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 * MUTO FREDERICK T 2. Issuer Name and Ticker or Trading Symbol IONIS PHARMACEUTICALS INC [ IONS ] 5. Relationship of Reporting Person(s) to Issuer (Check all applicable)__X__ Director                    _____ 10% Owner
_____ Officer (give title below)    _____ Other (specify below)
(Last)         (First)         (Middle)
2855 GAZELLE COURT
3. Date of Earliest Transaction (MM/DD/YYYY)
7/1/2021
(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

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
Non-Qualified Stock Option (right to buy)  $40.05  7/1/2021  7/1/2021  A     12000      7/1/2022 (1) 6/30/2031 (1) Common Stock  12000  $0.0  12000  D   
Restricted Stock Unit  $0.0 (2) 7/1/2021  7/1/2021  A     5333       (3)  (3) Common Stock  5333  $0.0  18441  D   

Explanation of Responses:
(1)  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.
(2)  Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.
(3)  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.

Reporting Owners
Reporting Owner Name / Address
Relationships
Director 10% Owner Officer Other
MUTO FREDERICK T
2855 GAZELLE COURT
CARLSBAD, CA 92010
X



Signatures
By: Patrick R. O'Neil, attorney-in-fact For: Frederick T. Muto 7/6/2021
**Signature of Reporting Person Date
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