Agreement#: AG-488381
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Proposed Stock Option Exchange Plan

Effective Date: December 31, 2008
Parties:

Isis Pharmaceuticals

Sectors: Biotechnology / Pharmaceuticals
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Exhibit 99.(a)(1)(G)


Proposed Stock Option Exchange Plan
? Purpose

? To continue to provide incentives to employees who are remaining at Isis with high exercise price options

? To enhance employee retention through more attractive options and extended vesting

1


Proposed Stock Option Exchange Plan

Plan: Allow existing employees to exchange outstanding options for new options as follows: Option Exercise Price
Exchange Ratio (new for old) Greater than or equal to $5 but less than $10 1:1.5 Greater than or equal to $10 but less than $15 1:2 Greater than or equal to $15 but less than $20 1:2.5 Greater than or equal to $20 1:3

2


Proposed Stock Option Exchange Plan ? New option will have following characteristics

? Approximately a 5-year term (expire December 31, 2008)

? New vesting over 3 years (33.34% vest on January 1, 2004, then 2.78% vest monthly thereafter for 2 years)

? Vesting accelerates in an acquisition

? Exercise price is the greater of:

? $5.00; or

? The Fair Market Value on the last day of the offering
? Available for all options granted prior to January 5, 2002

? New options will be non-qualified stock options not ISOs
? Board of Director members are not eligible to participate

3


Proposed Stock Option Exchange Plan

Effects of Option Exchange ? Old Option

? 3,000 shares

? $7 exercise price

? Fully vested

? 6-year term remaining ? New Option

? 2,000 shares

? $5.00 exercise price

? New 3-year vesting

? 5-year term remaining
Isis stock price
12/31/2006
Value old option
Value new option
$ 8 $ 3,000 $ 6, ...

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