BENNETT C FRANK

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: 0000874015-26-000239 · 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: 0000874015-26-000134 · edgardoc.xml · derivative · entry 7

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 48,626 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: 0000874015-26-000134 · edgardoc.xml · derivative · entry 6

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 2,406

Underlying: Common Stock · 16,463 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: 0000874015-26-000134 · edgardoc.xml · nonDerivative · entry 5

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 80,554

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 19, 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 $80.61 to $81.07 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: 0000874015-26-000134 · edgardoc.xml · nonDerivative · entry 4

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 81,356

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

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $79.605 to $80.555 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: 0000874015-26-000134 · edgardoc.xml · nonDerivative · entry 3

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 94,043

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 $78.60 to $79.60 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: 0000874015-26-000134 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 165,643

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: 0000874015-26-000134 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 117,017

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: 0000874015-26-000121 · 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: 100,554

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 27, 2026. These shares may not be sold until August 27, 2026.

SEC source: 0000874015-26-000104 · edgardoc.xml · derivative · entry 7

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 48,626 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: 0000874015-26-000104 · edgardoc.xml · derivative · entry 6

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 2,406

Underlying: Common Stock · 16,463 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: 0000874015-26-000104 · edgardoc.xml · nonDerivative · entry 5

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 80,293

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $82.775 to $83.34 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 (3) on this Form 4.

SEC source: 0000874015-26-000104 · edgardoc.xml · nonDerivative · entry 4

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 96,756

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: 0000874015-26-000104 · edgardoc.xml · nonDerivative · entry 3

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 80,293

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $82.775 to $83.34 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 (3) on this Form 4.

SEC source: 0000874015-26-000104 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 128,919

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: 0000874015-26-000104 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 80,293

F1 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $81.92 to $82.775 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: 0000874015-26-000112 · 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: 100,293

F1 · shares: On February 4, 2026, the reporting person filed a Form 4 reporting the sale of 20,000 shares of common stock and the exercise of 65,089 stock options, which transactions were executed in error and subsequently reversed on February 12, 2026. Shares beneficially owned by the reporting person as of February 12, 2026 is 100,293.

SEC source: 0000874015-26-000096 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 100,293

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $82.94 to $82.95 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.

SEC source: 0000874015-26-000096 · 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: 106,178

F1 · shares: Represents shares earned upon the vesting of performance-based restricted stock units ("PRSUs") for the performance period of the grant to the reporting person reported on January 18, 2023. The Compensation Committee certified achievement of the pre-established performance goal based on the Issuer's relative total shareholder return as compared to a peer group of companies at a level resulting in a vest of 167.27% of target shares. As reported at grant, the PRSUs could result in a payout of 0% to 200% based on actual achievement of the goal.

SEC source: 0000874015-26-000062 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 94,757

F2 · kind: 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.

F2 · shares: 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.

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $75.14 to $75.18 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 (3) on this Form 4.

SEC source: 0000874015-26-000062 · edgardoc.xml · derivative · entry 5

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 27,109

Underlying: Common Stock · 9,675 shares

Expires not disclosed

F8 · security: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

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.

F7 · derivative.exercise_date: 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.

F7 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000062 · edgardoc.xml · derivative · entry 4

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 17,434

Underlying: Common Stock · 21,055 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.

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.

F7 · derivative.exercise_date: 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.

F7 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000062 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 89,282

Underlying: Common Stock · 25,800 shares

Expires not disclosed

F4 · security: Grant to reporting person of Performance Restricted Stock Units (PRSUs) under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F5 · derivative.exercise_date: The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated.

F5 · derivative.expiration_date: The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated.

SEC source: 0000874015-26-000062 · 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: 103,734

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 Restricted Stock Unit awards.

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

SEC source: 0000874015-26-000017 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 19,350

Underlying: Common Stock · 19,350 shares

Expires 2036-01-01

F1 · derivative.exercise_date: Grant on 01/02/2026 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. Following this transaction, the option was exercisable as to 0 shares on 01/02/2026. 25% of the shares subject to the option will vest and become exercisable on 01/02/2027. Thereafter, the remaining shares subject to the option will vest and become exercisable in 36 equal monthly installments over the next 3 years.

SEC source: 0000874015-25-000227 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 82,679

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on May 13, 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 $59.25 to $59.86 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: 0000874015-25-000213 · edgardoc.xml · derivative · entry 5

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 46,800 shares

Expires 2026-01-01

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: 0000874015-25-000213 · edgardoc.xml · nonDerivative · entry 4

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 88,679

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 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on May 13, 2025.

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $61.26 to $61.995 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 (e) on this Form 4.

SEC source: 0000874015-25-000213 · edgardoc.xml · nonDerivative · entry 3

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 101,570

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on May 13, 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 $60.25 to $61.24 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: 0000874015-25-000213 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 135,479

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: 0000874015-25-000213 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 88,679

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on May 13, 2025.

SEC source: 0000874015-25-000189 · 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: 93,679

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 29, 2025. These shares may not be sold until March 2, 2026.

SEC source: 0000874015-25-000178 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 18,869

Underlying: Common Stock · 10,000 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: 0000874015-25-000178 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 93,466

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on May 13, 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 $43.75 to $44.25 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: 0000874015-25-000178 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 103,466

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: 0000874015-25-000098 · 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: 93,466

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 28,2025. These shares may not be sold until August 28, 2025.

SEC source: 0000874015-25-000075 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 93,146

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $32.21 to $32.86 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: 0000874015-25-000075 · 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: 94,473

F1 · shares: Represents shares earned upon the vesting of performance-based restricted stock units ("PRSUs") for the final performance period of the grant to the reporting person reported on January 19, 2022. The Compensation Committee certified achievement of the pre-established performance goal based on the Issuer's relative total shareholder return as compared to a peer group of companies at a level resulting in a vest of 150% of target shares. As reported at grant, the PRSUs could result in a payout of 0% to 150% based on actual achievement of the goal.

SEC source: 0000874015-25-000056 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 90,866

F2 · kind: 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.

F2 · shares: 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.

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $32.88 to $32.92 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: 0000874015-25-000056 · edgardoc.xml · derivative · entry 5

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 38,489

Underlying: Common Stock · 18,011 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.

F7 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F8 · derivative.exercise_date: 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.

F8 · derivative.expiration_date: 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.

SEC source: 0000874015-25-000056 · edgardoc.xml · derivative · entry 4

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 56,500

Underlying: Common Stock · 33,000 shares

Expires not disclosed

F6 · security: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F7 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F8 · derivative.exercise_date: 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.

F8 · derivative.expiration_date: 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.

SEC source: 0000874015-25-000056 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 63,482

Underlying: Common Stock · 22,000 shares

Expires not disclosed

F4 · security: Grant to reporting person of Performance Restricted Stock Units (PRSUs) under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F5 · derivative.exercise_date: The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated.

F5 · derivative.expiration_date: The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated.

SEC source: 0000874015-25-000056 · 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: 97,618

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 Restricted Stock Unit awards.

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

SEC source: 0000874015-25-000016 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 22,000

Underlying: Common Stock · 22,000 shares

Expires 2035-01-01

F1 · derivative.exercise_date: Grant on 01/02/2025 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. Following this transaction, the option was exercisable as to 0 shares on 01/02/2025. 25% of the shares subject to the option will vest and become exercisable on 01/02/2026. Thereafter, the remaining shares subject to the option will vest and become exercisable in 36 equal monthly installments over the next 3 years.

SEC source: 0000874015-24-000215 · 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: 79,607

F1 · shares: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 30, 2024. These shares may not be sold until February 28, 2025.

SEC source: 0000874015-24-000122 · edgardoc.xml · nonDerivative · entry 1

BENNETT C FRANK · CIK 0001073387 · Officer Level 14

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 79,462

F1 · kind: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 29, 2024. These shares may not be sold until August 31, 2024.