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These shares were sold in multiple transactions at prices ranging from $75.06 to $75.26 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 (3) on this Form 4."}],"balance_after":23713,"source":{"system":"sec-edgar","filing":"0000874015-26-000171","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":2,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000171/edgardoc.xml","form_type":"4"}},{"id":806332,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str 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These shares were sold in multiple transactions at prices ranging from $76.02 to $76.60 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 (3) on this Form 4."}],"balance_after":11714,"source":{"system":"sec-edgar","filing":"0000874015-26-000142","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":3,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000142/edgardoc.xml","form_type":"4"}},{"id":849625,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2026-03-11T20:18:53.000Z","date":"2026-03-10","kind":"sale","planned":true,"acquired":false,"shares":21191,"price":75.502,"value":1599962.882,"ownership":{"direct":true},"footnotes":[{"field":"shares","element":"transactionShares","label":"F1","text":"Shares sold pursuant to a Rule 10b5-1 Trading Plan adopted by the reporting person on December 8, 2025"},{"field":"price","element":"transactionPricePerShare","label":"F2","text":"The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $75.005 to $76.00 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."}],"balance_after":27800,"source":{"system":"sec-edgar","filing":"0000874015-26-000142","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":2,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000142/edgardoc.xml","form_type":"4"}},{"id":849624,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2026-03-11T20:18:53.000Z","date":"2026-03-10","kind":"exercise","planned":true,"acquired":true,"shares":32602,"price":46.1,"value":1502952.2,"ownership":{"direct":true},"balance_after":48991,"source":{"system":"sec-edgar","filing":"0000874015-26-000142","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":1,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000142/edgardoc.xml","form_type":"4"}},{"id":936211,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Restricted Stock Unit","published_at":"2026-01-21T01:18:39.000Z","date":"2026-01-15","kind":"exercise","planned":false,"acquired":false,"shares":7013,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"derivative.exercise_price","element":"conversionOrExercisePrice","label":"F7","text":"Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value."},{"field":"derivative.exercise_date","element":"exerciseDate","label":"F8","text":"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."},{"field":"derivative.expiration_date","element":"expirationDate","label":"F8","text":"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."}],"balance_after":29664,"derivative":{"exercise_date":"2026-01-15","underlying":"Common Stock","underlying_shares":7013},"source":{"system":"sec-edgar","filing":"0000874015-26-000066","document":"edgardoc.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":5,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000066/edgardoc.xml","form_type":"4"}},{"id":936210,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Restricted Stock Unit","published_at":"2026-01-21T01:18:39.000Z","date":"2026-01-15","kind":"grant","planned":false,"acquired":true,"shares":9675,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"security","element":"securityTitle","label":"F6","text":"Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. 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No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated."}],"balance_after":44500,"derivative":{"exercise_price":0,"exercise_date":"2027-01-15","underlying":"Common Stock","underlying_shares":25800},"source":{"system":"sec-edgar","filing":"0000874015-26-000066","document":"edgardoc.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":3,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000066/edgardoc.xml","form_type":"4"}},{"id":936208,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2026-01-21T01:18:39.000Z","date":"2026-01-16","kind":"sale","planned":false,"acquired":false,"shares":1823,"price":75.96,"value":138475.08,"ownership":{"direct":true},"footnotes":[{"field":"kind","element":"transactionCoding","label":"F2","text":"The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice."},{"field":"shares","element":"transactionShares","label":"F2","text":"The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice."},{"field":"price","element":"transactionPricePerShare","label":"F3","text":"The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $75.96 to $75.97 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 (3) on this Form 4."}],"balance_after":16389,"source":{"system":"sec-edgar","filing":"0000874015-26-000066","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":2,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000066/edgardoc.xml","form_type":"4"}},{"id":936207,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2026-01-21T01:18:39.000Z","date":"2026-01-15","kind":"exercise","planned":false,"acquired":true,"shares":7013,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"kind","element":"transactionCoding","label":"F1","text":"Acquired pursuant to vesting and release of shares in accordance with Restricted Stock Unit awards."},{"field":"shares","element":"transactionShares","label":"F1","text":"Acquired pursuant to vesting and release of shares in accordance with Restricted Stock Unit awards."}],"balance_after":18212,"source":{"system":"sec-edgar","filing":"0000874015-26-000066","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":1,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401526000066/edgardoc.xml","form_type":"4"}},{"id":948714,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Non-Qualified Stock Option (right to buy)","published_at":"2026-01-06T22:36:44.000Z","date":"2026-01-02","kind":"grant","planned":false,"acquired":true,"shares":19350,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"derivative.exercise_date","element":"exerciseDate","label":"F1","text":"Grant on 01/02/2026 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. 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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."},{"field":"derivative.expiration_date","element":"expirationDate","label":"F5","text":"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."}],"balance_after":36677,"derivative":{"underlying":"Common Stock","underlying_shares":12226},"source":{"system":"sec-edgar","filing":"0000874015-25-000119","document":"edgardoc.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":3,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401525000119/edgardoc.xml","form_type":"4"}},{"id":1170389,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2025-04-17T20:53:18.000Z","date":"2025-04-16","kind":"sale","planned":false,"acquired":false,"shares":3016,"price":28.36,"value":85533.76,"ownership":{"direct":true},"footnotes":[{"field":"kind","element":"transactionCoding","label":"F2","text":"The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice."},{"field":"shares","element":"transactionShares","label":"F2","text":"The sale was made pursuant to an automatic sale to cover the required tax withholding obligations pursuant to the 2011 Equity Incentive Plan Restricted Stock Unit Agreement and Grant Notice."},{"field":"price","element":"transactionPricePerShare","label":"F3","text":"The price reported in Column 4 is a weighted average price. These shares were sold in multiple transactions at prices ranging from $28.35 to $28.37 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 (3) on this Form 4."}],"balance_after":11199,"source":{"system":"sec-edgar","filing":"0000874015-25-000119","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":2,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401525000119/edgardoc.xml","form_type":"4"}},{"id":1170388,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Common Stock","published_at":"2025-04-17T20:53:18.000Z","date":"2025-04-15","kind":"exercise","planned":false,"acquired":true,"shares":12226,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"kind","element":"transactionCoding","label":"F1","text":"Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award."},{"field":"shares","element":"transactionShares","label":"F1","text":"Acquired pursuant to vesting and release of shares in accordance with a Restricted Stock Unit award."}],"balance_after":14215,"source":{"system":"sec-edgar","filing":"0000874015-25-000119","document":"edgardoc.xml","document_sequence":1,"table":"nonDerivative","row_type":"transaction","position":1,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401525000119/edgardoc.xml","form_type":"4"}},{"id":1300979,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Restricted Stock Unit","published_at":"2025-01-18T00:40:43.000Z","date":"2025-01-15","kind":"grant","planned":false,"acquired":true,"shares":28050,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"security","element":"securityTitle","label":"F3","text":"Grant to reporting person of Restricted Stock Units under the Ionis Pharmaceuticals, Inc. Amended and Restated 2011 Equity Incentive Plan."},{"field":"derivative.exercise_price","element":"conversionOrExercisePrice","label":"F4","text":"Each Restricted Stock Unit represents a contingent right to receive one share of Ionis common stock, or its equivalent cash value."},{"field":"derivative.exercise_date","element":"exerciseDate","label":"F5","text":"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."},{"field":"derivative.expiration_date","element":"expirationDate","label":"F5","text":"Restricted Stock Units vest in four equal annual installments. 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Amended and Restated 2011 Equity Incentive Plan."},{"field":"derivative.exercise_date","element":"exerciseDate","label":"F2","text":"The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated."},{"field":"derivative.expiration_date","element":"expirationDate","label":"F2","text":"The PRSUs may vest at the end of the three-year performance period following the date of grant based on the Issuer's relative total shareholder return as compared to a peer group of companies. The number of PRSUs reported represents the maximum that may be earned, which is 200% of the target number. No number of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the performance period may be anywhere from zero to the amount stated."}],"balance_after":18700,"derivative":{"exercise_price":0,"exercise_date":"2028-01-15","underlying":"Common Stock","underlying_shares":18700},"source":{"system":"sec-edgar","filing":"0000874015-25-000061","document":"edgardoc.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":1,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401525000061/edgardoc.xml","form_type":"4"}},{"id":1312095,"issuer":{"id":1182,"kind":"organization","name":"IONIS PHARMACEUTICALS INC","symbol":"IONS"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"EVP, Chf GL Pdt Str Ofcr"}}],"security":"Non-Qualified Stock Option (right to buy)","published_at":"2025-01-06T21:55:21.000Z","date":"2025-01-02","kind":"grant","planned":false,"acquired":true,"shares":18700,"price":0,"value":0.0,"ownership":{"direct":true},"footnotes":[{"field":"derivative.exercise_date","element":"exerciseDate","label":"F1","text":"Grant on 01/02/2025 to reporting person of stock options under the Ionis Pharmaceuticals, Inc. 2020 Equity Incentive Plan. Following this transaction, the option was exercisable as to 0 shares on\n01/02/2025. 25% of the shares subject to the option will vest and become exercisable on 01/02/2026. 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Following this transaction, the option was exercisable as to 0 shares on 02/26/2024. 25% of the shares subject to the option will vest and become exercisable on 02/26/2025.\nThereafter, the remaining shares subject to the option will vest and become exercisable in 36 equal monthly installments over the next 3 years."}],"balance_after":65203,"derivative":{"exercise_price":46.1,"exercise_date":"2025-02-26","expiration_date":"2034-02-25","underlying":"Common Stock","underlying_shares":65203},"source":{"system":"sec-edgar","filing":"0000874015-24-000133","document":"edgardoc.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":1,"url":"https://www.sec.gov/Archives/edgar/data/874015/000087401524000133/edgardoc.xml","form_type":"4"}},{"id":3007826,"issuer":{"id":145982,"kind":"organization","name":"AKCEA THERAPEUTICS, INC.","symbol":"AKCA"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne 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provided that 1/4th of the shares would vest one year after January 2, 2018 and 1/48th of the shares would vest monthly thereafter over the next three years, was cancelled in connection with the merger of the Issuer with a wholly owned subsidiary of Ionis Pharmaceuticals, Inc. in exchange for a cash payment of $230.23, representing the difference between the exercise price of the option and the acquisition price of $18.15."}],"balance_after":0,"derivative":{"exercise_price":17.38,"expiration_date":"2028-01-01","underlying":"Common Stock","underlying_shares":299},"source":{"system":"sec-edgar","filing":"0001209191-20-054616","document":"doc4.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":4,"url":"https://www.sec.gov/Archives/edgar/data/1662524/000120919120054616/doc4.xml","form_type":"4"}},{"id":3007823,"issuer":{"id":145982,"kind":"organization","name":"AKCEA THERAPEUTICS, INC.","symbol":"AKCA"},"owners":[{"id":52141,"kind":"person","name":"Jenne 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$18.15."}],"balance_after":0,"derivative":{"exercise_price":12.21,"expiration_date":"2027-06-04","underlying":"Common Stock","underlying_shares":32751},"source":{"system":"sec-edgar","filing":"0001209191-20-054616","document":"doc4.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":3,"url":"https://www.sec.gov/Archives/edgar/data/1662524/000120919120054616/doc4.xml","form_type":"4"}},{"id":3007822,"issuer":{"id":145982,"kind":"organization","name":"AKCEA THERAPEUTICS, INC.","symbol":"AKCA"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"Chief Commercial Officer"}}],"security":"Stock Option (right to 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follows: 1/4th of the shares vest one year after October 21, 2019;1/48th of the shares vest monthly thereafter over the next three years."}],"balance_after":50000,"derivative":{"exercise_price":18.94,"expiration_date":"2029-10-20","underlying":"Common Stock","underlying_shares":50000},"source":{"system":"sec-edgar","filing":"0001209191-19-053841","document":"doc4.xml","document_sequence":1,"table":"derivative","row_type":"transaction","position":2,"url":"https://www.sec.gov/Archives/edgar/data/1662524/000120919119053841/doc4.xml","form_type":"4"}},{"id":3389031,"issuer":{"id":145982,"kind":"organization","name":"AKCEA THERAPEUTICS, INC.","symbol":"AKCA"},"owners":[{"id":52141,"kind":"person","name":"Jenne Kyle","position":1,"cik":"0001791857","reported_name":"Jenne Kyle","relationship":{"director":false,"officer":true,"ten_percent_owner":false,"other":false,"officer_title":"Chief Commercial Officer"}}],"security":"Common 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