IONS

SEC source: 0000874015-26-000262 · edgardoc.xml · nonDerivative · entry 1

BENNETT C FRANK · CIK 0001073387 · EVP, Chief Scientific Officer

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 60,128

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2026. These shares may not be sold until February 28, 2027.

SEC source: 0000874015-26-000260 · edgardoc.xml · nonDerivative · entry 1

Monia Brett P · CIK 0001537529 · Director · Chief Executive Officer

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 242,760

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2026. These shares may not be sold until February 28, 2027.

SEC source: 0000874015-26-000261 · edgardoc.xml · nonDerivative · entry 1

O'NEIL PATRICK R. · CIK 0001564926 · EVP CLO & General Counsel

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 59,205

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2026. These shares may not be sold until February 28, 2027.

SEC source: 0000874015-26-000259 · edgardoc.xml · nonDerivative · entry 1

Birchler Brian · CIK 0001970151 · EVP, Corp and Development Ops

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 102,883

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2026. These shares may not be sold until February 28, 2027.

SEC source: 0000874015-26-000254 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · by Spouse

Disclosed balance after: 24,000

F3 · price: The price reported in Column 4 is a weighted average price. These shares were purchase in multiple transactions at prices ranging from $51.45 to $51.70 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 purchased at each separate price within the ranges set forth in footnote (3) on this Form 4.

F2 · ownership.nature: These securities are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2.

SEC source: 0000874015-26-000254 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · by Spouse

Disclosed balance after: 19,000

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchase in multiple transactions at prices ranging from $53.00 to $53.58 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 purchased at each separate price within the ranges set forth in footnote (1) on this Form 4.

F2 · ownership.nature: These securities are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2.

SEC source: 0000874015-26-000247 · edgardoc.xml · derivative · entry 1

Reikes Peter N · CIK 0001753652 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 3,399

Underlying: Common Stock · 3,399 shares

Expires not disclosed

F1 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F2 · derivative.exercise_date: Grant on July 15, 2026 to reporting person of Restricted Stock Unit Award under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors' Stock Option Plan. Restricted Stock Units vest in three equal annual installments, the first installment vesting on July 15, 2027. 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. The RSU shall be fully vested on July 15, 2029. The RSU is vested as to 0 shares on July 15, 2026.

F2 · derivative.expiration_date: Grant on July 15, 2026 to reporting person of Restricted Stock Unit Award under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors' Stock Option Plan. Restricted Stock Units vest in three equal annual installments, the first installment vesting on July 15, 2027. 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. The RSU shall be fully vested on July 15, 2029. The RSU is vested as to 0 shares on July 15, 2026.

SEC source: 0000874015-26-000246 · edgardoc.xml · derivative · entry 1

HANTSON LUDWIG · CIK 0001491435 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 3,399

Underlying: Common Stock · 3,399 shares

Expires not disclosed

F1 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F2 · derivative.exercise_date: Grant on July 15, 2026 to reporting person of Restricted Stock Unit Award under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors' Stock Option Plan. Restricted Stock Units vest in three equal annual installments, the first installment vesting on July 15, 2027. 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. The RSU shall be fully vested on July 15, 2029. The RSU is vested as to 0 shares on July 15, 2026.

F2 · derivative.expiration_date: Grant on July 15, 2026 to reporting person of Restricted Stock Unit Award under the Ionis Pharmaceuticals, Inc. Amended and Restated 2002 Non-Employee Directors' Stock Option Plan. Restricted Stock Units vest in three equal annual installments, the first installment vesting on July 15, 2027. 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. The RSU shall be fully vested on July 15, 2029. The RSU is vested as to 0 shares on July 15, 2026.

SEC source: 0000874015-26-000245 · edgardoc.xml · derivative · entry 2

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 2,301

Underlying: Common Stock · 5,220 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F3 · derivative.exercise_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F3 · derivative.expiration_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-26-000245 · edgardoc.xml · nonDerivative · entry 1

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 51,306

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-26-000244 · edgardoc.xml · derivative · entry 3

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 2,301

Underlying: Common Stock · 5,220 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F4 · derivative.exercise_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F4 · derivative.expiration_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-26-000244 · edgardoc.xml · nonDerivative · entry 1

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 161,233

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-26-000239 · edgardoc.xml · derivative · entry 4

BENNETT C FRANK · CIK 0001073387 · EVP, Chief Scientific Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 12,109

Underlying: Common Stock · 15,000 shares

Expires not disclosed

F5 · derivative.exercise_date: Restricted Stock Unit vested on January 15, 2026. Upon vesting, the restricted stock unit was paid out in whole shares of Ionis common stock.

F5 · derivative.expiration_date: Restricted Stock Unit vested on January 15, 2026. Upon vesting, the restricted stock unit was paid out in whole shares of Ionis common stock.

SEC source: 0000874015-26-000239 · edgardoc.xml · nonDerivative · entry 3

BENNETT C FRANK · CIK 0001073387 · EVP, Chief Scientific Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Trust

Disclosed balance after: 0

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 31, 2026.

F4 · price: 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.

SEC source: 0000874015-26-000239 · edgardoc.xml · nonDerivative · entry 2

BENNETT C FRANK · CIK 0001073387 · EVP, Chief Scientific Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Trust

Disclosed balance after: 15,000

F3 · shares: 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.

SEC source: 0000874015-26-000239 · edgardoc.xml · nonDerivative · entry 1

BENNETT C FRANK · CIK 0001073387 · EVP, Chief Scientific Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 75,018

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 31, 2026.

F2 · price: 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.

SEC source: 0000874015-26-000236 · edgardoc.xml · nonDerivative · entry 1

Kordasiewicz Holly B. · CIK 0002102721 · EVP, Chief Development Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 22,096

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 13, 2026

SEC source: 0000874015-26-000237 · edgardoc.xml · derivative · entry 3

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 10,111 shares

Expires 2034-06-30

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000237 · edgardoc.xml · nonDerivative · entry 2

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 3,811

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

F2 · price: 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.

SEC source: 0000874015-26-000237 · edgardoc.xml · nonDerivative · entry 1

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 13,922

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000232 · edgardoc.xml · derivative · entry 2

YANG MICHAEL J. · CIK 0001702283 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 9,451

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000232 · edgardoc.xml · derivative · entry 1

YANG MICHAEL J. · CIK 0001702283 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000231 · edgardoc.xml · derivative · entry 2

LOSCALZO JOSEPH · CIK 0001276128 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 7,521

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000231 · edgardoc.xml · derivative · entry 1

LOSCALZO JOSEPH · CIK 0001276128 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000230 · edgardoc.xml · derivative · entry 2

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 7,521

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000230 · edgardoc.xml · derivative · entry 1

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000229 · edgardoc.xml · derivative · entry 7

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 16,277

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F6 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F4 · shares: 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.

F7 · derivative.exercise_date: 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.

F7 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000229 · edgardoc.xml · derivative · entry 6

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F4 · shares: 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.

F5 · derivative.exercise_date: 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.

F5 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000229 · edgardoc.xml · derivative · entry 5

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 11,518 shares

Expires 2035-06-30

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000229 · edgardoc.xml · nonDerivative · entry 3

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 11,014

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

F2 · price: 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.

SEC source: 0000874015-26-000229 · edgardoc.xml · nonDerivative · entry 2

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 22,433

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.

SEC source: 0000874015-26-000229 · edgardoc.xml · nonDerivative · entry 1

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 22,532

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000228 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 12,198

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000228 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000227 · edgardoc.xml · derivative · entry 2

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 7,521

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000227 · edgardoc.xml · derivative · entry 1

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000226 · edgardoc.xml · derivative · entry 2

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 7,521

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000226 · edgardoc.xml · derivative · entry 1

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000212 · edgardoc.xml · derivative · entry 9

Monia Brett P · CIK 0001537529 · Director · Chief Executive Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 99,872

Underlying: Common Stock · 50,000 shares

Expires 2028-01-03

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000212 · edgardoc.xml · nonDerivative · entry 6

Monia Brett P · CIK 0001537529 · Director · Chief Executive Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 245,571

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025

F4 · price: 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.

SEC source: 0000874015-26-000212 · edgardoc.xml · nonDerivative · entry 5

Monia Brett P · CIK 0001537529 · Director · Chief Executive Officer

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 295,571

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000217 · edgardoc.xml · nonDerivative · entry 1

O'NEIL PATRICK R. · CIK 0001564926 · EVP CLO & General Counsel

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 61,470

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025.

SEC source: 0000874015-26-000218 · edgardoc.xml · derivative · entry 6

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Spouse

Disclosed balance after: 0

Underlying: Common Stock · 3,866 shares

Expires 2028-01-03

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000218 · edgardoc.xml · derivative · entry 5

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Spouse

Disclosed balance after: 0

Underlying: Common Stock · 1,769 shares

Expires 2032-01-02

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000218 · edgardoc.xml · nonDerivative · entry 3

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Spouse

Disclosed balance after: 4,669

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting persons spouse on November 25, 2025.

F2 · price: 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.

SEC source: 0000874015-26-000218 · edgardoc.xml · nonDerivative · entry 2

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Spouse

Disclosed balance after: 10,304

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000218 · edgardoc.xml · nonDerivative · entry 1

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Plan reported

Ownership: Indirect · by Spouse

Disclosed balance after: 8,535

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000216 · edgardoc.xml · derivative · entry 3

Schneider Eugene · CIK 0001838539 · EVP, Chf Clinical Develop Ofcr

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 26,000

Underlying: Common Stock · 26,000 shares

Expires 2027-01-01

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

SEC source: 0000874015-26-000216 · edgardoc.xml · nonDerivative · entry 2

Schneider Eugene · CIK 0001838539 · EVP, Chf Clinical Develop Ofcr

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 77,114

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 19, 2025.

F2 · price: 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.

SEC source: 0000874015-26-000216 · edgardoc.xml · nonDerivative · entry 1

Schneider Eugene · CIK 0001838539 · EVP, Chf Clinical Develop Ofcr

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 103,114

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.