Hayden Michael R

SEC source: 0001628280-26-058684 · wk-form4_1787606506.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 1,373,397

F1 · price: The price reported in Column 4 is a weighted-average price. These shares were acquired in multiple transactions at prices ranging from $10.49 to $10.70. The reporting person undertakes to provide the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares acquired at each separate price within the range set forth in this footnote.

F2 · ownership.direct: These shares are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2. The reporting person disclaims beneficial ownership of such securities, except to the extent of his indirect pecuniary interest, if any, therein.

SEC source: 0001628280-26-057007 · wk-form4_1786722614.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 1,319,784

F1 · price: The price reported in Column 4 is a weighted-average price. These shares were acquired in multiple transactions at prices ranging from $10.25 to $10.45. The reporting person undertakes to provide the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares acquired at each separate price within the range set forth in this footnote.

F2 · ownership.direct: These shares are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2. The reporting person disclaims beneficial ownership of such securities, except to the extent of his indirect pecuniary interest, if any, therein.

SEC source: 0001628280-26-056653 · wk-form4_1786647701.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 1,273,397

F1 · price: This transaction represents a charitable donation of 50,000 common shares made by Genworks 2 Consulting, Inc. on August 11, 2026.

F2 · ownership.direct: These shares are held by Genworks 2 Consulting, Inc. The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2 Consulting, Inc. The reporting person disclaims beneficial ownership of such securities, except to the extent of his indirect pecuniary interest, if any, therein.

SEC source: 0000874015-26-000254 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · by Spouse

Disclosed balance after: 24,000

F3 · price: The price reported in Column 4 is a weighted average price. These shares were purchase in multiple transactions at prices ranging from $51.45 to $51.70 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 purchased at each separate price within the ranges set forth in footnote (3) on this Form 4.

F2 · ownership.nature: These securities are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2.

SEC source: 0000874015-26-000254 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · by Spouse

Disclosed balance after: 19,000

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchase in multiple transactions at prices ranging from $53.00 to $53.58 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 purchased at each separate price within the ranges set forth in footnote (1) on this Form 4.

F2 · ownership.nature: These securities are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2.

SEC source: 0000874015-26-000228 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 12,198

Underlying: Common Stock · 2,301 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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.

F4 · derivative.exercise_date: 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.

F4 · derivative.expiration_date: 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.

SEC source: 0000874015-26-000228 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 5,369

Underlying: Common Stock · 5,369 shares

Expires 2036-06-30

F1 · shares: 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.

F2 · derivative.exercise_date: 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.

F2 · derivative.expiration_date: 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.

SEC source: 0001628280-26-042739 · wk-form4_1781283845.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 1,011,544

Underlying: Common Shares · 111,701 shares

Expires 2036-06-11

F1 · derivative.exercise_date: The shares subject to such option vest and become exercisable at the 2027 Annual General Meeting, subject to the Reporting Person's continuous service to the Issuer on each such date.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 13

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 56,400 shares

Expires 2035-02-01

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 12

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 45,150 shares

Expires 2034-02-01

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 11

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 27,400 shares

Expires 2033-02-09

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 10

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 25,000 shares

Expires 2032-05-16

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 9

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 12,500 shares

Expires 2031-04-15

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 8

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 7,000 shares

Expires 2030-06-22

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 7

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 7,000 shares

Expires 2030-04-05

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 6

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 22,730 shares

Expires 2029-07-30

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 5

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 2,933 shares

Expires 2029-01-30

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · derivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

Underlying: Common Stock · 27,647 shares

Expires 2028-11-09

F5 · derivative.exercise_date: As of immediately prior to and conditioned upon the occurrence of the effective time of the Merger, pursuant to the Merger Agreement, each outstanding option to purchase Shares (each, an "Option") became fully vested and exercisable, and to the extent not exercised prior to the effective time of the Merger, was cancelled and converted into the right to receive (i) an amount in cash (without interest and subject to deduction for any required withholding taxes) equal to the product of (A) an amount equal to the excess of the Closing Amount over the exercise price per Share with respect to such Option and (B) the number of Shares subject to such Option plus (ii) one CVR with respect to each Share subject to such Option (the "Option Consideration"); provided, however, that if the exercise price per Share of any Option was equal to or greater than the Closing Amount, but less than $20.50 (any such option, an "Out of the Money Option"), [continues to Footnote 6]

F6 · derivative.exercise_date: [Continues from Footnote 5] such Out of the Money Option was not entitled to any payment of the Closing Amount in respect thereof and each Out of the Money Option was converted into the right to receive the CVR included in the Option Consideration with respect to each Share underlying such Out of the Money Option and became entitled to receive, at each time a milestone payment becomes due and payable under the terms of the CVR Agreement, an amount in cash equal to the product of (i) the number of Shares subject to such Out of the Money Option, and (ii) the amount, if any, by which (A) the Closing Amount plus the applicable milestone payment plus any other milestone payment that previously became due and payable under the terms of the CVR Agreement exceeds (B) the exercise price per Share with respect to such Out of the Money Option plus the amounts, [continues to Footnote 7]

F7 · derivative.exercise_date: [Continues from Footnote 6] if any, paid to such Option holder with respect to such CVR in respect of any milestone payments that previously became due and payable under the terms of the CVR Agreement; provided further, that any Option with an exercise price that was equal to or greater than $20.50, was cancelled immediately prior to the effective time of the Merger without the receipt of any payment of the Closing Amount or CVR in respect thereof.

SEC source: 0001193125-25-259064 · ownership.xml · nonDerivative · entry 3

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 0

F1 · shares: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · shares: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

F1 · price: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · price: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

F4 · ownership.nature: These shares are held directly by The Hayden Family Trust, over which the Reporting Person's wife has sole voting and investment power.

SEC source: 0001193125-25-259064 · ownership.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 0

F1 · shares: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · shares: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

F1 · price: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · price: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

F3 · ownership.nature: These shares are held directly by Genworks 2 Consulting Inc., over which the Reporting Person's wife has sole voting and investment power.

SEC source: 0001193125-25-259064 · ownership.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 0

F1 · shares: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · shares: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

F1 · price: Disposed of pursuant to the Agreement and Plan of Merger (the "Merger Agreement"), dated as of September 17, 2025, by and among 89bio, Inc. (the "Issuer"), Roche Holdings, Inc. ("Parent") and Bluefin Merger Subsidiary, Inc., a wholly owned subsidiary of Parent ("Merger Sub"). On October 30, 2025, Parent and Merger Sub completed a tender offer pursuant to the terms of the Merger Agreement for all outstanding shares of common stock of the Issuer (each, a "Share") for an offer price of (i) $14.50 per Share in cash, without interest (the "Closing Amount") less any required withholding taxes, plus (ii) one non-tradeable contingent value right (each, a "CVR") representing the right to receive certain contingent payments of up to an aggregate amount of $6.00 per Share, [continues to Footnote 2]

F2 · price: [continues from Footnote 1] in cash, without interest less any required withholding taxes, upon the achievement of specified milestones on or prior to the applicable milestone outside dates, subject to and in accordance with the terms of the Contingent Value Rights Agreement (the "CVR Agreement") (the Closing Amount plus one CVR, collectively, the "Offer Price"). Merger Sub thereafter merged with and into the Issuer, with the Issuer continuing as the surviving corporation and a wholly owned subsidiary of Parent (the "Merger"). At the effective time of the Merger, each issued and outstanding Share (other than any Excluded Shares (as such term is defined in the Merger Agreement)) was cancelled in exchange for the right to receive the Offer Price.

SEC source: 0000874015-25-000157 · edgardoc.xml · derivative · entry 3

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 9,897

Underlying: Common Stock · 4,079 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F4 · derivative.exercise_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F4 · derivative.expiration_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-25-000157 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 54,298

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-25-000138 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 13,976

Underlying: Common Stock · 5,220 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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 2025 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F4 · derivative.exercise_date: Grant on July 1, 2025 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, 2025.

F4 · derivative.expiration_date: Grant on July 1, 2025 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, 2025.

SEC source: 0000874015-25-000138 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 11,518

Underlying: Common Stock · 11,518 shares

Expires 2035-06-30

F1 · shares: 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 2025 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F2 · derivative.exercise_date: Grant on July 1, 2025 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, 2025.

F2 · derivative.expiration_date: Grant on July 1, 2025 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, 2025.

SEC source: 0001628280-25-033735 · wk-form4_1751397189.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 899,843

Underlying: Common Shares · 238,864 shares

Expires 2035-06-12

F1 · derivative.exercise_date: The shares subject to such option vest and become exercisable at the 2026 Annual General Meeting, subject to the Reporting Person's continuous service to the Issuer on each such date.

SEC source: 0000874015-25-000125 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 50,219

F1 · price: The price reported in Column 4 is a weighted average price. These shares were purchase in multiple transactions at prices ranging from $31.50 to $32.09 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 purchased at each separate price within the ranges set forth in footnote (1) on this Form 4.

SEC source: 0000950170-25-014432 · ownership.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 56,400

Underlying: Common Stock · 56,400 shares

Expires 2035-02-03

F1 · derivative.exercise_date: This option represents a right to purchase a total of 56,400 shares of the Issuer's Common Stock, which will vest in full on February 1, 2026, subject to the Reporting Person's continued service to the Issuer through such date.

SEC source: 0000874015-24-000243 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 35,219

SEC source: 0000874015-24-000243 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 32,719

SEC source: 0000874015-24-000161 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 8,756

Underlying: Common Stock · 4,079 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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 2024 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F4 · derivative.exercise_date: Grant on July 1, 2024 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, 2024.

F4 · derivative.expiration_date: Grant on July 1, 2024 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, 2024.

SEC source: 0000874015-24-000161 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 10,111

Underlying: Common Stock · 10,111 shares

Expires 2034-06-30

F1 · shares: 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 2024 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F2 · derivative.exercise_date: Grant on July 1, 2024 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, 2024.

F2 · derivative.expiration_date: Grant on July 1, 2024 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, 2024.

SEC source: 0001628280-24-029673 · wk-form4_1719268228.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 660,979

Underlying: Common Shares · 163,934 shares

Expires 2034-06-21

SEC source: 0000950170-24-011481 · ownership.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 45,150

Underlying: Common Stock · 45,150 shares

Expires 2034-02-01

F1 · derivative.exercise_date: This option represents a right to purchase a total of 45,150 shares of the Issuer's Common Stock, which will vest in full on February 1, 2025, subject to the Reporting Person's continued service to the Issuer through such date.

SEC source: 0001703057-23-000032 · wk-form4_1695745559.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 1,323,397

F1 · price: The price reported in Column 4 is a weighted-average price. These shares were acquired in multiple transactions at prices ranging from $4.89 to $4.93. The reporting person undertakes to provide the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares acquired at each separate price within the range set forth in this footnote.

F2 · ownership.direct: These shares are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2. The reporting person disclaims beneficial ownership of such securities, except to the extent of his indirect pecuniary interest, if any, therein.

SEC source: 0001703057-23-000024 · wk-form4_1691598110.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 1,303,397

F1 · price: The price reported in Column 4 is a weighted-average price. These shares were acquired in multiple transactions at prices ranging from $5.89 to $5.91. The reporting person undertakes to provide the Issuer, any security holder of the Issuer, or the staff of the Securities and Exchange Commission, upon request, full information regarding the number of shares acquired at each separate price within the range set forth in this footnote.

F2 · ownership.direct: These shares are held by Genworks 2 Consulting, Inc. ("Genworks 2"). The Reporting Person's spouse has sole voting and investment power with respect to the shares held by Genworks 2. The reporting person disclaims beneficial ownership of such securities, except to the extent of his indirect pecuniary interest, if any, therein.

SEC source: 0000874015-23-000174 · edgardoc.xml · derivative · entry 5

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 4,677

Underlying: Common Stock · 5,333 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F5 · derivative.exercise_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F5 · derivative.expiration_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-23-000174 · edgardoc.xml · derivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 10,010

Underlying: Common Stock · 1,777 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F4 · derivative.exercise_date: Restricted Stock Units vest in four equal annual 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 the Company.

F4 · derivative.expiration_date: Restricted Stock Units vest in four equal annual 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 the Company.

SEC source: 0000874015-23-000174 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 30,219

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-23-000174 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 24,886

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-23-000156 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 11,787

Underlying: Common Stock · 4,677 shares

Expires not disclosed

F3 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F1 · shares: 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 2023 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F4 · derivative.exercise_date: Grant of Restricted Stock Unit award on July 3, 2023 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 3, 2023

F4 · derivative.expiration_date: Grant of Restricted Stock Unit award on July 3, 2023 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 3, 2023

SEC source: 0000874015-23-000156 · edgardoc.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Direct

Disclosed balance after: 10,321

Underlying: Common Stock · 10,321 shares

Expires 2033-07-02

F1 · shares: 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 2023 totals no more than $450,000 based on the aggregate grant date fair value as determined in accordance with FASB Topic ASC 718.

F2 · derivative.exercise_date: Grant on July 3, 2023 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 3, 2023.

F2 · derivative.expiration_date: Grant on July 3, 2023 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 3, 2023.

SEC source: 0000950170-23-010969 · ownership.xml · nonDerivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: No plan indicated

Ownership: Indirect · See footnote

Disclosed balance after: 61,538

F3 · ownership.nature: These shares are held directly by The Hayden Family Trust, over which the Reporting Person's wife has sole voting and investment power.

SEC source: 0000899243-23-004798 · doc4.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 27,400

Underlying: Common Stock · 27,400 shares

Expires 2033-02-09

F1 · derivative.exercise_date: This option represents a right to purchase a total of 27,400 shares of the Issuer's Common Stock, which will vest in full on February 9, 2024, subject to the Reporting Person's continued service to the Issuer through such date.

SEC source: 0001209191-22-059579 · doc4.xml · derivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 497,045

Underlying: Common Shares · 47,231 shares

Expires 2032-12-01

SEC source: 0000874015-22-000165 · edgardoc.xml · derivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 7,110

Underlying: Common Stock · 1,777 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F3 · derivative.exercise_date: Restricted Stock Units vest in four equal annual 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 the Company.

F3 · derivative.expiration_date: Restricted Stock Units vest in four equal annual 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 the Company.

SEC source: 0000874015-22-000165 · edgardoc.xml · nonDerivative · entry 1

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 23,109

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

SEC source: 0000874015-22-000138 · edgardoc.xml · derivative · entry 4

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 8,887

Underlying: Common Stock · 1,777 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F4 · derivative.exercise_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F4 · derivative.expiration_date: Restricted Stock Units vest in four equal annual installments and are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-22-000138 · edgardoc.xml · derivative · entry 3

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 10,664

Underlying: Common Stock · 5,333 shares

Expires not disclosed

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F2 · derivative.exercise_price: Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value.

F3 · derivative.exercise_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

F3 · derivative.expiration_date: 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 are delivered to the reporting person on the July 15th following the vesting date. Upon vesting, the Restricted Stock Units will be paid in whole shares of Ionis common stock or cash as may be determined by the Company.

SEC source: 0000874015-22-000138 · edgardoc.xml · nonDerivative · entry 2

Hayden Michael R · CIK 0001352908 · Director

10b5-1 filing: Not disclosed

Ownership: Direct

Disclosed balance after: 21,332

Exercise/conversion can include RSU settlement. Transaction price and option strike are different fields; a missing price is not zero. Derivative and underlying rows can describe the same event.

F1 · kind: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.

F1 · shares: Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award.