IONS

SEC source: 0000874015-23-000142 · edgardoc.xml · nonDerivative · entry 1

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 30,220

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: 0000874015-23-000140 · 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: 0000874015-23-000139 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 140,374

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

SEC source: 0000874015-23-000139 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Plan reported

Ownership: Direct

Disclosed balance after: 143,004

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

SEC source: 0000874015-23-000132 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 36,528

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 $36.19 to $36.50953 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: 0000874015-23-000131 · edgardoc.xml · nonDerivative · entry 2

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 24,312

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 $36.19 to $36.50953 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: 0000874015-23-000130 · edgardoc.xml · nonDerivative · entry 2

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 10,571

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 $36.20 to $36.50953 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: 0000874015-23-000132 · edgardoc.xml · derivative · entry 3

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

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 27,720

Underlying: Common Stock · 1,875 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: 0000874015-23-000132 · 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: 37,200

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: 0000874015-23-000131 · edgardoc.xml · derivative · entry 3

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 49,659

Underlying: Common Stock · 5,667 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: 0000874015-23-000131 · edgardoc.xml · nonDerivative · entry 1

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 26,894

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: 0000874015-23-000130 · edgardoc.xml · derivative · entry 4

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 47,261

Underlying: Common Stock · 10,838 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: 0000874015-23-000130 · edgardoc.xml · nonDerivative · entry 1

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 14,451

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: 0000874015-23-000115 · edgardoc.xml · nonDerivative · entry 1

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 32,516

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: 0000874015-23-000114 · 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: 0000874015-23-000112 · edgardoc.xml · nonDerivative · entry 1

Geary Richard S · CIK 0001442730 · EVP, Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 72,960

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: 0000874015-23-000113 · edgardoc.xml · nonDerivative · entry 1

HOUGEN ELIZABETH L · CIK 0001074773 · EVP, Finance & CFO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 75,659

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: 0000874015-23-000111 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 70,034

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: 0000874015-23-000096 · edgardoc.xml · nonDerivative · entry 2

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 31,941

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.52 to $40.90 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 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: 0000874015-23-000095 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 24,946

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.52 to $40.75 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: 0000874015-23-000092 · edgardoc.xml · nonDerivative · entry 2

HOUGEN ELIZABETH L · CIK 0001074773 · EVP, Finance & CFO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 75,496

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.56 to $40.64 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: 0000874015-23-000093 · edgardoc.xml · nonDerivative · entry 4

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 145,305

F4 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.37 to $40.95 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 (4) on this Form 4.

SEC source: 0000874015-23-000091 · edgardoc.xml · nonDerivative · entry 2

Geary Richard S · CIK 0001442730 · EVP, Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 72,385

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.62 to $40.70 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 sold at each separate price within the ranges set forth in footnote (2) on this Form 4.

SEC source: 0000874015-23-000090 · edgardoc.xml · nonDerivative · entry 2

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 21,227

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.60 to $40.70 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 sold at each separate price within the ranges set forth in footnote (2) on this Form 4.

SEC source: 0000874015-23-000089 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 69,651

F2 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $40.54 to $40.60 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: 0000874015-23-000096 · edgardoc.xml · nonDerivative · entry 1

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 33,756

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: 0000874015-23-000094 · 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: 0000874015-23-000095 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 26,359

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: 0000874015-23-000092 · edgardoc.xml · nonDerivative · entry 1

HOUGEN ELIZABETH L · CIK 0001074773 · EVP, Finance & CFO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 77,575

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: 0000874015-23-000093 · edgardoc.xml · nonDerivative · entry 3

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 169,956

F3 · 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: 0000874015-23-000093 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 144,584

F2 · 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 20, 2021. 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 100% 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: 0000874015-23-000093 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 127,374

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 17, 2020. 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 100% of target shares and a true-up of 72.24% of target shares pursuant to the alternative calculation. Since this PRSU award paid out less than 100% of target for tranche 1 and tranche 2 of such PRSU award, the alternative calculation applies, resulting in an additional payout of 1,146 shares under tranche 1 and 1,586 shares under tranche 2, yielding in the aggregate a total tranche 3 payout of 6,511 shares, or 172.24% of target

SEC source: 0000874015-23-000091 · edgardoc.xml · nonDerivative · entry 1

Geary Richard S · CIK 0001442730 · EVP, Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 74,305

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: 0000874015-23-000090 · edgardoc.xml · nonDerivative · entry 1

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,678

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: 0000874015-23-000089 · edgardoc.xml · nonDerivative · entry 1

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 71,464

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: 0000874015-23-000069 · edgardoc.xml · nonDerivative · entry 2

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 30,041

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 $39.66965 to $39.79044 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 · 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: 0000874015-23-000068 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,326

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 $39.503 to $39.66965 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: 0000874015-23-000066 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 120,863

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 $39.25257 to $40.045 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: 0000874015-23-000065 · edgardoc.xml · nonDerivative · entry 2

HOUGEN ELIZABETH L · CIK 0001074773 · EVP, Finance & CFO

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 73,435

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 $39.29 to $39.77 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: 0000874015-23-000064 · edgardoc.xml · nonDerivative · entry 2

Geary Richard S · CIK 0001442730 · EVP, Chief Development Officer

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 70,483

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 $39.33 to $40.04 inclusive. The reporting person undertakes to provide to Ionis Pharmaceuticals, Inc. any security holder of Ionis Pharmaceuticals, Inc. or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares sold at each separate price within the ranges set forth in footnote (3) on this Form 4.

SEC source: 0000874015-23-000063 · edgardoc.xml · nonDerivative · entry 2

Cadoret-Manier Onaiza · CIK 0001799355 · EVP, Chf GL Pdt Str & Oper Ofc

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,538

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 $39.25 to $39.70 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 sold at each separate price within the ranges set forth in footnote (3) on this Form 4.

SEC source: 0000874015-23-000061 · edgardoc.xml · nonDerivative · entry 2

Baroldi Joseph · CIK 0001813775 · EVP, Chief Business Officer

10b5-1 filing: Not disclosed

Ownership: Indirect · by Spouse

Disclosed balance after: 851

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 $39.76975 to $39.79032 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: 0000874015-23-000062 · edgardoc.xml · nonDerivative · entry 2

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

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 67,855

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 $38.65 to $39.36 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: 0000874015-23-000046 · edgardoc.xml · nonDerivative · entry 1

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 16,791

F1 · kind: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 17, 2022

F1 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 17, 2022

SEC source: 0000874015-23-000069 · edgardoc.xml · derivative · entry 3

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 43,397

Underlying: Common Stock · 15,780 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: 0000874015-23-000069 · edgardoc.xml · nonDerivative · entry 1

Swayze Eric · CIK 0001791058 · EVP Research

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 35,672

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.