X0306 4 2018-09-23 0000874015 IONIS PHARMACEUTICALS INC IONS 0001753652 Reikes Peter N C/O IONIS PHARMACEUTICALS, INC. 2855 GAZELLE COURT CARLSBAD CA 92010 1 0 0 0 Director Stock Option (right to buy) 49.14 2018-09-23 2018-09-23 4 A 0 32000 0 A 2019-09-23 2028-09-22 Common Stock 32000 32000 D Grant of September 23, 2018 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. The option vests and becomes exercisable in four equal annual installments, the first installment vesting on September 23, 2019. The option shall be fully vested and exercisable on September 23, 2022. The option is exercisable to 0 shares on September 23, 2018. /s/Patrick R. O'Neil, attorney-in-fact 2018-09-24