Financial Analysis

During the years ended December 31, 2025, 2024 and 2023 , our revenues were comprised of the following (in thousands): Year Ended December 31, 2025 2024 2023 Revenue: Commercial revenue: Product sales, net: TRYNGOLZA sales, net $ 107,526 $ - $ - DAWNZERA sales, net 7,789 - - Total product sales, net 115,315 - - Royalty revenue: SPINRAZA royalties 212,280 216,090 240,379 WAINUA royalties 49,090 20,207 - Other royalties 24,159 21,010 32,424 Total royalty revenue 285,529 257,307 272,803 Other commercial revenue 35,004 35,769 35,788 Total commercial revenue 435,848 293,076 308,591 Research and development revenue: Collaborative agreement revenue 465,785 332,647 352,657 WAINUA joint development revenue 42,078 79,415 126,399 Total research and development revenue 507,863 412,062 479,056 Total revenue $ 943,711 $ 705,138 $ 787,647

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6. Fair Value Measurements The following tables present the major security types we held at December 31, 2025 and 2024 that we regularly measure and carry at fair value . The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securities fair value (in thousands): At Quoted Prices in Active Markets Significant Other Observable Inputs December 31, 2025 (Level 1) (Level 2) Cash equivalents (1) $ 213,579 $ 213,579 $ - Corporate debt securities (2) 1,184,608 - 1,184,608 Debt securities issued by U.S. government agencies (3) 148,631 - 148,631 Debt securities issued by the U.S. Treasury (3) 1,012,746 1,012,746 - Debt securities issued by states of the U.S. and political subdivisions of the states (3) 6,943 - 6,943 Publicly traded equity securities included in other current assets (4) 3,012 3,012 - Total $ 2,569,519 $ 1,229,337 $ 1,340,182 At Quoted Prices in Active Markets Significant Other Observable Inputs December 31, 2024 (Level 1) (Level 2) Cash equivalents (1) $ 180,445 $ 180,445 $ - Corporate debt securities (3) 1,032,066 - 1,032,066 Debt securities issued by U.S. government agencies (3) 208,998 - 208,998 Debt securities issued by the U.S. Treasury (3) 806,724 806,724 - Debt securities issued by states of the U.S. and political subdivisions of the states (3) 7,524 - 7,524 Other municipal debt securities (3) 696 - 696 Publicly traded equity securities included in other c …

FairValueDisclosuresTextBlock · excerpt; the full note is in the filing

9. Income Taxes We adopted ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures , on a prospective basis for the year ended December 31, 2025. Loss before income taxes is comprised of (in thousands): Year Ended December 31, 2025 2024 2023 United States $ (381,180 ) $ (460,712 ) $ (334,707 ) Foreign 1,579 644 742 Loss before income taxes $ (379,601 ) $ (460,068 ) $ (333,965 ) Our income tax expense (benefit) was as follows (in thousands): Year Ended December 31, 2025 2024 2023 Current: Federal $ (1,015 ) $ (5,492 ) $ 35,861 State 2,580 (848 ) (3,687 ) Foreign 221 169 147 Total current income tax expense (benefit) 1,786 (6,171 ) 32,321 Deferred: Federal - - - State - - - Total deferred income tax expense (benefit) - - - Total income tax expense (benefit) $ 1,786 $ (6,171 ) $ 32,321 Our expense (benefit) for income taxes differs from the amount computed by applying the U.S. federal statutory rate to loss before income taxes. The sources and tax effects of the differences, applying ASU 2023-09 prospectively, are as follows (in thousands): Year Ended December 31, 2025 Pre-tax loss $ (379,601 ) Statutory rate (79,716 ) 21.0 % State and local income tax, net of federal income tax effect (a) 353 (0.1 )% Foreign tax effects (118 ) 0.0 % Effect of cross-border tax laws 459 (0.1 )% Changes in unrecognized tax benefits 12,145 (3.2 )% Changes in valuation allowances 93,773 (24.7 )% Tax credits: Research and development tax credits (17,754 ) 4.7 % Orphan drug tax c …

IncomeTaxDisclosureTextBlock · excerpt; the full note is in the filing

11. Legal Proceedings From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates. On September 10, 2025, Arrowhead Pharmaceuticals, Inc., or Arrowhead, filed a lawsuit in the District of Delaware, or the Delaware Lawsuit, seeking a declaratory judgment that our patent US9,593,333 is invalid or not infringed by use of Arrowhead's ApoCIII inhibitor plozasiran. On September 11, 2025, we filed a lawsuit in the Central District of California, or the California Lawsuit, asserting infringement of that same patent by Arrowhead's announced intention to commercialize plozasiran in November 2025. On December 23, 2025, the Delaware Lawsuit was dismissed in favor of the California Lawsuit. On …

LegalMattersAndContingenciesTextBlock · excerpt; the full note is in the filing

Recent Accounting Standards In November 2023, the Financial Accounting Standards Board, or FASB, issued Accounting Standard Update, or ASU, 2023-07, which provides updated guidance on segment reporting. The guidance requires public companies to disclose significant expenses that are regularly provided to the CODM, other segment items for each reportable segment and measures of segment profit or loss used by the CODM for allocating resources. In addition, the updated guidance requires public companies with a single reportable segment to provide all disclosures required under Accounting Standards Codification, or ASC, Topic 280, Segment Reporting , and public companies to include in interim reports all disclosures related to a reportable segment's profit or loss and assets that are currently required in annual reports. We adopted the annual reporting requirements in our 2024 Annual Report on Form 10-K and began providing the interim reporting requirements in our Quarterly Report on Form 10-Q in the first quarter of 2025. Refer to Note 12, Segment Information , for further details on our segment information. In December 2023, the FASB issued ASU 2023-09, which provides updated guidance on income tax disclosures. The new guidance requires companies to provide additional disaggregation of information related to the income tax rate reconciliation and income tax payments. In addition, the guidance eliminates certain existing disclosure requirements related to uncertain tax positions …

NewAccountingPronouncementsPolicyPolicyTextBlock · excerpt; the full note is in the filing

10. Employment Benefits We have employee 401(k) salary deferral plans covering all employees. Employees could make contributions by withholding a percentage of their salary up to the IRS annual limits of $23,500 and $31,000 in 2025 for employees under 50 years old and employees 50 years old or over, respectively. We made approximately $10.6 million, $8.6 million and $7.1 million in matching contributions for the years ended December 31, 2025, 2024 and 2023, respectively.

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3. Revenues During the years ended December 31, 2025, 2024 and 2023 , our revenues were comprised of the following (in thousands): Year Ended December 31, 2025 2024 2023 Revenue: Commercial revenue: Product sales, net: TRYNGOLZA sales, net $ 107,526 $ - $ - DAWNZERA sales, net 7,789 - - Total product sales, net 115,315 - - Royalty revenue: SPINRAZA royalties 212,280 216,090 240,379 WAINUA royalties 49,090 20,207 - Other royalties 24,159 21,010 32,424 Total royalty revenue 285,529 257,307 272,803 Other commercial revenue 35,004 35,769 35,788 Total commercial revenue 435,848 293,076 308,591 Research and development revenue: Collaborative agreement revenue 465,785 332,647 352,657 WAINUA joint development revenue 42,078 79,415 126,399 Total research and development revenue 507,863 412,062 479,056 Total revenue $ 943,711 $ 705,138 $ 787,647 Revenue Sources The following are sources of revenue and when we typically recognize revenue. Commercial Revenue In December 2024, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA (olezarsen) for the treatment of familial chylomicronemia syndrome, or FCS. Following the approval, we launched TRYNGOLZA and began earning revenue from TRYNGOLZA sales. In August 2025, the FDA approved DAWNZERA (donidalorsen) for prophylaxis to prevent attacks of hereditary angioedema, or HAE, in adult and pediatric patients 12 years of age and older. Following the approval, we launched DAWNZERA and began earning revenue from DAWNZERA sales . We earn …

RevenueFromContractWithCustomerTextBlock · excerpt; the full note is in the filing

12. Segment Information We operate as a single operating segment, Ionis operations, focused on the research, development and commercialization of our RNA-targeted medicines to bring better futures to people with serious diseases. As the CODM, our Chief Executive Officer manages our company, reviews operating results, assesses performance and allocates resources on an aggregate basis using consolidated net income or loss as the key measure of segment profit or loss. As such, results of our operations are reported on a consolidated basis for purposes of management and segment reporting. Ionis operations derives its revenues from commercial and R&D revenue sources. Refer to Note 3, Revenues , for further details on our sources of revenue. The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands): Year Ended December 31, 2025 2024 2023 Revenue $ 943,711 $ 705,138 $ 787,647 Less: Cost of sales 14,008 10,415 8,686 Drug discovery 125,156 114,350 125,649 Drug development 486,199 527,259 530,332 Medical affairs 32,005 27,229 19,454 Manufacturing and development chemistry 87,314 57,729 65,293 R&D support 94,847 82,559 81,019 Selling, general and administrative 351,992 230,478 205,135 Other segment items (1) 133,577 109,016 118,365 Consolidated net loss $ (381,387 ) $ (453,897 ) $ (366,286 ) (1) Other segment items include stock-based compensation expense, investment income, interest expense, gain or loss on inves …

SegmentReportingDisclosureTextBlock · excerpt; the full note is in the filing

8. Stockholders Equity Preferred Stock We are authorized to issue up to 15 million shares of blank check Preferred Stock. As of December 31, 2025, there were no shares of Preferred Stock outstanding. We have designated Series C Junior Participating Preferred Stock but have no issued or outstanding shares as of December 31, 2025. Common Stock At December 31, 2025 and 2024, we had 300 million shares of common stock authorized, of which 163.3 million and 157.9 million were issued and outstanding, respectively. As of December 31, 2025, total common shares reserved for future issuance were 45.1 million. During the years ended December 31, 2025, 2024 and 2023, we issued 5.4 million, 2.1 million and 2.3 million shares of common stock, respectively, for stock option exercises, vesting of restricted stock units, and ESPP purchases. We received net proceeds from these transactions of $192.6 million, $33.6 million and $49.4 million in 2025, 2024 and 2023, respectively. In September 2024, we completed the sale of 11.5 million shares of our common stock through a public offering at a price of $43.50 per share. We received net proceeds of $489.1 million from the sale of these shares net of underwriting discounts and commissions and other offering expenses of $11.2 million. Stock Plans 2011 Equity Incentive Plan In 2011, our Board of Directors adopted, and the stockholders subsequently approved, a stock option plan that provides for the issuance of stock options, stock appreciation rights, …

StockholdersEquityNoteDisclosureTextBlock · excerpt; the full note is in the filing

11. Convertible Debt 0 Percent Convertible Senior Notes due 2030 In November 2025, we completed a $770.0 million offering of our 0% Notes due 2030. At June 30, 2026 , we had the following 0% Notes due 2030 outstanding (in millions except interest rate and price per share data): 0% Notes due 2030 Outstanding principal balance $ 770.0 Unamortized debt issuance costs $ 16.6 Maturity date December 2030 Interest rate 0 % Effective interest rate 0.5 % Conversion price per share $ 98.10 Total shares of common stock subject to conversion 7.8 1.75 Percent Convertible Senior Notes due 2028 In 2023, we completed a $575.0 million offering of our 1.75% Notes due 2028. At June 30, 2026, we had the following 1.75% Notes due 2028 outstanding (in millions except interest rate and price per share data): 1.75% Notes due 2028 Outstanding principal balance $ 575.0 Unamortized debt issuance costs $ 5.7 Maturity date June 2028 Interest rate 1.75 % Effective interest rate 2.3 % Conversion price per share $ 53.73 Total shares of common stock subject to conversion 10.7 0 Percent Convertible Senior Notes due 2026 and Call Spread In April 2026, we paid the remaining principal balance of our 0% Notes due 2026 with $432.5 million of cash at maturity. In addition, we settled the conversion obligation in excess of principal by issuing 1.8 million shares of common stock to the holders of the 0% Notes due 2026 who exercised their conversion option. In conjunction with the 2021 offering, we entered into a call …

DebtDisclosureTextBlock · excerpt; the full note is in the filing

During the three and six months ended June 30, 2026 and 2025, our revenues consisted of the following (in thousands): Three Months Ended Six Months Ended June 30, June 30, 2026 2025 2026 2025 Revenue: Commercial revenue: Product sales, net: TRYNGOLZA sales, net $ 4,574 $ 19,273 $ 31,674 $ 25,561 DAWNZERA sales, net 26,565 - 42,420 - Total product sales, net 31,139 19,273 74,094 25,561 Royalty revenue: SPINRAZA royalties 53,486 54,337 97,196 102,347 WAINUA royalties 16,436 10,415 27,145 19,787 Other royalties 6,036 5,200 9,941 11,983 Total royalty revenue 75,958 69,952 134,282 134,117 Other commercial revenue 11,526 13,531 18,058 19,246 Total commercial revenue 118,623 102,756 226,434 178,924 Research and development revenue: Collaborative agreement revenue 133,137 336,921 253,797 381,951 WAINUA joint development revenue 16,189 12,372 33,811 22,785 Total research and development revenue 149,326 349,293 287,608 404,736 Total revenue $ 267,949 $ 452,049 $ 514,042 $ 583,660

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9. Stock-based Compensation Expense The following table summarizes stock-based compensation expense for the three and six months ended June 30, 2026 and 2025 (in thousands): Three Months Ended Six Months Ended June 30, June 30, 2026 2025 2026 2025 Cost of sales $ 176 $ 610 $ 323 $ 710 Research, development and patent expense 25,098 19,542 49,804 39,840 Selling, general and administrative expense 20,321 9,538 38,743 18,858 Stock-based compensation expense, net of amounts capitalized 45,595 29,690 88,870 59,408 Capitalized stock-based compensation expense - 509 18 1,000 Total stock-based compensation expense $ 45,595 $ 30,199 $ 88,888 $ 60,408 As of June 30, 2026, total unrecognized estimated stock-based compensation expense related to non-vested stock options, RSUs and PRSUs was $58.4 million, $166.6 million and $23.9 million, respectively. Our actual expenses will likely differ from these estimates because we will adjust our unrecognized stock-based compensation expense for future forfeitures, including any PRSUs that do not vest. We expect to recognize the cost of stock-based compensation expense related to our non-vested stock options, RSUs and PRSUs over a weighted average amortization period of 1.3 years, 1.6 years and 1.6 years, respectively. Stock Options: The weighted-average grant date fair value of stock options granted to employees for the six months ended June 30, 2026 and 2025 was $38.07 and $16.51 per share, respectively. In the second quarter of 2026, two new me …

DisclosureOfCompensationRelatedCostsShareBasedPaymentsTextBlock · excerpt; the full note is in the filing

8. Fair Value Measurements The following tables present the major security types we held at June 30, 2026 and December 31, 2025 that we regularly measure and carry at fair value. The following tables segregate each security type by the level within the fair value hierarchy of the valuation techniques we utilized to determine the respective securitys fair value (in thousands): At Quoted Prices in Active Markets Significant Other Observable Inputs June 30, 2026 (Level 1) (Level 2) Cash equivalents (1) $ 155,741 $ 155,741 $ - Corporate debt securities (2) 986,465 - 986,465 Debt securities issued by U.S. government agencies (3) 145,272 - 145,272 Debt securities issued by the U.S. Treasury (4) 646,877 646,877 - Debt securities issued by states of the U.S. and political subdivisions of the states (3) 5,752 - 5,752 Publicly traded equity securities included in other current assets (5) 47,768 47,768 - Total $ 1,987,875 $ 850,386 $ 1,137,489 At Quoted Prices in Active Markets Significant Other Observable Inputs December 31, 2025 (Level 1) (Level 2) Cash equivalents (1) $ 213,579 $ 213,579 $ - Corporate debt securities (6) 1,184,608 - 1,184,608 Debt securities issued by U.S. government agencies (3) 148,631 - 148,631 Debt securities issued by the U.S. Treasury (3) 1,012,746 1,012,746 - Debt securities issued by states of the U.S. and political subdivisions of the states (3) 6,943 - 6,943 Publicly traded equity securities included in other current assets (5) 3,012 3,012 - Total $ 2,569,5 …

FairValueDisclosuresTextBlock · excerpt; the full note is in the filing

12. Legal Proceedings From time to time, we are involved in legal proceedings arising in the ordinary course of our business. Periodically, we evaluate the status of each legal matter and assess our potential financial exposure. If we consider the potential loss from any legal proceeding to be probable and we can reasonably estimate the amount, we accrue a liability for the estimated loss. The outcome of any proceeding is not determinable in advance. Therefore, we are required to use significant judgment to determine the probability of a loss and whether the amount of the loss is reasonably estimable. Our assessment of a potential liability and the amount of accruals we recorded are based only on the information available to us at the time. As additional information becomes available, we reassess the potential liability related to the legal proceeding and may revise our estimates. On September 11, 2025, we sued Arrowhead Pharmaceuticals, Inc., in the Central District of California asserting that Arrowhead's announced intention to commercialize plozasiran in November 2025 would infringe our patent US9,593,333. Arrowhead is now commercializing plozasiran and the lawsuit is ongoing. Arrowhead has filed its Answer to our Complaint and Counterclaims asserting that our patent US9,593,333 is invalid or not infringed by use of plozasiran. On June 1, 2026, Biogen received notice that Somerset Therapeutics, LLC had filed an Abbreviated New Drug Application, or ANDA, seeking approval to …

LegalMattersAndContingenciesTextBlock · excerpt; the full note is in the filing

Recent Accounting Standards In July 2025, the FASB issued ASU 2025-05, which amended the guidance in ASC 326 to simplify the estimation of credit losses on accounts receivable and contract assets from revenue transactions. The amended guidance allows companies to elect a practical expedient to assume that conditions as of the balance sheet date will remain unchanged for the remaining life of the asset when estimating the expected credit losses of the asset. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Companies that elect the practical expedient are required to apply the amendments prospectively. We adopted this update in the first quarter of 2026 on a prospective basis and elected the practical expedient. The updated guidance did not have a material impact on our condensed consolidated financial statements. In September 2025, the FASB issued ASU 2025-06, which amended and simplified the existing guidance for software costs. The amended guidance removes references to software development stages and allows companies to begin capitalizing software costs when management has authorized and committed to funding the software project and it is probable that the project will be completed with the software performing the intended function. This update is effective for annual periods beginning after December 15, 2027 and interim periods within those annual periods. Early adoption of this guidance is permi …

NewAccountingPronouncementsPolicyPolicyTextBlock · excerpt; the full note is in the filing

4. Revenues During the three and six months ended June 30, 2026 and 2025, our revenues consisted of the following (in thousands): Three Months Ended Six Months Ended June 30, June 30, 2026 2025 2026 2025 Revenue: Commercial revenue: Product sales, net: TRYNGOLZA sales, net $ 4,574 $ 19,273 $ 31,674 $ 25,561 DAWNZERA sales, net 26,565 - 42,420 - Total product sales, net 31,139 19,273 74,094 25,561 Royalty revenue: SPINRAZA royalties 53,486 54,337 97,196 102,347 WAINUA royalties 16,436 10,415 27,145 19,787 Other royalties 6,036 5,200 9,941 11,983 Total royalty revenue 75,958 69,952 134,282 134,117 Other commercial revenue 11,526 13,531 18,058 19,246 Total commercial revenue 118,623 102,756 226,434 178,924 Research and development revenue: Collaborative agreement revenue 133,137 336,921 253,797 381,951 WAINUA joint development revenue 16,189 12,372 33,811 22,785 Total research and development revenue 149,326 349,293 287,608 404,736 Total revenue $ 267,949 $ 452,049 $ 514,042 $ 583,660 Revenue Sources The following are sources of revenue and when we typically recognize revenue. Commercial Revenue In June 2026, the U.S. Food and Drug Administration, or FDA, approved TRYNGOLZA for the treatment of sHTG. Following the approval, we launched TRYNGOLZA for the treatment of sHTG and began earning revenue from TRYNGOLZA sales for the sHTG indication. TRYNGOLZA is also approved in the U.S. for the treatment of familial chylomicronemia syndrome, or FCS . In April 2026, we lowered the Whole …

RevenueFromContractWithCustomerTextBlock · excerpt; the full note is in the filing

13. Segment Information We operate as a single operating segment, Ionis operations, focused on the research, development and commercialization of our RNA-targeted medicines to bring better futures to people with serious diseases. The CODM, our Chief Executive Officer, manages our company, reviews operating results, assesses performance and allocates resources on an aggregate basis using consolidated net income or loss as the key measure of segment profit or loss. As such, results of our operations are reported on a consolidated basis for purposes of management and segment reporting. Ionis operations derives its revenues from commercial and R&D revenue sources. Refer to Note 4, Revenues , for further details on our sources of revenue. The following table sets forth information on segment profit or loss, including significant segment expenses (in thousands): Three Months Ended Six Months Ended June 30, June 30, 2026 2025 2026 2025 Revenue $ 267,949 $ 452,049 $ 514,042 $ 583,660 Less: Cost of sales 2,563 3,541 5,398 4,904 Drug discovery 29,120 30,255 57,677 57,244 Drug development 103,958 117,689 208,140 230,635 Medical affairs 11,318 7,826 21,307 13,468 Manufacturing and development chemistry 20,639 21,545 40,947 35,826 R&D support 26,974 20,607 49,405 41,159 Selling, general and administrative 130,075 81,081 262,012 148,061 Other segment items (1) 57,948 45,954 76,330 75,750 Consolidated net income (loss) $ (114,646 ) $ 123,551 $ (207,174 ) $ (23,387 ) (1) Other segmen …

SegmentReportingDisclosureTextBlock · excerpt; the full note is in the filing

2. Significant Accounting Policies Our significant accounting policies have not changed substantially from those included in our Annual Report on Form 10-K for the year ended December 31, 2025. Recent Accounting Standards In July 2025, the FASB issued ASU 2025-05, which amended the guidance in ASC 326 to simplify the estimation of credit losses on accounts receivable and contract assets from revenue transactions. The amended guidance allows companies to elect a practical expedient to assume that conditions as of the balance sheet date will remain unchanged for the remaining life of the asset when estimating the expected credit losses of the asset. This update is effective for annual periods beginning after December 15, 2025 and interim periods within those annual periods. Companies that elect the practical expedient are required to apply the amendments prospectively. We adopted this update in the first quarter of 2026 on a prospective basis and elected the practical expedient. The updated guidance did not have a material impact on our condensed consolidated financial statements. In September 2025, the FASB issued ASU 2025-06, which amended and simplified the existing guidance for software costs. The amended guidance removes references to software development stages and allows companies to begin capitalizing software costs when management has authorized and committed to funding the software project and it is probable that the project will be completed with the software perform …

SignificantAccountingPoliciesTextBlock · excerpt; the full note is in the filing