X0306 4 2020-12-15 0000874015 IONIS PHARMACEUTICALS INC IONS 0000897667 CROOKE STANLEY T C/O IONIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD, CA 92010 1 1 0 0 Exec Chairman of the Board Common Stock 2020-12-15 2020-12-15 4 S 0 39000 49.775 D 600391 I by trust Common Stock 2020-12-17 2020-12-17 4 S 0 1407 50.5 D 174 I by wife Common Stock 2021 D Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on January 2, 2020. The price reported in column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $49.50 to $50.00, 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 (2) of this Form 4. Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person's wife on January 2, 2020. /s/Patrick R. O'Neil, attorney-in-fact 2020-12-17