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)
EVP, Chf Corp Dev and Cml Offc
(Last)          (First)          (Middle)

2855 GAZELLE COURT
3. Date of Earliest Transaction (MM/DD/YYYY)

1/3/2022
(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 Security3. Trans. Date3A. Deemed Execution Date, if any4. 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 Date7. 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)
CodeV(A)(D)Date ExercisableExpiration DateTitleAmount or Number of Shares
Non-Qualified Stock Option (right to buy) $32.6 1/3/2022 1/3/2022 A   33118    1/3/2023 (1)1/2/2032 Common Stock 33118 $0.0 33118 D  

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. Following this transaction, the option was exercisable as to 0 shares on 01/03/2022. 25% of the shares subject to the option will vest and become exercisable on 01/03/2023. Thereafter, the remaining shares subject to the option will vest and become exercisable in 36 equal monthly installments over the next 3 years.

Reporting Owners
Reporting Owner Name / Address
Relationships
Director10% OwnerOfficerOther
Cadoret-Manier Onaiza
2855 GAZELLE COURT
CARLSBAD, CA 92010


EVP, Chf Corp Dev and Cml Offc

Signatures
By: Patrick R. O'Neil, attorney-in-fact For: Onaiza Cadoret-Manier1/5/2022
**Signature of Reporting PersonDate

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