X0508 4 2025-10-15 0 0000874015 IONIS PHARMACEUTICALS INC IONS 0002037721 Devers Shannon L. 2855 GAZELLE COURT CARLSBAD CA 92010 0 1 0 0 EVP, Chief Human Resources Ofc 1 Common Stock 2025-10-15 4 M 0 6000 48.51 A 21937 D Common Stock 2025-10-15 4 S 0 6000 72.9423 D 15937 D Common Stock 2025-10-15 4 M 0 2820 0.0 A 18757 D Common Stock 2025-10-16 4 S 0 1263 73.6213 D 17494 D Non-Qualified Stock Option (right to buy) 48.51 2025-10-15 4 M 0 6000 0.0 D 2021-04-05 2027-04-04 Common Stock 6000 0 D Restricted Stock Unit 0.0 2025-10-15 4 M 0 2820 0.0 D 2025-10-15 Common Stock 2820 60406 D Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on September 3, 2024. The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $72.775 to $73.04 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. Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award. The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice. Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value. Restricted Stock Units vest in four equal annual installments. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. By: Patrick R. O'Neil, attorney-in-fact For: Shannon L. Devers 2025-10-16