FORM 4 [ ] 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 OF SECURITIES
                                                                                  
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Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940
                      
1. Name and Address of Reporting Person * Cadoret-Manier Onaiza 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)
Chief Corp Dev and Cml Officer
(Last)         (First)         (Middle)
2855 GAZELLE COURT
3. Date of Earliest Transaction (MM/DD/YYYY)
4/15/2021
(Street)
CARLSBAD, CA 92010
(City)       (State)       (Zip)
4. If Amendment, Date Original Filed (MM/DD/YYYY)
 
6. Individual or Joint/Group Filing (Check Applicable Line) _X _ Form filed by One Reporting Person
___ Form filed by More than One Reporting Person

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned
1.Title of Security
(Instr. 3)
2. Trans. Date 2A. Deemed Execution Date, if any 3. Trans. 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  4/15/2021  4/15/2021  M(1)    5667 (1) A $0.0  6159  D   
Common Stock  4/15/2021  4/15/2021  F(2)    1960 (2) D $41.03  4199  D   

Table II - Derivative Securities Beneficially Owned (e.g., puts, calls, warrants, options, convertible securities)
1. Title of Derivate Security
(Instr. 3)
2. Conversion or Exercise Price of Derivative Security 3. Trans. Date 3A. Deemed Execution Date, if any 4. Trans. 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 7. Title and Amount of Securities Underlying Derivative Security
(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
Restricted Stock Unit  $0.0 (3) 4/15/2021  4/15/2021  M        5667    (4)  (4) Common Stock  5667  $0.0  17000  D   

Explanation of Responses:
(1)  Acquired pursuant to vesting and release of shares in accordance with Restricted Stock Unit awards.
(2)  Shares withheld to cover the required tax withholding obligations pursuant to the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan.
(3)  Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.
(4)  Restricted Stock Units vest in four equal monthly installments. Upon vesting, the Restricted Stock Units will be paid out in whole shares of Ionis common stock or cash as may be determined by Ionis.

Reporting Owners
Reporting Owner Name / Address
Relationships
Director 10% Owner Officer Other
Cadoret-Manier Onaiza
2855 GAZELLE COURT
CARLSBAD, CA 92010


Chief Corp Dev and Cml Officer

Signatures
By: Patrick R. O'Neil, attorney-in-fact For: Onaiza Cadoret-Manier 4/19/2021
**Signature of Reporting Person Date