Neither FMR LLC nor Edward C. Johnson 3d nor Abigail P. Johnson has the sole power to vote or direct the voting of the shares
owned directly by the various investment companies registered under the Investment CompanyAct (‘‘Fidelity Funds’’) advised by
FidelityManagement &Research Company (‘‘FMRCo’’), a wholly owned subsidiary of FMR LLC, which power resides with the
Fidelity Funds’ Boards of Trustees. FidelityManagement &Research Company carries out the voting of the shares under written
guidelines established by the Fidelity Funds’ Boards of Trustees.
(4) Various persons at BlackRock, Inc. have the right to receive or the power to direct the receipt of dividends from, or the proceeds from
the sale of shares of our common stock.
(5) ClearBridgeAdvisors, LLC, is an investment adviser registered under the Investment Advisers Act
.
ClearBridgeAdvisors has sole
voting power to direct the vote of 8,778,431 shares and sole power to dispose or direct the disposition of 9,034,520 shares.
(6) The Vanguard Group has sole voting power to direct the vote of 158,221 shares, sole power to dispose or direct the disposition of
7,124,050 shares, and shared dispositive power for 147,821 shares. Vanguard Fiduciary Trust Company , a wholly-owned subsidiary of
The Vanguard Group, Inc., is the beneficial owner of 147,821 shares or 0.12%of the Common Stock outstanding of Isis as a result of
its serving as investment manager of collective trust accounts. Vanguard Investments Australia, Ltd., a wholly-owned subsidiary of The
Vanguard Group, Inc., is the beneficial owner of 10,400 shares of Isis’ Common Stock outstanding as a result of its serving as
investment manager of Australian investment offerings.
(7) BBBiotechAG shares voting and dispositive powers with its wholly owned subsidiary, Biotech Target N.V.
(8) Includes 70 shares owned by Dr. Berthelsen’s daughter for which he disclaims beneficial ownership. Includes 99,689 shares of common
stock issuable upon exercise of options held by Dr. Berthelsen that are exercisable on or beforeApril 19, 2015.
(9) Includes 8,438 shares of common stock issuable upon exercise of options held byMr. Castleman that are exercisable on or before
April 19, 2015.
(10) Includes shares of common stock held by Dr. Crooke and 411,868 shares of common stock issuable upon exercise of options held by
Dr. Crooke that are exercisable on or beforeApril 19, 2015. Also includes 1,297 shares of common stock and 44,896 shares of
common stock issuable upon exercise of options held by Rosanne Crooke, Dr. Crooke’s wife, which are exercisable on or before
April 19, 2015. Dr. Crooke disclaims beneficial ownership of the shares of common stock owned and issuable upon exercise of options
held by his wife.
(11) Includes 100 shares of common stock beneficially owned byMr. Klein’s son and 13,126 shares of common stock issuable upon
exercise of options held byMr. Klein that are exercisable on or beforeApril 19, 2015.
(12) Includes 5,625 shares of common stock issuable upon exercise of options held byMr. Loscalzo that are exercisable on or before
April 19, 2015.
(13) Includes 1,500 shares of common stock beneficially owned through the Cooley LLP Salary Deferral and Profit Sharing Plan and 99,689
shares of common stock issuable upon exercise of options held byMr. Muto that are exercisable on or beforeApril 19, 2015.
(14) Includes 64,988 shares of common stock issuable upon exercise of options held byMs. Parshall that are exercisable on or before
April 19, 2015.
(15) Includes 74,689 shares of common stock issuable upon exercise of options held byMr. Wender that are exercisable on or before
April 19, 2015.
(16) Includes 52,312 shares of common stock issuable upon exercise of options held by Dr. Monia that are exercisable on or before
April 19, 2015.
(17) Includes 41,931 shares of common stock issuable upon exercise of options held by Dr. Geary that are exercisable on or beforeApril 19,
2015.
(18) Includes 100,998 shares of common stock issuable upon exercise of options held byMs. Hougen that are exercisable on or before
April 19, 2015.
(19) Includes an aggregate of 1,194,610 shares issuable upon exercise of options held by all current Directors and executive officers as a
group that are exercisable on or beforeApril 19, 2015.
Securities Authorized for Issuance Under Equity Compensation Plans
The following table sets forth information regarding outstanding options and shares reserved for future
issuance under our equity compensation plans as of December 31, 2014.
Plan Category
Number of Shares
to be Issued
Upon Exercise of
Outstanding Options
WeightedAverage
Exercise Price of
Outstanding
Options
Number of Shares
Remaining
Available for
Future Issuance
Equity compensation plans approved by stockholders(a) . .
7,122,771
$$19.69
3,208,151(c)
Equity compensation plans not approved by
stockholders(b). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
256,176
$ 14.75
—
Total . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7,378,947
$ 19.52
3,208,151
(a) Consists of four Isis plans: 1989 Stock Option Plan, Amended and Restated 2002 Non-Employee Directors’ Stock Option Plan, 2011
Equity Incentive Plan and Employee Stock Purchase Plan, or ESPP.
(b) Consists of the 2000 Broad-Based Equity Incentive Plan, more fully described below. The 2000 Broad-Based Equity Incentive Plan
expired on January 5, 2010.
(c) Of these shares, 370,136 remained available for purchase under the ESPP as of December 31, 2014. The ESPP incorporates an
evergreen formula pursuant to which on January 1 of each year, we automatically increase the aggregate number of shares reserved for
issuance under the plan by 150,000 shares.
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