Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Investor Presentation (October 2026)
39 slides from Ionis Pharmaceuticals's investor presentation, October 2026
Slide 1: Corporate Presentation
Corporate Presentation October 2026 Nasdaq: IONS
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies and our expectations regarding development and re
Slide 3: Well Positioned for Accelerating Growth
Well Positioned for Accelerating Growth Fully integrated, commercial-stage biotechnology company High-value innovative pipeline built on groundbreaking RNA-targeting technology Successful commercial launches enabled by breakthrough clinical results Clear path to accelerating revenue growth, sustaine
Slide 4: Building Commercial Momentum
Building Commercial Momentum Providing multi-billion-dollar revenue potential for Ionis1 First Broad Patient First Independent Continued Strong HAE Launch Driving Population Launch Neurology Launch FCS Patient Demand Revenue Growth Underway Underway First disease-modifying First FDA-approved treatme
Slide 5: Delivering a Steady Cadence of New Medicines
Delivering a Steady Cadence of New Medicines1,2 Sapablursen (PV) Salanersen (SMA) Obudanersen 4 Independent launches in 2025-2026 Ulefnersen (Angelman syndrome) (FUS-ALS) 3 Sefaxersen Partner (IgAN) launches by end of 2027 Bepirovirsen (CHB) (Alexander disease) (sHTG) (HAE) (FCS) 2026 Launches 2027
Slide 6: Delivering Transformational Medicines in Focused Therapeutic Areas
Delivering Transformational Medicines in Focused Therapeutic Areas Cardiometabolic Rare and prevalent patient populations Neurology in focused disease First- or best-in-class medicines that areas First- or best-in-class medicines target cardiometabolic diseases, the to address a broad range of leadi
Slide 7: Building a Leading Cardiometabolic Pipeline
Building a Leading Cardiometabolic Pipeline 1,2 2 3 Wholly Owned Medicines Partnered Medicines 5 Medicines Approved Medicine 3 7 1. Timing and expectations based on current assumptions and subject to change. 2. Assuming approval. 3. TRYNGOLZA is now approved in the U.S.; see Full Prescribing Informa
Slide 8: Strong Foundation for TRYNGOLZA Launch in sHTG
Strong Foundation for TRYNGOLZA Launch in sHTG1 Increasing FCS Demand Continued in Q2:2026 Strong Q-o-Q Increase in Demand3 Demand3 in Robust efficacy and safety Q2:2026 TRYNGOLZA • Significant and sustained triglyceride reductions FCS product sales of • Substantial reduction in acute pancreatitis e
Slide 9: Now Approved
NOW APPROVED Indicated as an adjunct to diet to reduce triglycerides (TG) and the risk of acute pancreatitis in adults with severe hypertriglyceridemia (sHTG: TG greater than or equal to 500 mg/dL) TRYNGOLZA is now approved in the U.S.; see Full Prescribing Information. 9
Slide 10: TRYNGOLZA: sHTG Launch Off to Encouraging Start
TRYNGOLZA: sHTG Launch Off to Encouraging Start1,2 • Landmark approval as the first-ever medicine to prevent acute pancreatitis in sHTG1 • Leveraging strong foundation established with FCS launch Annual Peak Product Revenue Opportunity3 • Prescriptions from cardiologists, endocrinologists and lipido
Slide 11: TRYNGOLZA: Positioned to be the New Standard of Care for sHTG
Groundbreaking clinical results2: 〉 Highly statistically significant and clinically meaningful mean reductions in fasting triglycerides of up to 72% on top of standard of care 〉 86% of patients reached TGs <500 mg/dL TRYNGOLZA: 〉 Up to 54% of patients’ TGs normalized (≤150 mg/dL) Positioned to be th
Slide 12: Leading the Way in the Treatment of Neurological Diseases
Leading the Way in the Treatment of Neurological Diseases with an Advancing Pipeline 1,2 8 5 Wholly Owned Medicines Partnered Medicines 13 Medicines Approved Medicines 3-6 1. Timing and expectations based on current assumptions and subject to change. 2. Assuming approval. 3. ZANVASTRO is now approve
Slide 13: Now Approved
NOW APPROVED The first and only disease modifying therapy approved by the FDA for the treatment of pediatric and adult patients with Alexander disease 1. ZANVASTRO is now approved in the U.S.; see Full Prescribing Information.
Slide 14: ZANVASTRO: Ionis' First Independent Neurology Medicine Launch
ZANVASTRO: Ionis’ First Independent Neurology Medicine 1 Launch ZANVASTRO for the treatment of Alexander disease First and only disease modifying treatment approved for Alexander disease Broad label, enabling treatment for children and adults with Alexander disease ambulatory status children and adu
Slide 15: ZANVASTRO: Ionis' First Independent Neurology Launch
Substantial Unmet Need Alexander disease: An ultra-rare, progressive and often fatal neurological disorder First approved disease modifying treatment ZANVASTRO: Broad Label Ionis’ First ZANVASTRO indication enables treatment for children and adults with Independent Alexander disease Neurology Launch
Slide 16: Obudanersen: A Promising Investigational Medicine for Angelman Syndrome
Obudanersen: A Promising Investigational Medicine for Angelman Syndrome • >100k people in major geographies with Angelman syndrome, The a severe, rare neurodevelopmental disorder1 Opportunity • Significant unmet need with no approved disease-modifying treatments • Positive results seen in the HALOS
Slide 17: Expressive Communication: Continued Improvement
Expressive Communication: Continued Improvement Observed on Bayley-4 at 18 Months1 Change on Bayley-4 Expressive Communication Obudanersen vs. Natural History Improvements on Bayley-4 measure of expressive Improvement communication exceed natural history2 Consistent improvements across additional as
Slide 18: Responder Analysis: Continued Benefit in Multiple Domains
Responder Analysis: Continued Benefit in Multiple Domains Assessed in the HALOS Study1-3 Responders on Bayley-4 Responders on ≥ 1 Responders on ≥ 2 Responders on ≥ 3 Expressive Bayley-4 Domains Bayley-4 Domains Bayley-4 Domains Communication 6 months 61% 95% 84% 68% 12 months 64% 97% 89% 75% 18 mont
Slide 19: Extending the SMA Franchise
Extending the SMA Franchise Nusinersen High Dose • Now approved in U.S., EU and Japan Salanersen • Designed with a novel Ionis chemistry to achieve strong efficacy & once-yearly dosing • Interim Phase 1 data showed that once-yearly dosing with both doses tested was well tolerated and led to substant
Slide 20: Diranersen: A Differentiated Approach in Targeting Tau
Diranersen: A Differentiated Approach in Targeting Tau Tau is a potentially attractive target in Alzheimer’s disease: • AD is a progressive neurodegenerative disease characterized by cerebral accumulation of amyloid plaques and tau NFTs1 • The burden of tau NFTs is closely linked to neurodegeneratio
Slide 21: Diranersen Shows Substantial Tau Reduction in the CSF and Brain
Diranersen is the Only Tau Directed Agent to Show Substantial Tau Reduction in the CSF and Brain1 • 50-65% reduction from baseline in soluble total tau in CSF across dose arms at week 72 • Confirms target engagement • First reported substantial reduction in tau PET by an anti- tau agent in a Phase 2
Slide 22: Phase 2 CELIA Study Results
Phase 2 CELIA Study Results: 60mg Q24W Demonstrated a Promising Efficacy Profile Across Multiple Endpoints Diranersen CDR-SB ADAS-COG* MMSE ADCS-ADL-MCI ADCOMS iADRS • CDR-SB and ADCOMS 60mg Q24W 26% 42% 50% 0% 23% 30% inline with anti-amyloid agents1 Anti- CDR-SB ADAS-COG* MMSE ADCS-ADL-MCI ADCOMS
Slide 23: Diranersen: Advancing to Phase 3
Diranersen Targeting Tau for Alzheimer’s Disease Advancing to Phase 31-2 Diranersen: Next Steps Encouraging emerging clinical profile with unprecedented impact • Ongoing long-term on tau reduction and cogitative extension study With 94% of patients who • Ongoing analyses of the completed the stu
Slide 24: DAWNZERA Launch Gaining Momentum
DAWNZERA Launch Gaining Momentum1 Delivering on What HAE Patients Need Most First and Only RNA-Targeted Treatment to Prevent HAE Attacks Generated $42 million in H1:2026 Indicated for prophylaxis to prevent attacks of HAE in adult and +63% pediatric patients ≥12 years old $26 • Prescriptions written
Slide 25: U.S. HAE Market Dynamics
~7,000 people with HAE in the U.S.3 ~75% of people with HAE in the U.S. are on LTPs U.S. HAE ~1,000 allergists/ immunologists treat 90% of HAE patients Market Dynamics Underscore ~20% of people with HAE have historically switched treatments annually DAWNZERA’s Potential1,2 >90% of people with HAE ar
Slide 26: DAWNZERA's Robust Efficacy Profile and Switch Data
DAWNZERA’s Robust Efficacy Profile and Switch Data1-3 DAWNZERA’s Robust Efficacy Profile and Switch Data1-3 94% of switch patients 84% Total Mean surveyed preferred Reduction in HAE Attack Rates DAWNZERA across Q4W and Q8W over 1 year in OLE2 Reasons participants chose for preferring DAWNZERA: 62% E
Slide 27: Partnered Medicines Amplify Our Opportunities
Partnered Medicines Amplify Our Opportunities Multiple Positive Phase 3 Readouts in 20261 Bepirovirsen Sefaxersen Ulefnersen (HBV) H1:26 (IgAN) 2026 (FUS-ALS) 2026 ~300M patients >400k patients 1% of all ALS cases Addressable worldwide worldwide worldwide Population2 1st and only investigational 1st
Slide 28: Bepirovirsen: Poised to be an Important Advance for Chronic Hepatitis B
Bepirovirsen: Poised to be an Important Advance for Millions of People Living with Chronic Hepatitis B1 Unprecedented Functional Cure Rates >240M Estimated Peak Sales People Worldwide >$2.5B 5 in Phase 3 Program3 Live with Chronic • 19% functional cure rate in the Hepatitis B2 Eligible for: Additi
Slide 29: Accelerating Revenue from Steady Cadence of Independent Launches
Accelerating Revenue from Steady Cadence of Independent Launches1,2 Multiple medicines >$5B in mid-stage development Obudanersen in Potential Annual Peak Product (Angelman syndrome) Multi-Billion-Dollar Revenue from Recent Launches and Late-Stage Medicines >$1B (Alexander disease) >$100M Multiple (s
Slide 30: Royalty Growth Opportunities from Partnered Medicines
Royalty Growth Opportunities from Approved and Late-Stage Partnered Medicines1,2 ~$1B Sapablursen (PV) in Potential Annual Salanersen Peak Royalties2 (SMA) >$150M Sefaxersen >$230M (IgAN) Bepirovirsen >$100M (HBV) >$275M 2026 2027 >$225M Launch Launch Launch Timing Today 2028+ 1. Assuming approval.
Slide 31: Significant Upside Potential from Late-Stage Partnered Programs
Significant Upside Potential from Late-Stage Partnered Programs Total Remaining Royalties2 >$1.7B Milestone Payments2 Sapablursen $660M Mid-teens in Remaining PV Partner Payments Salanersen Tiered, mid-teens SMA >$500M to mid-20% Sefaxersen >$390M Tiered, high-teens to 20% Royalties IgAN Bepirovirse
Slide 32: Marketed Products and Planned Launches
Ionis-Owned Medicines >$5B in Potential Annual Peak Product Revenue2 Marketed Products and Planned Launches Provide Substantial Revenue Growth >$6B Opportunity1 Partner Medicines ~$1B in Potential Annual Peak Royalties2 1. Assumes additional approvals through 2028. Estimated timing of potential U.S.
Slide 33: H1:2026 Financial Highlights
H1:2026 Financial Highlights1 Commercial Revenue: $226M R&D Revenue: $288M Revenues $32M in TRYNGOLZA product sales Significant YoY increase driven $514M $42M in DAWNZERA product sales by multiple payments as 27% increase year-over-year (YoY) partnered programs advance3 R&D Expenses2: $377M
Slide 34: On Track to Achieve our 2026 Financial Guidance
On Track to Achieve our 2026 Financial Guidance1,2 Revenue Operating Loss Cash $875-$900M $425-475M3 >30% vs 20252 Similar to 20252 >$1.6B Numerous diverse revenue sources Investing in multiple launches, Supports investments for launches, including broad sHTG pipeline and technology TRYNGOLZA net pr
Slide 35: Committed to Goal of Sustained Positive Cash Flow
Ionis is Committed to Goal of Sustained Positive Cash Flow1 Key Drivers New product launches Growing royalty revenue Critical investments for growth Positive Cash Flow 2022 2027 2028 and beyond Solid financial foundation Disciplined expense Today management 1. Based on current assumptions, subject t
Slide 36: Driving Accelerating Growth
Driving Accelerating Growth1,2 Sustained Positive Cash Flow Accelerating Revenue Growth Fully-integrated commercial stage biotechnology company Positive clinical trial results enabling steady cadence of approvals and launches Established leadership in cardiometabolic and neurology drug discovery and
Slide 37: 2026 Key Value-Driving Events
2026 Key Value-Driving Events1 Clinical Events Regulatory Actions Product Launches Phase 3 Phase 2 Pelacarsen Phase 2 Phase 2 Bepirovirsen DAWNZERA TRYNGOLZA ZANVASTRO DAWNZERA Clinical Data Events Lp(a) HORIZON data Clinical Daa Events EU approval U.S. approval U.S. submission ClinicalEU Data Event
Slide 38: Ionis Corporate Responsibility Strategy Supports Long-term Value Creation
Ionis Corporate Responsibility Strategy Supports Long-term Value Creation Ionis Corporate Responsibility Strategic Pillars Innovate to Empower Operate improve the lives our people and responsibly of people with communities and sustainably serious disease We innovate across the We are committed t
Slide 39: Accelerating Growth through Life-Changing Medicines
Accelerating Growth through Life-Changing Medicines
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