X0306 4 2018-03-15 0000874015 IONIS PHARMACEUTICALS INC IONS 0001206369 KLEIN JOSEPH III C/O IONIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD CA 92010 1 0 0 0 Common Stock 2018-03-15 2018-03-15 4 M 0 900 24.42 A 10839 D Common Stock 2018-03-15 2018-03-15 4 S 0 900 50.45 D 9939 D Common Stock 2018-03-15 2018-03-15 4 M 0 900 24.42 A 10839 D Common Stock 2018-03-15 2018-03-15 4 S 0 900 51.59 D 9939 D Common Stock 2018-03-15 2018-03-15 4 M 0 200 24.42 A 10139 D Common Stock 2018-03-15 2018-03-15 4 S 0 200 52.11 D 9939 D Common Stock 100 I By son Employee Stock Option (right to buy) 24.42 2018-03-15 2018-03-15 4 M 0 2000 0 A 2020-07-01 2026-06-30 Common Stock 2000 2000 D Acquired as a result of exercising a stock option pursuant to Rule 10b5-1 Trading Plan. The purchase and sale reported on this Form 4 was effective pursuant to Rule 10b5-1 Trading Plan adopted by the reporting person on 10/11/2017. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $49.97 to $50.95, 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) on this Form 4. 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 $51.85, 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) on this Form 4. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $52.03 to $52.18, 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 (4) on this Form 4. /s/Patrick R. O'Neil, attorney-in-fact 2018-03-15