O'NEIL PATRICK R.

SEC source: 0000874015-25-000091 · 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: 56,245

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on February 21, 2024.

SEC source: 0000874015-25-000085 · 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: 57,452

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on February 21, 2024.

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $31.56 to $31.715 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: 0000874015-25-000079 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 63,617

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $32.20 to $32.84 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: 0000874015-25-000079 · 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: 65,023

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: 0000874015-25-000063 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 61,203

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 $32.82 to $32.883 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: 0000874015-25-000063 · edgardoc.xml · derivative · entry 5

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 60,724

Underlying: Common Stock · 19,690 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: 0000874015-25-000063 · edgardoc.xml · derivative · entry 4

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 80,414

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: 0000874015-25-000063 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 64,801

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: 0000874015-25-000063 · 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: 68,563

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: 0000874015-25-000029 · edgardoc.xml · derivative · entry 1

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

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: 0000874015-24-000219 · 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: 48,873

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: 0000874015-24-000108 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 48,661

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 Performance 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 $49.60 to $49.80 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: 0000874015-24-000198 · primary_doc.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: 48,627

F1 · shares: The original Form 4 filed on February 2, 2024 reported 1,961 restricted stock units sold by the reporting person which has been revised by this amendment to reflect the actual amount of shares sold and beneficially owned by Mr. O'Neil.

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $49.60 to $49.80 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.

F1 · balance_after: The original Form 4 filed on February 2, 2024 reported 1,961 restricted stock units sold by the reporting person which has been revised by this amendment to reflect the actual amount of shares sold and beneficially owned by Mr. O'Neil.

SEC source: 0000874015-24-000108 · 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: 50,622

F1 · shares: Represents shares earned upon the vesting of performance-based restricted stock units ("PRSUs") for the second 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: 0000874015-24-000084 · 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: 46,802

SEC source: 0000874015-24-000080 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 53,252

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 $50.35 to $50.43, 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) of this Form 4.

SEC source: 0000874015-24-000080 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 47,414

Underlying: Common Stock · 20,641 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.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · 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.

F5 · 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: 0000874015-24-000080 · 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: 60,996

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: 0000874015-24-000056 · edgardoc.xml · derivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 68,055

Underlying: Common Stock · 20,400 shares

Expires not disclosed

F3 · security: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · 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.

F5 · 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: 0000874015-24-000056 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 42,801

Underlying: Common Stock · 17,000 shares

Expires not disclosed

F1 · security: Grant to reporting person of Performance Restricted Stock Units (PRSUs) under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F2 · 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.

F2 · 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: 0000874015-24-000024 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 27,200

Underlying: Common Stock · 27,200 shares

Expires 2034-01-01

F1 · derivative.exercise_date: Grant on 01/02/2024 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 01/02/2024. 25% of the shares subject to the option will vest and become exercisable on 01/02/2025. 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: 0000874015-23-000242 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 20,825 shares

Expires 2024-01-02

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: 0000874015-23-000242 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 40,355

F1 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $51.30 to $51.60 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 (1) on this Form 4.

SEC source: 0000874015-23-000242 · 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: 61,180

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: 0000874015-23-000140 · 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: 40,355

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 16, 2022.

SEC source: 0000874015-23-000114 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,882

F1 · kind: Reporting shares purchased under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 28, 2023. These shares may not be sold until August 28, 2023.

SEC source: 0000874015-23-000094 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,581

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.75 to $40.97 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: 0000874015-23-000094 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 43,501

F1 · shares: Represents shares earned upon the vesting of performance-based restricted stock units ("PRSUs") for the first 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: 0000874015-23-000072 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 39,679

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 16, 2022.

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $39.60 to $39.80 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: 0000874015-23-000072 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 44,179

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 16, 2022.

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $39.30 to $39.60 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: 0000874015-23-000067 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 48,679

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 $39.44163 to $39.54855 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: 0000874015-23-000067 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 47,655

Underlying: Common Stock · 21,871 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.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · 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.

F5 · 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: 0000874015-23-000067 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 56,515

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: 0000874015-23-000048 · edgardoc.xml · derivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 69,526

Underlying: Common Stock · 17,207 shares

Expires not disclosed

F3 · security: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · 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.

F5 · 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: 0000874015-23-000048 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,801

Underlying: Common Stock · 14,338 shares

Expires not disclosed

F1 · security: Grant to reporting person of Performance Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F2 · derivative.exercise_date: Represents an award of performance based restricted stock units ("PRSUs"). 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.

F2 · derivative.expiration_date: Represents an award of performance based restricted stock units ("PRSUs"). 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: 0000874015-23-000016 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,942

Underlying: Common Stock · 22,942 shares

Expires 2033-01-02

F1 · derivative.exercise_date: Grant on 01/03/2023 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 01/03/2023. 25% of the shares subject to the option will vest and become exercisable on 01/03/2024. 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: 0000874015-22-000155 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 34,644

F1 · kind: Reporting shares acquired under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2022. These shares may not be sold until February 28, 2023.

SEC source: 0000874015-22-000095 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 34,536

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on January 6, 2020.

F2 · price: The price reported in column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $39.75 to $40.25, 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) of this Form 4.

SEC source: 0000874015-22-000090 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 41,328

F1 · kind: Reporting shares acquired under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 28, 2022. These shares may not be sold until August 28, 2022.

SEC source: 0000874015-22-000055 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 52,319

Underlying: Common Stock · 21,086 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 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 Ionis.

F4 · 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 Ionis.

SEC source: 0000874015-22-000055 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 40,593

F2 · kind: Shares withheld to cover the required tax withholding obligations pursuant to the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F2 · shares: Shares withheld to cover the required tax withholding obligations pursuant to the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

SEC source: 0000874015-22-000055 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 48,094

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: 0000874015-22-000038 · edgardoc.xml · derivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 73,405

Underlying: Common Stock · 15,284 shares

Expires not disclosed

F3 · security: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · 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 Ionis.

F5 · 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 Ionis.

SEC source: 0000874015-22-000038 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 11,463

Underlying: Common Stock · 11,463 shares

Expires not disclosed

F1 · security: Grant to reporting person of Performance Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F2 · shares: Represents an award of performance based restricted stock units ("PRSUs"). One-third of the PRSUs may vest at the end of three separate performance periods spread over the three years 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 150% 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 each performance period may be anywhere from zero to the amount stated.

F2 · derivative.exercise_date: Represents an award of performance based restricted stock units ("PRSUs"). One-third of the PRSUs may vest at the end of three separate performance periods spread over the three years 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 150% 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 each performance period may be anywhere from zero to the amount stated.

F2 · derivative.expiration_date: Represents an award of performance based restricted stock units ("PRSUs"). One-third of the PRSUs may vest at the end of three separate performance periods spread over the three years 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 150% 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 each performance period may be anywhere from zero to the amount stated.

SEC source: 0000874015-22-000014 · edgardoc.xml · derivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,567

Underlying: Common Stock · 30,567 shares

Expires 2032-01-02

F1 · derivative.exercise_date: Grant on 01/03/2022 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 01/03/2022. 25% of the shares subject to the option will vest and become exercisable on 01/03/2023. 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: 0000874015-21-000156 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,008

F1 · kind: Reporting shares acquired under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on August 31, 2021. These shares may not be sold until February 28, 2022.

SEC source: 0000874015-21-000068 · edgar.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 26,699

F1 · kind: Reporting 197 shares acquired under the Ionis Pharmaceuticals, Inc. Amended and Restated 2000 Employee Stock Purchase Plan on February 26, 2021. These 197 shares may not be sold until August 26, 2021.

SEC source: 0000874015-21-000049 · edgar.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 26,502

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on January 6, 2020.

SEC source: 0000874015-21-000033 · edgar.xml · derivative · entry 4

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 32,253

Underlying: Common Stock · 16,504 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.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · derivative.exercise_date: Restricted Stock Units vest in four equal monthly 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 Ionis.

F5 · derivative.expiration_date: Restricted Stock Units vest in four equal monthly 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 Ionis.

SEC source: 0000874015-21-000033 · edgar.xml · derivative · entry 3

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 25,868

Underlying: Common Stock · 25,868 shares

Expires not disclosed

F3 · derivative.exercise_price: Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.

F4 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · derivative.exercise_date: Restricted Stock Units vest in four equal monthly 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 Ionis.

F5 · derivative.expiration_date: Restricted Stock Units vest in four equal monthly 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 Ionis.