IONS

SEC source: 0000874015-21-000136 · edgardoc.xml · derivative · entry 8

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,219

Underlying: Common Stock · 889 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.

F5 · 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 and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F7 · derivative.expiration_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000136 · edgardoc.xml · derivative · entry 7

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 13,108

Underlying: Common Stock · 5,333 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.

F5 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F6 · derivative.exercise_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F6 · derivative.expiration_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000136 · edgardoc.xml · nonDerivative · entry 5

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,126

F2 · kind: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on September 18, 2020.

F2 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on September 18, 2020.

F3 · price: The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $34.78 to $35.68 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: 0000874015-21-000136 · edgardoc.xml · nonDerivative · entry 4

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 22,460

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000136 · edgardoc.xml · nonDerivative · entry 3

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,682

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000136 · edgardoc.xml · nonDerivative · entry 2

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 20,016

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000136 · edgardoc.xml · nonDerivative · entry 1

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 19,127

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000135 · edgardoc.xml · derivative · entry 4

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 15,997

Underlying: Common Stock · 1,778 shares

Expires not disclosed

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

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

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

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

SEC source: 0000874015-21-000135 · edgardoc.xml · derivative · entry 3

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 17,775

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

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

F3 · derivative.exercise_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F3 · derivative.expiration_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000135 · edgardoc.xml · nonDerivative · entry 2

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 16,000

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000135 · edgardoc.xml · nonDerivative · entry 1

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,222

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000134 · edgardoc.xml · derivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,441

Underlying: Common Stock · 1,778 shares

Expires not disclosed

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

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

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

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

SEC source: 0000874015-21-000134 · edgardoc.xml · derivative · entry 3

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 14,219

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

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

F3 · derivative.exercise_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F3 · derivative.expiration_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000134 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,445

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000134 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,667

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000133 · edgardoc.xml · derivative · entry 1

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,000

Underlying: Common Stock · 8,000 shares

Expires not disclosed

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

F2 · derivative.exercise_date: Grant of July 15, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 15, 2021.

F2 · derivative.expiration_date: Grant of July 15, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 15, 2021.

SEC source: 0000874015-21-000132 · edgardoc.xml · derivative · entry 9

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 9,775

Underlying: Common Stock · 1,778 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.

F5 · derivative.exercise_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F5 · derivative.expiration_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000132 · edgardoc.xml · derivative · entry 8

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 11,553

Underlying: Common Stock · 666 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.

F5 · derivative.exercise_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F5 · derivative.expiration_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000132 · edgardoc.xml · derivative · entry 7

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,219

Underlying: Common Stock · 889 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.

F5 · derivative.exercise_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F5 · derivative.expiration_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000132 · edgardoc.xml · derivative · entry 6

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 13,108

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

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

F4 · derivative.exercise_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F4 · derivative.expiration_date: Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-21-000132 · edgardoc.xml · nonDerivative · entry 4

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 109,649

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000132 · edgardoc.xml · nonDerivative · entry 3

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 107,871

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000132 · edgardoc.xml · nonDerivative · entry 2

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 107,205

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000132 · edgardoc.xml · nonDerivative · entry 1

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 106,316

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 pursuant to a Restricted Stock Unit Award.

F1 · shares: Acquired pursuant to vesting and release of shares pursuant to a Restricted Stock Unit Award.

SEC source: 0000874015-21-000118 · edgardoc.xml · derivative · entry 2

Reikes Peter N · CIK 0001753652 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 19,552

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000118 · edgardoc.xml · derivative · entry 1

Reikes Peter N · CIK 0001753652 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000119 · edgardoc.xml · derivative · entry 2

WENDER JOSEPH H · CIK 0001073384 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,441

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000119 · edgardoc.xml · derivative · entry 1

WENDER JOSEPH H · CIK 0001073384 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000117 · edgardoc.xml · derivative · entry 2

PARSHALL B LYNNE · CIK 0001073385 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 23,529

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000117 · edgardoc.xml · derivative · entry 1

PARSHALL B LYNNE · CIK 0001073385 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000116 · edgardoc.xml · derivative · entry 2

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,441

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000116 · edgardoc.xml · derivative · entry 1

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000115 · edgardoc.xml · derivative · entry 2

LOSCALZO JOSEPH · CIK 0001276128 · Director · Chairman of Board

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,441

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000115 · edgardoc.xml · derivative · entry 1

LOSCALZO JOSEPH · CIK 0001276128 · Director · Chairman of Board

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000114 · edgardoc.xml · derivative · entry 2

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,441

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000114 · edgardoc.xml · derivative · entry 1

KLEIN JOSEPH III · CIK 0001206369 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000111 · edgardoc.xml · derivative · entry 1

Diaz Allene M. · CIK 0001773314 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,000

Underlying: Common Stock · 18,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on June 2, 2022. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on June 2, 2022. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000113 · edgardoc.xml · derivative · entry 2

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 23,108

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000113 · edgardoc.xml · derivative · entry 1

HERMAN JOAN E · CIK 0001248398 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000112 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 19,552

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000112 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000110 · edgardoc.xml · derivative · entry 2

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 18,441

Underlying: Common Stock · 5,333 shares

Expires not disclosed

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

F3 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

F3 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of Restricted Stock Unit award under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. These Restricted Stock Units vest 100% on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier, and will be delivered to the reporting person on the July 15th following the vesting date. The Restricted Stock Unit is vested as to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000110 · edgardoc.xml · derivative · entry 1

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 12,000

Underlying: Common Stock · 12,000 shares

Expires 2031-06-30

F1 · derivative.exercise_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

F1 · derivative.expiration_date: Grant of July 1, 2021 to reporting person of stock options under the Amended and Restated Ionis Pharmaceuticals, Inc. 2002 Non-Employee Directors' Stock Option Plan. 100% of the shares subject to the option vest and become exercisable on either the first anniversary of the date of grant or the next regularly scheduled annual meeting of stockholders of the Company, whichever occurs earlier. The option is exercisable to 0 shares on July 1, 2021.

SEC source: 0000874015-21-000088 · edgardoc.xml · derivative · entry 4

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 15,000 shares

Expires 2021-06-30

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

SEC source: 0000874015-21-000088 · edgardoc.xml · nonDerivative · entry 2

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 100,983

F2 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on March 12, 2021.

SEC source: 0000874015-21-000088 · edgardoc.xml · nonDerivative · entry 1

BERTHELSEN SPENCER R · CIK 0001181548 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 115,983

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: Acquired as a result of exercising a stock option that was scheduled to expire on June 30, 2021. The purchase reported on this Form 4 was effected pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person March 12, 2021.

SEC source: 0000874015-21-000085 · edgardoc.xml · derivative · entry 9

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 5,000 shares

Expires 2021-06-30

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

SEC source: 0000874015-21-000085 · edgardoc.xml · derivative · entry 8

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 5,000

Underlying: Common Stock · 5,000 shares

Expires 2021-06-30

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

SEC source: 0000874015-21-000085 · edgardoc.xml · derivative · entry 7

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,000

Underlying: Common Stock · 5,000 shares

Expires 2021-06-30

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

SEC source: 0000874015-21-000085 · edgardoc.xml · nonDerivative · entry 6

MUTO FREDERICK T · CIK 0001181560 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 31,683

F2 · shares: Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on September 18, 2020.