA
) composition, or derivative thereof, that has
activity solely through an immunostimulatory mechanism and has no RNAi activity against a human
gene transcript or viral genomic sequence.
IOC Product
means a product containing, comprised of or based on IOCs or IOC derivatives.
Inex Collaboration IP
means, generally (a) any improvement, invention or Know-How first
discovered or developed by employees of Tekmira or its Affiliates or other persons not employed by
Alnylam acting on behalf of Tekmira, in the performance of the Collaboration, the Manufacturing
Activities, and/or Tekmiras obligations under the Original Agreements, and (b) any Patent Rights
which claim, cover or relate to such Know-How. Inex Collaboration IP excludes Tekmiras interest
in Joint Collaboration IP.
Inex In-License
means an agreement between Tekmira or its Affiliates, and a Third Party,
pursuant to which Tekmira or any of its Affiliates Control(s) Inex Technology relating to the
Alnylam Field under a license or sublicense from such Third Party, including without limitation,
the Existing Inex In-Licenses.
Inex IOC Field
means the treatment, prophylaxis and diagnosis of diseases in humans using
an IOC Product.
Inex IOC Technology
means, generally (a) Know-How Controlled by Tekmira or its Affiliates
with respect to IOC Products and/or IOCs, and (b) Patent Rights Controlled by Tekmira and its
Affiliates that claim such Know-How or the identification, characterization, optimization,
construction, expression, formulation, delivery, use or production of an IOC Product and/or IOC,
and are useful or necessary to Develop, Commercialize and/or Manufacture IOC Products in the Field.
Inex Know-How
means, generally, Know-How Controlled by Tekmira or its Affiliates with
respect to an RNAi Product or miRNA Product (excluding any Inex Collaboration IP, Tekmiras
interest in Joint Collaboration IP and any such Know-How sublicensed to Alnylam pursuant to the UBC
Sublicense).
Inex Patent Rights
means, generally, Patent Rights Controlled by Tekmira or its
Affiliates that claim (a) Inex Know-How or (b) the identification, characterization, optimization,
construction, expression, formulation, delivery, use or production of an RNAi Product or miRNA
Product, and are useful or necessary to Develop, Commercialize and/or Manufacture RNAi Products or
miRNA Products in the Alnylam Field (excluding any Patent Rights included in Inex Collaboration IP,
Tekmiras interest in Joint Collaboration IP and any such Patent Rights licensed to Alnylam
pursuant to the UBC Sublicense).
Page 16 of 61
Inex Royalty Product
means any (a) Inex Development Product that, but for the licenses
granted hereunder, would be Covered by one or more Valid Claims under the Alnylam Core Patent
Rights or the Alnylam Lipidoid Patent Rights, or (b) IOC Product that but for the licenses granted
hereunder, would be Covered by one or more Valid Claims under the Alnylam IOC Technology.
Inex Technology
means, collectively, Inex Know-How and Inex Patent Rights.
Inex-UBC License Agreement
means that certain license agreement between Tekmira and the
University of British Columbia (
UBC
) dated effective July 1, 1998, as amended by
Amendment Agreement between Tekmira and UBC dated effective July 11, 2006, and Second Amendment
Agreement dated effective the Effective Date.
Joint Collaboration IP
means, generally (a) any improvement, discovery or Know-How first
discovered or developed jointly by the Parties or their Affiliates or others acting on behalf of
Tekmira and Alnylam in the performance of the Collaboration, the Manufacturing Activities and/or
the obligations of the Parties under the Original Agreements, and (b) any Patent Rights which
claim, cover or relate to such Know-How.
Manufacturing Activities
means those activities performed by a party relating to the
manufacture and supply of Alnylam Royalty Products.
miRNA Product
means a product containing, comprised of or based on native or chemically
modified RNA oligomers designed to either modulate an miRNA and/or provide the function of an
miRNA.
Necessary Third Party IP
means, on a country-by-country basis, Know-How or Patent Rights
in such country owned or controlled by a Third Party that cover a Royalty Product.
Pre-Existing Alliance Agreements
are listed on Schedule 1.79 to the Tekmira Agreement.
RNAi Product
means a product containing, comprised of or based on siRNAs or siRNA
derivatives or other moieties effective in gene function modulation and designed to modulate the
function of particular genes or gene products by causing degradation of a Target mRNA to which such
siRNAs or siRNA derivatives are complementary (
RNAi Interference Mechanism
), and that is
not an miRNA Product.
Royalty Product
means, either (a) an Alnylam Royalty Product, or (b) an Inex Royalty
Product.
Selection Term
means the period commencing on the Effective Date and continuing for five
(5) Contract Years thereafter, unless such period is extended pursuant to Section 2.2 of the
Tekmira Agreement.
Small Interfering RNA
or
siRNA
means a double-stranded ribonucleic acid (RNA)
composition designed to act primarily through an RNA Interference Mechanism that
Page 17 of 61
consists of either (a) two separate oligomers of native or chemically modified RNA that are
hybridized to one another along a substantial portion of their lengths, or (b) a single oligomer of
native or chemically modified RNA that is hybridized to itself by self-complementary base-pairing
along a substantial portion of its length to form a hairpin.
Target
means: (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide; (b)
variants of a polypeptide, cellular entity or nucleic acid described in clause (a); (c) a defined
non-peptide entity, including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a virus will be regarded as a single Target; or (d) a naturally occurring
interfering RNA or miRNA or precursor thereof.
Third Party Liposome Patent Rights
means, with respect to an Alnylam Royalty Product, (a)
the Alnylam Lipidoid Patent Rights and/or (b) other technology comprising a lipid component or
liposomal formulation useful or necessary for the Development, Manufacture or Commercialization of
such Alnylam Royalty Product and Controlled by Alnylam under a license from a Third Party, and in
each case with respect to which Intellectual Property Rights Alnylam has granted to Tekmira a
non-exclusive, royalty- and milestone fee-bearing (on a pass-through basis) license to Develop,
Manufacture and Commercialize Inex Royalty Products in the Alnylam Field in the case of Inex
Development Product, and in the Inex IOC Field in the case of IOC Products.
UBC Sublicense Documents
means the collective reference to (a) the Sublicense Agreement
dated as of the Effective Date between the Parties (the
UBC Sublicense
), (b) the Consent
and Agreement dated as of the Effective Date among the Parties and UBC, and (c) the Assignment
dated the Effective Date between Tekmira and UBC.
Page 18 of 61
ROCHE
License and Collaboration Agreement dated July 8, 2007, by and among Alnylam Pharmaceuticals, Inc.,
F. Hoffmann-La Roche Ltd (
Roche Basel
) and Hoffmann-La Roche Inc. (together with Roche
Basel,
Roche
) (
Roche Agreement
), effective on August 9, 2007 (
Effective
Date
)
Brief Description of Technology Covered by License
Alnylam granted Roche and its Affiliates a non-exclusive, worldwide license under Alnylams
rights to Architecture and Chemistry IP and Delivery IP as it existed at the effective time of the
Agreement, to develop and commercialize RNAi Products for treatment/prophylaxis of indications in
at least the fields of cancer, certain liver diseases, metabolic disease and pulmonary disease.
Roche has the option to enter additional therapeutic fields and, prior to granting exclusive
licenses in the other Fields, Alnylam must give Roche a right of first negotiation.
Limitations on Scope of License
Any license granted by Alnylam to a Third Party under Architecture and Chemistry IP or Delivery IP
would be subject to the following limitations:
License Grant to Roche
. Roche and its Affiliates have a non-exclusive, worldwide license
to develop and commercialize RNAi Products for the treatment/prophylaxis of indications in at least
the primary fields of cancer, certain liver diseases, metabolic disease and pulmonary disease)
and
any additional fields (which are listed in a schedule to the Roche Agreement) to which
Roche acquires non-exclusive rights (collectively,
Field
).
Designated Targets
. If Roche selects a Target which is not a Blocked Target and such
Target is cleared through the Novartis ROFO mechanism, Roche has non-exclusive rights within the
scope of its basic license grant to develop and commercialize RNAi Products directed to such
Designated Target in the Field.
Alnylam/Roche Discovery Collaboration
. Roche and Alnylam have agreed to collaborate on a
specified number of targets during the term of the agreement.
ROFN
. If Alnylam intends to grant to any Third Party an exclusive license to any
particular additional field which has not yet been acquired by Roche, Alnylam must first offer
Roche the right to extend its non-exclusive licenses into such additional field upon payment of a
specified field option fee.
Extension into Additional Fields
. Roche may extend its development and commercialization
activities directed to a Target into any additional field, provided that Roche notify Alnylam of
such extension and pay certain milestone payments.
Prosecution and Enforcement
Page 19 of 61
Alnylam is obligated to take reasonable measures to protect and, to the extent Alnylam has
such a right, to enforce the IP being licensed to Roche under the Roche Agreement.
Alnylam is also obligated to assume control of the defense of any aspects of any third
party infringement claim that involves the validity, scope and/or enforceability of such licensed
IP. Roche has the right to control the defense of any other third party infringement claim or
aspect thereof related to the licensed IP. Alnylam must keep Roche advised of status and consider
Roches recommendations.
Definitions
Architecture and Chemistry Intellectual Property
refers, generally, to Know-How
and Patent Rights listed on
Schedule C
to the Roche Agreement, in each case Controlled by
Alnylam as of the Effective Date, and covering (a) the general structure, architecture, or design
of double-stranded oligonucleotide molecules which engage RNAi mechanisms in a cell; (b) chemical
modifications of double-stranded oligonucleotides (including any modification to the base, sugar or
internucleoside linkage, nucleotide mimetics, and any end modifications) which do not abolish the
RNAi activity of the double-stranded oligonucleotides in (a); (c) manufacturing techniques for the
double-stranded oligonucleotide molecules or chemical modifications of (a) and (b); or (d) all uses
or applications of double-stranded oligonucleotide molecules or chemical modifications in (a) or
(b);
but
excluding
(i) IP to the extent specifically related to Blocked Targets,
and (ii) Delivery IP. Includes future Patent Rights that claim priority to or common priority with
any of the aforementioned Patent Rights.
Blocked Target
means any Target that is subject to a contractual obligation of a
Pre-Existing Alliance Agreement that would be breached by the inclusion of such Target as a
Designated Target under this Agreement
Delivery Intellectual Property
refers, generally, to Know-How and Patent Rights
listed on
Schedule C
to the Roche Agreement, in each case Controlled by Alnylam as of the
Effective Date, and covering (a) delivery technologies necessary or useful for delivery of
double-stranded oligonucleotide molecules; or (b) manufacturing techniques for such delivery
technologies of (a);
but
excluding
Patent Rights which relate specifically to
Blocked Targets. Includes future Patent Rights that claim priority to or common priority with any
of the aforementioned Patent Rights.
RNAi Compound
means any compound that, in vitro or otherwise, functions through
the mechanism of RNAi and consists of or encodes double-stranded oligonucleotides, and which
double-stranded oligonucelotides optionally may be chemically modified to contain modified
nucleotide bases or non-RNA nucleotides, and optionally may be administered in conjunction with a
delivery vehicle or vector.
RNAi Product
means any product that contains one or more RNAi Compounds as an
active ingredient.
Page 20 of 61
Target
means (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide; (b)
variants of a polypeptide (including any splice variant thereof), cellular entity or nucleic acid
described in clause (a); or (c) a defined non-peptide entity, including a microorganism, virus,
bacterium or single cell parasite;
provided
that
the entire genome of a virus shall
be regarded as a single Target.
Page 21 of 61
NOVARTIS
Research Collaboration and License Agreement between Novartis Institutes for BioMedical Research,
Inc. and Alnylam Pharmaceuticals, Inc., effective October 12, 2005, as amended by the Addendum Re:
Influenza Program effective as of December 13, 2005, Amendment No. 1 to such Addendum effective as
of March 14, 2006, and Amendment No. 2 to such Addendum effective as of May 5, 2006 (
Novartis
Agreement
)
Brief Description of Technology Covered by License
|
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Alnylam granted Novartis a right to exclusively develop a certain number of Targets using
intellectual property controlled by Alnylam during the term of the Agreement. Some of the
Targets would be developed through collaborative work between Novartis and Alnylam. In
addition, Novartis has the right to convert their license from an exclusive license with
respect to certain Targets to a broad, non-exclusive license.
|
Scope of Rights
Novartis may select a specified number of Targets (
Selected Targets
). Alnylam
and Novartis entered into a Research Collaboration to identify and optimize RNAi Compounds directed
against Selected Targets and develop improved RNAi technology to enable and enhance the utility of
such RNAi Compounds. (Section 2)
Alnylam granted Novartis and its Affiliates worldwide licenses under Alnylam Intellectual
Property to (i) perform Novartiss obligations under the Research Collaboration, (ii) Discover RNAi
Compounds, (iii) Discover RNAi Compounds directed at the Selected Targets, and (iv) Discover,
Develop, Commercialize or Manufacture Discovered RNAi Compounds and Collaboration Products. The
rights under clauses (i) and (ii) are non-exclusive and non-sublicenseable, under clause (iii) are
exclusive and non-sublicenseable, and under clause (iv) are exclusive and sublicenseable.
(Sections 3.1(a) and (b))
For a period of time, Novartis has an option, exercisable upon notice and payment of a fee,
to obtain for itself and its Affiliates a non-exclusive, non-sublicenseable (except to third party
contractors), worldwide, perpetual license under Broad RNAi Intellectual Property for any human,
veterinary or agricultural applications (the
Adoption License
). Alnylam may not grant
any exclusive rights or licenses under any Broad RNAi Intellectual Property except with respect to
an opportunity Novartis does not acquire under the ROFO or in accordance with agreements existing
before the effective date of the Novartis Agreement. (Section 3.1(c) and (e))
Exclusivity
: Alnylam and its Affiliates may not, either alone or directly or
indirectly in conjunction with a Third Party, conduct Discovery of any RNAi Compound or RNAi
Products directed to a Selected Target, or Discovery, Development, Commercialization or Manufacture
of Discovered RNAi Compounds, Collaboration
Page 22 of 61
Products, or RNAi Compounds or RNAi Products directed to Selected Targets. Alnylam and its
Affiliates may not grant to any Third Party any rights under Alnylam Intellectual Property to
engage in any of the foregoing activities. (Section 2.6(a))
ROFO
: If Alnylam or any of its Affiliates seek, directly or indirectly in
conjunction with a Third Party (with limited exceptions), or to license a Third Party (with limited
exceptions) the right, to Discover, Develop, Commercialize or Manufacture any RNAi Compounds or
RNAi Products directed at a Target(s), Alnylam must first provide written notice to Novartis.
Novartis has a period of time to accept or reject the opportunity. If Novartis rejects an
opportunity for a program for which no IND has been filed in the US or Major Market Countries, or
Novartis and Alnylam are unable to come to terms on a post-IND program, Alnylam may, within a
specified period of time, enter an agreement with a Third Party, which can be no more favorable
overall to such Third Party than those offered to Novartis under Section 2.6(c)(i). (Sections
2.6(b) and (c))
In-Licensing IP
: To the extent applicable, Alnylam must comply with Sections
2.6(b) and (c) when acquiring or licensing rights from Third Parties. In the course of acquiring
or licensing additional Broad RNAi Intellectual Property or any other Alnylam Intellectual Property
covering a Collaboration Product, Alnylam must use its best efforts to ensure that such rights
include the right to sublicense to Novartis such Broad RNAi Intellectual Property or other Alnylam
Intellectual Property. (Sections 2.6(d), 3.1(f))
Technology Transfer
: Alnylam will periodically deliver to Novartis all Alnylam
Intellectual Property specifically relating to the Discovered RNAi Compounds, relating to the
Research Collaboration, or otherwise necessary or useful to the Discovery, Development,
Commercialization or Manufacture of Discovered RNAi Compounds or Collaboration Products. Once
Novartis acquires the Adoption License, Alnylam will periodically deliver to Novartis all Broad
RNAi Intellectual Property. The deliveries will include un-redacted copies of agreements that
directly or indirectly grant or restrict rights in Alnylam Intellectual Property, which may be
redacted to comply with confidentiality obligations and to exclude terms that do not relate to
Novartiss rights or obligations; provided, that Alnylam will use commercially reasonable efforts
to ensure that Novartis is granted access to un-redacted copies of such agreements.
Alnylam may not assign, license or otherwise grant any rights or dispose of any Broad RNAi
Intellectual Property or other Alnylam Intellectual Property covering a Collaboration Product
without making such disposition expressly subject to Novartiss rights. (Section 3.1(g))
IP Ownership, Prosecution and Enforcement
(Section 6)
Novartis owns all IP jointly created by the parties in the Research Collaboration.
Novartis grants Alnylam a worldwide, non-exclusive, sublicenseable (solely to Controlled
Contractors) license under such jointly-created IP that is Broad RNAi Intellectual Property, to
engage in any and all research activities directed to human, veterinary or agricultural
applications.
Page 23 of 61
Novartis has a step-in right to prosecute Alnylam Patent Rights that pertain to a
Discovered RNAi Compound or a Licensed Product.
Alnylam will promptly report in writing to Novartis any known or suspected infringement or
misappropriation of Alnylam Intellectual Property and will provide Novartis with all available
evidence supporting such infringement or misappropriation.
Alnylam has the right to protect the Alnylam Intellectual Property, and Alnylam will
consult with Novartis regarding the status of any such action and will provide Novartis with copies
of all material documents relating to such action. Notwithstanding the foregoing, Novartis has the
sole and exclusive right to initiate a suit under Alnylam Intellectual Property to protect a
Discovered RNAi Compound, a Licensed Product or IP created solely by Novartis or jointly by
Novartis and Alnylam in the Research Collaboration; Alnylam must provide reasonable assistance at
Novartis request. Recoveries will be shared in a specified manner.
Novartis and Alnylam will cooperate in responding to a claim challenging the validity of
any Alnylam Patent Right covering a Discovered RNAi Compound or a Licensed Product.
Definitions
Adopted Product
means a product containing RNAi Compound(s) that are Discovered,
Developed, Commercialized or Manufactured pursuant to the Adoption License.
Alnylam Intellectual Property
means Know-How and Patent Rights now or in the future
owned or licensed by Alnylam or its Affiliates, including Broad RNAi Intellectual Property.
Broad RNAi Intellectual Property
means all Know-How and Patent Rights now or in the
future owned or licensed by Alnylam or its Affiliates that relate to RNAi technology, products or
processes, including (a) the general structure, architecture, or design of nucleic acid based
molecules which engage RNAi mechanisms in a cell; (b) chemical modifications of nucleic acids
(including any modification to the base, sugar or internucleoside linkage, nucleotide mimetics, and
any end modifications) which do not abolish the RNAi activity of the nucleic acid molecules in (a);
(c) manufacturing techniques for the nucleic acid based molecules or chemical modifications of (a)
and (b); and (d) all uses or applications of nucleic acid based molecules or chemical modifications
in (a) or (b); but excluding Patents which relates solely to (i) a specific Target or small group
of Targets; or (ii) delivery technologies which may be broadly employed for delivery of nucleic
acid based molecules.
Collaboration Product
means any product that contains one or more Discovered RNAi
Compound(s) as active ingredient(s).
Page 24 of 61
Discovered RNAi Compound
means an RNAi Compound directed to a Selected Target that
is Discovered during the course of a program under the Novartis Agreement, together with all
derivatives of such RNAi Compound, where
derivative
means a compound that may contain
modified nucleotides or may have been modified by chemical or molecular genetic means but which
still, at least in vitro, functions through an RNAi mechanism against the same Target.
Licensed Products
means the Collaboration Products and the Adopted Products.
RNAi Compound
means any compound that in vitro or otherwise functions through the
mechanism of RNAi and consists of or encodes double-stranded RNA, and which double-stranded RNA is
optionally chemically modified to contain modified nucleotide bases or non-RNA nucleotides, and
optionally may be administered in conjunction with a delivery vehicle or vector.
RNAi Product
means any product that contains one or more RNAi Compounds as an active
ingredient.
Target
means: (a) a polypeptide or entity comprising a combination of at least one
polypeptide and other macromolecules, that is a site or potential site of therapeutic intervention
by a therapeutic agent; or a nucleic acid which is required for expression of such polypeptide; (b)
variants of a polypeptide, cellular entity or nucleic acid described in clause (a); (c) a defined
non-peptide entity, including a microorganism, virus, bacterium or single cell parasite; provided
that the entire genome of a virus shall be regarded as a single Target; or (d) a naturally
occurring interfering RNA or microRNA or precursor thereof.
Page 25 of 61
ROCKEFELLER (Tuschl)
License Agreement between The Rockefeller University and Alnylam Pharmaceuticals, Inc. effective
May 8, 2006 (
Tuschl Agreement
)
Brief Summary of Technology Covered by License
:
The Rockefeller University granted Alnylam a license to intellectual property developed by Dr.
Thomas Tuschl relating to sequence-specific inhibition of microRNAs (RU 681) (also known as Tuschl
IV).
Scope of License (Section 1.1)
Alnylams non-exclusive, world-wide, sublicensable license is limited to a license to
research, develop, make, have made, use, have used, import, have imported, sell, offer for sale and
have sold Licensed Products for human and animal therapeutics.
Rockefeller Patent Rights were developed with funding from the U.S. National Institutes of
Health. The United States government retains rights in such intellectual property, including, but
not limited to, requirements that products, which result from such intellectual property and are
sold in the United States, must be substantially manufactured in the United States.
Certain Sublicense Terms (Section 1.5)
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Alnylam will only have the right to grant sublicenses if such sublicense (a) is granted
in conjunction with a license or sublicense of Alnylams rights under proprietary
intellectual property that is in addition to the Rockefeller Patent Rights, and (b) is
granted in connection with a bona fide collaboration with one or more third parties
established by written agreement that is for purposes of research and/or development of
products under a jointly prepared research plan.
|
|
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Alnylam will prohibit the sublicensee from further sublicensing and require the
sublicensee to comply with the terms and conditions of the Tuschl Agreement (other than
Alnylams payment and reporting obligations).
|
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■
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Within thirty (30) days after Alnylam enters into a sublicense agreement, Alnylam will
deliver to Rockefeller a copy of the sublicense agreement which may be redacted except
with respect to terms, including financial terms that re not relevant to Alnylams
obligations under the Tuschl Agreement.
|
Upon an Alnylam bankruptcy event, payments due to Alnylam from its Affiliates or
sublicensees under the sublicense agreement in the form of milestone payments and royalties on
Licensed Products will, upon notice from Rockefeller to such Affiliate or sublicensee, become
payable directly to Rockefeller for the account of Alnylam. Upon receipt of such funds,
Rockefeller will remit to Alnylam the amount by which such payments exceed the amounts owed by
Alnylam to Rockefeller.
Page 26 of 61
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■
|
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Alnylam is primarily liable to Rockefeller for any act or omission of a sublicensee
that would be a breach of the Stoffel Agreement if performed or omitted by Alnylam, and
Alnylam will be deemed to be in breach of the Stoffel Agreement as a result of such act or
omission.
|
Diligence (Section 2)
|
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Alnylam must provide Rockefeller within 30 days of the third and each subsequent
anniversary of the Effective Date with written progress reports discussing the
development, evaluation, testing and commercialization of all Licensed Products.
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Payment Obligations (Sections 3 and 4)
The following milestones are payable for each Licensed Product against an individual Gene
Target:
|
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Receipt of IND approval.
|
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$
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[***]
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Dosing of first patient in Phase II Clinical Trials.
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$
|
[***]
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Dosing of first patient in Phase III Clinical Trials.
|
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$
|
[***]
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Receipt of NDA approval.
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$
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[***]
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A [***]% royalty is payable to Rockefeller on Net Sales of Licensed Products by Alnylam,
its Affiliates and its sublicensees (no offsets).
If Rockefeller grants a license under the Rockefeller Patent Rights to any third party,
which will permit such third party to manufacture or sell for any use within the scope of the
license at a lower royalty rate than that provided in the Tuschl Agreement, Rockefeller will
promptly notify Alnylam of such license, including all material terms and conditions of such
license, and offer to Alnylam the lower royalty rates and all of the material terms and conditions
of such license. If Alnylam accepts such terms in writing, the royalty rate and all material terms
and conditions of such notice shall thereafter apply to Alnylam and the parties will promptly
execute an amendment to the Tuschl Agreement reflecting such terms and conditions.
Alnylam must pay Rockefeller a one-time fee of $[***] within 30 days after granting a
sublicense to a permitted sublicensee.
Payments are due to Rockefeller within 60 days after the end of the quarter in which the
royalties or fees accrue.
Books and Records (Sections 4.3 and 4.4)
Sub-licensees are required to keep complete and accurate books and records to verify Sales,
Net Sales, and all of the royalties, fees, and other payments payable under
Page 27 of 61
the Tuschl Agreement. The records for each quarter will be maintained for at least 3 years after
submission of the applicable report required under the Tuschl Agreement.
Upon reasonable prior written notice to Alnylam, sublicensees will provide an independent,
reputable CPA appointed by Rockefeller and reasonably acceptable to Alnylam with access to all of
the books and records required by the Tuschl Agreement to conduct a review or audit of Sales, Net
Sales, and all of the royalties, fees, and other payments payable under the Tuschl Agreement. If
the audit determines that Alnylam has underpaid any royalty payment by 5% or more, Alnylam will
also promptly pay the costs of the review or audit.
Non-Use of Name (Section 5.4)
Sublicensees may not use the name, logo, seal, trademark, or service mark (including any
adaptation of them) of Rockefeller or any Rockefeller school, organization, employee, student or
representative, without the prior written consent of Rockefeller.
Termination (Section 6.2)
Alnylam may terminate for convenience
Alnylam must promptly inventory all finished product and works-in-product of Licensed
Products of its sublicensees. Inventory may be sold off unless Rockefeller terminates for a breach
by Alnylam or its sublicensees or Alnylams bankruptcy.
Prosecution and Enforcement (Section 7)
Rockefeller controls the preparation, prosecution and maintenance of the Rockefeller Patent
Rights and the selection of patent counsel, with input from Alnylam. Alnylam will be copied on,
and allowed to comment upon, all substantive issues in the patent prosecution.
Alnylam shall pay a pro rata share, not to exceed [***]%, for all reasonable out of pocket
attorney charges and official fees incident to the preparation, prosecution, and maintenance of
such patent applications and patents, not exceeding $[***]/year. If Rockefeller chooses not to
prosecute or maintain the patent rights, Alnylam may do so and receive a credit against its royalty
obligations in an amount equal to its expenses.
Alnylam must inform Rockefeller promptly after learning of infringement of the Rockefeller
Patent Rights. Alnylam and Rockefeller will consult each other concerning response to
infringement. Rockefeller may enforce any infringement of the Rockefeller Patent Rights at
Rockefellers expense and retain the recoveries. If Rockefeller requests Alnylam to join such
enforcement litigation and Alnylam elects to do so, the recoveries will be shared between Company
and Rockefeller in proportion with their respective shares of the aggregate litigation
expenditures. Alnylam has step-in enforcement rights. Alnylam must not settle or compromise any
such litigation in a manner that imposes any
Page 28 of 61
obligations or restrictions on Rockefeller or grants any rights to the Rockefeller Patent Rights
without Rockefellers prior written permission. Step-in recoveries, after Alnylams expenses are
reimbursed, are treated as Net Sales subject to royalties.
Definitions
Gene Target
means a genomic microRNA locus, any portion thereof, any RNA transcribed
from within or overlapping such locus or portion, and all transcript and allelic variants thereof.
Licensed Products
means products that are researched, developed, made, made for,
used, used for, imported, imported for, sold, sold for or offered for sale by Alnylam or its
Affiliates or sublicensees and that either (i) in the absence of this Agreement, would infringe at
least one Valid Claim of the Rockefeller Patent Rights, or (ii) use a process or machine covered by
a Valid Claim of Rockefeller Patent Rights.
Net Sales
means with respect to each Licensed Product the gross amount invoiced by
Alnylam or its Affiliates or sublicensees on sales or other dispositions of such product to third
parties less Qualifying Costs directly attributable to a sale and actually taken and/or identified
on the invoice and borne by Company, or its Affiliates or sublicensees.
Qualifying Costs
means: (a) customary discounts in the trade for quantity purchased, prompt payment or wholesalers
and distributors; (b) credits, allowances or refunds for claims or returns or retroactive price
reductions (including government healthcare programs and similar types of rebates) that do not
exceed the original invoice amount; (c) prepaid outbound transportation expenses and transportation
insurance premiums; and (d) sales, transfer, excise and use taxes and other fees imposed by a
governmental agency. Sales for clinical study purposes or compassionate, named patient or similar
use shall not constitute Net Sales
Rockefeller Patent Rights
means a patent application entitled Anti Micro-RNA
Oligonucleotide Molecules and related patent family, relating to sequence-specific inhibition of
microRNAs (RU 681).
Page 29 of 61
STANFORD (Sarnow/miR-122)
Co-Exclusive License Agreement among The Board of Trustees of the Leland Stanford Junior
University, Alnylam Pharmaceuticals, Inc. and Isis Pharmaceuticals, Inc. effective August 31, 2005
(each of Alnylam and Isis, a
Licensee
) (Sarnow/miR-122)
Brief Summary of Technology Covered by License
:
Co-exclusive license to use of mir-122 to reduce HCV replication (Stanford Docket S04-097);
research done in Sarnow lab supported by NIAID.
Scope of License
(Section 3):
Stanford grants to each of the Licensees a co-exclusive, worldwide right and license under
the Licensed Patents in the Exclusive Licensed Field of Use to develop, make, have made, use, have
used, import, offer to sell, and sell Licensed Products in the Licensed Territory.
Stanford grants to each of Licensees a non-exclusive, worldwide right and license under the
Licensed Patent in the Non-Exclusive Licensed Field of Use to develop, make, have made, use, have
used, import, offer to sell and sell Licensed Products in the Licensed Territory.
Stanford retains the right, on behalf of itself and all other non-profit academic research
institutions, to practice the Licensed Patents for any non-profit purpose, including sponsored
research and collaborations. Licensee agrees that, notwithstanding any other provision of this
Agreement, it has no right to enforce the Licensed Patents against any such institution. Stanford
and any such other institution have the right to publish any information included in the Licensed
Patents. If Stanford alters its requirements for license agreements with respect to the subjects
addressed in this Section, or enters into a license agreement with terms more favorable to a
licensee than those set forth in this Section, Stanford agrees to negotiate in good faith with the
Licensees to amend the terms of this Section based upon the reasonable written request of either
Licensee.
The Bayh-Dole Act, including U.S. manufacturing obligations, applies.
Sublicensing Rights (Section 4)
:
Each Licensee may grant sublicenses in connection with (Section 4.1):
a bona fide collaboration with one or more third parties established by written agreement
(i) for purposes of research and/or development of products under a jointly prepared research plan;
and (ii) which includes a license or sublicense of such Licensees rights under related
intellectual property covering proprietary know-how or patent rights in addition to a sublicense to
the Licensed Patents; and/or
Page 30 of 61
provision of services to such Licensee, including without limitation contract
manufacturing, and other services relating to development and commercialization of Licensed
Products.
If both of Licensees or their sublicensees are unable or unwilling to serve or develop a
potential market or market territory for which there is a company willing to be a sublicensee,
Stanford may request the Licensees to negotiate in good faith a sublicense under the Licensed
Patents.
Any sublicense:
will prohibit any grant of a further sublicense by a sublicensee;
will expressly include the provisions of Articles 8 (Royalty Reports, Payments, and
Accounting), 9 (Exclusions and Negations of Warranties) and 10 (Indemnity) for the benefit of
Stanford;
will require the assumption of all obligations, including the payment of royalties
specified in the sublicense, to Stanford or its designee, if this Agreement is terminated; and
is subject to this Agreement.
Each Licensee will submit to Stanford a copy of each sublicense after it becomes effective,
which copy may be redacted except as to matters directly pertinent to such Licensees obligations
under this Agreement.
If either Licensee grants a sublicense pursuant to Section 4.1(A), and receives an upfront
payment in connection therewith, the following amounts, if applicable, will be due to Stanford from
such Licensee within 60 days of the full execution of the agreement establishing such
collaboration:
(A) if such agreement includes an upfront payment equal to or less than $[***], a payment
will be due to Stanford in the amount of $[***];
(B) if such agreement includes an upfront payment greater than $[***] and equal to or less
than $[***], a payment will be due to Stanford in the amount of $[***];
(C) if such agreement includes an upfront payment greater than $[***], a payment will be
due to Stanford in the amount of $[***].
If Licensees jointly enter into a bona fide collaboration with a third party, the relevant
upfront payment shall be due only once for such collaboration. Any amounts representing the
reimbursement of costs previously incurred by a Licensee, including fully burdened personnel costs
and patent expenses, will not be included in determining the amount of any up front payment.
Page 31 of 61
If Licensee pays all royalties due Stanford from a sublicensees Net Sales, Licensee may
grant that sublicensee a royalty-free or non-cash sublicense or cross-license.
Diligence
:
Each Licensee will use commercially reasonable efforts to (a) develop, manufacture, and
sell Licensed Products and develop markets for Licensed Products; and (b) meet the milestones shown
in its respective Appendix (see below). If a Licensee does not meet a milestone in its Appendix by
its corresponding date, it will have 30 days to submit to Stanford a specific written plan designed
to meet its obligations under this Section as promptly as possible using commercially reasonable
efforts. Each plan shall be subject to Stanfords written approval, which will not be unreasonably
withheld. Such Licensee will have 3 months to demonstrate to Stanfords reasonable satisfaction
its compliance with such plan.
(Appendices) Each Licensee will be solely responsible for meeting the following diligence
milestones in its development programs:
By the end of the year 2006, such Licensee will commence optimization of miRNA inhibitors.
By the end of the year 2007, such Licensee will select the method of delivery for such
miRNA inhibitors.
By the end of the year 2008, such Licensee (i) optimize a lead miRNA inhibitor and (ii)
propose additional clinical milestones to Stanford.
By the end of the year 2010, such Licensee will complete preclinical development
If Alnylam and Isis are jointly developing a given Licensed Product, both will be deemed in
compliance with their respective diligence obligations if either of Alnylam and Isis is fulfilling
such obligations.
By March 1 of each year, each Licensee will submit a written annual report to Stanford
covering the preceding calendar year.
Payment Obligations (Section 7)
:
The following annual maintenance fees are due under this Agreement:
(A) $[***] on the first 4 anniversaries of the Effective Date;
(B) $[***] on the 5
th
through 8th anniversaries of the Effective Date; and
(C) $[***] on the 9th anniversary of the Effective Date and each anniversary thereafter.
Page 32 of 61
Unless instructed otherwise by Licensees, Stanford will send invoices for one half of the
above amounts to each Licensee.
(Section 7.3)
The following milestones are payable for each Licensee for the first
Licensed Product in the Exclusive Field of Use:
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IND acceptance in U.S. or first dosing of a subject outside the U.S.
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$
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[***]
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Dosing of first subject in first Phase III Clinical Trial
|
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$
|
[***]
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NDA approval in U.S. or a foreign equivalent
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$
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[***]
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Milestones payable with respect to the first Licensed Product of each Licensee in the
Non-Exclusive Field of Use are [***]%) of those above..
Milestones payable with respect to the second Licensed Product (i.e. a new molecular
entity) of each Licensee in the Non-Exclusive Field of Use are [***]%) of those in the first chart
above.
For clarity, if Alnylam achieves any of the above milestone events, it does not relieve
Isis of the obligation to pay similar milestones when Isis, or its sublicensee achieves the same
milestone events; provided, however, that if Alnylam and Isis are jointly developing a given
Licensed Product, payments are due only once in respect of the achievement of a milestone event for
such Licensed Product.
(Section 7.4) Each Licensee will pay Stanford earned royalties on Net Sales of [***]% of
Net Sales of such Licensees Licensed Product. If a Licensee becomes obligated to pay royalties to
any third parties in connection with the sale of a Licensed Product, the royalties due to Stanford
from such Licensee under this Section for such Licensed Product will be reduced in connection with
amounts paid to such third parties as follows: for every [***]% of Net Sales which is paid to such
third parties (in the aggregate) in a given calendar year, the royalty rate due to Stanford will be
reduced by [***]%. In no event, however, will the royalty payable to Stanford by such Licensee be
reduced below a floor of [***]%. If the Licensees are jointly developing and/or commercializing a
Licensed Product, the royalty set forth above shall be due only once with respect to such Licensed
Product.
Royalty payments due to Stanford under Section 7.4 above in a particular year will be
reduced by the license maintenance fee paid by such Licensee and applicable to such year.
Non-Use of Names (Section 12.2)
:
The Licensees will not identify Stanford in any promotional statement, or otherwise use the
name of any Stanford faculty member, employee, or student, or any
Page 33 of 61
trademark, service mark, trade name, or symbol of Stanford or its affiliated hospitals and clinics,
including the Stanford name, unless Stanford has given its prior written consent or as required by
law, rule or regulation. Permission may be withheld at Stanfords sole discretion.
Prosecution and Enforcement (Section 13)
:
Subject to Stanfords approval, Isis will coordinate and be responsible for preparing,
filing, prosecuting and maintaining the Licensed Patents in Stanfords name. The parties shall
work together to develop a prosecution strategy and decide in which countries the Licensed Patents
will be filed.
Isis will
(i) keep Stanford and Alnylam informed as to the filing, prosecution, maintenance and
abandonment, as applicable, of the Licensed Patents;
(ii) furnish Stanford and Alnylam copies of documents relevant to any such filing,
prosecution maintenance and abandonment, as applicable;
(iii) allow Stanford and Alnylam reasonable opportunity to timely comment on documents to
be filed with any patent office which would affect the Licensed Patents;
(iv) give good faith consideration to the comments and advice of Stanford and Alnylam;
provided however that Stanford will have the opportunity to provide Isis with final approval on how
to proceed in any response or taking any such action; and
(v) provide copies of any official written communications relating to the Licensed Patents
to Stanford and Alnylam within 10 days of Isis receiving such communication and Stanford and
Alnylam will provide any applicable comments to Isis no later than 5 days prior to the first
deadline (without extensions) to file a response or take any action relating to such communication.
Isis may use counsel of its choice, which must be acceptable to Stanford and Alnylam, for
the filing, prosecution and maintenance of the Licensed Patents and the Licensees shall be billed
directly by such counsel.
A Licensee or the Licensees will reimburse Stanford the following costs:
all Stanfords reasonable and actual out-of-pocket patenting expenses incurred after the
Effective Date related to the Licensed Patents.
If one and only one Licensee decides to abandon ongoing prosecution and/or maintenance of
any of the Licensed Patents, on a country-by-country and Licensed Patent-by-Licensed Patent basis,
the continuing Licensee will pay 100% of the ongoing expenses for such Licensed Patent. Stanford
shall have the right to continue payment for such Licensed Patent in its own discretion and at its
own expense if both Licensees
Page 34 of 61
decide to abandon ongoing prosecution and/or maintenance of the Licensed Patents. If Stanford
decides to maintain such Licensed Patent, the license with respect to such Licensed Patent in such
country under this Agreement shall terminate with respect to the ceasing Licensee(s). Cessation of
payment by one Licensee as to a Licensed Patent will not affect the rights of the other Licensee
with respect to such Licensed Patent. If Isis is the Licensee wishing to cease payment of a
Licensed Patent, the responsibility for the prosecution of such Licensed Patent will transfer to
Stanford.
Each Licensee may assign its rights and obligations under Sections 13.1 and 13.2 to a
sublicensee, subject to prior notification to and approval from Stanford.
Stanford has the first right to institute action against a third party infringer which will
be executed (if at all) within 90 days after Stanford first becomes aware of the infringing
activity, and may name one or both Licensees as a party for standing purposes. Each Licensee may
elect to jointly prosecute the action (with Stanford) by providing written notice within 30 days
after the date of the notice from Stanford. If both Licensees elect not to jointly prosecute,
Stanford may pursue the suit, at its sole cost (including costs of litigation) and in such event
will be entitled to retain the entire amount of any recovery or settlement that is in excess of the
parties costs; if one or both Licensees elect to jointly prosecute, Stanford and the jointly
prosecuting Licensees will proceed in accordance with the Joint Suit provisions. If a Licensee
elects not to join a suit, that Licensee will discuss in good faith with Stanford the assignment of
rights, causes of action, and damages necessary for Stanford to prosecute the alleged infringement.
Joint Suit
. If Stanford and either or both Licensees are jointly prosecuting an
action against a third party infringer, they will share the out-of-pocket costs and any recovery or
settlement equally; and agree how they will exercise control over the action.
(Sections 13.6 and 13.7) If Stanford elects not to participate in a suit, either or both
Licensee(s) may institute and prosecute a suit so long as it conforms with the requirements of this
Section. The Licensee(s) will reach agreement on the institution and prosecution of such suit and
the sharing of such costs among themselves and will diligently pursue the suit and the Licensee(s)
instituting the suit will bear the entire cost (including necessary expenses incurred by Stanford)
of the litigation. The Licensee(s) will keep Stanford reasonably apprised of all developments in
the suit, and will seek Stanfords input and approval on any substantive submissions or positions
taken in the litigation regarding the scope, validity and enforceability of the Licensed Patents.
The Licensee(s) will not prosecute, settle or otherwise compromise any such suit in a manner that
adversely affects Stanfords interests without Stanfords prior written consent. If either or both
Licensees sue under Section 13.6, then any recovery in excess of any unrecovered litigation costs
and fees will be shared with Stanford as follows:
Any recovery for past sales by the infringer of products, which, if sold by a Licensee,
would be Licensed Products will be deemed Net Sales for purposes of this Agreement, and such
Licensees will pay Stanford royalties;
Page 35 of 61
Licensee and Stanford will negotiate in good faith appropriate compensation to Stanford for
any non-cash settlement, non-cash cross-license or payment for the right to make future sales.
Term and Termination (Section 14, 18.1)
:
Any termination shall only terminate this Agreement between Stanford and the affected
Licensee, and it shall remain in full force and effect between Stanford and the non-affected
Licensee.
Each Licensee may terminate its rights and obligations under this Agreement by giving
Stanford at least 30 days written notice.
A breach by one Licensee of its obligations to Stanford under this Agreement may not be
used as a basis for termination of this Agreement by the non-breaching Licensee, nor may a breach
of any obligation arising between the Licensees under this Agreement be used as a basis for
termination by one Licensee.
Assignment (Section 15)
:
Each Licensee may assign this Agreement as part of a sale, regardless of whether such a
sale occurs through an asset sale, stock sale, merger or other combination, or any other transfer
of such Licensees entire business, or that part of the Licensees business to which this Agreement
relates.
Definitions
:
Exclusive Licensed Field of Use
means the research, development, commercialization
and monitoring of therapeutics for the treatment and prevention of Hepatitis C and directly related
conditions and diseases (including without limitation chronic hepatitis, cirrhosis and primary
liver cancer). The Exclusive Field of Use specifically
excludes
:
(A) diagnostics; and
(B) commercialization of reagents.
Licensed Patents
means Stanfords U.S. Provisional Patent Application, Serial Number
[***], and the related patent family. Licensed Patent excludes any continuation-in-part (CIP)
patent application or patent unless the subject matter of such CIP patent application is
specifically described or claimed in another Licensed Patent and is filed within three (3) years of
the Effective Date. Licensed Patents exclude any claims relating to new matter that is invented by
Stanford after the Effective Date.
Page 36 of 61
Licensed Product
means a product in either the Exclusive Licensed Field of Use or
the Non-Exclusive Licensed Field of Use the making, using, importing or selling of which, absent
this license, infringes a Valid Claim of a Licensed Patent.
Non-Exclusive Licensed Field of Use
means the research, development,
commercialization and monitoring of therapeutics for the treatment and prevention of all conditions
or diseases other than Hepatitis C and directly related conditions or diseases.
Page 37 of 61
GARCHING (Co-Exclusive)
License Agreement among Garching Innovation GmbH (
GI
), Alnylam Pharmaceuticals, Inc. and
Isis Pharmaceuticals, Inc. effective October 18, 2004
Brief Summary of Technology Covered by License
:
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|
The Max Planck Society granted co-exclusive rights Alnylam and Isis to patent applications
(known as Tuschl III) based on the microRNA work of Dr. Thomas Tuschl. These microRNAs have
the potential to be new drug targets or therapeutic products and are the subjects of the
licensed patent applications.
|
Scope of License (Section 2.1):
GI hereby grants to each Alnylam and ISIS and their Affiliates a royalty-bearing
co-exclusive worldwide license, with the right to grant sublicenses, under the Patent Rights to
develop, make, have made, use, sell and import Licensed Products in the Field.
MPG retains the right to practice under the Patent Rights for non-commercial scientific
research, teaching, education, non-commercial collaboration (including industry-sponsored
scientific collaborations) and publication purposes.
Alnylam and ISIS acknowledge that the German government retains a royalty-free,
non-exclusive, non-transferable license to practice any government-funded invention claimed in any
Patent Rights for government purposes.
Sublicensing (Section 2.2)
:
Alnylam and ISIS may each grant sublicenses to the rights granted to them under Section 2.1
to Third Parties, however only (i) as Naked Sublicenses, (ii) in connection with a Drug Discovery
Collaboration or Development Collaboration, or (iii) to a Sales Partner.
Each Naked Sublicense shall be subject to the prior written approval of GI, which shall not
unreasonably be withheld. Alnylam or ISIS, as applicable, shall inform GI in writing at least 30
days prior to the intended signature of any such sublicense agreement in sufficient detail (in
particular regarding financial terms and other relevant information) to permit GI to decide whether
or not to approve. Any requested approval is deemed to be granted if GI does not refuse the
approval in writing within 30 days after receiving the necessary information; in particular, GI may
withhold its approval if GI deems the received information not sufficient.
Each sublicense granted under this Agreement shall be subject and subordinate to, and
consistent with, the terms and conditions of this Agreement. Alnylam or ISIS, as applicable, shall
be liable that any subsequent sublicenses granted by the Sublicensees are subject and subordinate
to, and consistent with, the terms and conditions of this Agreement. In the event of a material
default by any sublicensee under an Isis or
Page 38 of 61
Alnylam sublicense, the applicable party will inform GI and take commercially reasonable efforts to
cause the sublicensee to cure the default or will terminate the sublicense. (Section 4.6)
Within 30 days after the signature of each sublicense granted under this Agreement, Alnylam
or ISIS, as applicable, shall provide GI with a reasonably redacted copy of the signed sublicense
agreement.
Diligence (Section 4)
:
Alnylam and ISIS shall each use commercially reasonable efforts, and shall oblige their
Affiliates and Sublicensees to use commercially reasonable efforts, to develop and commercialize
their respective Licensed Products.
Semi-annual progress reports. ALNYLAM and ISIS shall each furnish, and require their
Affiliates to furnish to ALNYLAM and ISIS, to GI in writing, semi-annually, within 60 days after
the end of each calendar half year, with a report, stating in reasonable detail the activities and
the progress of their efforts (including the efforts of their Sublicensees) during the immediately
preceding half year to develop and commercialize their respective Licensed Products, on a
product-by-product and country-by-country basis. The report shall also contain a discussion of
intended development and commercialisation efforts for the calendar half year in which the report
is submitted.
Financial Obligations (Section 5)
:
Alnylam and ISIS shall each pay to GI the following milestone payments for each of their
respective Licensed Products (including Licensed Products of their Affiliates and Sublicensees)
within 30 days:
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Milestone Event
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Milestone Payment
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First Initiation of Phase I Clinical Study
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$
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[***]
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First Initiation of Phase II Clinical Study
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$
|
[***]
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First Initiation of Phase III Clinical Study
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$
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[***]
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Regulatory Approval in USA, Japan or Europe
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$
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[***]
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Each of the above milestone payment is due from the Party that is engaged in the
development and commercialization of such Licensed Product.
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For each Licensed Product, milestone payments will only be due the first time such Licensed
Product achieves such milestone. A Licensed Product will be considered the same Licensed
Product as long as it has not been modified in such a way (unless as the result of
stabilizing, formulation or delivery technology) that would require the filing of a
different IND for such Licensed Product.
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Royalties (Section 5.3):
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Page 39 of 61
Alnylam and ISIS shall each pay to GI for each of their respective Licensed Products
(including Licensed Products of their Affiliates and Sublicensees) covered by Valid Claims the
following running royalties on the incremental portion of annual Net Sales:
Less than or equal to $[***] US Dollars [***]%
Between $[***] US Dollars and $[***] US Dollars [***]%
Between $[***] US Dollars and $[***] US Dollars [***]%
Greater than $[***] US Dollars [***]%
Alnylam and ISIS shall each pay to GI for each of their respective Licensed Products
(including Licensed Products of their Affiliates and Sublicensees) covered by Pending Claims [***]%
of running royalties above
If Alnylam or ISIS, or any of their Affiliates or Sublicensees, licenses any patents or
patent applications Controlled by a Third Party in order to make, use, or sell a Licensed Product
(explicitly excluding, without limitation, any Third Party patents and patent applications covering
any formulation, stabilization, or delivery technology, or any target for a Licensed Product) the
running royalties set forth in Sec. 5.3 will be reduced, on a country-by-country and
product-by-product basis, from the date running royalties have to be actually paid to such Third
Party, by [***]% of any running royalty owed to a Third Party for the manufacture, use or sale of a
Licensed Product, provided however that the running royalties due to GI will not be reduced to less
than [***]%.
The running royalties stated in Section 5.3 shall in no event be reduced by the application
of this Section 5.4 to less than a minimum royalty rate of (i) [***]% for Licensed Products covered
by Valid Claims, and (ii) [***]% for Licensed Products covered by Pending Claims.
In no event shall the total cumulative running royalty burden of Alnylam or Isis for a
Licensed Product arising out of this Agreement and any Existing GI Licenses, calculated on a
product-by-product and country-by-country basis, exceed [***]% for such a Licensed Product.
Sublicense Revenues (Section 5.5):
Subject to Section 5.5(d), in the event that Alnylam or ISIS grant a
Naked
Sublicense
to a Third Party pursuant to Section 2.2 (a), Alnylam or ISIS, as applicable, shall
pay to GI [***]% of their respective Sublicense Consideration received, due within 30 days after
receipt.
Subject to Section 5.5(d), in the event that Alnylam or ISIS grant a sublicense to a Third
Party pursuant to Section 2.2 (a) in connection with a Drug Discovery Collaboration or Development
Collaboration, Alnylam or ISIS, as applicable, shall pay to
Page 40 of 61
GI the following percentages of their respective Sublicense Consideration received, due within 30
days after receipt:
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Sublicense granted
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Percentage due to GI
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Up to, but not including, filing of an IND:
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[***]
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%
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After filing of an IND
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[***]
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%
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After initiation of Phase II Clinical Study
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[***]
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%
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After initiation of Phase III Clinical Study
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[***]
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%
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After filing of a NDA
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[***]
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%
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If Alnylam or ISIS receives any non-cash Sublicense Consideration, Alnylam or ISIS, as
applicable, shall pay GI, at GIs election, either (i) a cash payment equal to the fair market
value of the Sublicense Consideration, or (ii) the in-kind portion, if practicable, of the
Sublicense Consideration.
(Section 5.5(d)) If Alnylam or ISIS grant a sublicense that includes, in addition to the
Patent Rights, patents or patent applications Controlled by Alnylam or ISIS, the percentage of the
Sublicense Consideration due to GI shall be based on the value reasonably attributable to the
Patent Rights relative to the value of the patents or patent applications Controlled by Alnylam or
ISIS included in such sublicense (such relative value of the Patent Rights hereinafter the Patent
Rights Value).
Together with the copy of any sublicense agreement to be provided to GI according to Sec.
2.2, Alnylam or ISIS, as applicable, shall suggest to GI the Patent Rights Value based on a good
faith fair market value determination, together with any information reasonably necessary or useful
for GI to evaluate such suggestion.
If a fair market value has to be determined, the Party obliged to suggest such fair
market value shall provide the other Party in due time with a good faith determination of the fair
market value, together with any information necessary or useful to support such determination. The
other Party shall have the right to provide the suggesting Party in due time with a
counter-determination of the fair market value, which shall include any information necessary or
useful to support such counter-determination.
Prosecution and Enforcement (Section 6)
:
GI shall, in its sole discretion, apply for, seek issuance of, maintain, or abandon the
Patent Rights during the Term.
Alnylam, ISIS and GI shall cooperate, if necessary and appropriate, with each other in
gaining patent term extension wherever applicable to the Patent Rights, and shall use reasonable
efforts to agree upon a joint strategy relating to patent term extensions.
Page 41 of 61
Alnylam and ISIS shall together pay to GI [***]%, and each of Alnylam and ISIS shall pay
[***]% of such [***]% share, of all fees and costs, including attorneys fees, relating to the
filing, prosecution, maintenance and extension of the Patent Rights, which incur during the Term.
If Alnylam or ISIS wish to cease payment for any of the Patent Rights, GI shall have the
right to continue payment for such Patent Rights in its own discretion and at its own expense; such
Patent Rights shall no longer be covered by this Agreement with respect to the ceasing party from
the date Alnylam or ISIS informs GI of its cessation of payments.
Enforcement (Section 6.3):
Alnylam and ISIS shall each promptly inform GI in writing if they become aware of any
suspected or actual infringement of the Patent Rights by any Third Party, and of any available
evidence thereof.
Subject to the right of each Alnylam and ISIS to join in the prosecution of infringements
set forth below, GI shall have the right, but not the obligation, to prosecute (whether judicial or
extrajudicial) in its own discretion and at its own expense, all infringements of the Patent
Rights. The total costs of any such sole infringement action shall be borne by GI, and GI shall
keep any recovery or damages (whether by way of settlement or otherwise) derived therefrom. In any
such infringement suits, Alnylam and ISIS shall each, at GIs expense, cooperate with GI in all
respects.
Alnylam and ISIS shall each have the right at their sole discretion to join GIs
prosecution of any infringements of the Patent Rights. GI and the joining Party(ies) will agree in
good faith on the sharing of the total cost of any such joint infringement action and the sharing
of any recovery or damages derived therefrom.
If GI decides not to prosecute infringements of the Patent Rights, neither solely nor
jointly with Alnylam or ISIS, GI shall offer to Alnylam and ISIS to prosecute (whether jointly by
Alnylam and ISIS or solely by one of them) any such infringement in their own discretion and at
their own expense. GI shall, at the expense of the prosecuting Party(ies), cooperate. The total
cost of any such sole infringement action shall be borne by the prosecuting Party(ies), and the
prosecuting Party(ies) shall keep any recovery or damages derived therefrom.
If a Party prosecuting infringements intends to settle the infringement (such as granting a
license or entering a settlement agreement), any such arrangement needs the prior written approval
of the other Parties, which shall not unreasonably be withheld. Any sublicense granted by Alnylam
or ISIS to a Third Party infringer shall be regarded and treated as a Naked Sublicense under this
Agreement.
Page 42 of 61
Term and Termination (Section 9)
:
Alnylam and ISIS shall each have the right to terminate this Agreement, for any reason,
upon at least 3 months prior written notice to GI. Termination of this Agreement by either Isis or
Alnylam shall not be deemed to be termination by the other.
If at least 50% of issued and outstanding shares of Alnylam or ISIS are assigned or
transferred to a Third Party, Alnylam or ISIS, as applicable, shall provide GI, upon GIs request,
with written reports in reasonable detail on the actual and intended future activities of Alnylam
or ISIS, as applicable, to develop and commercialize Licensed Products. If the reports are not
provided to GI in due time and/or in sufficient detail, after 60 days written notice from GI, such
failure will be a material breach, and GI shall have the right to terminate this Agreement with
respect to such breaching party in accordance with the procedures set forth in Section 9.6. Alnylam
or ISIS, as applicable, shall inform GI promptly of the implementation of any such assignment or
transfer.
GI shall have the right to terminate this Agreement upon 30 days prior written notice to
Alnylam or ISIS, if Alnylam or ISIS, as applicable, or any of their Affiliates, attack, or have
attacked or support an attack through a Third Party, the validity of any of the Patent Rights.
If any license granted to Alnylam or ISIS under this Agreement is terminated, any
sublicense under such license granted prior to termination of said license shall remain in full
force and effect, provided that (i) the Sublicensee is not then in breach of its sublicense
agreement, and (ii) the Sublicensee agrees, in writing within 30 days after the effective date of
termination, to be bound to GI as licensor under the terms and conditions of the sublicense
agreement, provided that GI shall have no other obligation than to leave the sublicense granted by
Alnylam or ISIS in place.
Non-Use of Names (Section 4.5)
:
Neither Alnylam nor ISIS, nor their Affiliates or Sublicensees, may use the name of Max
Planck Institute, Max Planck Society, Garching Innovation or any variation, adaptation, or
abbreviation thereof, or of any of its trustees, officers, faculty, students, employees, or agents,
or any trademark owned by any of the aforementioned, in any promotional material or other public
announcement or disclosure without the prior written consent of GI or in the case of an individual,
the consent of that individual.
Assignment (Section 10.4)
:
Neither this Agreement no any rights or obligations may be assigned or otherwise
transferred by Alnylam or ISIS to a Third Party without the prior written consent of GI.
Notwithstanding the foregoing, Alnylam and ISIS each may assign this Agreement to a Third Party in
connection with the merger, consolidation, or sale of all or substantially all of their assets or
that portion of their business to which this Agreement relates; provided, however, that this
Agreement shall immediately terminate if the proposed Third Party assignee fails to agree in
writing to be bound by the terms and conditions of this
Page 43 of 61
Agreement on or before the effective date of assignment. After the effective date of assignment,
the Third Party assignee shall provide GI, upon GIs request, with written reports in reasonable
detail on the actual and intended future activities of the Third Party assignee to develop and
commercialize Licensed Products. If the Third Party assignee does not maintain a program to
develop and commercialize Licensed Products that is substantially similar or greater in scope to
the program of Alnylam or ISIS after the effective date of assignment, then GI has the right to
limit the scope of the co-exclusive license granted under this Agreement to such Licensed Products
actually covered by the program of the Third Party assignee.
Definitions
:
Development Collaboration
means a collaboration by Alnylam and/or ISIS with a Third
Party whose purpose is the (i) further development and/or commercialization of a Licensed Product
discovered by Isis or Alnylam either on their own or as part of a Drug Discovery Collaboration or
(ii) further joint development and/or joint commercialization of Licensed Products, in each case,
beginning after the initiation of IND-Enabling Tox Studies for such Licensed Products.
Collaborations that do not include or involve the licensed Patent Rights shall
not
constitute Development Collaborations.
Drug Discovery Collaboration
means a collaboration by Alnylam and/or ISIS with a
Third Party whose purpose is the joint discovery, joint development and/or joint optimization of
Licensed Products up to, but not including, IND-Enabling Tox Studies for such Licensed Products.
Existing GI Licenses
means any license agreement between Alnylam and GI in force and
effect prior to the Effective Date of this Agreement and relating to patents or patent applications
of MPG that also cover the manufacture, use and sale of Licensed Products.
Field
means use of Licensed Products
(i) for each Partys internal and collaborative research use, and
(ii) for all therapeutic and prophylactic uses in human diseases,
specifically excluding any commercial provision of Licensed Products as research reagents for
research purposes, and any diagnostic use.
Licensed Products
means any product, or part thereof, the manufacture, use or sale
of which, absent the license granted hereunder, would infringe one or more Pending Claims or one or
more Valid Claims of the Patent Rights.
Naked Sublicenses
means any sublicense to the Patent Rights granted by Alnylam
and/or ISIS to a Third Party that is not a license in connection with a Drug Discovery
Collaboration, Development Collaboration or Sales Partner agreement. Licenses that do not include
or involve rights to the Patents Rights shall not constitute Naked Sublicenses.
Page 44 of 61
Patent Rights
means the patents and applications listed on Exhibit A and the related
patent family.
Sales Partner
means any legal entity that is granted a sublicense to the Patent
Rights by Alnylam, ISIS, their Affiliates or Sublicensees solely to market, promote, distribute or
sell, or otherwise dispose of, Licensed Products in finished form.
Sublicense Consideration
means any consideration, whether in cash (e.g. initial or
upfront payments, technology access fees, annual fixed payments) or in kind (e.g. devices,
services, use rights, equity), received by Alnylam or ISIS and their Affiliates from Sublicensees
as consideration for the sublicense granted. Sublicense Consideration specifically excludes (i) any
milestone payments relating to the achievement of certain clinical events, (ii) any running
royalties on sales of products, (iii) payments specifically committed to reimburse Alnylam or ISIS
for the fully-burdened cost of research and development, (iv) payments made by the Sublicensee in
consideration of equity (shares, options, warrants or any other kind of securities) of Alnylam or
ISIS at fair market value, and (iv) equity (shares, options, warrants or any other kind of
securities) of the Sublicensee purchased by Alnylam or ISIS at fair market value.
Page 45 of 61
MIT
Amended and Restated Exclusive Patent License Agreement between Massachusetts Institute of
Technology (
MIT
) and Alnylam, dated May 9, 2007 (
MIT Agreement
)
Brief Summary of Technology Covered by License
:
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M.I.T. granted Alnylam exclusive rights to develop and commercialize for human RNAi
therapeutics certain technology relating to novel lipid compositions that are potential
components of cationic liposomal formulations for cellular delivery of oligonucleotides. The
technology was developed in the laboratory of Professor Robert Langer.
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Limitations on Scope of License (Sections 2.1, 2.3 and 2.5)
The license granted to Alnylam is limited to a exclusive (for the Exclusive Period),
worldwide license under the Patent Rights to develop, make, have made, use and import Library
Products and Licensed Processes to develop, make, have made, use, sell, offer to sell, lease, and
import Licensed Products in the Field and to develop and perform Licensed Processes in the Field.
Alnylam does not have the right to sell or offer for sale the Library Products separately
from a sale or offer for sale of a Licensed Product.
MIT retains the right to practice under the Patent Rights for research, teaching, and
educational purposes. The U.S. federal government retains a royalty-free, non-exclusive,
non-transferable license to practice any government-funded invention claimed in any Patent Rights
as set forth in 35 USC 201-211, and the regulations promulgated thereunder, including the
requirement that Library Products, whether or not part of Licensed Products, used or sold in the
U.S. must be manufactured substantially in the U.S.
The Patent Rights may not be asserted against non-for-profit research institutions that
practice the Patent Rights for research funded by (i) the institutions themselves, (ii) not-for
profit foundations, or (iii) any federal, state or municipal government. Alnylam may assert the
Patent Rights against not-for-profit research institutions only if the infringement activity of the
not-for-profit research institution was performed in the fulfillment of research sponsored by a
for-profit entity and the assertion of infringement must be limited to those specific activities.
Restrictions on Sublicensing by Alnylam (Sections 2.1 and 2.3)
Alnylam may grant sublicenses under commercially reasonable terms and conditions only
during the Exclusive Period. Any sublicenses by Alnylam may extend past the expiration date of the
Exclusive Period, but any exclusivity of such sublicense will expire upon the expiration of the
Exclusive Period.
Page 46 of 61
The sublicense must incorporate terms and conditions sufficient to enable Alnylam and its
Affiliates to comply with the MIT Agreement. Such sublicenses will also include provisions to
provide that if Sublicensee brings a Patent Challenge against MIT (except as required under a court
order or subpoena), Alnylam may terminate the sublicense.
Upon termination of the MIT Agreement, any Sublicensee not then in default will have the
right to seek a license from MIT, and MIT agrees to negotiate such licenses in good faith under
reasonable terms and conditions.
Alnylam may permit third parties (i) to use Library Products and Licensed Processes for the
purpose of research with academic or nonprofit institutions and contract research, including for
the conduct of clinical trials of a Licensed Product, and (ii) to sell Licensed Products under an
agency, consignment or equivalent arrangement, wherein such rights are not sublicense rights.
Alnylam will promptly furnish MIT with a fully signed photocopy of any sublicense
agreement, which copy may be redacted except with respect to terms directly relevant to Alnylams
obligations under the MIT Agreement.
Diligence and Reporting (Sections 3.1 and 3.2)
Sublicensees are required to use diligent efforts to develop Library Products and Licensed
Products and to introduce Licensed Products into the commercial market; thereafter Sublicensees are
required to make Licensed Products reasonably available to the public. Specifically, the following
obligations must be fulfilled:
Written reports are due within [***] days after the end of each calendar year on the
progress of efforts during the immediately preceding calendar year to develop and commercialize
Licensed Products. Such reports will include the number of [***], a description of [***], and the
[***]that have been tested. The report will also contain a discussion of intended efforts and
sales projections for the year in which the report is submitted.
Funding for research at MIT pursuant to the Budget set forth in Attachment C of the
Research Agreement.
By [***], Library Products will be evaluated for use in [***].
Prior to [***], at least [***] will be advanced to [***] studies in support of [***] for
[***] studies.
Filing of [***] for Licensed Product [***]by [***].
Commencement of [***] trial for a Licensed Product within [***] years of IND filing for
such Licensed Product.
Page 47 of 61
First Commercial Sale of a Licensed Product within [***] for each such Licensed Product.
If any Sublicensee is determined to have failed to fulfill any obligation under Sections
3.1(a) and 3.1(c) (g) above, MIT may treat such failure as a material breach, subject to any
changes to such diligence requirements as may be mutually-agreed by the parties below.
If Alnylam anticipates a failure to meet an obligation set forth in Section 3.1(c), (d),
(e), (f) or (g) above will occur, Alnylam will promptly advise MIT, and representatives of each
party will meet to review the reasons for anticipated failure. Alnylam and MIT will enter into a
written amendment to the MIT Agreement with respect to any mutually agreed upon change(s) to the
relevant obligation. If, after good faith discussion, Alnylam and MIT are unable to agree upon an
amendment to the obligation, Alnylam, at its discretion, may elect to extend the due date to meet
the obligation for such diligence obligation by one year by providing written notice to MIT along
with payment in the amount of $[***]. Alnylam may extend the due date of each diligence obligation
set forth in Section 3.1(c), (d), (e), (f) or (g) of the MIT Agreement only once during the term.
Financial Obligations (Section 4.1)
License Maintenance Fees
:
Alnylam will pay MIT the following license maintenance fees on the dates set forth below:
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Each January 1st for 2008 and 2009
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$
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[***]
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Each January 1st for 2010 and 2011
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$
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[***]
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Each January 1st for 2012 and 2013
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$
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[***]
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Each January 1
st
for 2014 and 2015
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$
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[***]
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Each January 1
st
of every year thereafter
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$
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[***]
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The annual license maintenance fee is nonrefundable, but may be credited to running
royalties subsequently due on Net Sales earned during the same calendar year, if any. License
maintenance fees paid in excess of running royalties due in such calendar year will not be
creditable to amounts due for future years.
Royalty Payments
:
Running royalties of [***]% of Net Sales of Licensed Products and Licensed Processes are
due within [***] days of the end of each calendar quarter.
If Alnylam or an Affiliate is legally required to pay royalties to one or more third
parties in order to obtain a license or similar right necessary to practice the Patent Rights,
Alnylam will be entitled to credit up to [***]% of the amounts payable to such third
Page 48 of 61
parties against the royalties due to MIT for the same reporting period; provided, however, that (i)
in no event will the running royalties due to MIT, when aggregated with any other offsets and
credits allowed under the MIT Agreement, be less than [***]% of Net Sales in any reporting period,
and (ii) royalties due to third parties with respect to [***] patents (see
Appendix B
to
MIT Agreement) will not qualify for purposes of the foregoing offset against royalties.
Milestone Payments
:
Alnylam will pay MIT the amounts set forth below upon achievement by Alnylam or any of its
Affiliates or Sublicensees of certain milestone events as set forth below. Payments will be due in
respect of the achievement of such milestone events for each first Licensed Product containing an
miRNA Therapeutic(s) and/or an siRNA Therapeutic(s) towards a specific Target or a specific
combination of Targets; provided, however, that if in the course of development a given Licensed
Product is discontinued and replaced with a different Licensed Product for the same therapeutic
indication containing an miRNA Therapeutic(s) and/or an siRNA Therapeutic(s) towards at least one
Target that was also a Target of the discontinued Licensed Product, milestone payments already paid
for the discontinued Licensed Product will not be due for achievement of the same milestone
event(s) by the substituted Licensed Product.
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Milestone Event
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Payment
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Filing of an Investigational New Drug Application (or equivalent)
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$
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[***]
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Dosing of first patient in a Phase 2 clinical trial (or equivalent)
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$
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[***]
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Dosing of first patient in a Phase 3 clinical trial (or equivalent)
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$
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[***]
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First Commercial Sale
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$
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[***]
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In the event of an assignment as described in Article 10 of the MIT Agreement, the
milestone payments set forth above that have not yet come due, will instead be replaced with the
milestone events and payments set forth below.
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Milestone Event
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Payment
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Filing of Investigational New Drug Application (or equivalent)
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$
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[***]
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Dosing of first patient in a Phase 2 clinical trial (or equivalent)
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$
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[***]
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Dosing of first patient in a Phase 3 clinical trial (or equivalent)
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$
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[***]
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First Commercial Sale
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$
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[***]
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The milestone events set forth in the two tables above are intended to be successive. In
addition and notwithstanding the foregoing, if any milestone is reached without achieving a
preceding milestone, then the amount which would have been payable on achievement of the preceding
milestone will be payable upon achievement of the next successive milestone. Alnylam will notify
MIT within ten (10) days of the achievement of any of the above milestones by Alnylam or any of its
Affiliates or Sublicensees.
Sublicense Income
:
If Alnylam or an Affiliate grants a sublicense of its rights under Section 2.1 of the MIT
Agreement, Alnylam will pay MIT, as applicable:
[***]% of all Sublicense Income received by Alnylam or Affiliates from Sublicensees which
are also receiving rights to substantial technology and/or patent rights owned or controlled by
Alnylam or Affiliates related to the development of Licensed Products, whether such Sublicense
Income is received under the same agreement as the sublicense to Alnylams rights under Section 2.1
of the MIT Agreement and/or in a separate agreement. (To the extent that the only other patents
and/or technology rights received by Sublicensees are sublicense rights under the patent rights
listed in
Appendix B
, then any sharing of Sublicense Income will fall under clause (b)
below); and
[***]% of all Sublicense Income received by Alnylam or Affiliates from Sublicensees if such
Sublicensees are receiving a sublicense to Alnylams rights under Section 2.1 of the MIT Agreement
alone or with a sublicense to the patent rights listed in
Appendix B
, without substantial
additional technology and/or other patent rights from Alnylam or Affiliates, whether or not in the
same agreement, as part of the same business arrangement related to Licensed Products.
Such amount will be payable for each reporting period and will be due to MIT within [***]
days of the end of each reporting period.
Reports (Sections 5.1 and 5.2)
Prior to First Commercial Sale of a Licensed Product or first commercial performance of a
Licensed Process, Alnylam is required to deliver annual reports within [***] days of the end of
each calendar year, containing information concerning the immediately preceding year, as further
described in Section 5.2 of the MIT Agreement (see below). The date of First Commercial Sale of a
Licensed Product or commercial performance of a Licensed Process must be reported to MIT within
[***] days of its occurrence.
After First Commercial Sale of a Licensed Product or commercial performance of a Licensed
Process, reports are required to be delivered to MIT within [***] days of the end of each reporting
period containing information concerning the immediately preceding reporting period, as further
described in Section 5.2 of the MIT Agreement (see below).
Page 50 of 61
Section 5.2 states that reports must include at least the following information for the
immediately preceding reporting period:
the number of Licensed Products sold, leased, or distributed to independent third parties
in each country and, if applicable, the number of [***] used in the provision of services in each
country;
a description of Licensed Processes performed in each country as may be pertinent to a
royalty accounting under the MIT Agreement;
gross price charged in each country and, if applicable, the gross price charged for each
Licensed Product used to provide services in each country; and the gross price charged for each
Licensed Process performed in each country;
calculation of Net Sales in each country, including a listing of applicable deductions;
total royalty payable on Net Sales in U.S. dollars, together with the exchange rate used
for conversion;
the amount of Sublicense Income received by Alnylam and its Affiliates and the amount due
to MIT from such sublicense income, including an itemized breakdown of the sources of income
comprising the Sublicense Income;
[***] categorized by rights relating to [***];
the dates on which milestone events are achieved and the milestone payments due; and
[***] in accordance with the requirements of Article [***] of the MIT Agreement.
If no amounts are due to MIT for any reporting period, the report will so state.
Recordkeeping and Audit Rights (Section 5.4)
Sublicensees are required to maintain complete and accurate records reasonably relating to
(i) the rights and obligations under the MIT Agreement, and (ii) any amounts payable to MIT in
relation to the MIT Agreement, which records will contain sufficient information to permit MIT to
confirm the accuracy of any reports and payments delivered to MIT and compliance in other respects
with the MIT Agreement. Such records will be retained for at least [***] years following the end
of the calendar year to which they pertain, during which time a certified public accountant
selected by MIT (who will be required to enter into a confidentiality obligation with Sublicensee)
may inspect such records upon advance notice and during normal business hours solely for the
purpose of verifying any reports and payments or compliance in other respects with the MIT
Agreement.
Page 51 of 61
Prosecution and Enforcement (Sections 6.1, 7.1-7.3 and 7.7)
MIT will prepare, file, prosecute, and maintain all of the Patent Rights. Alnylam will
cooperate with MIT in such filing, prosecution and maintenance.
So long as Alnylam remains the exclusive licensee of the Patent Rights in the Field,
Alnylam, to the extent permitted by law, will have the right, under its own control and at its own
expense, to prosecute any third party infringement of the Patent Rights in the Field, subject to
Sections 2.5(c) (Non-assert), 7.4 (Offsets) and 7.5 (Recovery) of the MIT Agreement. Prior to
commencing any such action, Alnylam will consult with MIT and will consider the views of MIT
regarding the advisability of the proposed action and its effect on the public interest.
If Alnylam is unsuccessful in persuading the alleged infringer to desist or fails to have
initiated an infringement action within a reasonable time after Alnylam first becomes aware of the
basis for such action, MIT will have the right, at its sole discretion, to prosecute such
infringement under its sole control and at its sole expense, and to keep any recovery.
If a Patent Challenge is brought against Alnylam by a third party, MIT, at its option, will
have the right within 20 days after commencement of such action to take over the sole defense of
the action. If MIT does not exercise this right, Alnylam may take over the sole defense of such
action.
So long as Alnylam remains the exclusive licensee of the Patent Rights in the Field,
Alnylam will have the sole right to sublicense any alleged infringer in the Field for future use of
the Patent Rights in accordance with Alnylams rights under and the terms and conditions of this
Agreement. Any upfront fees as part of such sublicense will be shared equally between Alnylam and
MIT; other revenues to Alnylam pursuant to such sublicense will be treated as set forth in Article
4 of the MIT Agreement.
Consequences of a Patent Challenge by Sublicensee (Sections 12.5 and 4.3)
If a Sublicensee brings a Patent Challenge against MIT (except as required under a court
order or subpoena), MIT may send a written demand to Alnylam to terminate the sublicense. If
Alnylam fails to so terminate such sublicense within 30 days of MITs demand, MIT may immediately
terminate the MIT Agreement and/or the license granted thereunder.
Notwithstanding the foregoing, if MIT decides not to terminate the MIT Agreement and the
Patent Challenge is successful, Alnylam will have no right to recoup any royalties paid during the
period of challenge. If the Patent Challenge is unsuccessful, Alnylam will reimburse MIT for all
of its costs and expenses it incurred as a result of such Patent Challenge, including without
limitation attorneys fees, court costs, litigation related disbursements, and third party and
expert witness fees (collectively,
Litigation Costs
). Reimbursement for Litigation Costs
will be made within thirty (30) days of receipt of one or more invoices from MIT for such
Litigation Costs.
Page 52 of 61
Certain Termination Rights (Sections 12.1, 12.2 and 12.4)
Alnylam has the right to terminate the MIT Agreement for any reason upon at least 6 months
prior written notice to MIT and payment of all amounts due to MIT through the effective date of
termination.
If Alnylam ceases to carry on its business related to the MIT Agreement, MIT will have the
right to terminate the MIT Agreement immediately upon written notice to Alnylam.
MIT, at its sole discretion, may terminate the Exclusive Period upon ten (10) days written
notice to Alnylam if any of the following events occurs: (a) Alnylam is in uncured material
default under the Research Agreement, including uncured failure to make any payments due
thereunder; or (b) the Research Agreement is terminated for any reason other than for (i) material
breach by MIT, (ii) the inability of Dr. Robert Langer to continue to serve as Principal
Investigator, and the inability of the parties to agree upon a replacement Principal Investigator,
an interim Principal Investigator, or an alternate arrangement for the performance of the Research
after Dr. Langer is no longer able to serve as Principal Investigator (capitalized terms used in
the foregoing clause have the meanings ascribed to them in the Research Agreement); or (iii)
circumstances beyond MITs reasonable control that preclude the continuation of the Research, as
provided for under the Research Agreement.
Definitions
Development Candidate
means a pre-clinical Licensed Product which possesses desirable
properties of a therapeutic agent for the treatment of a clinical condition based on
in vitro
and
animal proof-of-concept studies.
Exclusive Period
means the term of the MIT Agreement.
Field
means therapeutic use in humans.
Immunomodulatory Nucleic Acid
means a nucleic acid molecule that (i) stimulates or blocks
immune system functions, and (ii) the nucleotide sequence of which does not specifically target and
modulate gene expression. Immunomodulatory Nucleic Acid specifically excludes siRNA, miRNA and
nucleic acids that function through an RNA interference mechanism.
Library Component
means a Library Product which is a set of reaction products formed by
an addition reaction between two individual monomers, which set will include all reaction products
and combinations within such set, including all isomers; and any compounds identical to any of the
foregoing, including individual reaction products within such set, regardless of the means by which
said compounds are prepared, manufactured or synthesized.
Library Product
means any product that, in whole or in part: (i) absent the license
granted hereunder, would infringe one or more Valid Claims of the Patent Rights; or
Page 53 of 61
(ii) is manufactured by using a Licensed Process or that, when used, practices a Licensed Process.
Licensed Process
means any process that, in whole or in part: (i) absent the license
granted hereunder, would infringe one or more Valid Claims of the Patent Rights; or (ii) when
practiced, uses a Library Product.
Licensed Product
means any product that contains both (i) an RNAi Product and (ii) a
Library Product. Licensed Product specifically excludes any products containing or incorporating
any other therapeutically or pharmaceutically active agents, including without limitation proteins
or peptides, antibodies, Small Molecules, non-siRNA and non-miRNA nucleic acids, and
Immunomodulatory Nucleic Acids.
miRNA
(
microRNA
) means a class of endogenous, non-coding, sequence specific
ribonucleic acid (RNA) between 21 to 25 nucleotides in length that modulates gene expression.
miRNA specifically excludes messenger RNA, and any other RNA that encodes a polypeptide, and
Immunomodulatory Nucleic Acids.
miRNA Therapeutic
means a therapeutic containing, composed of or based on oligomers of
native or chemically modified RNA designed to either modulate an miRNA and/or provide the function
of an miRNA.
ND98 Library Component
means the Library Component which is described in
Appendix
C
of the MIT Agreement.
Patent Rights
means the patent applications listed on
Appendix A
to the MIT
Agreement entitled Amine-Containing Lipids and Uses Thereof and A Combination Library of
Lipidoids: Efficient Systemic siRNA Delivery, and resulting patents and patent applications.
Research Agreement
means the sponsored research agreement between MIT and Alnylam
effective on May 8, 2007.
Research Support Payment
means payments to Alnylam or an Affiliate from a Sublicensee for
the purposes of funding the costs of
bona fide
research and development of Licensed Products and/or
Library Products under a jointly prepared research plan and only to the extent such payments were
spent on such research and development of Licensed Products and/or Library Products, and only to
fund or pay for direct and indirect costs and fully loaded personnel costs, all as calculated under
GAAP. For the avoidance of doubt, Research Support Payments will mean payments that are expressly
intended only to fund or pay for (i) equipment, supplies, products or services, and (ii) the use of
employees and/or full time consultants, incurred or to be incurred on behalf of such Sublicensee to
achieve a research or development goal for Licensed Products and/or Library Products.
RNAi Product
means a product containing one or more siRNA Therapeutics and/or miRNA
Therapeutics towards one or more Targets. For the avoidance of doubt, RNAi Product specifically
includes siRNA Therapeutics and miRNA Therapeutics in
Page 54 of 61
association with other molecules which are not therapeutically or pharmaceutically active, but
which function to improve delivery to cells, including, without limitation, siRNA and miRNA
Therapeutics which are covalently linked to, or otherwise associated with, lipids, carbohydrates,
peptides, proteins, aptamers and Small Molecules.
siRNA
(
small interfering RNA
) means a double-stranded ribonucleic acid (RNA)
molecule designed to act through an RNA interference mechanism that consists of either (a) two
separate oligomers of native or chemically modified RNA that are hybridized to one another along a
substantial portion of their lengths, or (b) a single oligomer of native or chemically modified RNA
that is hybridized to itself by self-complementary base-pairing along a substantial portion of its
length to form a hairpin. siRNA specifically excludes messenger RNA, and any other RNA that
encodes a polypeptide, and Immunomodulatory Nucleic Acids.
siRNA Therapeutic
means a therapeutic containing, composed of or based on siRNA and
designed to modulate the function of particular genes or gene products by causing degradation of a
messenger RNA to which such siRNA is complementary, and that is not an miRNA Therapeutic.
Small Molecule
means a non-polymeric bioactive molecule that is not a peptide, protein,
DNA, RNA or a complex carbohydrate.
Sublicense Income
means any payments that Alnylam or an Affiliate receives from a
Sublicensee in consideration of the sublicense of the rights granted Alnylam and Affiliates under
Section 2.1 of the MIT Agreement, including without limitation equity, license fees, milestone
payments (net of any sums due to MIT under this Agreement for the same milestone event), license
maintenance fees, and other payments, but specifically excluding:
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royalties on Net Sales;
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minimum royalty upfront payments only to the extent such payments
equal actual royalties due to Alnylam;
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fair market value of equity investments in Alnylam or an Affiliate by
a Sublicensee;
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reimbursement of out of pocket patent expenses for the Patent Rights;
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Research Support Payments;
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loan proceeds paid to Alnylam by a Sublicensee in an arms length,
full recourse debt financing; and
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any amounts received under an indemnification obligation.
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For clarity, the amounts received by Alnylam or its affiliates related to the development of
Licensed Products will be considered Sublicense Income.
Target
means (a) a single gene, as defined in the NCBI Entrez Gene database or any
successor database thereto, or a product of such gene, that is a site or potential site of
therapeutic intervention by an siRNA Therapeutic and/or an miRNA Therapeutic; (b) naturally
occurring variants of a gene or gene product described in clause (a); or (c) a naturally occurring
interfering RNA or miRNA or precursors thereof; provided that for the purposes of this definition a
viral genome will be regarded as a single gene, and that the DNA sequence encoding a specific miRNA
precursor will also be regarded as a single gene.
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TEKMIRA/UBC
The Sublicense Agreement between Tekmira and Alnylam, dated January 8, 2007 (
UBC Sublicense
Agreement
)
Brief Summary of Technology Covered by License
: See Tekmira-Alnylam Agreement above.
Limitations on Scope of License (Sections 3.1 and 3.3)
The sublicense granted to Alnylam is limited to an exclusive, worldwide license under the
rights granted to Tekmira in the University License Agreement (see below) with respect to
Technology to research, develop, manufacture, have made, distribute, import, use, sell and have
sold Products in and for the Alnylam Field. In addition, any sublicense granted by Tekmira to
Alnylam would be subject to Tekmiras sublicense to Esperion Technologies, Inc. of certain
technology relating to liposome compositions and methods for the treatment of atherosclerosis.
Under the University License Agreement, Tekmira obtained from the University an exclusive,
worldwide license to use and sublicense the Technology and to make, have made, distribute, import
and use goods, the manufacture, use or sale of which would, but for the license granted herein,
infringe a Valid Claim of any Patent, including a license to use and sublicense the Technology for
(a) the delivery of and use with nucleic acid constructs, and (b) the treatment, prophylaxis and
diagnosis of diseases in humans using an RNAi Product or miRNA Product, and to research, develop,
make, have made, distribute, import, use, sell and have sold RNAi Products and miRNA Products.
University retains the right to use the Technology without charge in any manner whatsoever
for non-commercial research, scholarly publication, educational or other non-commercial use.
Restrictions on Sublicensing by Alnylam (Sections 3.2 and 4.2)
Any further sublicense granted by Alnylam to a third party would be subject to the grant of
the following licenses by Alnylam to Tekmira under Alnylams rights in the Technology: (a) to
perform Tekmiras obligations under the Collaboration with respect to Products, and the
Manufacturing Activities, on a non-exclusive basis, and (b) to develop, manufacture and
commercialize Inex Royalty Products for the treatment, prophylaxis and diagnosis of diseases in
humans, on an exclusive basis.
Alnylam may grant sublicenses to third parties with respect to the Technology only upon
written notice to Tekmira and the University, and
provided
that
the Sublicensee
agrees (i) to perform the terms of the UBC Sublicense Agreement as if such Sublicensee were Alnylam
under the UBC Sublicense Agreement; (ii) to represent that Sublicensee is not, as of the effective
date of the relevant sublicense agreement, engaged in a dispute with the University; and (iii) to
be subject to a written sublicense agreement that contains terms consistent with the terms of this
Agreement described in Section
Page 57 of 61
4.2(c) of the UBC Sublicense Agreement (see below) and that provides that the University is a third
party beneficiary of, and has the right to enforce directly against the sublicensee, the terms in
such sublicense agreement that are consistent with the terms listed in Section 4.2(c)(ii) of the
UBC Sublicense Agreement.
Section 4.2(c)(ii) of the UBC Sublicense Agreement states that the terms of this
Agreement means (i) the terms set forth in the UBC Sublicense Agreement; (ii) terms in such
sublicense agreement consistent with Sections 1.3 (Alnylam Consent to Certain Disclosures to the
University), 1.7 (Rights of the University), 2.1 (Limited Warranties), 2.2 (Disclaimer of Product
Liability), 2.3 (Indemnification of the University), 2.4 (Monetary Cap Respecting UBC License), 2.5
(Disclaimer of Consequential Losses by the University), 2.6 (Litigation), 2.7 (UBC Trademark), 2.8
(Confidentiality of Terms) and 2.13 (Alnylam Warranties) of the Consent Agreement among Alnylam,
Tekmira and the University of even date with the UBC Sublicense Agreement (
Consent
Agreement
); and (iii) other customary and reasonable terms, including but not limited to terms
relating to breach and termination, that are consistent with Alnylams obligations to Tekmira under
the UBC Sublicense Agreement and the Tekmira Agreement.
Any sublicense granted by Alnylam under the UBC Sublicense Agreement will survive
termination of the licenses or other rights granted to Alnylam under the UBC Sublicense Agreement,
and be assumed by Tekmira, as long as (i) the sublicensee is not then in breach of its sublicense
agreement, (ii) the sublicensee agrees in writing to be bound to Tekmira as a sublicensor and to
the University under the terms and conditions of the UBC Sublicense Agreement, and (iii) the
sublicensee agrees in writing that in no event will Tekmira assume any obligations or liabilities,
or be under any obligation or requirement of performance, under any such sublicense extending
beyond Tekmiras obligations and liabilities under the UBC Sublicense Agreement.
Alnylam is required to furnish Tekmira with a copy of each sublicense granted within 30
days after execution. Any such copy may contain reasonable redactions as Alnylam may make,
provided
that
such redactions do not include provisions necessary to demonstrate
compliance with the requirements of the UBC Sublicense Agreement. If University requests of
Tekmira that a less redacted version of any sublicense be provided to University, Alnylam agrees to
discuss in good faith with Tekmira and the University the Universitys concerns.
Financial Obligations (Section 5.0)
The consideration for the rights granted to Alnylam to the Technology under the UBC
Sublicense Agreement, and the consideration for the rights granted by Tekmira to Alnylam to other
technologies under the Tekmira Agreement, is the payment by Alnylam of milestones and royalties in
accordance with Article 7 of the Tekmira Agreement.
Prosecution and Enforcement (Section 7.7)
Tekmira will have the right, with reasonable input from Alnylam, to identify any process,
use or products arising out of the Technology that may be patentable and will
Page 58 of 61
take all reasonable steps to apply for a patent in the name of the University, provided that
Tekmira pays all costs of applying for, registering, and maintaining the patent in those
jurisdictions in which Tekmira determines that a Patent is required.
On the issuance of a patent for the Technology, Tekmira will have the right to become, and
will become the licensee of the same, all pursuant to the terms contained in the University License
Agreement, and Alnylam will have the right to become, and will become the sublicensee of such
rights pursuant to the terms contained in the UBC Sublicense Agreement.
Should Tekmira:
discontinue pursuing one or more patent applications, patent protection or patent
maintenance in relation to the Patent(s) or any continuation, continuation in-part, division,
reissue, re-examination or extension thereof; or
not pursue patent protection in relation to the Patent(s) in any specific jurisdiction; or
discontinue or not pursue patent protection in relation to any further process, use or
products arising out of the Technology in any jurisdiction;|
then Tekmira will provide Alnylam with notice of its decision to discontinue or not to
pursue such patent protection concurrently with the notice provided to the University by Tekmira
pursuant to Section 6.6 of the University License Agreement.
In the event of an alleged infringement by a third party of the Technology or any right
with respect to the Technology, or any complaint by Alnylam alleging any infringement by a third
party with respect to the Technology or any right with respect to the Technology, in each case that
is licensed to Alnylam under the UBC Sublicense Agreement, Alnylam will, subject to Tekmira having
first obtained the Universitys consent as required by Article 7 of the University License
Agreement, have the right to prosecute such litigation at Alnylams expense.
In the event of any litigation, Alnylam will keep Tekmira fully informed of the actions and
positions taken or proposed to be taken by Alnylam (on behalf of itself or a sublicensee) and
actions and positions taken by all other parties to such litigation.
In the event of an alleged infringement of the Technology or any third party use of the
Technology which is Confidential Information, Alnylam and Tekmira agree that they will reasonably
cooperate to enjoin such third partys use of the Technology.
If any complaint alleging infringement or violation of any patent or other proprietary
rights is made against Alnylam (or a sublicensee of Alnylam) with respect to the manufacture, use
or sale of Product, then:
Page 59 of 61
Alnylam will promptly notify Tekmira upon receipt of any such complaint and will keep
Tekmira fully informed of the actions and positions taken by the complainant and taken or proposed
to be taken by Tekmira (on behalf of itself or a sublicensee);
Alnylam (or any sublicenseee, as the case may be) will pay all costs and expenses incurred
by Alnylam (or any sublicensee of Alnylam) in investigating, resisting, litigating and settling
such a complaint, including the payment of any award or damages and/or costs to any third party;
and
if as a result of such suit it is decided that a Product infringes any valid claim on a
patent owned by another, Tekmira will consider fair distribution of Royalty Income.
Diligence and Reporting (Section 10.2)
Alnylam is required to use its reasonable commercial efforts to promote, market and sell
the Products and utilize the Technology and to meet or cause to be met the market demand for the
Products and the utilization of the Technology.
Alnylam is required to deliver to Tekmira an annual report, due on December 31 of each
year, which summarizes the major activities Alnylam has undertaken in the course of the preceding
12 months to develop and commercialize and/or market the Technology. The report must include an
outline of the status of any Products in clinical trials and the existence of any sublicenses of
the Technology.
Certain Termination Rights (Section 16.1)
If Alnylams rights to Inex Technology are terminated under the Tekmira Agreement, the UBC
Sublicense Agreement and the license granted to Alnylam thereunder also terminates.
Definitions
Capitalized terms not otherwise defined below have the meanings given to them under the Tekmira
Agreement.
1999 CRA
means the Collaborative Research Agreement between Tekmira and the University
dated effective January 1, 1999 and successor agreements to such Know-How.
2007 CRA
means the Collaborative Research Agreement between Tekmira and the University
dated effective January 1, 2007 and successor agreements to such Know-How.
Alnylam Field
means the use of Products for the treatment, prophylaxis and diagnosis of
diseases in humans.
Improvements
means, generally (i) any and all patents and any and all patent applications
that claim priority to Patents; and (ii) any and all inventions arising therefrom. Notwithstanding
anything to the contrary in the University License Agreement, ownership of all Improvements (A)
that fall within clause (i) above will be
Page 60 of 61
assigned to the University; and (B) that fall within clause (ii) above will follow inventorship as
determined by U.S. patent law, except that the University will own all Improvements made by its
employees, whether alone or jointly with Tekmira, under the 1999 CRA or 2007 CRA.
miRNA Product
means a product containing, comprised of or based on native or chemically
modified RNA oligomers designed to either modulate a micro RNA transcript and/or provide the
function of a micro RNA transcript.
Patent(s)
means, generally, the patents and patent applications, including certain
Wheeler Patents, listed on Schedule A to the UBC Sublicense Agreement, and any claims of CIPs and
of resulting patents which are to the UBC Sublicense Agreement, and any reissues of such patents.
Product(s)
means any RNAi Product or miRNA Product that, the manufacture, use or sale of
which would, but for the license granted herein, infringe a Valid Claim of one or more of the
Patent(s).
RNAi Product
means a product containing, comprised of or based on small interfering RNAs
or small interfering RNA derivatives or other moieties effective in gene function modulation and
designed to modulate the function of particular genes or gene products by causing degradation of a
target mRNA to which such small interfering RNAs or small interfering RNA derivatives are
complementary, and that is not an miRNA Product.
Technology
means the Patent(s) and any and all knowledge, know-how and/or technique or
techniques invented, developed and/or acquired, being invented, developed and/or acquired by the
University solely or jointly with Tekmira relating to the Patent(s), including, without limitation,
all research, data, specifications, instructions, manuals, papers or other materials of any nature
whatsoever, whether written or otherwise, relating to same.
University License Agreement
means the License Agreement dated effective July 1, 1998, as
amended, pursuant to which Tekmira is the exclusive licensee of certain Patents owned by the
University of British Columbia (the
University
).
Page 61 of 61
Exhibit 10.4
Execution
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
REGULUS THERAPEUTICS INC.
FOUNDING INVESTOR RIGHTS AGREEMENT
REGULUS THERAPEUTICS INC.
FOUNDING INVESTOR RIGHTS AGREEMENT
This Founding Investor Rights Agreement
(the Agreement) is entered into as of the
1st day of January 2009, by and among
Regulus Therapeutics Inc.
, a Delaware corporation (the
Company
) on the one hand, and
Isis Pharmaceuticals, Inc.
, a Delaware Corporation (
Isis
) and
Alnylam Pharmaceuticals, Inc.
, a Delaware corporation (
Alnylam
) who are each holders of the
Companys Series A Preferred Stock (the
Preferred Stock
) on the other hand. Isis and Alnylam may
be referred to hereinafter collectively as the
Founding Investors
and each individually as a
Founding Investor
. The Company, Isis and Alnylam may be referred to hereinafter collectively as
the
Parties
and each individually as a
Party
.
Recitals
Whereas,
the Company was formerly a Delaware limited liability company with the
Founding Investors as its only members;
Whereas
, the Company converted to a Delaware corporation in January 2009;
Whereas
,
in connection with the Companys conversion to a Delaware corporation, the
Founding Investors received the Preferred Stock in exchange for their membership interests in the
limited liability company; and
Whereas
,
in connection with the issuance of the Preferred Stock, the parties desire
to enter into this Agreement in order to grant registration, information rights, buy-out rights and
other rights to the Founding Investors as set forth below.
Now, Therefore,
in consideration of these premises and for other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto
agree as follows:
SECTION 1. DEFINITIONS.
Capitalized terms used herein and not defined elsewhere herein have the meanings set forth in
Exhibit A.
SECTION 2.
RESTRICTIONS ON TRANSFER
.
No Founding Investor may directly or indirectly sell, assign, transfer, pledge, hypothecate, or
otherwise deal with or encumber or dispose of in any way (each a Transfer) such Founding
Investors Shares or Registrable Securities, whether in whole or in part, voluntarily or
involuntarily, by operation of law or otherwise, except in accordance with the terms and conditions
set forth in this Section 2.
2.1 Restrictions on Transfer Before Initial Offering.
Except as provided in this Section 2,
before the Companys Initial Offering, each Founding Investor agrees that it may not
1.
and will not Transfer its Shares or Registrable Securities without the prior written consent
of the other Founding Investor.
2.2 Restrictions on Transfer After Initial Offering.
Each Holder agrees not to make any
disposition of all or any portion of the Shares or Registrable Securities unless and until:
(a)
there is then in effect a registration statement under the Securities Act covering such
proposed disposition and such disposition is made in accordance with such registration statement;
or
(b)
(i) The transferee has agreed in writing to be bound by the terms of this Agreement,
(ii) such Holder will have notified the Company of the proposed disposition and will have furnished
the Company with a detailed statement of the circumstances surrounding the proposed disposition,
and (iii) if reasonably requested by the Company, such Holder will have furnished the Company with
an opinion of counsel, reasonably satisfactory to the Company, that such disposition will not
require registration of such shares under the Securities Act. It is agreed that the Company will
not require opinions of counsel for transactions made pursuant to Rule 144, except in unusual
circumstances. After its Initial Offering, the Company will not require any transferee pursuant to
Rule 144 to be bound by the terms of this Agreement if the shares so transferred do not remain
Registrable Securities hereunder following such transfer.
2.3 Exempt Transfers.
Notwithstanding the provisions of Sections 2.1 and 2.2 above, no such
restriction will apply to a transfer by a Founding Investor that is:
(a)
a Transfer by a Founding Investor to an Affiliate of such Founding Investor;
provided,
however
, that (i) the Affiliate of such transferring Founding Investor must have the resources,
assets, experience, qualifications, permits and other rights necessary to perform under this
Agreement and each of the Ancillary Agreements and (ii) the transferee will agree in writing to be
subject to the terms of this Agreement to the same extent as if it were an original Founding
Investor hereunder.
(b)
Transfer pursuant to a Change in Control of such Founding Investor. In the event of a
Change in Control of a Founding Investor, the other Founding Investor may initiate a Buy-Out
pursuant to Section 4.
2.4 Stock Legends.
Each certificate representing Shares or Registrable Securities will be
stamped or otherwise imprinted with legends substantially similar to the following (in addition to
any legend required under applicable state securities laws):
THE SECURITIES REPRESENTED HEREBY HAVE NOT BEEN REGISTERED UNDER THE
SECURITIES ACT OF 1933 (THE
ACT
) AND MAY NOT BE OFFERED, SOLD OR
OTHERWISE TRANSFERRED, ASSIGNED, PLEDGED OR HYPOTHECATED UNLESS AND
UNTIL REGISTERED UNDER THE ACT OR UNLESS THE COMPANY HAS RECEIVED AN
OPINION OF COUNSEL SATISFACTORY TO THE COMPANY AND ITS COUNSEL THAT
SUCH
2.
REGISTRATION IS NOT REQUIRED.
THE SALE, PLEDGE, HYPOTHECATION OR TRANSFER OF THE SECURITIES
REPRESENTED BY THIS CERTIFICATE IS SUBJECT TO THE TERMS AND
CONDITIONS OF A CERTAIN INVESTOR RIGHTS AGREEMENT BY AND BETWEEN THE
STOCKHOLDER AND THE COMPANY. COPIES OF SUCH AGREEMENT MAY BE
OBTAINED UPON WRITTEN REQUEST TO THE SECRETARY OF THE COMPANY.
(a)
The Company will be obligated to promptly reissue unlegended certificates at the request
of any Holder thereof if the Company has completed its Initial Offering and the Holder has obtained
an opinion of counsel (which counsel may be counsel to the Company) reasonably acceptable to the
Company to the effect that the securities proposed to be disposed of may lawfully be so disposed of
without registration, qualification and legend,
provided that
the second legend listed above will
be removed only at such time as the Holder of such certificate is no longer subject to any
restrictions hereunder.
(b)
Any legend endorsed on an instrument pursuant to applicable state securities laws and the
stop-transfer instructions with respect to such securities will be removed upon receipt by the
Company of an order of the appropriate blue sky authority authorizing such removal.
SECTION 3.
COVENANTS OF THE COMPANY
.
3.1 Financial Information and Reporting.
(a)
The Company will cause to be maintained complete books and records accurately reflecting
the accounts, business and transactions of the Company on a calendar-year basis and with sufficient
detail and completeness customary and usual for businesses of the type engaged in by the Company.
The Companys books and records and financial statements will be kept using the accrual method of
accounting and in accordance with U.S. generally accepted accounting principles. The Company will
maintain a system of internal accounting controls which are sufficient to provide reasonable
assurance that (w) transactions are executed in accordance with the Companys signature authority
policy; (x) transactions are recorded as necessary to permit preparation of the financial
statements of the Company and to maintain accountability for the Companys assets; (y) access to
the Companys assets is permitted only in accordance with managements authorization; and (z) the
reporting of the Companys assets is compared with existing assets at regular intervals. The
Companys financial statements will be audited annually by an independent nationally recognized
public accounting firm approved by the Companys Board of Directors.
(b)
During Consolidation Period
. For so long as (1) Isis independent auditors advise Isis
that Isis should consolidate Regulus financial statements with Isis financial statements or (2)
Regulus is using Isis financial systems (the
Consolidation Period
) Regulus will do the
following:
3.
(i)
Commencing with respect to the fiscal year ending December 31, 2008, and for each fiscal
year during the term hereof, the Company will deliver or mail to each Founding Investor the audited
annual financial statements of the Company at least [***] ([***]) [***] prior to the earliest date
by which either Founding Investor is required to file its annual report on Form 10-K for such
fiscal year (or such earlier time as may be required by either Founding Investor to satisfy its
reporting obligations under law, including without limitation, the rules and regulations of the
SEC), which financial statements will have been prepared in accordance with U.S. generally accepted
accounting principles.
(ii)
For each fiscal quarter during the term hereof, the Company will deliver or mail to each
Founding Investor an unaudited balance sheet of the Company as at the end of such quarter and
unaudited statements of income and cash flows of the Company for such quarter and for the current
fiscal year to the end of such fiscal quarter within [***] ([***]) days after the end of each
fiscal quarter of the Company (or such earlier time as may be required by a Founding Investor to
satisfy its reporting obligations under law, including without limitation, the rules and
regulations of the SEC).
(iii)
Commencing with the month ending on January 31, 2009, the Company will deliver to each
Founding Investor an unaudited balance sheet of the Company as at the end of such month and
unaudited statements of income and of cash flows of the Company for such month and for the current
fiscal year to the end of such month promptly following the Companys completion of the review of
its financial statements for such month (other than the last month of any fiscal quarter) (or such
earlier time as may be required by a Founding Investor to satisfy its reporting obligations under
law, including without limitation, the rules and regulations of the SEC).
(iv)
The income statements and balance sheets referred to in this Section 3.1 will be
accompanied by the report thereon, if any, of any independent accountants engaged by the Company or
by the certificate of the President that such financial statements were prepared without audit from
the books and records of the Company.
(v)
The Company will use the same accounting firm as Isis uses to audit its financial
statements.
(vi)
The Companys principal executive officer and principal financial officer, or persons
performing similar functions, will provide certifications to Isis corresponding to those required
under Sections 302 and 906 of the Sarbanes-Oxley Act of 2002, and the Company will provide to Isis
an attestation report of its auditors with respect to the Companys internal controls, as may be
requested by Isis external auditors.
(vii)
If after reasonable discussions in good faith, the Companys audit committee and Isis
audit committee cannot resolve any dispute with respect to accounting policies and practices for
the Companys financial reporting, the Parties agree that they will apply the accounting policy or
practice proposed by Isis audit committee.
(c)
After the Consolidation Period
. After the Consolidation Period and until neither Isis nor
Alnylam is required to record their respective share of Regulus profit/loss,
4.
Regulus will provide Isis and Alnylam the information as specified on
Exhibit E
attached hereto.
(d)
Once Isis and Alnylam are no longer required to record their respective share of Regulus
income/losses, Regulus will not be required to provide the information to Isis and Alnylam outlined
in Section 3.1(c) above. However, Regulus will provide to Isis and/or Alnylam any financial
information reasonably requested by either company so that such company can determine if an
impairment in Regulus exists, and Regulus will make its management available to Isis and/or Alnylam
for reasonable inquiries regarding its financials.
3.2 Tax Matters.
(a)
The Company will prepare or cause to be prepared, at the Companys expense, all tax
returns and statements, if any, that must be filed on behalf of the Company with any taxing
authority, and will make timely filing thereof, including filings pursuant to extensions permitted
under applicable federal and state tax regulations. With respect to the Companys tax return for
the fiscal year ended December 31, 2008, the Company will provide a draft of such tax return to
each Founding Investor within a reasonable amount of time prior to filing such return to allow each
Founding Investor an opportunity to review and comment on such return. In addition, the Company
will give due consideration to each Founding Investors comments regarding the tax return for the
year ended December 31, 2008.
(b)
Each Founding Investor may request from the Company any information reasonably necessary
for the Founding Investor to complete any of its tax returns or compute estimated tax payments and
the Company will, within a reasonable period of time following the request, provide such
information to the requesting Founding Investor.
3.3 Confidentiality of Records.
Each Founding Investor agrees to use the same degree of care
as such Founding Investor uses to protect its own confidential information to keep confidential and
not disclose to any party any information furnished to such Founding Investor pursuant to
Section 3.1 and 3.2 hereof that the Company identifies as being confidential or proprietary (so
long as such information is not in the public domain), except that such Founding Investor may
disclose such proprietary or confidential information (i) to any partner, subsidiary or parent of
such Founding Investor as long as such partner, subsidiary or parent is advised of and agrees or
has agreed to be bound by the confidentiality provisions of this Section 3.3 or comparable
restrictions; (ii) at such time as it enters the public domain through no fault of such Founding
Investor; (iii) that is communicated to it free of any obligation of confidentiality; (iv) that is
developed by Founding Investor or their respective agents independently of and without reference to
any confidential information communicated by the Company; or (v) as required by applicable law.
Upon request by the Company, each Founding Investor agrees to enter into a separate confidentiality
agreement with the Company.
3.4 Reservation of Common Stock.
The Company will at all times reserve and keep available,
solely for issuance and delivery upon the conversion of the Preferred Stock, all Common Stock
issuable from time to time upon such conversion.
5.
3.5 Board of Directors.
The Board will consist of up to [***] ([***]) directors (each, a
Director
). Alnylam will have the right to designate [***] ([***]) Directors who need not be
Independent Directors (the
Alnylam Directors
). Isis will have the right to designate [***]
([***]) Directors who need not be Independent Directors (the
Isis Directors
). The President of
the Company will, at all times while in office, be a Director. The remaining two members will be
independent industry representatives approved by the other Directors then serving on the Board.
Other than the President, each Director will serve at the pleasure of the Founding Investor
designating such Director until such Directors removal by the designating Founding Investor or
such Directors resignation. If there is a vacancy on the Board, the vacancy will be filled by the
Founding Investor, if any, who initially designated the Director, except if the vacancy is caused
by the termination of the President, such vacancy will be filled when the then existing Board
appoints the new President. Any Founding Investor may remove, at any time and for any reason, any
or all of the Directors designated by such Founding Investor and, subject to the Independent
Director requirements, designate in lieu thereof any individual(s) to serve the remainder of the
relevant term.
(a)
Observers
. The right to attend all or particular meetings of the Board (
Observer
Rights
) may be granted to any Person designated by a Founding Investor upon the approval of the
other Founding Investor (such approval not to be unreasonably withheld or delayed);
provided,
however,
that any Person granted Observer Rights, and/or any representative of such Person
attending meetings of the Board, will agree in writing to be subject to appropriate confidentiality
obligations if requested by a Director;
provided, further,
that such holder of Observer Rights may
be excluded from any meeting or any portion of a meeting for which any Director believes (i) such
meeting or portion will involve a discussion of information that the Company or the Founding
Investor designating such Director considers to be a trade secret or of a confidential or
proprietary nature, (ii) exclusion of such holder of Observer Rights is desirable in order to
preserve the attorney client-privilege or (iii) exclusion is otherwise merited.
(b)
Other Attendees
. Any Director may invite a subject matter expert to attend any meeting of
the Board;
provided, however,
that any Person granted attendance rights will agree in writing to be
subject to appropriate confidentiality obligations if requested by a Director and provided further
that no other Director objects to such experts presence. Upon such objection, the expert will be
excluded from any meeting or any portion of a meeting.
(c)
The Directors designated as of the Effective Date are set forth on
Exhibit B
hereto.
3.6 Directors Liability and Indemnification.
The Companys Certificate of Incorporation and
Bylaws will provide (a) for elimination of the liability of a Director to the maximum extent
permitted by law and (b) for indemnification of Directors for acts on behalf of the Company to the
maximum extent permitted by law. In addition, the Company will enter into and use its best efforts
to at all times maintain reasonable and customary indemnification agreements with each of its
Directors to indemnify such directors to the maximum extent permissible under applicable law.
3.7 Operating Plan.
The Company will use commercially reasonable efforts to operate the
Company in accordance with the Approved Operating Plan (as defined below). The
6.
initial Operating Plan, dated April 30, 2008 attached hereto as
Exhibit C
(the
Initial Operating Plan
), will be deemed the
Approved Operating Plan
for the period beginning on
September 6, 2007 and ending on December 31, 2009 (such period, the
Initial Commitment Period
).
(a)
No later than September 30, 2009, and no later than September 30 in each fiscal year
thereafter, Regulus management will prepare and submit to the Board a proposal for revising the
Approved Operating Plan then in effect (
Proposed Operating Plan
), which will include a proposed
Development Plan (
Proposed Development
Plan
), proposed Operating Budget (
Proposed Operating
Budget
).
(b)
Each Proposed Operating Plan that has been prepared and submitted by Regulus management
in accordance with Section 3.7(a) will be considered at the first meeting of the Board following
its submission and will be subject to the approval of the Board. The Chairperson will call a
special meeting of the Board for this purpose at the request of any Director if the next scheduled
regular meeting is later than December 31 of the year in which submission is made. Any such
Proposed Operating Plan (or any amendment thereto) that is approved by the Board will be considered
the
Approved Operating Plan
for all purposes of this Agreement until amended or replaced.
(c)
If, after the Initial Commitment Period, the Board is unable to approve a Proposed
Operating Plan that has been prepared and submitted by Regulus management in accordance with
Section 3.7(a) within three months following the date such Proposed Operating Plan is submitted for
approval (a
Stalemate
), either Founding Investor may initiate a Buy-Out in accordance with
Section 4;
provided, however,
that in the event sufficient funding is available to the Company to
continue to carry out the Development Plan after the Initial Commitment Period, a Stalemate will
not be deemed to have occurred, and neither Founding Investor may initiate a Buy-Out, until a date
[***] ([***]) days prior to the date on which all of the Companys funds are expected to be
depleted as determined based on the Approved Operating Plan then in effect.
3.8 Scientific Advisory Board.
The Company will maintain a Scientific Advisory Board (
SAB
)
consisting of at least three (3) members. The initial members and chairperson of the SAB will be
as set forth on
Exhibit B
. Any changes to the composition of the Scientific Advisory
Board, including the removal or appointment of the chairperson, will be approved by the Board. The
SAB will meet at least at least three time a year until December 31, 2009 and will initially be
responsible for (i) advising the Company as to research goals and plans, (ii) reviewing research
data and advising the Company with respect to interpretation of such research data, as requested by
the Board, President or Chief Scientific Officer; and (iii) advising the Company with respect to
research and development decisions, as requested by the Board, President or Chief Scientific
Officer.
3.9 Termination of Covenants.
All covenants of the Company contained in Section 3 of this
Agreement (other than the provisions of Section 3.1 and 3.3) will expire and terminate as to each
Founding Investor upon the earlier of (i) the effective date of the registration statement
pertaining to an Initial Offering or (ii) upon a Liquidation Event, Acquisition or Asset Transfer
7.
(in each case as defined in the Companys Certificate of Incorporation as such may be amended
from time to time).
SECTION 4. BUY-OUT.
4.1 Right to Initiate Buy-Out.
Within (a) solely in the event of a Stalemate occurring after
the end of the Initial Commitment Period (as further described in Section 3.7(c), the [***] ([***])
day period following such Stalemate, (b) at any time, whether before or after the end of the
Initial Commitment Period, during the [***] ([***]) day period following notice from a Founding
Investor that it has entered into a binding agreement providing for a Change of Control of such
Founding Investor (such [***] ([***]) or [***] ([***]) day period, a
Buy-Out Notice Period
), or
(c) as provided for in the License Agreement, either Founding Investor (in the case of (a)), the
Founding Investor receiving the notice of a Change in Control (in the case of (b)), or the Founding
Investor or Founding Investors as specified in the License Agreement (in the case of (c) (in each
case, the
Initiating Founding Investor
) has the right, exercisable upon written notice to the
Company and the other Founding Investor (the
Buy-Out Notice
), to initiate the sale of the Company
or the distribution the Companys assets, including the Company Intellectual Property and Companys
rights in Licensed IP, in accordance with the terms set forth on
Exhibit D
(the
Buy-Out
).
4.2 Voting Agreement; Cooperation.
If any Founding Investor initiates a Buy-Out under Section
4.1, each Founding Investor agrees to vote or act with respect to their Shares, Registrable
Securities and designated members of the Board so as to authorize and approve the Buyout unless
Exhibit D expressly allows a Founding Investor to withhold such vote or action. Each Party further
agrees to assist the other Parties in every proper way to consummate the Buy-Out, effect the
Buy-Out, including but not limited to executing and delivering such documents and performing such
other acts as a Party may reasonably request in connection with effecting the Buy-Out.
4.3 Preservation of Intent.
If any term, covenant or condition of this Section 4 or Exhibit D
or the application thereof to any Party or circumstance, to any extent, is invalid or
unenforceable, then (a) the remainder of this Section 4 and Exhibit D, or the application of such
term, covenant or condition to Parties or circumstances other than those as to which it is invalid
or unenforceable, will not be affected thereby and each term, covenant or condition of this Section
4 and Exhibit D will be valid and be enforced to the fullest extent permitted by law; and (b) the
Parties hereto covenant and agree to renegotiate any such term, covenant or application thereof in
good faith in order to provide a reasonably acceptable alternative to the term, covenant or
condition of this Section 4 and Exhibit D or the application thereof that is invalid or
unenforceable, it being the intent of the Parties that the basic purposes of this Section 4 and
Exhibit D are to be effectuated.
4.4 Termination of Buy-Out
. The provisions set forth in this Section 4 will expire and
terminate upon the effective date of the registration statement pertaining to an Initial Offering.
8.
SECTION 5.
RIGHTS OF FIRST REFUSAL
5.1 Subsequent Offerings.
Subject to applicable securities laws, each Founding Investor will
have a right of first refusal to purchase its
pro rata
share of all Equity Securities, as defined
below, that the Company may, from time to time, propose to sell and issue after the date of this
Agreement, other than the Equity Securities excluded by Section 5.6 hereof. Each Founding
Investors
pro rata
share is equal to the ratio of (a) the number of shares of the Companys Common
Stock (including all shares of Common Stock issuable or issued upon conversion of the Shares or
upon the exercise of outstanding warrants or options) of which such Founding Investor is deemed to
be a holder immediately prior to the issuance of such Equity Securities to (b) the total number of
shares of the Companys outstanding Common Stock (including all shares of Common Stock issued or
issuable upon conversion of the Shares or upon the exercise of any outstanding warrants or options)
immediately prior to the issuance of the Equity Securities. The term
Equity Securities
will mean
(i) any Common Stock, Preferred Stock or other security of the Company, (ii) any security
convertible into or exercisable or exchangeable for, with or without consideration, any Common
Stock, Preferred Stock, or other security (including any option to purchase such a convertible
security), (iii) any security carrying any warrant or right to subscribe to or purchase any Common
Stock, Preferred Stock or other security or (iv) any such warrant or right.
5.2 Exercise of Rights.
If the Company proposes to issue any Equity Securities, it will give
each Founding Investor written notice of its intention, describing the Equity Securities, the price
and the terms and conditions upon which the Company proposes to issue the same. Each Founding
Investor will have [***] ([***]) days from the giving of such notice to agree to purchase its
pro
rata
share of the Equity Securities for the price and upon the terms and conditions specified in
the notice by giving written notice to the Company and stating therein the quantity of Equity
Securities to be purchased. Notwithstanding the foregoing, the Company will not be required to
offer or sell such Equity Securities to any Founding Investor who would cause the Company to be in
violation of applicable federal securities laws by virtue of such offer or sale.
5.3 Issuance of Equity Securities to Other Persons
. The Company will have [***] ([***]) days
thereafter to sell the Equity Securities in respect of which the Founding Investors rights were
not exercised, at a price not lower and upon general terms and conditions not materially more
favorable to the purchasers thereof than specified in the Companys notice to the Founding
Investors pursuant to Section 5.2 hereof. If the Company has not sold such Equity Securities
within [***] ([***]) days of the notice provided pursuant to Section 5.2, the Company will not
thereafter issue or sell any Equity Securities, without first offering such securities to the
Founding Investors in the manner provided above.
5.4 Termination and Waiver of Rights of First Refusal.
The rights of first refusal
established by this Section 5 will not apply to, and will terminate upon the earlier of (i) the
effective date of the registration statement pertaining to the Companys Initial Offering or
(ii) an Acquisition. Notwithstanding Section 7.5 hereof, the rights of first refusal established
by this Section 5 may be amended, or any provision waived with and only with the written consent of
the Company and the Founding Investors holding a majority of the Registrable Securities held by all
Founding Investors.
9.
5.5 Assignment of Rights of First Refusal.
The rights of first refusal of each Founding
Investor under this Section 5 may be assigned to the same parties, subject to the same restrictions
as any transfer of registration rights pursuant to Section 6.7.
5.6 Excluded Securities.
The rights of first refusal established by this Section 5 will have
no application to any of the following Equity Securities:
(a)
shares of Common Stock and/or options, warrants or other Common Stock purchase rights and
the Common Stock issued pursuant to such options, warrants or other rights issued to employees,
officers or directors of, or consultants or advisors to, the Company or any subsidiary pursuant to
stock purchase or stock option plans or other arrangements that are approved by the Board of
Directors;
(b)
stock issued or issuable pursuant to any rights or agreements, options, warrants or
convertible securities outstanding as of the date of this Agreement; and stock issued pursuant to
any such rights or agreements granted after the date of this Agreement, so long as the rights of
first refusal established by this Section 5 were complied with, waived, or were inapplicable
pursuant to any provision of this Section 5.6 with respect to the initial sale or grant by the
Company of such rights or agreements;
(c)
any Equity Securities issued for consideration other than cash pursuant to a merger,
consolidation, acquisition or similar business combination approved by the Board of Directors;
(d)
any Equity Securities issued in connection with any stock split, stock dividend or
recapitalization by the Company;
(e)
any Equity Securities issued pursuant to any equipment loan or leasing arrangement, real
property leasing arrangement, or debt financing from a bank or similar financial or lending
institution approved by the Board of Directors;
(f)
any Equity Securities that are issued by the Company pursuant to a registration statement
filed under the Securities Act;
(g)
any Equity Securities that are issued by the Company in connection with any underwritten
public offering;
(h)
any Equity Securities issued in connection with strategic transactions involving the
Company and other entities, including, without limitation (i) joint ventures, manufacturing,
marketing or distribution arrangements or (ii) technology transfer or development arrangements;
provided
that the issuance of shares therein has been approved by the Companys Board of Directors;
and
(i)
Any Equity Securities issued to third-party service providers in exchange for or as
partial consideration for services rendered to the Company.
10.
SECTION 6.
REGISTRATION RIGHTS; MARKET STAND-OFF
.
6.1 Piggyback Registrations.
The Company will notify all Holders of Registrable Securities in
writing at least fifteen (15) days prior to the filing of any registration statement under the
Securities Act for purposes of a public offering of securities of the Company (including, but not
limited to, registration statements relating to secondary offerings of securities of the Company,
but excluding Special Registration Statements) and will afford each such Holder an opportunity to
include in such registration statement all or part of such Registrable Securities held by such
Holder. Each Holder desiring to include in any such registration statement all or any part of the
Registrable Securities held by it will, within fifteen (15) days after the above-described notice
from the Company, so notify the Company in writing. Such notice will state the intended method of
disposition of the Registrable Securities by such Holder. If a Holder decides not to include all
of its Registrable Securities in any registration statement thereafter filed by the Company, such
Holder will nevertheless continue to have the right to include any Registrable Securities in any
subsequent registration statement or registration statements as may be filed by the Company with
respect to offerings of its securities, all upon the terms and conditions set forth herein.
(a) Underwriting.
If the registration statement of which the Company gives notice under this
Section 6.3 is for an underwritten offering, the Company will so advise the Holders of Registrable
Securities. In such event, the right of any such Holder to include Registrable Securities in a
registration pursuant to this Section 6.3 will be conditioned upon such Holders participation in
such underwriting and the inclusion of such Holders Registrable Securities in the underwriting to
the extent provided herein. All Holders proposing to distribute their Registrable Securities
through such underwriting will enter into an underwriting agreement in customary form with the
underwriter or underwriters selected for such underwriting by the Company. Notwithstanding any
other provision of this Agreement, if the underwriter determines in good faith that marketing
factors require a limitation of the number of shares to be underwritten, the number of shares that
may be included in the underwriting will be allocated, first, to the Company; and second, to the
Holders on a
pro rata
basis based on the total number of Registrable Securities held by the
Holders; provided, however, that such reduction will not be permitted unless such registration
does not include shares of any other selling stockholders. If any Holder disapproves of the terms
of any such underwriting, such Holder may elect to withdraw therefrom by written notice to the
Company and the underwriter, delivered at least ten (10) business days prior to the effective date
of the registration statement. Any Registrable Securities excluded or withdrawn from such
underwriting will be excluded and withdrawn from the registration. For any Holder which is a
partnership, limited liability company or corporation, the partners, retired partners, members,
retired members and stockholders of such Holder, or the estates and family members of any such
partners, retired partners, members and retired members and any trusts for the benefit of any of
the foregoing persons will be deemed to be a single Holder, and any
pro rata
reduction with
respect to such Holder will be based upon the aggregate amount of shares carrying registration
rights owned by all entities and individuals included in such Holder, as defined in this
sentence.
(b) Right to Terminate Registration.
The Company will have the right to terminate or
withdraw any registration initiated by it under this Section 6.1 whether or not any
11.
Holder has elected to include securities in such registration. The Registration Expenses of
such withdrawn registration will be borne by the Company in accordance with Section 6.3 hereof.
6.2
Form S-3
Registration.
In case the Company receives from any Holder or Holders of
Registrable Securities a written request or requests that the Company effect a registration on
Form S-3 (or any successor to Form S-3) or any similar short-form registration statement and any
related qualification or compliance with respect to all or a part of the Registrable Securities
owned by such Holder or Holders, the Company will:
(a)
promptly give written notice of the proposed registration, and any related qualification
or compliance, to all other Holders of Registrable Securities; and
(b)
as soon as practicable, effect such registration and all such qualifications and
compliances as may be so requested and as would permit or facilitate the sale and distribution of
all or such portion of such Holders or Holders Registrable Securities as are specified in such
request, together with all or such portion of the Registrable Securities of any other Holder or
Holders joining in such request as are specified in a written request given within fifteen (15)
days after receipt of such written notice from the Company;
provided, however
, that the Company
will not be obligated to effect any such registration, qualification or compliance pursuant to
this Section 6.2:
(i)
if Form S-3 is not available for such offering by the Holders;
(ii)
if the Holders, together with the holders of any other securities of the Company entitled
to inclusion in such registration, propose to sell Registrable Securities and such other securities
(if any) at an aggregate price to the public of less than fifteen million dollars ($15,000,000);
(iii)
if within thirty (30) days of receipt of a written request from any Holder or Holders
pursuant to this Section 6.2, the Company gives notice to such Holder or Holders of the Companys
intention to make a public offering within ninety (90) days, other than pursuant to a Special
Registration Statement;
(iv)
if the Company will furnish to the Holders a certificate signed by the Chairman of the
Board of Directors of the Company stating that in the good faith judgment of the Board of Directors
of the Company, it would be seriously detrimental to the Company and its stockholders for such
Form S-3 registration to be effected at such time, in which event the Company will have the right
to defer the filing of the Form S-3 registration statement for a period of not more than one
hundred twenty (120) days after receipt of the request of the Holder or Holders under this
Section 6.2;
provided
, that such right to delay a request will be exercised by the Company not more
than twice in any twelve (12) month period;
(v)
if the Company has, within the twelve (12) month period preceding the date of such
request, already effected one (1) registration on Form S-3 for the Holders pursuant to this
Section 6.2, or
12.
(vi)
in any particular jurisdiction in which the Company would be required to qualify to do
business or to execute a general consent to service of process in effecting such registration,
qualification or compliance.
(c)
Subject to the foregoing, the Company will file a Form S-3 registration statement
covering the Registrable Securities and other securities so requested to be registered as soon as
practicable after receipt of the requests of the Holders.
6.3 Expenses of Registration.
Except as specifically provided herein, all Registration
Expenses incurred in connection with any registration, qualification or compliance pursuant to
Section 6.1 or 6.2 herein will be borne by the Company. All Selling Expenses incurred in
connection with any registrations hereunder, will be borne by the holders of the securities so
registered
pro rata
on the basis of the number of shares so registered. The Company will not,
however, be required to pay for expenses of any registration proceeding begun pursuant to
Section 6.2, the request of which has been subsequently withdrawn by the Initiating Holders unless
(a) the withdrawal is based upon material adverse information concerning the Company of which the
Initiating Holders were not aware at the time of such request or (b) the Holders of a majority of
Registrable Securities agree to deem such registration to have been effected as of the date of such
withdrawal for purposes of determining whether the Company will be obligated pursuant to Section
6.2(b)(v), as applicable, to undertake any subsequent registration, in which event such right will
be forfeited by all Holders). If the Holders are required to pay the Registration Expenses, such
expenses will be borne by the holders of securities (including Registrable Securities) requesting
such registration in proportion to the number of shares for which registration was requested. If
the Company is required to pay the Registration Expenses of a withdrawn offering pursuant to
clause (a) above, then such registration will not be deemed to have been effected for purposes of
determining whether the Company will be obligated pursuant to Section 6.2(b)(v) to undertake any
subsequent registration.
6.4 Obligations of the Company.
Whenever required to effect the registration of any
Registrable Securities, the Company will, as expeditiously as reasonably possible:
(a)
prepare and file with the SEC a registration statement with respect to such Registrable
Securities and use all commercially reasonable efforts to cause such registration statement to
become effective, and, upon the request of the Holders of a majority of the Registrable Securities
registered thereunder, keep such registration statement effective for up to thirty (30) days or,
if earlier, until the Holders have completed the distribution related thereto; provided, however,
that at any time, upon written notice to the participating Holders and for a period not to exceed
sixty (60) days thereafter (the Suspension Period), the Company may delay the filing or
effectiveness of any registration statement or suspend the use of any registration statement (and
the Initiating Holders hereby agree not to offer or sell any Registrable Securities pursuant to
such registration statement during the Suspension Period) if the Company reasonably believes that
there is or may be in existence material nonpublic information or events involving the Company,
the failure of which to be disclosed in the prospectus included in the registration statement
could result in a Violation (as defined below). In the event that the Company will exercise its
right to delay the filing or effectiveness or suspend the use of a registration hereunder, the
applicable time period during which the
13.
registration statement is to remain effective will be extended by a period of time equal to
the duration of the Suspension Period. The Company may extend the Suspension Period for an
additional consecutive sixty (60) days with the consent of the Holders of a majority of the
Registrable Securities registered under the applicable registration statement, which consent will
not be unreasonably withheld. If so directed by the Company, all Holders registering shares under
such registration statement will (i) not offer to sell any Registrable Securities pursuant to the
registration statement during the period in which the delay or suspension is in effect after
receiving notice of such delay or suspension; and (ii) use their commercially reasonable efforts
to deliver to the Company (at the Companys expense) all copies, other than permanent file copies
then in such Holders possession, of the prospectus relating to such Registrable Securities
current at the time of receipt of such notice. Notwithstanding the foregoing, the Company will
not be required to file, cause to become effective or maintain the effectiveness of any
registration statement other than a registration statement on Form S-3 that contemplates a
distribution of securities on a delayed or continuous basis pursuant to Rule 415 under the
Securities Act.
(b)
Prepare and file with the SEC such amendments and supplements to such registration
statement and the prospectus used in connection with such registration statement as may be
necessary to comply with the provisions of the Securities Act with respect to the disposition of
all securities covered by such registration statement for the period set forth in subsection (a)
above.
(c)
Furnish to the Holders such number of copies of a prospectus, including a preliminary
prospectus, in conformity with the requirements of the Securities Act, and such other documents as
they may reasonably request in order to facilitate the disposition of Registrable Securities owned
by them.
(d)
Use its commercially reasonable efforts to register and qualify the securities covered by
such registration statement under such other securities or Blue Sky laws of such jurisdictions as
will be reasonably requested by the Holders;
provided
that the Company will not be required in
connection therewith or as a condition thereto to qualify to do business or to file a general
consent to service of process in any such states or jurisdictions.
(e)
In the event of any underwritten public offering, enter into and perform its obligations
under an underwriting agreement, in usual and customary form, with the managing underwriter(s) of
such offering. Each Holder participating in such underwriting will also enter into and perform
its obligations under such an agreement.
(f)
Notify each Holder of Registrable Securities covered by such registration statement at
any time when a prospectus relating thereto is required to be delivered under the Securities Act
of the happening of any event as a result of which the prospectus included in such registration
statement, as then in effect, includes an untrue statement of a material fact or omits to state a
material fact required to be stated therein or necessary to make the statements therein not
misleading in the light of the circumstances then existing. The Company will use commercially
reasonable efforts to amend or supplement such prospectus in order to cause such prospectus not to
include any untrue statement of a material fact or omit to
14.
state a material fact required to be stated therein or necessary to make the statements
therein not misleading in the light of the circumstances then existing.
(g)
Use its commercially reasonable efforts to furnish, on the date that such Registrable
Securities are delivered to the underwriters for sale, if such securities are being sold through
underwriters, (i) an opinion, dated as of such date, of the counsel representing the Company for
the purposes of such registration, in form and substance as is customarily given to underwriters
in an underwritten public offering, addressed to the underwriters, if any, and (ii) a letter,
dated as of such date, from the independent certified public accountants of the Company, in form
and substance as is customarily given by independent certified public accountants to underwriters
in an underwritten public offering addressed to the underwriters.
6.5 Delay of Registration; Furnishing Information.
(a)
No Holder will have any right to obtain or seek an injunction restraining or otherwise
delaying any such registration as the result of any controversy that might arise with respect to
the interpretation or implementation of this Section 6.
(b)
It will be a condition precedent to the obligations of the Company to take any action
pursuant to Section 6.1 or 6.2 that the selling Holders will furnish to the Company such
information regarding themselves, the Registrable Securities held by them and the intended method
of disposition of such securities as will be required to effect the registration of their
Registrable Securities.
(c)
The Company will have no obligation with respect to any registration requested pursuant
to Section 6.2 if the number of shares or the anticipated aggregate offering price of the
Registrable Securities to be included in the registration does not equal or exceed the number of
shares or the anticipated aggregate offering price required to originally trigger the Companys
obligation to initiate such registration as specified in Section 6.2.
6.6 Indemnification.
In the event any Registrable Securities are included in a registration
statement under Section 6.1 or 6.2:
(a)
To the extent permitted by law, the Company will indemnify and hold harmless each Holder,
the partners, members, officers and directors of each Holder, as applicable, any underwriter (as
defined in the Securities Act) for such Holder and each person, if any, who controls such Holder
or underwriter within the meaning of the Securities Act or the Exchange Act, against any losses,
claims, damages, or liabilities (joint or several) to which they may become subject under the
Securities Act, the Exchange Act or other federal or state law, insofar as such losses, claims,
damages or liabilities (or actions in respect thereof) arise out of or are based upon any of the
following statements, omissions or violations (collectively a
Violation
) by the Company: (i) any
untrue statement or alleged untrue statement of a material fact contained in such registration
statement or incorporated by reference therein, including any preliminary prospectus or final
prospectus contained therein or any amendments or supplements thereto, (ii) the omission or
alleged omission to state therein a material fact required to be stated therein, or necessary to
make the statements therein not misleading, or
15.
(iii) any violation or alleged violation by the Company of the Securities Act, the Exchange
Act, any state securities law or any rule or regulation promulgated under the Securities Act, the
Exchange Act or any state securities law in connection with the offering covered by such
registration statement; and the Company will reimburse each such Holder, partner, member, officer,
director, underwriter or controlling person for any legal or other expenses reasonably incurred by
them in connection with investigating or defending any such loss, claim, damage, liability or
action;
provided however
, that the indemnity agreement contained in this Section 6.6(a) will not
apply to amounts paid in settlement of any such loss, claim, damage, liability or action if such
settlement is effected without the consent of the Company, which consent will not be unreasonably
withheld, nor will the Company be liable in any such case for any such loss, claim, damage,
liability or action to the extent that it arises out of or is based upon a Violation which occurs
in reliance upon and in conformity with written information furnished expressly for use in
connection with such registration by such Holder, partner, member, officer, director, underwriter
or controlling person of such Holder.
(b)
To the extent permitted by law, each Holder will, if Registrable Securities held by such
Holder are included in the securities as to which such registration qualifications or compliance
is being effected, indemnify and hold harmless the Company, each of its directors, its officers
and each person, if any, who controls the Company within the meaning of the Securities Act, any
underwriter and any other Holder, as applicable, selling securities under such registration
statement or any of such other Holders partners, directors or officers or any person who controls
such Holder, against any losses, claims, damages or liabilities (joint or several) to which the
Company or any such director, officer, controlling person, underwriter or other such Holder, or
partner, director, officer or controlling person of such other Holder may become subject under the
Securities Act, the Exchange Act or other federal or state law, insofar as such losses, claims,
damages or liabilities (or actions in respect thereto) arise out of or are based upon any of the
following statements: (i) any untrue statement or alleged untrue statement of a material fact
contained in such registration statement or incorporated reference therein, including any
preliminary prospectus or final prospectus contained therein or any amendments or supplements
thereto, (ii) the omission or alleged omission to state therein a material fact required to be
stated therein, or necessary to make the statements therein not misleading, or (iii) any violation
or alleged violation by the Company of the Securities Act (collectively, a
Holder Violation
),
in each case to the extent (and only to the extent) that such Holder Violation occurs in reliance
upon and in conformity with written information furnished by such Holder under an instrument duly
executed by such Holder and stated to be specifically for use in connection with such
registration; and each such Holder will reimburse any legal or other expenses reasonably incurred
by the Company or any such director, officer, controlling person, underwriter or other Holder, or
partner, officer, director or controlling person of such other Holder in connection with
investigating or defending any such loss, claim, damage, liability or action if it is judicially
determined that there was such a Holder Violation;
provided, however,
that the indemnity agreement
contained in this Section 6.6(b) will not apply to amounts paid in settlement of any such loss,
claim, damage, liability or action if such settlement is effected without the consent of the
Holder, which consent will not be unreasonably withheld;
provided further
, that in no event will
any indemnity under this Section 6.6 exceed the net proceeds from the offering received by such
Holder, as applicable.
16.
(c)
Promptly after receipt by an indemnified party under this Section 6.6 of notice of the
commencement of any action (including any governmental action), such indemnified party will, if a
claim in respect thereof is to be made against any indemnifying party under this Section 6.6,
deliver to the indemnifying party a written notice of the commencement thereof and the
indemnifying party will have the right to participate in, and, to the extent the indemnifying
party so desires, jointly with any other indemnifying party similarly noticed, to assume the
defense thereof with counsel mutually satisfactory to the parties;
provided, however,
that an
indemnified party will have the right to retain its own counsel, with the fees and expenses
thereof to be paid by the indemnifying party, if representation of such indemnified party by the
counsel retained by the indemnifying party would be inappropriate due to actual or potential
differing interests between such indemnified party and any other party represented by such counsel
in such proceeding. The failure to deliver written notice to the indemnifying party within a
reasonable time of the commencement of any such action will relieve such indemnifying party of any
liability to the indemnified party under this Section 6.6 to the extent, and only to the extent,
prejudicial to its ability to defend such action, but the omission so to deliver written notice to
the indemnifying party will not relieve it of any liability that it may have to any indemnified
party otherwise than under this Section 6.6.
(d)
If the indemnification provided for in this Section 6.6 is held by a court of competent
jurisdiction to be unavailable to an indemnified party with respect to any losses, claims, damages
or liabilities referred to herein, the indemnifying party, in lieu of indemnifying such
indemnified party thereunder, will to the extent permitted by applicable law contribute to the
amount paid or payable by such indemnified party as a result of such loss, claim, damage or
liability in such proportion as is appropriate to reflect the relative fault of the indemnifying
party on the one hand and of the indemnified party on the other in connection with the
Violation(s) or Holder Violation(s) that resulted in such loss, claim, damage or liability, as
well as any other relevant equitable considerations. The relative fault of the indemnifying party
and of the indemnified party will be determined by a court of law by reference to, among other
things, whether the untrue or alleged untrue statement of a material fact or the omission to state
a material fact relates to information supplied by the indemnifying party or by the indemnified
party and the parties relative intent, knowledge, access to information and opportunity to
correct or prevent such statement or omission;
provided
,
that
in no event will any contribution by
a Holder, as applicable, hereunder exceed the net proceeds from the offering received by such
Holder, as applicable.
(e)
The obligations of the Company and Holders under this Section 6.6 will survive completion
of any offering of Registrable Securities, as applicable, in a registration statement and, with
respect to liability arising from an offering to which this Section 6.6 would apply that is
covered by a registration filed before termination of this Agreement, such termination. No
indemnifying party, in the defense of any such claim or litigation, will, except with the consent
of each indemnified party, consent to entry of any judgment or enter into any settlement which
does not include as an unconditional term thereof the giving by the claimant or plaintiff to such
Indemnified Party of a release from all liability in respect to such claim or litigation.
17.
6.7 Assignment of Registration Rights.
The rights to cause the Company to register
Registrable Securities pursuant to this Section 6 may be assigned by a Holder to a transferee or
assignee of Registrable Securities (for so long as such shares remain Registrable Securities) that
(a) is a subsidiary, parent, general partner, limited partner, retired partner, member or retired
member, stockholder or other affiliate of a Holder that is a corporation, partnership or limited
liability company, (b) acquires all of such Holders Registrable Securities in connection with the
sale of all or substantially all of such Holders business, or (c) acquires at least two hundred
thousand (200,000) shares of Registrable Securities (as adjusted for stock splits and
combinations); or (d) is an entity affiliated by common control (or other related entity) with such
Holder
provided, however,
(i) the transferor will, within ten (10) days after such transfer,
furnish to the Company written notice of the name and address of such transferee or assignee and
the securities with respect to which such registration rights are being assigned and (ii) such
transferee will agree to be subject to all restrictions set forth in this Agreement.
6.8 Limitation on Subsequent Registration Rights.
Other than as provided in Section 5.10,
after the date of this Agreement, the Company will not enter into any agreement with any holder or
prospective holder of any securities of the Company that would grant such holder rights to demand
the registration of shares of the Companys capital stock, or to include such shares in a
registration statement that would reduce the number of shares includable by the Holders.
6.9 Market Stand-Off Agreement.
Each Holder hereby agrees that such Holder, as the case may
be, will not sell, transfer, make any short sale of, grant any option for the purchase of, or enter
into any hedging or similar transaction with the same economic effect as a sale, any Common Stock
(or other securities) of the Company held by such Holder (other than those included in the
registration) during (i) the 180-day period following the effective date of the Initial Offering
(or such longer period, not to exceed 34 days after the expiration of the 180-day period, as the
underwriters or the Company will request in order to facilitate compliance with NASD Rule 2711 or
NYSE Member Rule 472 or any successor rule), and (ii) the 90-day period following the effective
date of a registration statement of the Company filed under the Securities Act (or such longer
period, not to exceed 18 days after the expiration of the 90-day period, as the underwriters or the
Company will request in order to facilitate compliance with NASD Rule 2711);
provided,
that, with
respect to (i) and (ii) above, all officers, directors of the Company and all entities who hold
Common Stock (or Securities Convertible into Common Stock) in an amount that is greater than 1% of
the Companys then issued and outstanding Common Stock are bound by and have entered into similar
agreements. The obligations described in this Section 6.9 will not apply to a Special Registration
Statement.
6.10 Agreement to Furnish Information.
Each Holder hereby agrees to execute and deliver such
other agreements as may be reasonably requested by the Company or the underwriter that are
consistent with such Holders obligations under Section 6.9, as applicable, or that are necessary
to give further effect thereto. In addition, if requested by the Company or the representative of
the underwriters of Common Stock (or other securities) of the Company, each Holder will provide,
within ten (10) days of such request, such information as may be required by the Company or such
representative in connection with the completion of any public offering of the Companys securities
pursuant to a registration statement filed under the Securities Act. The obligations described in
Section 6.9 and this Section 6.10 will not apply to a Special
18.
Registration Statement. The Company may impose stop-transfer instructions with respect to the
shares of Common Stock (or other securities) subject to the foregoing restriction until the end of
said day period. Each Holder agrees that any transferee of any shares of Registrable Securities
will be bound by Sections 6.9 and 6.10. The underwriters of the Companys stock are intended third
party beneficiaries of Sections 6.9 and 6.10 and will have the right, power and authority to
enforce the provisions hereof as though they were a party hereto.
6.11 Rule 144 Reporting.
With a view to making available to the Holders, as applicable, the
benefits of certain rules and regulations of the SEC which may permit the sale of the Registrable
Securities to the public without registration, the Company agrees to use its best efforts to:
(a)
Make and keep public information available, as those terms are understood and defined in
SEC Rule 144 or any similar or analogous rule promulgated under the Securities Act, at all times
after the effective date of the first registration filed by the Company for an offering of its
securities to the general public;
(b)
File with the SEC, in a timely manner, all reports and other documents required of the
Company under the Exchange Act; and
(c)
So long as a Holder owns any Registrable Securities, as applicable, furnish to such
Holder forthwith upon request: a written statement by the Company as to its compliance with the
reporting requirements of said Rule 144 of the Securities Act, and of the Exchange Act (at any
time after it has become subject to such reporting requirements); a copy of the most recent annual
or quarterly report of the Company filed with the Commission; and such other reports and documents
as a Holder may reasonably request in connection with availing itself of any rule or regulation of
the SEC allowing it to sell any such securities without registration.
6.12 Termination of Registration Rights.
The right of any Holder to request registration or
inclusion of Registrable Securities in any registration pursuant to Sections 6.1 or 6.2 hereof will
terminate upon the earlier of: (i) the date three (3) years following an Initial Offering; or (ii)
following the Initial Offering, such time as all Registrable Securities issuable or issued upon
conversion of the Shares held by and issuable to such Holder (and its affiliates) may be sold
pursuant to Rule 144 during any ninety (90) day period. Upon such termination, such shares will
cease to be Registrable Securities hereunder for all purposes.
SECTION 7.
MISCELLANEOUS
.
7.1 Governing Law.
This Agreement will in all respects be governed by and construed in
accordance with the substantive laws of the State of Delaware, without regard to its choice of law
rules.
7.2 Successors and Assigns.
Except as otherwise expressly provided herein, the provisions
hereof will inure to the benefit of, and be binding upon, the parties hereto and their respective
successors, assigns, heirs, executors, and administrators and will inure to the benefit of and be
enforceable by each person who will be a holder of Registrable Securities from time to time;
provided, however
, that prior to the receipt by the Company of adequate written notice of
19.
the transfer of any Registrable Securities specifying the full name and address of the
transferee, the Company may deem and treat the person listed as the holder of such shares in its
records as the absolute owner and holder of such shares for all purposes, including the payment of
dividends or any redemption price.
7.3 Entire Agreement.
This Agreement, together with the Ancillary Agreements, including the
exhibits and schedules hereto and thereto, constitutes the entire agreement among the Founding
Investors and the Company with respect to the specific subject matter hereof, and supersedes all
prior and contemporaneous agreements, representations, and understandings of the parties with
respect to such specific subject matter. No party hereto will be liable or bound to the other in
any manner by any warranties, representations or covenants with respect to the subject matter
hereof except as specifically set forth herein. Notwithstanding the foregoing and except as
provided herein or in any Ancillary Agreement, neither the dissolution of the Company nor the
termination of any Ancillary Agreement will have any affect on any other agreement or contract
between the Founding Investors, and the termination or cancellation of any such other agreement or
contract will have no effect on this Agreement or any Ancillary Agreement.
7.4 Severability.
If one or more provisions of this Agreement are held by a proper court or
arbitral tribunal to be unenforceable under applicable law, the unenforceable portions of such
provisions, or such provisions in their entirety, to the extent necessary and permitted by law,
will be severed herefrom, and the balance of this Agreement will be enforceable in accordance with
its terms.
7.5 Amendment and Waiver.
(a)
Except as otherwise expressly provided, this Agreement may be amended or modified, and
the obligations of the Company and the rights of the Holders under this Agreement may be waived,
only upon the written consent of (i) the Company, and (ii) a 2/3 majority of shares held by the
Founding Investors.
(b)
For the purposes of determining the number of Holders or Founding Investors entitled to
vote or exercise any rights hereunder, the Company will be entitled to rely solely on the list of
record holders of its stock as maintained by or on behalf of the Company.
7.6 Delays or Omissions.
It is agreed that no delay or omission to exercise any right, power,
or remedy accruing to any party, upon any breach, default or noncompliance by another party under
this Agreement will impair any such right, power, or remedy, nor will it be construed to be a
waiver of any such breach, default or noncompliance, or any acquiescence therein, or of any similar
breach, default or noncompliance thereafter occurring. It is further agreed that any waiver,
permit, consent, or approval of any kind or character on any partys part of any breach, default or
noncompliance under the Agreement or any waiver on such partys part of any provisions or
conditions of this Agreement must be in writing and will be effective only to the extent
specifically set forth in such writing. All remedies, either under this Agreement, by law, or
otherwise afforded to any party, will be cumulative and not alternative.
7.7 Notices.
Except where otherwise specifically provided in this Agreement, all notices,
requests, consents, approvals and statements will be in writing and will be deemed to
20.
have been properly given by (i) personal delivery, (ii) electronic facsimile transmission,
(iii) electronic mail, or by (iv) nationally recognized overnight courier service, addressed in
each case, to the intended recipient as set forth below:
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To the Company:
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Regulus Therapeutics LLC
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1896 Rutherford Road
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Carlsbad, California 92008
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Attention: President
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With a copy to:
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Alnylam and/or Isis at the addresses below
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To Alnylam:
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Alnylam Pharmaceuticals, Inc.
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300 Third Street, 3
rd
Floor
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Cambridge, MA 02142
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Attention: Vice President, Legal
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With a copy to:
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WilmerHale
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60 State Street
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Boston, MA 02109
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Attention: Steven D. Singer, Esq.
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To Isis:
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Isis Pharmaceuticals, Inc.
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1896 Rutherford Road
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Carlsbad, California 92008
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Attention: Chief Financial Officer
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With a copy to:
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Isis Pharmaceuticals, Inc.
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1896 Rutherford Road
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Carlsbad, California 92008
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Attn: General Counsel
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(fax) 760-268-4922
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Such notice, request, demand, claim or other communication will be deemed to have been duly given
on (a) the date of personal delivery, (b) the date actually received if by facsimile or electronic
mail; or (c) on the third business day after delivery to a nationally recognized overnight courier
service, as the case may be. Any Party may change the address to which notices, requests, demands,
claims, and other communications hereunder are to be delivered by giving the other Parties notice
in the manner herein set forth.
7.8 Fees and Expenses.
Each party will pay all costs and expenses that it incurs with respect
to the negotiation, execution, delivery and performance of this Agreement. If any action at law or
in equity is necessary to enforce or interpret the terms of any of this Agreement, the prevailing
party will be entitled to reasonable attorneys fees, costs and necessary disbursements
21.
in addition to any other relief to which such party may be entitled. For purposes of this
Section 7.8, prevailing party means the net winner of a dispute, taking into account the claims
pursued, the claims on which the pursuing party was successful, the amount of money sought, the
amount of money awarded, and offsets or counterclaims pursued (successfully or unsuccessfully) by
the other Party. If a written settlement offer is rejected and the judgment or award finally
obtained is equal to or more favorable to the offeror than an offer made in writing to settle, the
offeror is deemed to be the prevailing party from the date of the offer forward.
7.9 Titles and Subtitles; Form of Pronouns; Construction and Definitions.
The titles of the
Sections and paragraphs of this Agreement are for convenience only and are not to be considered in
construing this Agreement. All pronouns used in this Agreement will be deemed to include
masculine, feminine and neuter forms, the singular number includes the plural and the plural number
includes the singular and will not be interpreted to preclude the application of any provision of
this Agreement to any individual or entity. Unless the context otherwise requires, (i) each
reference in this Agreement to a designated Section, Schedule, Exhibit, or Appendix is to
the corresponding Section, Schedule, Exhibit, or Appendix of or to this Agreement; (ii) the word
or will not be applied in its exclusive sense; (iii) including will mean including, without
limitation; (iv) references to $ or dollars will mean the lawful currency of the United
States; and (v) herein, hereof, hereunder and other words of similar import refer to this
Agreement as a whole and not to any particular Section or other subdivision. References in this
Agreement to particular sections of the Securities Act or to any provisions of Delaware law will be
deemed to refer to such sections or provisions as they may be amended or succeeded after the date
of this Agreement.
7.10 Counterparts.
This Agreement may be executed in two or more counterparts, each of which
will be deemed an original, but all of which together will constitute one and the same instrument,
and will become effective when there exist copies hereof which, when taken together, bear the
authorized signatures of each of the parties hereto. Only one such counterpart signed by the party
against whom enforceability is sought needs to be produced to evidence the existence of this
Agreement.
7.11 Aggregation of Stock.
All shares of Registrable Securities held or acquired by
affiliated entities or persons or persons or entities under common management or control will be
aggregated together for the purpose of determining the availability of any rights under this
Agreement.
7.12 Specific Performance.
The failure of any party to this Agreement to perform its
agreements and covenants hereunder, including but not limited to Section 4, may cause irreparable
injury to the other parties to this Agreement for which monetary damages, even if available, will
not be an adequate remedy. Accordingly, each of the parties hereto hereby consents to the granting
of equitable relief (including specific performance and injunctive relief) by any court of
competent jurisdiction to enforce any Members obligations hereunder. The parties further agree to
waive any requirement for the securing or posting of any bond in connection with the obtaining of
any such equitable relief and that this Section 7.12 is without prejudice to any other rights that
the Founding Investors and the Company hereto may have for any failure to perform this Agreement.
22.
7.13 Termination.
This Agreement will terminate and be of no further force or effect upon the
earlier of (i) a Liquidation Event, Acquisition or Asset Transfer; or (ii) the date three (3) years
following the Closing of the Initial Offering that results in the conversion of all outstanding
shares of Preferred Stock.
[THIS SPACE INTENTIONALLY LEFT BLANK]
23.
In Witness Whereof,
the parties hereto have executed this
Founding
Investor Rights Agreement
as of the date set forth in the first paragraph hereof.
COMPANY:
Regulus Therapeutics Inc.
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By:
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/s/ K.G. Xanthopoulos
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FOUNDING INVESTORS:
Isis Pharmaceuticals, Inc.
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By:
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/s/ B. Lynne Parshall
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Alnylam Pharmaceuticals, Inc.
1.
EXHIBIT A
DEFINITONS
1.1
Ancillary Agreements
means the License Agreement and the Services Agreement each as
amended from time to time.
1.2
Change of Control
means, with respect to a Founding Investor (the Affected Founding
Investor), the earlier of (x) the public announcement of and (y) the closing of: (a) a merger,
reorganization or consolidation involving the Affected Founding Investor in which its shareholders
immediately prior to such transaction would hold less than 50% of the securities or other ownership
or voting interests representing the equity of the surviving entity immediately after such merger,
reorganization or consolidation, or (b) a sale to a Third Party of all or substantially all of the
Affected Founding Investors assets or business relating to this Agreement. Any Founding Investor
will notify each other Founding Investor within two (2) Business Days of entering into an agreement
which, if consummated, would result in a Change of Control.
1.3
Common Stock
means the Common Stock of the Company.
1.4
Exchange Act
means the Securities Exchange Act of 1934, as amended.
1.5
Form S-3
means such form under the Securities Act as in effect on the date hereof or any
successor or similar registration form under the Securities Act subsequently adopted by the SEC
which permits inclusion or incorporation of substantial information by reference to other documents
filed by the Company with the SEC.
1.6
Holder
means any person owning of record Registrable Securities that have not been sold
to the public or any assignee of record of such Registrable Securities in accordance with
Section 6.7 hereof.
1.7
Independent Director
means a Director who is not an (i) Affiliate, director or officer
of, or an immediate family member of, any director or officer of the Founding Investor designating
such Director, or (ii) an officer or employee of, or immediate family member of any officer or
employee of, the Company.
1.8
Initial Offering
means the Companys first firm commitment underwritten public offering
of its Common Stock registered under the Securities Act.
1.9
License Agreement
means that certain Amended and Restated License and Collaboration
Agreement by and among the Company, Alnylam and Isis dated January 1, 2008, as amended from time to
time.
1.10
Person
means a natural person, company, corporation, partnership, trust or other
organization or legal entity of any type, whether or not formally organized.
1.11
Register, registered,
and
registration
refer to a registration effected by
preparing and filing a registration statement in compliance with the Securities Act, and the
declaration or ordering of effectiveness of such registration statement or document.
1.12
Registrable Securities
means (a) Common Stock issuable or issued upon conversion of the
Shares and (b) any Common Stock issued as (or issuable upon the conversion or exercise of any
warrant, right or other security which is issued as) a dividend or other distribution with respect
to, or in exchange for or in replacement of, such above-described securities. Notwithstanding the
foregoing, Registrable Securities will not include any securities (i) sold by a person to the
public either pursuant to a registration statement or Rule 144, (ii) sold in a private transaction
in which the transferors rights under Section 6 of this Agreement are not assigned or (iii)
eligible for resale pursuant to Rule 144 without volume limitations.
1.13
Registrable Securities then outstanding
will be the number of shares of Common Stock
that are Registrable Securities and either (a) are then issued and outstanding or (b) are issuable
pursuant to then exercisable or convertible securities.
1.14
Registration Expenses
will mean all expenses incurred by the Company in complying with
Sections 6.1 or 6.2, including, without limitation, all registration and filing fees, printing
expenses, fees and disbursements of counsel for the Company, reasonable fees and disbursements not
to exceed ten thousand dollars ($10,000) of a single special counsel for the Holders, if
applicable, blue sky fees and expenses and the expense of any special audits incident to or
required by any such registration (but excluding the compensation of regular employees of the
Company which will be paid in any event by the Company).
1.15
SEC
or
Commission
means the Securities and Exchange Commission.
1.16
Securities Act
will mean the Securities Act of 1933, as amended.
1.17
Selling Expenses
will mean all underwriting discounts and selling commissions
applicable to the sale.
1.18
Shares
will mean the Companys Preferred Stock issued pursuant to the Purchase
Agreement held from time to time by the Founding Investors and their permitted assigns.
1.19
Special Registration Statement
will mean (i) a registration statement relating to any
employee benefit plan or (ii) with respect to any corporate reorganization or transaction under
Rule 145 of the Securities Act, any registration statements related to the issuance or resale of
securities issued in such a transaction or (iii) a registration related to stock issued upon
conversion of debt securities.
EXHIBIT B
INITIAL DIRECTORS
AND
INITIAL SAB MEMBERS
Board of Directors:
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Name
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Title
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Kleanthis G. Xanthopoulos, Ph.D.
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President, Regulus Therapeutics LLC
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David Baltimore, Ph.D.
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Independent Director nominated by Alnylam
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Stelios Papadopoulos, Ph.D.
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Independent Director nominated by Isis
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John M. Maraganore, Ph.D.
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Alnylam Director
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Barry E. Greene
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Alnylam Director
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Stanley T. Crooke, M.D., Ph.D.
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Isis Director
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B. Lynne Parshall, J.D.
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Isis Director
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SAB Members:
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Name
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Title
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David Baltimore, Ph.D.
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Member and Chairperson
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David Bartel, Ph.D.
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Member
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Scott Hammond, Ph.D.
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Member
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Markus Stoffel, M.D., Ph.D.
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Member
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Thomas Tuschl, Ph.D.
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Member
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Philip Zamore, Ph.D.
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Member
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EXHIBIT C
OPERATING PLAN
[***]
EXHIBIT D
TERMS OF BUY-OUT
Capitalized terms used but not otherwise defined herein will have the meaning ascribed to them in
the Agreement or the License Agreement.
1.1 Negotiated Resolution.
Following the Companys receipt of the Buy-Out Notice, the
Founding Investors will take all actions necessary to cause the sale of the Company to a Third
Party or a Founding Investor (whether through merger, acquisition of 100% of the Equity Securities
or purchase of all or substantially all of the assets of the Company) (a
Sale
). The Company
promptly thereafter will retain a reputable investment bank chosen by mutual agreement (such
agreement not to be unreasonably withheld, conditioned or delayed) of the Founding Investors and
the Company (the
Investment Banker
) to assist with the valuation and possible Sale of the
Company;
provided, however
, that in the event that due to then-current market conditions a Sale
would be impractical because it would be reasonably like to result in proceeds from such Sale to
either Founding Investor that are substantially below such Founding Investors cost basis in its
investment in the Company, as determined based on the written advice of the Investment Banker
(
Poor Market Conditions
), then the Founding Investors will mutually determine whether
notwithstanding such market conditions to attempt to Sell the Company to a Third Party or a
Founding Investor;
and
,
provided, further however
, that, notwithstanding anything in this Exhibit D
or Section 4.2 to the contrary, neither Founding Investor will be required to agree to enter into,
or to approve the Companys entering into, such a Sale. Any such Sale will be subject to all other
terms agreed upon by the Founding Investors and the Company, which will be documented in a separate
written agreement among the parties (a
Sale Agreement
).
1.2 Non-Negotiated Resolution.
(a)
If (i) Poor Market Conditions exist and the Founding Investors do not determine pursuant
to Section 1.1 to attempt a Sale of the Company, or (ii) the Founding Investors have not within
[***] ([***]) days after the Companys receipt of the Buy-Out Notice, or such longer period as
mutually agreed to by the Founding Investors (such period, the Buy-Out Negotiation Period),
executed a Sale Agreement, the Company will, except as otherwise set forth in this Section 1.2,
distribute and assign to the Founding Investors, or their designated Affiliate, jointly, in
accordance with Pro Rata Share, all of the Companys rights, interests and assets, other than any
contracts and/or arrangements between the Company and Third Parties that the Board determines
cannot or should not be assigned (Third Party Contracts) (provided that the Parties agree to use
commercially reasonable efforts to provide for the assignment of all Third Party Contracts), and
the provisions of this Section 1.2 will apply. For purposes of this Exhibit D,
Pro Rata Share
means, with respect to each Investor at any particular moment, the ratio of (a) the number of
shares of the Companys Common Stock (not including any shares of Common Stock issuable or issued
upon conversion of the Shares or upon the exercise of outstanding warrants or options) of which
such Investor is deemed to be a holder immediately prior to the moment in question to (b) the total
number of shares of the Companys outstanding
Common Stock (not including any shares of Common Stock issued or issuable upon conversion of
the Shares or upon the exercise of any outstanding warrants or options) immediately prior to the
moment in question.
(b) Distribution of Intellectual Property.
(i)
Upon the distribution of the Companys assets pursuant to this Section 1.2, each Founding
Investor or its designated Affiliate will receive, subject to Third Party Rights and Third Party
Contracts, (1) a co-exclusive license under Company Intellectual Property Controlled by the Company
at the end of the Buy-Out Negotiation Period, for any and all purposes, and (2) a co-exclusive
license under Licensed IP licensed to the Company at the end of the Buy-Out Negotiation Period, for
any and all purposes within the scope of the license granted to the Company (collectively, the
Distributed IP);
provided, however
, that (y) to the extent that one Founding Investor has
obtained a license in connection with an Opt-In Election or obtains a license pursuant to Section
1.2(d) or 1.2(e), the licenses to the Distributed IP under this Section 1.2(b) will not include the
right to Develop, Manufacture or Commercialize the Program/Project Compounds or Program/Project
Therapeutics subject to such Opt-In election or license pursuant to Section 1.2(d) or 1.2(e); and
(z) to the extent that a Founding Investor has obtained a license in connection with Section 2.3 of
the License Agreement, the licenses to the Distributed IP under this Section 1.2(b) will be subject
to such license granted to such Founding Investor. For purposes of this Section 1.2(b)(i),
co-exclusive means that such license is exercisable by each Founding Investor or its designated
Affiliate, and that the Company retains no rights to exercise any such licensed Intellectual
Property.
(ii)
The rights granted to each Founding Investor in this Section 1.2(b) will be (1)
royalty-bearing, as set forth in Section 1.2(b)(iii) below, and (2) sublicenseable solely (A) to
such Founding Investors Affiliates or (B) by such Founding Investor or its Affiliates to a Third
Party pursuant to a Bona Fide Collaboration;
provided
that, (x) each such sublicense will be
subject and subordinate to, and consistent with, the terms and conditions of the License Agreement
and this Exhibit D, and will provide that any such sublicensee will not further sublicense except
on terms consistent with this clause; (y) such Founding Investor will remain responsible for the
performance of its sublicensees, and will ensure that all such sublicensees comply with the
relevant provisions of the License Agreement and this Exhibit D and (z) in the event of a material
default by any of its sublicensees under a sublicense agreement, such Founding Investor will inform
the Company and the other Founding Investor and will take such action, after consultation with such
other parties, which, in such Founding Investors reasonable business judgment, will address such
default.
(iii)
Each Founding Investor will, to the extent it, its Affiliates and/or Sublicensees
develop a Royalty-Bearing Product under Intellectual Property distributed from the Company to the
Founding Investor pursuant to this Section 1.2(b) that does not become subject to Section 1.2(d) or
1.2(e): (x) pay to the other Founding Investor (or its designated Affiliate) a royalty of [***]% on
Net Sales of such Royalty-Bearing Products sold by the selling Founding Investor, its Affiliates
and/or Sublicensees, on a Royalty-Bearing Product-by-Royalty-Bearing Product and a
country-by-country basis, during the Royalty Term (
provided, however
, that, for the remainder of
the relevant Royalty Term following the end of both the relevant Exclusivity Period, the royalty
rate will be [***]%), and (y) be responsible for all milestones, royalties and
other payments payable to Third Parties in respect of the exercise of such license by such
selling Founding Investor, its Affiliates and/or Sublicensees, including without limitation any
amounts payable by either Founding Investor or the Company to its Third Party licensors with
respect to the license and sublicense granted to such Founding Investor pursuant to this Section
1.2(b). The royalty-paying Founding Investor will use Commercially Reasonable Efforts to benefit
from offsets to the amounts payable to such Founding Investors Third Party licensors.
(c) Retained Assets and Rights.
Following the distribution of the Companys assets pursuant
to this Section 1.2, the Company will not maintain any interest in or right to any assets of the
Company, including Intellectual Property, except to the extent the Board determines is necessary to
maintain Third Party Contracts or its obligations to Opt-In Parties or Founding Investors pursuant
to the Buy-Out. Notwithstanding the foregoing, the Parties will use their Commercially Reasonable
Efforts to remove any restrictions on, and facilitate the distribution of, the Companys assets
pursuant to this Section 1.2.
(d) Research Program Selection and Transfer.
(i)
Within [***] ([***]) Business Days following the distribution of the Companys assets in
accordance with Section 1.2(a) and (b), the non-Initiating Founding Investor will submit a bid,
consisting [***] (
First Selection Right Bid
), to the Initiating Founding Investor to obtain the
first right to select a Research Program from the most recent Program/Project List with respect to
which such Founding Investor desires to acquire exclusive rights;
provided, however
, that in the
event the non-Initiating Founding Investor does not submit such a bid with [***] ([***]) Business
Days, the Initiating Founding Investor may assume the rights of the non-Initiating Founding
Investor set forth in this Section 1.2(d) with respect to the First Selection Right Bid. The
Initiating Founding Investor will have [***] ([***]) Business Days to notify the non-Initiating
Founding Investor of its acceptance or rejection of such First Selection Right Bid.
(ii)
If the Initiating Founding Investor accepts such First Selection Right Bid,
(1)
The non-Initiating Founding Investor will have the right, upon payment to the Initiating
Founding Investor of the [***] set forth in the First Selection Right Bid (which [***] will be due
and payable within [***] ([***]) Business Days after acceptance of such bid), to select one
Research Program (
Selected Program
). Upon such selection, the non-Initiating Founding Investor
will obtain the license set forth in clause (vi) below under Intellectual Property directed to such
Selected Program; and.
(2)
Each of the Founding Investors, starting with the Initiating Founding Investor, will then
take turns selecting (by written notice within [***] ([***]) Business Days following the last
selection by the other Founding Investor) a Research Program (other than the Selected Program),
until all Research Programs on the Program/Project List have been selected by the Founding
Investors (and each such selected Research Program is a Selected Program hereunder), and each
Founding Investor will obtain the rights set forth in clause (vi) below under Intellectual Property
directed to the Research Program selected by such Founding Investor.
(iii)
If the Initiating Founding Investor rejects such First Selection Right Bid, such
Founding Investor will submit to the non-Initiating Founding Investor, concurrently with such
notice of rejection, a counterbid which is higher than such First Selection Right Bid by at least
[***]% or $[***] (whichever is higher). The non-Initiating Founding Investor will have [***]
([***]) Business Days to accept or reject such counterbid.
(iv)
If the non-Initiating Founding Investor accepts such counterbid, the Initiating Founding
Investor will have the right, upon payment to the non-Initiating Founding Investor of the amount
set forth in such counterbid (which amount will be due and payable within [***] ([***]) Business
Days after acceptance of such counterbid), to select a Research Program (other than a Selected
Program) and each such selected Research Program is a
Selected Program
hereunder. Upon
completion of the Buy-Out, the Initiating Founding Investor will obtain from the non-Initiating
Founding Investor the rights set forth in clause (vi) below with respect to the Research Program
selected by such Founding Investor.
(v)
If the non-Initiating Founding Investor rejects such counterbid, then such non-Initiating
Founding Investor will submit, concurrently with such notice of rejection, its counterbid to the
Initiating Founding Investors counterbid, which counterbid must be higher than the Initiating
Founding Investors counterbid by at least [***]%, and the process will repeat itself until a bid
is accepted or no counterbid exceeds the prior bid or counterbid by at least [***]%.
(vi)
Each Founding Investor will grant to the other Founding Investor which purchased a
Selected Program hereunder (the
Buy-Out Party
), subject to Third Party Rights, an exclusive (to
the fullest extent possible) license under Distributed IP (which, with respect to Licensed IP
therein, is within the scope of the license granted to the Founding Investor by the Company), to
Develop, Manufacture and/or Commercialize the miRNA Compound(s) and miRNA Therapeutics included in
such Selected Program in the Field.
(vii)
Such licenses to Distributed IP will be (1) royalty-bearing as set forth in Section
1.2(d)(viii) below, and (2) sublicenseable;
provided
that, (x) each such sublicense will be subject
and subordinate to, and consistent with, the terms and conditions of this Exhibit D, and will
provide that any such Sublicensee will not further sublicense except on terms consistent with this
clause; (y) such Founding Investor will remain responsible for the performance of its Sublicensees,
and will ensure that all such Sublicensees comply with the relevant provisions of the License
Agreement and this Exhibit D and (z) in the event of a material default by any of its Sublicensees
under a sublicense agreement, such Founding Investor will inform the Company and the other Founding
Investor and will take such action, after consultation with such other Parties, which, in such
Founding Investors reasonable business judgment, will address such default.
(viii)
Each Founding Investor selecting a Selected Program will (1) pay to the other Founding
Investor (or its designated Affiliate) a royalty of [***]% on Net Sales of any Royalty-Bearing
Product with respect to such Selected Program, on a Royalty-Bearing Product-by-Royalty-Bearing
Product and a country-by-country basis, during the Royalty Term (
provided, however
, that, for the
remainder of the relevant Exclusivity Period, the royalty rate will be [***]%, and (2) be
responsible for milestones, royalties and other payments payable to
Third Parties in respect of the exercise of such license by such selling Founding Investor,
its Affiliates and/or Sublicensees, including without limitation any amounts payable by either
Founding Investor or the Company to its Third Party licensors with respect to the licenses granted
to such Founding Investor pursuant to Section 1.2(a). The royalty-paying Founding Investor will
use Commercially Reasonable Efforts to benefit from offsets to the amounts payable to such Founding
Investors Third Party licensors.
(ix)
Each Founding Investor will assign or exclusively license to the other Founding Investor,
to the fullest extent possible, all of its rights and obligations in assets, other than
Intellectual Property, distributed by the Company to the Founding Investors pursuant to Section
1.2(a), to the extent such assets are solely related to any of the other Founding Investors
Selected Programs. In the event any such assets are related to Selected Programs of both Founding
Investors, each Founding Investors will assign to or exclusively license the other, to the fullest
extent possible, the rights to such assets as they relate to the other Founding Investors Selected
Programs.
(e) Development Project Selection and Transfer.
(i)
Within [***] ([***]) Business Days following the completion of the distribution of the
Companys assets pursuant to Section 1.2(a), the non-Initiating Party (the
Bidding Party
) will
have the right to submit to the other Founding Investor a bid, which need not be limited to a [***]
(
Project Bid
), with respect to one or more Development Projects included in the most recent
Program/Project List;
provided
that, a separate Project Bid must be submitted for each and every
Development Project for which the Party is bidding. Notwithstanding the foregoing, in the event
the non-Initiating Party does not submit such a bid within [***] Business Days, the Initiating
Party may assume the rights of the non-Initiating Party set forth in this Section 1.2(e) with
respect to a Project Bid. The non-Bidding Party will have [***] ([***]) Business Days to notify
the Bidding Party of its acceptance or rejection of a Project Bid made by the Bidding Party, on a
Project Bid-by-Project Bid basis.
(ii)
If the non-Bidding Party accepts a Project Bid or does not reject a Project Bid and
provide a counterbid in accordance with clause (iii) below (in which case the Project Bid is deemed
accepted) within such [***] ([***]) Business Day period, the Bidding Party, subject to compliance
with its payment obligations under the terms of such Project Bid (including, without limitation,
payment of any upfront fees to the non-Bidding Party), will obtain the rights set forth in clause
(vi) below with respect to the Development Project covered by such accepted Project Bid.
(iii)
If the non-Bidding Party rejects a Project Bid, the non-Bidding Party (Counterbidding
Party) will submit to the Bidding Party, concurrently with its notice of rejection, a counterbid
with terms which are more favorable, when taken as a whole, to the Bidding Party than the terms set
forth in the Project Bid, by at least the greater of (1) [***]% (as measured by industry standards)
or (2) $[***] (if the Project Bid is less than or equal to $[***]). The Bidding Party will have
[***] ([***]) Business Days to accept or reject such counterbid.
(iv)
If the Bidding Party accepts such counterbid or does not reject such counterbid and
provide a counterbid in accordance with clause (v) below (in which case the
Counterbidding Partys counterbid is deemed accepted) within such [***] ([***]) Business Day
period, the Counterbidding Party, subject to compliance with its payment obligations under the
terms of such counterbid (including, without limitation, payment of any upfront fees to the Bidding
Party), will obtain the rights set forth in clause (vi) below with respect to the Development
Project covered by such accepted counterbid.
(v)
If the Bidding Party rejects such counterbid, such Bidding Party will submit, concurrently
with its notice of rejection, its counterbid to the Counterbidding Partys counterbid, which
counterbid must be higher than the Counterbidding Partys counterbid by at least [***]% (as
measured by industry standards), and the process will repeat itself until a bid for a Development
Project is accepted;
provided, however
, that, if a Founding Investor to which a counterbid is
submitted determines in good faith that the terms of such counterbid are not more favorable to such
Founding Investor, taken as a whole, than the terms offered in such Founding Investors most-recent
prior bid, by at least [***]% (as measured by industry standards), then at any time within the
[***] ([***]) day period during which such Founding Investor may accept or reject such counterbid,
such Founding Investor (the
Contesting Party
) may notify the other Parties thereof and will have
the right to submit such matter to a reputable investment bank (
Qualified Third Party
) chosen by
mutual agreement of the Founding Investors. If the Founding Investors are unable to agree upon a
Qualified Third Party within [***] ([***]) Business Days after receipt of the Contesting Partys
notice, the Company (through a vote of its Board) will select a Qualified Third Party within [***]
([***]) Business Days after the end of such initial [***] ([***]) Business Day period and will
promptly notify the Founding Investors of the Qualified Third Party selected. The Founding
Investors will then submit the dispute to such Qualified Third Party and will instruct such
Qualified Third Party to determine whether the counterbid most-recently proposed by the
non-Contesting Party is more favorable, taken as a whole, than the terms proposed by the Contesting
Party, by at least [***]% (as measured by industry standards) and to deliver a written report to
both Founding Investors within [***] ([***]) Business Days following submission of such dispute to
such Qualified Third Party. Such Qualified Third Partys determination will be binding on the
Founding Investors. If such Qualified Third Party determines that the counterbid proposed by the
non-Contesting Party constitutes a sufficient counterbid, such counterbid will be deemed accepted
by the Contesting Party. If such Qualified Third Party determines that the counterbid proposed by
the non-Contesting Party does not constitute a sufficient counterbid, then the immediately
preceding bid or counterbid terms proposed by the Contesting Party will be deemed accepted by the
non-Contesting Party. The Founding Investor against whom the Qualified Third Party finds will bear
the costs of such Qualified Third Party.
(vi)
Each Founding Investor will grant to the other Founding Investor that purchased a
Development Project hereunder (the Buy-Out Party), subject to Third Party Rights, an exclusive (to
the fullest extent possible) sublicense under Distributed IP (which, with respect to Licensed IP
therein, is within the scope of the license granted to the Founding Investor by the Company), to
Develop, Manufacture and/or Commercialize miRNA Compounds and miRNA Therapeutics included in the
Development Project in the Field.
(vii)
Such license to such Development Project will be (1) royalty-bearing in accordance with
the terms of the accepted bid covering such Development Project, and (2) sublicenseable;
provided
that, (1) each such sublicense will be subject and subordinate to,
and consistent with, the terms and conditions of this Exhibit D, and will provide that any
such Sublicensee will not further sublicense except on terms consistent with this clause; (2) such
Founding Investor will remain responsible for the performance of its Sublicensees, and will ensure
that all such Sublicensees comply with the relevant provisions of the License Agreement and this
Exhibit D and (3) in the event of a material default by any of its Sublicensees under a sublicense
agreement, such Founding Investor will inform the Company and the other Founding Investor and will
take such action, after consultation with such other Parties, which, in such Founding Investors
reasonable business judgment, will address such default.
(viii)
Each Founding Investor will assign or exclusively license to the other Founding
Investor, to the fullest extent possible, all of its rights and obligations in assets, other than
Intellectual Property, distributed by the Company to the Founding Investors pursuant to Section
1.2(a) to the extent such assets are solely related to any of the other Founding Investors
Selected Development Projects. In the event any such assets are related to Development Programs of
both Founding Investors, each Founding Investor will assign to the other, to the fullest extent
possible, the rights to such assets as they relate to the other Founding Investors Development
Programs.
(ix)
The Parties will promptly negotiate in good faith and execute a written agreement
substantially in accordance with the terms of the accepted bid covering each such Development
Project.
(f) Company Following Buy-Out
. In the event of a Buy-Out pursuant to this Section 1.2, the
Company will not be dissolved if, in the discretion of the Board, it should continue to exist for
the purpose of maintaining Third Party Contracts and/or receiving payments from Third Parties that
may become due to the Company following the completion of the Buy-Out, making tax and other
distributions, filing tax and other required reports and conducting any activity necessary for the
purpose of dissolving the Company pursuant to Section 10 (the
Post Buy-Out Activities
). In the
event the Company is not dissolved following the completion of a Buy-Out pursuant to this Section
1.2, the Company will be prohibited from engaging in any activities other than the Post Buy-Out
Activities, and any assets acquired by the Company after the completion of the Buy-Out will be
distributed as determined by the Managing Board, unless otherwise distributable under then-existing
agreements.
(g) Diligence.
Each Founding Investor will use Commercially Reasonable Efforts to Develop and
Commercialize the miRNA Compounds and miRNA Therapeutics covered by the Research Program or
Development Project purchased by such Founding Investor under this Section 1.2, at such Founding
Investors own expense, in the Field, either by itself or with or through its Affiliates or
Sublicensees.
(h) Non-Compete.
With respect to any Research Program or Development Project, the non-Opt-In
Party or non-Buy-Out Party will not, itself or through its Affiliates or with Third Parties,
Discover, Develop, Manufacture or Commercialize the relevant Opt-In Products or Buy-Out Products
during the period (i) prior to first commercial sale of an Opt-In Product or Buy-Out Product with
respect to such Research Program or Development Project anywhere in the world, as long as the
relevant Opt-In Party or Buy-Out Party reasonably believes that the Opt-In Product or Buy-Out
Product would be a Royalty-Bearing Product upon first
commercial sale, and (ii) after first commercial sale of a Royalty-Bearing Product with
respect to such Research Program or Development Project anywhere in the world, until the expiration
of all Royalty Terms for all Royalty-Bearing Products for such Research Program or Development
Project; provided, however, that each Party will be entitled to grant Permitted Licenses.
1.3
Section 365(n)
of the Bankruptcy Code.
All rights and licenses granted under this Exhibit
D and Section 4 of this Agreement are and will otherwise be deemed to be for purposes of Section
365(n) of the United States Bankruptcy Code (Title 11, U.S. Code), as amended (the Bankruptcy
Code), licenses of rights to intellectual property as defined in Section 101(35A) of the
Bankruptcy Code. The Parties will retain and may fully exercise all of their respective rights and
elections under the Bankruptcy Code. The Parties agree that each Party, as licensee of such rights
under this Agreement, will retain and may fully exercise all of its rights and elections under the
Bankruptcy Code or any other provisions of Applicable Law outside the United States that provide
similar protection for intellectual property. The Parties further agree that, in the event of
the commencement of a bankruptcy proceeding by or against a Party under the U.S. Bankruptcy Code or
analogous provisions of applicable law outside the United States, the Party that is not subject to
such proceeding will be entitled to a complete duplicate of (or complete access to, as appropriate)
such intellectual property and all embodiments of such intellectual property, which, if not already
in the non subject Partys possession, will be promptly delivered to it upon the non subject
Partys written request thereof. Any agreements supplemental hereto will be deemed to be
agreements supplementary to this Agreement for purposes of Section 365(n) of the Bankruptcy Code.
EXHIBIT E
Financial Requirement for Equity Accounting
Once Regulus is no longer consolidated into Isis financials and is not using Isis
financial systems, then Regulus may hire its own auditors subject to the requirements
below that are necessary to ensure that Isis and Alnylam receive in a timely manner
the information each needs to record its share of Regulus income/losses.
1.
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Regulus auditors will be an independent registered public
accounting firm of recognized national standing.
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2.
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Regulus will provide Isis and Alnylam the audited annual financial
statements of Regulus no later than [***] ([***]) weeks after the end of each
fiscal year, including the related notes thereto. The financial statements
include the following:
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a.
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A balance sheet of Regulus as of the close of such
fiscal year.
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b.
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A statement of net income for such fiscal year.
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c.
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A statement of cash flows for such fiscal year.
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d.
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The related notes thereto.
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e.
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These financial statements will contain in comparative
form the figures for the previous fiscal year.
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f.
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An opinion of Regulus auditors that the above
financial statements present fairly, in all material respects, the
financial position of Regulus and its results of operations and cash
flows. Also, that the financial statements have been prepared in
conformity with GAAP and that the audit by Regulus auditors has been made
in accordance with generally accepted auditing standards and that audit
provides a reasonable basis for the auditors opinion.
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3.
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Regulus will provide Isis and Alnylam an unaudited balance sheet of
Regulus as of the end of each quarter and unaudited statements of income and cash
flows of Regulus for such quarter and for the current fiscal year to the end of
such fiscal quarter within [***] ([***]) calendar days after the end of each
fiscal quarter of Regulus, including the related notes thereto.
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a.
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The financial statements will be those outlined in
2(a) (f) above.
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b.
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These financial statements will be reviewed by
Regulus auditors, which review will be complete prior to Regulus
providing the above financial statements to Isis and Alnylam.
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c.
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These financial statements will include a certificate
signed by the CEO and CFO of Regulus stating that these financial
statements were prepared in conformity with GAAP from the books and
records of Regulus and that there were no changes in the internal control
environment of Regulus that would materially affect the integrity of these
statements.
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4.
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Regulus will provide Isis and Alnylam with an unaudited balance
sheet of Regulus as of the end of each month and unaudited statements of income
and of cash flows of Regulus for such month and for the current fiscal year to
the end of such month promptly following Regulus completion of the review of its
financial statements for such month (other than the last month of any fiscal
quarter).
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a.
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The financial statements will be those outlined in
2(a) (f) above, excluding 2(d).
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5.
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The financial statements referred to above will be accompanied by
the report thereon of the independent accountants engaged by Regulus as described
in 2(f) above. Additionally, Regulus will provide to Isis and/or Alnylam any
supplemental schedules reasonably required by either company, and Regulus will
make its management available to Isis and/or Alnylam for reasonable inquiries
regarding its financials.
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6.
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Regulus will provide Isis and Alnylam with any certificate that may
be reasonably necessary to meet Isis and Alnylams SOX 404 requirements.
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7.
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If Isis and/or Alnylams filing requirements change, all three
companies together will review the timing outlined above. If filing requirements
for either Isis or Alnylam are accelerated, Regulus agrees to provide the
information in #2 and #3 above on the timeline that Isis and/or Alnylam
reasonably determines is necessary to meet its filing requirements.
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