Statement of Changes in Beneficial Ownership (Form 4)

FORM 4 Check this box if no longer subject to Section 16. Form 4 or Form 5 obligations may continue. See Instruction 1(b). Check this box to indicate that a transaction was made pursuant to a contract, instruction or written plan that is intended to satisfy the affirmative defense conditions of Rule 10b5-1(c). See Instruction 10.

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

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1. Name and Address of Reporting Person * KLEIN JOSEPH III 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 (Month/Day/Year) 07/01/2026 (Street) CARLSBAD, CA 92010 4. If Amendment, Date Original Filed (Month/Day/Year) 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 (Month/Day/Year) 2A. Deemed Execution Date, if any (Month/Day/Year) 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 07/01/2026 M 11,518 A $39.94 22,532 D Common Stock 07/01/2026 S 99(1) D $79.45 22,433 D Common Stock 07/01/2026 S 11,419(1) D $79.0394(2) 11,014 D Common Stock 200 I by Son(3)

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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 (Month/Day/Year)

3A. Deemed Execution Date, if any (Month/Day/Year)

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 (Month/Day/Year)

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)

$39.94

07/01/2026

M

11,518

07/01/2026

06/30/2035

Common Stock

11,518

$ 0

0

D

Non-Qualified Stock Option (right to buy)

$79.19

07/01/2026

A

5,369(4)

07/01/2027(5)

06/30/2036(5)

Common Stock

5,369

$ 0

5,369

D

Restricted Stock Unit

$ 0 (6)

07/01/2026

A

2,301(4)

(7)

(7)

Common Stock

2,301

$ 0

16,277

D

Reporting Owners

Reporting Owner Name / Address	Relationships
	Director	10% Owner	Officer	Other
KLEIN JOSEPH III 2855 GAZELLE COURT CARLSBAD, CA 92010	X

Signatures

By: Patrick R. O'Neil, attorney-in-fact For: Joseph Klein, III		07/06/2026
**Signature of Reporting Person		Date

Explanation of Responses:

*	If the form is filed by more than one reporting person, see Instruction 4(b)(v).
**	Intentional misstatements or omissions of facts constitute Federal Criminal Violations. See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).
(1)	Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on November 25, 2025.
(2)	The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $78.39 to $79.38 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 (2) on this Form 4.
(3)	The reporting person disclaims beneficial ownership of all securities held by his son, and this report should not be deemed an admission that the reporting person is the beneficial owner of such securities for purposes of Section 16 or for any other purpose.
(4)	Pursuant to the Company's Non-Employee Director Compensation Policy, these grants were adjusted downward such that the non-employee Director's annual equity compensation in 2026 totals no more than $400,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.
(5)	Grant on July 1, 2026 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, 2026.
(6)	Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.
(7)	Grant of Restricted Stock Unit award on July 1, 2026 to the reporting person 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; however, the reporting person has elected to defer delivery of such shares until the earlier to occur of the 30th day following the reporting person's Separation from Service from the Company or the date of a Change in Control of the Company, both as defined in Treasury Regulation Section 1.409A. These Restricted Stock Units are vested as to 0 shares on July 1, 2026.

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