IONIS PHARMACEUTICALS INC IONS

56% shingled-prose overlap between the two filings.

2025: 200,000 chars · 2026: 200,000 chars

• Committee Report:84% overlap (671 → 671 chars)
• Pay Ratio (Item 402(u)):0% overlap (431 → 60,000 chars)
• Say-on-Pay proposal:76% overlap (1,960 → 1,960 chars)

• changed2025 2024NEOs, 2025 2024“Say on Pay” Vote and Summary of Recent Compensation and Governance Changes
• changedOn December 31, 2025, 2024,our Chief Executive Officer, Chief Financial Officer, and our four9 threeother most highly compensated executive officers, called our “named executive officers” or “NEOs,” were as follows:
• changedHougen Executive Vice President, Chief Financial OfficerKyleJenneExecutiveVicePresident,ChiefGlobalProductStrategyOfficer Richard S.
• changedGeary Executive Vice President, Chief Development Officer Brian Birchler Executive Vice President, Corporate and Development Operations Eric Swayze Executive Vice President, Research Patrick R.
• changedIn June 2025, 2024,we held a stockholder advisory vote on the compensation of our named executive officers.
• changedIn evaluating our general compensation practices during 2025 2024and in early 2026, 2025,we were mindful of the strong support our stockholders expressed for our compensation philosophies and practices.
• changedYear Implemented Compensation or Governance Change 2026 Revised our Non-Employee Director Compensation Policy to reduce the cap on annual equity awards such that incumbent non-employee directors will receive no more than $400,000 in annual equity compensation per year and newly appointed non-employee directors will receive no more than $600,000 in initial equity compensation, in both cases based on the aggregate grant date fair value 2026 Increased the proportion of PRSUs to be awarded to our executive officers beginning in 2026 as follows: from 33% to 40% of our CEO’s total equity awards and from 20% to 40% of our other executive officers’ total equity awards 2023 Increased the vesting term of initial equity awards granted to our non-employee directors upon joining the Board such that all initial awards vest equally over three years instead of vesting in one year 2023 Modified our executive clawback policy to align with the SEC’s clawback policy rules 2023 Revised the structure of our performance-based equity awards such that they have a single vesting period at the end of three years and require a higher relative TSR percentile rank for maximum payout of the awards (increased from the 75th percentile to the 90th percentile) 2023 Increased the ownership requirements in our stock ownership and holding guidelines applicable to ournon-employeedirectors2023Revisedour Non-EmployeeDirectorCompensationPolicysuchthat(1)incumbentnon-employeedirectorswillreceivenomorethan$450,000inannualequitycompensationperyearbasedontheaggregategrantdatefairvalue,and(2)newlyappointednon-employee directors willreceivenomorethan$675,000ininitialequitycompensationbasedontheaggregategrantdatefairvalue2022IncreasedtheallocationofourCEO’sperformance-basedequityawardsfrom20%to33%ofhistotalequityawards2022 Implemented PRSUs performance-basedequityawardsfor our other executiveofficersaccountingfor20%oftheirtotalequityawards2022Increasedtheownershiprequirementsinourstockownershipandholdingguidelinesapplicabletoourexecutive officers andnon-employeedirectors2021AdoptedaNon-EmployeeDirectorCompensationPolicythatappliestoournon-employeedirectorswherebytheCompensationCommittee,withinputfromitsindependentcompensationconsultant,mayreducethenumberofsharestobeautomaticallyissuedonagrantdateforeachsuchaward2020 Implemented PRSUs performance-basedequityawardsfor our CEO 2020Reducedthesizeoftheannualequityawardsfornon-employeedirectors,andattheAnnualMeetingofStockholdershadourstockholdersapprovesuchreducedequityawardsaspartoftheNon-EmployeeDirectors’StockOptionPlan
• new9Dr. Geary was no longer serving as an executive officer as of December 31, 2025.
• newHad Dr. Geary been serving in that capacity on December 31, 2025, he would have been a named executive officer, and as such, is included as a named executive officer in this Proxy Statement.
• newWith two independent commercial launches now underway, we have transitioned into a fully integrated commercial-stage biotechnology company.
• newWe currently have seven marketed medicines: TRYNGOLZA® (olezarsen), DAWNZERATM (donidalorsen), WAINUA® (eplontersen), SPINRAZA® (nusinersen), QALSODY® (tofersen), TEGSEDI® (inotersen) and WAYLIVRA® (volanesorsen).
• changedWe also have a rich innovative late-andmid-stagepipeline across our focus areas of inneurology, cardiometabolic diseases cardiologyand select areas of high patient need.
• changedWe currently have ten ninemedicines in Phase 3 development and multiple additional medicines in early and mid-stage development.
• new2025 was a defining year for Ionis, marked by the execution of our first two independent launches and multiple positive data readouts across our rich pipeline.
• newOur first launch was for TRYNGOLZA following approval in December 2024 for adults with familial chylomicronemia syndrome (“FCS”), as an adjunct to diet.
• newOur second launch was for DAWNZERA following approval in August 2025 for patients 12 years of age and older with hereditary angioedema (“HAE”).
• newIn addition, we are positioned to independently launch two additional medicines in 2026 assuming regulatory approval: olezarsen for the treatment of severe hypertriglyceridemia (“sHTG”), our first anticipated launch in a broad patient population, and zilganersen for Alexander disease (“AxD”), our first launch from our wholly owned neurology portfolio.
• changedFocusing Withafocuson our Ionis-owned pipeline, pipelinewe advanced numerous medicines in development.
• newWe currently have three wholly-owned medicines in late-stage development, including obudanersen for Angelman syndrome, which we advanced into a Phase 3 study in the second quarter of 2025.
• changedWe are advancing additional wholly-owned medicines in early and mid-stage development.With Witha commitment to progress advanceour RNA-targeting technology, we have expanded our technology platform to include siRNA, and we are forging ahead towards advancingour goals to optimize delivery and expand our therapeutic opportunities.
• new2025 was a defining year for Ionis, marked by the execution of our first two independent launches and multiple positive data readouts from our rich pipeline.
• changedOur ongoing and upcoming keyrecentachievements,combinedwithourindependent and partnered product launches anticipatedoverthenextfewyears,position us well to help millions of patients with serious diseases.
• changedOurstrongprogressin2024,Coupled with our disciplined financial management, we are positioned positionsuswell for continued growth and value creation in the years ahead.
• changedFurther, we also have numerous partnered medicines medicines,that enable our innovative science to reach more patients, while allowing us to focus our efforts on advancing the medicines we plan to commercialize.
• newOur partnered pipeline has also recently delivered positive data readouts, including positive Phase 3 data for bepirovirsen in chronic hepatitis B and Phase 2 data for sapablursen in polycythemia vera.
• changedOur key recent achievements, combined with our ongoing and planned independent and partnered product launches, launchesanticipatedoverthenextthreeyears,position us well to help millions of patients with serious diseases.
• changedOur multiple sources of revenue and our capital structure enable our continued investment to support ongoing and upcomingplanned launches and to advance advancingour wholly owned medicines in development.
• changedIn 2025, we earned revenues of $944 $705million in2024and ended the year 2024with a cash and short-term investment balance of $2.7 $2.3billion.
• newOur strong progress in 2025, coupled with our disciplined financial management, position us well for continued growth and value creation in the years ahead.
• newThe Compensation Committee considered this performance context, including progress toward durable commercial execution and balance sheet strength, when evaluating overall year-end compensation outcomes and the rigor of forward-looking goals.
• changed(1)For the year ended December 31, 2025. 2024.
• new(2)Non-GAAP financial measure that excludes non-cash compensation expense related to equity awards.
• changedFor a detailed reconciliation of non-GAAP and GAAP measures, see Appendix C. B.
• changedWe currently have ten ninemedicines in Phase 3 development and multiple additional medicines in early and mid-stage development.
• changed(1)Granted GrantedSobi exclusive rights to commercialize olezarsen in countries outside of the U.S., Canada and China.
• changedFor example, we: • Increased the proportion of PRSUs to be awarded to our executive officers beginning in 2026 as follows: from 33% to 40% of our CEO’s total equity awards and from 20% to 40% of our other executive officers’ total equity awards • Allocated approximately 60% 63%of our Chief Executive Officer’s 2025 2024compensation in the form of performance-based compensation, which we consider to consist of cash bonuses, stock options andPRSUs;•Eachyeargrant33%ofourChiefExecutiveOfficer’sannualtotalequityawardsintheformofPRSUsand 20%ofourotherexecutiveofficers’annualtotalequityawardsintheformofPRSUs; • Revised our PRSU structure for grants made beginning in 2023 andgoingforwardsuch that: ○ awards willhave a single vesting period at the end of three years; and ○ the relative TSR percentile rank for maximum payout of the awards increased from the 75th percentile to the 90th percentile.
• changed• Place a maximum limit on cash bonuses and do not guarantee a cash bonus – cash bonuses can be, and have been, zero; and • Empower our Compensation Committee with the ability to reduce the Company Performance Factor (used to determine cash bonuses) for our executive officers based on Company performance. performance,whichoccurredin2021.
• changedEngage an independent compensation consultant The Compensation Committee has retained a compensation consultant whose relationship with the Company was confirmed to be independent for 2025. 2024.
• changedHold a “say on pay” vote annually Provides an effective way for us to obtain information on stockholder sentiment about our executive compensation program each year. year
• changedFor 2025, 2024,Aon primarily provided the Compensation Committee advice in the following areas:
• changed•selecting the 2025 2024Peer Group used to assess executive officer and non-employee director compensation;
• new•assessing our bonus targets for non-executive employees;
• changed•performing the valuation calculations for our CEO’s and executive officers’ PRSU awards that vested and paid out in 2025; 2024;and
• changed•performing the valuation calculations for equity awards granted in 2020-2025 2020-2024to calculate compensation actually paid pursuant to Item 402(v) of Regulation S-K.
• changedIn 2025, 2024,we paid Aon approximately $203,000 $185,668for Aon’s consulting services directly related to Compensation Committee support.
• changedIn addition, management of the Company engaged affiliates of Aon for other services in 2025 2024that were not related to Aon’s Compensation Committee consulting services.
• newOur Human Resources department obtained general benchmarking survey data, for which we paid approximately $49,000.
• changedAdditionally, in 2025 2024our Finance department engaged Aon to provide equity valuation services, for which we
• changedforwhichwepaid approximately $30,000, $32,635,and an affiliate of Aon for insurance brokerage services, for which we paid approximately $726,000. $347,270.
• changedFor 2025 2024performance, the Compensation Committee awarded a Company Performance Factor of 190% 125%in recognition of the Company’s strong performance, achieving achievementofalmost all its goals for the year across all aspects of our business and, for andoverachievementofa significant number of these goals, exceeding the target performance. goals.
• changedFor grants made in 2022 through 2025, at target level of achievement, the PRSU awards represent 33% of our CEO’s total equity awards and 20% of each of the other executive officer’s total equity awards.
• changedBeginning with grants made in 2026, 2022,at target level of achievement, the PRSU awards represent 40% 33%of all our CEO’stotalequityawardsand20%ofeachotherexecutive officers’ officer’stotal equity awards.
• newBeginning with grants made in 2026, at target level of achievement, the PRSU awards represent 40% of all our executive officers’ total equity awards.
• changedWe structure structuredthePRSU awards to pay out based on relative TSR, which we believe is the best way to directly tie performance that positively impacts stockholders with the payout that the executive officers receive at the end of the performance period.
• newPRSU grants have a single vesting period at the end of three years following the grant date.
• changedNo •Nonumber of PRSUs is guaranteed to vest and the actual number of PRSUs that will vest at the end of the eachperformance period may be anywhere from zero to the maximum amount depending on the Company’s relative TSR. TSR;and
• changedIf •Ifthe Company’s TSR is negative over the performance period, the payout will not exceed 100% of the target number even if the percentile rank exceeds the 50th percentile.
• newBelow are the PRSU payout thresholds (with linear interpolation for performance between percentile ranks):
• changedThe PRSUs granted to all our executive officers in 2023, 2022,including our NEOs, paid out to our NEOs in January 2026 2025as follows:
• newPerformance Period Ionis’ TSR Relative TSR Percentile Ranking Percent of Target Number Total Shares Earned 1of 1 99.64% 80th 167.27% Dr. Monia: 122,214 Ms. Hougen: 13,562 Dr. Geary: 11,991 Mr. Birchler: 11,991 Dr. Swayze: 11,991 Mr. O’Neil: 11,991
• changed2025 2024NEO Compensation: Performance-Based vs. Non-Performance-Based
• changedThe charts below illustrate the proportion of our CEO’s and average NEOs’ (excluding the CEO) 2025 2024total compensation that was allocated among performance-based compensation and non-performance-based compensation.
• changed2025 2024CEO Compensation: Performance-Based vs. Non-Performance-Based
• changedThe performance-based compensation reflected below includes the CEO’s cash bonus for 2025 2024performance ($2,398,049), ($1,024,662),fair value of stock options granted in 2025 ($1,438,105), 2024($3,004,746),and fair value of PRSU awards granted in 2025 ($4,147,630). 2024($5,627,878).
• changedThe non-performance-based compensation reflected below includes the CEO’s 2025 2024base salary ($1,051,776) ($1,008,898)and fair value of time-vested RSU awards granted in 2025 ($4,297,208). 2024($4,681,270).
• changed2025 2024Average NEO Compensation: Performance-Based vs. Non-Performance-Based The performance-based compensation reflected below includes the NEOs’ (excluding the CEO) average cash bonus for 2025 2024performance ($663,799), ($373,004),average fair value of stock options granted in 2025 ($396,775), 2024($995,193),and average fair value of PRSU awards granted in 2025 ($580,839). 2024($597,876).
• changedThe non-performance-based compensation reflected below includes the NEOs’ (excluding the CEO) average 2025 2024base salary ($626,556) ($581,813)and average fair value of time-vested RSU awards granted in 2025 ($1,185,597). 2024($1,487,762).
• newIn addition, as we continue to transition from primarily a research and development organization to independently commercializing our own medicines, our compensation program must support both the continued advancement of our innovative pipeline and the build-out and scaling of our commercial capabilities.
• newThis includes planning for and executing multiple product launches, expanding our commercial infrastructure, and supporting the investments necessary to independently bring our medicines to patients.
• changedAs such, it is essential that we set goals that incentivize our employees to execute our long-term strategy, because we believe our long-term strategy should continue to reward our stockholders into the future.
• newManaging this portfolio also requires the ability to execute multiple product launches in overlapping timeframes without compromising the continued advancement of earlier-stage programs.
• changedAs a result, we use a mix of financial and operational objectives that reflect those achievements that we believe should drive near and longer term stockholder shareholdervalue.
• changedIn other words, we want to structure our objectives to reward success based on judgment, rather than the making of “bad bets.” On at least a quarterly basis, the Board evaluates our progress toward inachieving these objectives.
• changedIt takes a significant period of time and a substantial investment to recruit and develop employees who possess the experience and talent necessary to lead at Ionis given our transformative technology, rich drug development pipeline and expanding portfolio of emergingcommercial medicines. business.
• changedOur current executive officers have on average approximately 22 23years and individually as much as over 36 35years of tenure at Ionis.
• changedWorking alongside our long-tenured employees, these senior-level commercial executives will help us ensure we tofully realize the potential of our innovative medicines reaching patients and their healthcare providers.
• newTo recognize our employees, including our named executive officers, who deliver long-term productivity to the Company, Ionis has two cash-based awards: the “Career Achievement Award” in the amount of $50,000 to recognize our distinguished, long-tenured, senior-level contributors, including Board members, who made extraordinary contributions that helped determine the Company’s future, and the “Commitment to Ionis Award” to thank employees for their commitment to the Company.
• newIn 2025, none of our named executive officers received a Career Achievement Award, but Dr. Geary and Mr. Birchler each received a Commitment to Ionis Award to recognize 30 years of service, and Ms. Hougen received a Commitment to Ionis Award to recognize 25 years of service.
• changedYears of Service Award 1 ​$1,000 5 $5,000 10 $10,000 15 $15,000 20 $20,000 25 $25,000 30 $30,000 35 $35,000 40 $40,000
• changedAs a result, we have structured the various components of our compensation system to reflect accountability both for the successes and failures (both long-term and short-term) of Ionis and of our employees.

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