IONS

Represents a transfer of 15,000 shares of common stock from direct ownership to indirect ownership held by the Clarence Frank Bennett TTEE Bennett Living Trust Dated 3/12/2008, of which the reporting person is the co-trustee with spouse.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 31, 2026.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $85.015 to $85.730 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $85.040 to $85.730 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 13, 2026

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 31, 2026.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $83.070 to $84.065 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.

Restricted Stock Unit vested on January 15, 2026. Upon vesting, the restricted stock unit was paid out in whole shares of Ionis common stock.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant of Restricted Stock Unit award on July 1, 2026 to the reporting person under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier; however, the reporting person has elected to defer delivery of such shares until the earlier to occur of the 30th day following the reporting person's Separation from Service from the Company or the date of a Change in Control of the Company, both as defined in Treasury Regulation Section 1.409A. These Restricted Stock Units are vested as to 0 shares on July 1, 2026.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant of Restricted Stock Unit award on July 1, 2026 to the reporting person under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier; however, the reporting person has elected to defer delivery of such shares until the earlier to occur of the 30th day following the reporting person's Separation from Service from the Company or the date of a Change in Control of the Company, both as defined in Treasury Regulation Section 1.409A. These Restricted Stock Units are vested as to 0 shares on July 1, 2026.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $78.39 to $79.38 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.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant of Restricted Stock Unit award on July 1, 2026 to the reporting person under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier; however, the reporting person has elected to defer delivery of such shares until the earlier to occur of the fifth anniversary of the vesting date, the 30th day following the reporting person's Separation from Service from the Company or the date of a Change in Control of the Company, both as defined in Treasury Regulation Section 1.409A. These Restricted Stock Units are vested as to 0 shares on July 1, 2026.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2026.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2026.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2026.

Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant on July 1, 2026 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2026.

Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

Grant of Restricted Stock Unit award on July 1, 2026 to the reporting person under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier; however, the reporting person has elected to defer delivery of such shares until the earlier to occur of the fifth anniversary of the vesting date, the 30th day following the reporting person's Separation from Service from the Company or the date of a Change in Control of the Company, both as defined in Treasury Regulation Section 1.409A. These Restricted Stock Units are vested as to 0 shares on July 1, 2026.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $80 to $81 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 19, 2025.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $81.00 to $81.34 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting persons spouse on November 25, 2025.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $80.00 to $80.52 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 6, 2026.

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $79.00 to $79.46 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $78.005 to $78.78 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $78.00 to $78.87 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on September 12, 2025.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 13, 2026

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $72.68 to $73.67 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.

Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 13, 2026

The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $73.735 to $74.28 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.