X0306 4 2020-12-02 0000874015 IONIS PHARMACEUTICALS INC IONS 0001537529 Monia Brett P C/O IONIS PHARMACEUTICALS, INC. 2855 GAZELLE CT. CARLSBAD, CA 92010 1 1 0 0 Chief Executive Officer Common Stock 2020-12-02 2020-12-02 4 M 0 21160.0 39.87 A 50039.0 D Common Stock 2020-12-02 2020-12-02 4 S 0 21160.0 51.32 D 28879.0 D Employee Stock Option (right to buy) 39.87 2020-12-02 2020-12-02 4 M 0 21160.0 0.0 D 2015-01-02 2021-01-01 Common Stock 0.0 23840.0 D Acquired as a result of exercising a stock option that was scheduled to expire on 1/1/21. The purchase reported on this Form 4 was effected pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on April 3, 2019. Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on April 3, 2019. The price reported in column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $51.00 to $51.70, inclusive. The reporting person undertakes to provide to Ionis Pharmaceuticals, Inc., any security holder of Ionis Pharmaceuticals, Inc. or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnote (3) of this Form 4. /s/Patrick R. O'Neil, attorney-in-fact 2020-12-04