Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Q4 2025 Earnings Presentation
28 slides from Ionis Pharmaceuticals's earnings presentation, Feb 25, 2026
Slide 1: YE:2025 Business Update and Financial Results
YE:2025 Business Update and Financial Results February 25, 2026 Nasdaq: IONS 1
Slide 2: On Today's Earnings Call
On Today’s Earnings Call Brett Monia, Holly Kordasiewicz, Kyle Jenne Ph.D. Ph.D. Chief Global Product Beth Hougen Strategy Officer Chief Financial Officer Chief Executive Officer Chief Development Officer Eugene Schneider, M.D. Eric Swayze, Ph.D. Chief Clinical Executive Vice President, Development
Slide 3: 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 4: Introduction
Introduction Brett Monia, Ph.D. Chief Executive Officer 4
Slide 5: Strong Track Record of Industry-Leading Success
Strong Track Record of Industry-Leading Success1-4 Key Recent Achievements 6 Positive Phase 3 4 Approved Data Readouts Medicines 2 Independent 11Medicines in Launches Late-Stage Development 1. TRYNGOLZA is approved in the U.S. for Familial Chylomicronemia Syndrome (FCS) in adults as an adjunct to di
Slide 6: Strong Momentum Across the Business
Strong Momentum Across the Business Providing multi-billion-dollar revenue potential for Ionis1 Preparations Preparations on First Independent Second Independent on Track for First Track for First Launch Exceeding Launch Underway Broad Patient Independent Expectations Population Launch Neurology Lau
Slide 7: Delivering a Steady Cadence of New Medicines
Delivering a Steady Cadence of New Medicines1,2 ION582 (Angelman syndrome) 4 Sefaxersen Independent (IgAN) launches in 2025-2026 Eplontersen (ATTR-CM) Pelacarsen 4 (Lp(a)-CVD) Key partner launches by end of 2027 Bepirovirsen (CHB) Zilganersen (Alexander disease) Olezarsen (sHTG) (HAE) (FCS) 2026 Lau
Slide 8: Delivering Important Pipeline Achievements
Delivering Important Pipeline Achievements Holly Kordasiewicz, Ph.D. Chief Development Officer 8
Slide 9: Olezarsen: 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 Olezarsen: 〉 86% of olezarsen-treated patients achieved triglyceride levels below 500 mg/dL Positioned to be the 〉 Up to 54%
Slide 10: Late-Stage Ionis-Owned Neurology Opportunities: Zilganersen and Obudanersen
Late-Stage Ionis-Owned Neurology Opportunities: Zilganersen and Obudanersen1 Zilganersen Obudanersen for the Treatment of Alexander Disease for the Treatment of Angelman Syndrome First and only investigational medicine to demonstrate Significant unmet need with no approved clinically meaningful dise
Slide 11: Leading the Way in the Treatment of Neurological Diseases
Wholly Owned Medicines Leading the Way in Indication Preclinical Ph1 Ph2 Ph3 the Treatment of Zilganersen Alexander disease NDA submitted Neurological Diseases (GFAP) ION582 Angelman syndrome (UBE3A-ATS) ION464 Multiple System Atrophy 6 6 (SNCA) ION717 Prion disease (PRNP) Wholly Owned Medicines Par
Slide 12: 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 Donidalorsen Olezarsen Zilganersen DAWNZERA Clinical Data Events Lp(a) HORIZON data Clinical Daa Events EU approval U.S. approval U.S. submission ClinicalEU Data
Slide 13: Building on our Commercial Success
Building on our Commercial Success Kyle Jenne Chief Global Product Strategy Officer 13
Slide 14: TRYNGOLZA Outperforms Expectations in First Year of Launch
TRYNGOLZA Outperforms Expectations in First Year of Launch as the First FDA-Approved Treatment for FCS1 Generated $108 million in 2025 56% $50 $32 Robust efficacy and safety • Significant and sustained triglyceride reductions $19 • Substantial reduction in acute pancreatitis events Convenience of on
Slide 15: Strong Commercial Execution Driving Increasing TRYNGOLZA Demand
Strong Commercial Execution and Compelling Product Profile Driving Increasing TRYNGOLZA Demand1,2 Strong Robust Physician Broad Patient Uptake Engagement Access Effective patient identification efforts; strong Targeting ~20,000 physicians with Broad FCS access and coverage referral and patient growt
Slide 16: sHTG Launch Preparations Confirm Strong Enthusiasm for Olezarsen
sHTG Launch Preparations Confirm Strong Enthusiasm for Olezarsen Groundbreaking Robust Ongoing Pivotal sHTG Results1 HCP Demand Payer Engagement Highly statistically significant and Educating on clinical and clinically meaningful reductions Strong enthusiasm for economic burden of disease in fasting
Slide 17: Olezarsen: Poised to Become Ionis' First Blockbuster Medicine
Olezarsen: Poised to Become Ionis’ First Blockbuster Medicine >3 million people with sHTG in the U.S.1 • Includes >1 million people with high-risk sHTG1 • Early launch focus on high-risk sHTG with >880 mg/dL or ≥500 mg/dL + AP history and/or comorbidities Annual Peak Product Revenue Opportunity3 • H
Slide 18: DAWNZERA Launch off to Encouraging Start
DAWNZERA Launch off to Encouraging Start1 Delivering on What HAE Patients Need Most First and Only RNA-Targeted Treatment to Prevent HAE Attacks Indicated for prophylaxis to prevent attacks of Encouraging Early Launch HAE in adult and pediatric patients Momentum ≥12 years old Prescriptions written f
Slide 19: Zilganersen: Our First Anticipated Substantial Unmet Need
Substantial Unmet Need Alexander disease is a rare, progressive and often fatal neurological condition No approved disease-modifying treatments Zilganersen: Groundbreaking Phase 3 Data Our First First time an investigational medicine has shown a positive disease- modifying impact in Alexander diseas
Slide 20: Innovative Commercial Organization with Proven Ability to Bring Medicines to People
Innovative Commercial Organization with Proven Ability to Bring Medicines to People with Serious Diseases BB Top-Tier Demonstrated Scaling Capabilities Team Strong Initial for Upcoming Launch Execution Launches 20
Slide 21: YE:2025 Financial Performance and 2026 Financial Guidance
YE:2025 Financial Performance and 2026 Financial Guidance Beth Hougen Chief Financial Officer 21
Slide 22: YE:2025 Financial Highlights
YE:2025 Financial Highlights1 Exceeded 2025 Guidance Commercial Revenue: $436M R&D Revenue: $508M Revenues $108M in TRYNGOLZA product sales Reflects the value Ionis’ technology $944M Total commercial revenues increased creates as partnered programs ~49% YoY advance R&D Expenses2: $826M SG&A Ex
Slide 23: 2026 Revenue Guidance Reflects Growing Commercial Revenue and Substantial Partner Revenue
2026 Revenue Guidance Reflects Growing Commercial Revenue and Substantial Partner Revenue1 Revenue: $800-$825 million2 + ~20% vs 20253 Assumes olezarsen standard review TRYNGOLZA DAWNZERA Royalties R&D Revenue Strong FCS patient demand Strong launch expected to continue SPINRAZA to remain fundamenta
Slide 24: 2026 Financial Guidance Reflects Fully Integrated Commercial-Stage Biotech
2026 Financial Guidance Reflects Fully Integrated Commercial-Stage Biotech Launching Multiple Medicines1-3 Revenue Operating Loss Cash $800-$825 million $500-550 million3 ~$1.6 + ~20% vs 20254 Similar level to 20254 billion Numerous diverse revenue Investing in multiple launches, Investments for lau
Slide 25: Conclusion
Conclusion Brett Monia, Ph.D. Chief Executive Officer 25
Slide 26: Well Positioned to Continue Driving Accelerating Growth: Key Catalysts in 2026
Well Positioned to Continue Driving Accelerating Growth Key Catalysts in 20261 5 Phase 3 Bepirovirsen Pelacarsen 4 NDA Zilganersen Bepirovirsen 3 Olezarsen Zilganersen Eplontersen Pelacarsen Launches Bepirovirsen Data Sefaxersen Submissions Eplontersen Readouts Ulefnersen Multiple Alzheimer’s Diseas
Slide 27: Q&A
Q&A IONIS
Slide 28: Breakthrough Therapies Driving Accelerating Growth
Breakthrough Therapies Driving Accelerating Growth 28
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