Sec Form 3 Filing - Birchler Brian @ IONIS PHARMACEUTICALS INC - 2023-03-14

FORM 3 Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b).

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934, Section 17(a) of the Public Utility Holding Company Act of 1935 or Section 30(h) of the Investment Company Act of 1940

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1. Name and Address of Reporting Person Birchler Brian 2. Issuer Name and Ticker or Trading Symbol IONIS PHARMACEUTICALS INC [ IONS] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable) _____ Director _____ 10% Owner X __ Officer (give title below) _____ Other (specify below) EVP, Corp and Development Ops (Last) (First) (Middle) 2855 GAZELLE COURT 3. Date of Earliest Transaction (MM/DD/YY) 03/14/2023 (Street) CARLSBAD, CA92010 4. If Amendment, Date Original Filed (MM/DD/YY) 6. Individual or Joint/Group Filing (Check Applicable Line) __ X __ Form filed by One Reporting Person _____ Form filed by More than One Reporting Person (City) (State) (Zip)

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned 1.Title of Security (Instr. 3) 2. Transaction Date (MM/DD/YY) 2A. Deemed Execution Date, if any (MM/DD/YY) 3. Transaction Code (Instr. 8) 4. Securities Acquired (A) or Disposed of (D) (Instr. 3, 4 and 5) 5. Amount of Securities Beneficially Owned Following Reported Transaction(s) (Instr. 3 and 4) 6. Ownership Form: Direct (D) or Indirect (I) (Instr. 4) 7. Nature of Indirect Beneficial Ownership (Instr. 4) Code V Amount (A) or (D) Price Common Stock 35,325 D

Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned ( e.g. , puts, calls, warrants, options, convertible securities) 1. Title of Derivative Security (Instr. 3) 2. Conversion or Exercise Price of Derivative Security 3. Transaction Date (MM/DD/YY) 3A. Deemed Execution Date, if any (MM/DD/YY) 4. Transaction Code (Instr. 8) 5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5) 6. Date Exercisable and Expiration Date (MM/DD/YY) 7. Title and Amount of Underlying Securities (Instr. 3 and 4) 8. Price of Derivative Security (Instr. 5) 9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s) (Instr. 4) 10. Ownership Form of Derivative Security: Direct (D) or Indirect (I) (Instr. 4) 11. Nature of Indirect Beneficial Ownership (Instr. 4) Code V (A) (D) Date Exercisable Expiration Date Title Amount or Number of Shares Non-Qualified Stock Option (right to buy) $ 32.6 ( 1 ) 01/02/2032 Common Stock 19,500 D Non-Qualified Stock Option (right to buy) $ 35.25 ( 2 ) 03/19/2032 Common Stock 15,000 D Non-Qualified Stock Option (right to buy) $ 37.58 ( 3 ) 01/02/2033 Common Stock 22,942 D Non-Qualified Stock Option (right to buy) $ 47.34 ( 4 ) 01/02/2024 Common Stock 26,982 D Non-Qualified Stock Option (right to buy) $ 49.25 ( 5 ) 01/01/2025 Common Stock 31,500 D Non-Qualified Stock Option (right to buy) $ 53.77 ( 6 ) 01/01/2026 Common Stock 23,900 D Non-Qualified Stock Option (right to buy) $ 56.78 ( 7 ) 01/03/2028 Common Stock 22,000 D Non-Qualified Stock Option (right to buy) $ 60.89 ( 8 ) 01/01/2027 Common Stock 26,063 D Non-Qualified Stock Option (right to buy) $ 61.57 ( 9 ) 01/01/2024 Common Stock 15,500 D Performance Restricted Stock Units ( 10 ) $ 0 ( 11 ) ( 11 ) Common Stock 14,338 D Restricted Stock Unit ( 12 ) $ 0 01/15/2024( 13 ) 01/15/2024( 13 ) Common Stock 2,896 D Restricted Stock Unit ( 12 ) $ 0 01/15/2024( 14 ) 01/15/2025( 14 ) Common Stock 4,888 D Restricted Stock Unit ( 12 ) $ 0 01/15/2024( 15 ) 01/15/2026( 15 ) Common Stock 7,312 D Restricted Stock Unit ( 12 ) $ 0 04/15/2023( 16 ) 04/15/2026( 16 ) Common Stock 7,500 D Restricted Stock Unit ( 12 ) $ 0 01/15/2024( 17 ) 01/15/2027( 17 ) Common Stock 17,207 D

Reporting Owners Reporting Owner Name / Address Relationships Director 10% Owner Officer Other Birchler Brian 2855 GAZELLE COURT CARLSBAD, CA92010 EVP, Corp and Development Ops Signatures By: Patrick R. O'Neil, attorney-in-fact For: Brian Birchler 03/24/2023 Signature of Reporting Person Date

Explanation of Responses:

( 1 )Grant on 01/03/2022 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option will be vested and become exercisable on 01/03/2023. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 5,687 shares on 03/14/2023. ( 2 )Grant on 03/20/2022 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option will be vested and become exercisable on 03/20/2023. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 0 shares on 03/14/2023. ( 3 )Grant on 01/03/2023 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option will be vested and become exercisable on 01/03/2024. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 0 shares on 03/14/2023. ( 4 )Grant on 01/03/2017 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option vested and became exercisable on 01/03/2018. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 26,982 shares on 03/14/2023. ( 5 )Grant on 01/02/2018 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option vested and became exercisable on 01/02/2019. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 31,500 shares on 03/14/2023. ( 6 )Grant on 01/02/2019 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option vested and became exercisable on 01/02/2020. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 23,900 shares on 03/14/2023. ( 7 )Grant on 01/04/2021 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option will be vested and become exercisable on 01/04/2022. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 11,916 shares on 03/14/2023. ( 8 )Grant on 01/02/2020 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option will be vested and become exercisable on 01/02/2021. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 20,633 shares on 03/14/2023. ( 9 )Grant on 01/02/2015 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. 25% of the shares subject to the option vested and became exercisable on 01/02/2016. Thereafter, the remaining shares subject to the option vested and became exercisable in 36 equal monthly installments. The option is exercisable as to 15,500 shares on 03/14/2023 ( 10 )Grant to reporting person of Performance Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan. ( 11 )Represents an award of performance based restricted stock units ("PRSUs"). The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated. ( 12 )Each restricted stock unit represents a contingent right to receive one share of Isis common stock, or its equivalent cash value. ( 13 )The restricted stock units vest in four equal annual installments, the first installment vesting on January 15, 2021. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2024. ( 14 )The restricted stock units vest in four equal annual installments, the first installment vesting on January 15, 2022. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2025. ( 15 )The restricted stock units vest in four equal annual installments, the first installment vesting on January 15, 2023. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2026. ( 16 )The restricted stock units vest in four equal annual installments, the first installment vesting on April 15, 2022. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. The RSU shall be fully vested on April 15, 2026. ( 17 )The restricted stock units vest in four equal annual installments, the first installment vesting on January 15, 2023. Upon vesting, the restricted stock units will be paid out in whole shares of Ionis common stock or cash as may be determined by the Company. The RSU shall be fully vested on January 15, 2027.

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