Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Q3 2025 Earnings Presentation
35 slides from Ionis Pharmaceuticals's earnings presentation, Oct 29, 2025
Slide 1: Q3:2025 Business Update and Financial Results
Q3:2025 Business Update and Financial Results October 29, 2025 Nasdaq: IONS 1
Slide 2: On Today's Earnings Call
On Today’s Earnings Call Brett Monia, Ph.D. Kyle Jenne Beth Hougen Richard Geary, Ph.D. Chief Global Product Strategy Chief Executive Officer Chief Development Officer Chief Financial Officer Officer Eugene Schneider, M.D. Eric Swayze, Ph.D. Chief Clinical Development Executive Vice President, Resea
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: Delivering Transformational Medicines in Focused Therapeutic Areas
Delivering Transformational Medicines in Focused Therapeutic Areas Rare and prevalent Neurology patient populations in focused disease Cardiometabolic areas First- or best-in-class medicines First- or best-in-class medicines that to address a broad range of target cardiometabolic diseases, the disea
Slide 6: Q3:2025: Strong Momentum Across the Business
Q3:2025: Strong Momentum Across the Business Providing multi-billion-dollar revenue potential for Ionis1 First Independent Positive Phase 3 Positive Phase 3 Second Independent Launch Exceeding Data Data Launch Underway Expectations Olezarsen in sHTG Zilganersen in AxD Statistically significant & Sta
Slide 7: Delivering A Steady Cadence of New Medicines
Delivering A Steady Cadence of New Medicines1,2 Additional medicines ION582 (Angelman syndrome) Sefaxersen (IgAN) 4 Independent launches in 2025-2026 Pelacarsen Eplontersen (ATTR-CM) 4 Key partner (Lp(a)-CVD) launches by end 2027 Bepirovirsen (HBV) Zilganersen (Alexander disease) Olezarsen (sHTG) (H
Slide 8: Delivering Important Pipeline Achievements
Delivering Important Pipeline Achievements Richard Geary, Ph.D. Chief Development Officer 8
Slide 9: Olezarsen Achieved Highly Statistically Significant Reductions in Fasting Triglycerides at 6 Months
Olezarsen Achieved Highly Statistically Significant Reductions in Fasting Triglycerides at 6 Months1 Primary Endpoint Placebo Olezarsen Olezarsen 50 mg 80 mg CORE % Reduction from baseline2 0.5% 63% 73% % Placebo-adjusted reduction4 63% 72% Up to a 72% P-value3 p<0.0001 p<0.0001 placebo-adjusted COR
Slide 10: Olezarsen Demonstrated a Highly Statistically Significant Reduction in Acute Pancreatitis Events
Olezarsen Demonstrated a Highly Statistically Significant Reduction in Acute Pancreatitis Events 1-3 85% (p=0.0002) First and only treatment to significantly reduce Reduction in acute pancreatitis events compared to placebo1-3 acute pancreatitis events in people with sHTG Secondary endpoint, pooled
Slide 11: Olezarsen: Poised to be the New Standard of Care for sHTG
Olezarsen: Poised to be the New Standard of Care for sHTG1 Groundbreaking Clinical Results2: Highly statistically significant and clinically meaningful mean reductions in fasting triglycerides of up to 72% First and only medicine to significantly reduce acute pancreatitis events in people with sHTG
Slide 12: Zilganersen for the Treatment of Alexander Disease
Zilganersen for the Treatment of Alexander Disease First and Only Investigational Medicine to Demonstrate Clinically Meaningful and Disease-Modifying Impact1 Alexander Disease (AxD)2-5 Fatal and Progressive Ultra-Rare Childhood Neurological Disorder Characterized by gross/fine motor and cognitive im
Slide 13: Zilganersen Improves Gross Motor Function
Zilganersen Improves Gross Motor Function1 Zilganersen Pooled Primary Endpoint (50mg) Placebo Primary Analysis Set (10MWT) n=17 n=13 Better Zilganersen 50 mg (Cohort B) n = 17 Pooled Placebo (Cohorts A + B) n = 13 Baseline (m/s)2 Mean 1.2 1.1 % Change at Week 61 Mean -1.0% -36.9% Least Squares Mean
Slide 14: ION582: A Promising New Investigational Medicine for Angelman Syndrome
ION582: A Promising New Investigational Medicine for Angelman Syndrome ION582 Potential to address a significant unmet need with no approved disease-modifying treatments U.S. Breakthrough, Fast Track, Rare Pediatric and Orphan designations; EU Orphan designation Positive Results Seen in the HALOS St
Slide 15: Expressive Communication: Continued Improvement Observed on Bayley-4 at 18 Months
Expressive Communication: Continued Improvement Observed on Bayley-4 at 18 Months1 Change on Bayley-4 Expressive Communication ION582 vs. Natural History Improvements on Bayley-4 measure of expressive Improvement communication exceed natural history2 Consistent improvements across additional assessm
Slide 16: Focused High-Value Wholly Owned Pipeline to Drive Continued Growth
Focused High-Value Wholly Owned Pipeline to Drive Continued Growth Indication Prevalence1 Next Events2 Olezarsen Severe hypertriglyceridemia FDA approval and launch 2026 (ApoC-III) ION775 Cardiometabolic (ApoC-III) Severe hypertriglyceridemia Ph2 start 2026 ION501 Myocardial disease Complete IND TOX
Slide 17: Building on the Commercial Success of TRYNGOLZA
Building on the Commercial Success of TRYNGOLZA Kyle Jenne Chief Global Product Strategy Officer 17
Slide 18: TRYNGOLZA: First and Only FDA-Approved Treatment for FCS
TRYNGOLZA: First and Only FDA-Approved Treatment for FCS1 TRYNGOLZA Product Sales, net (millions) ~70% $32 Robust efficacy and safety $19 Significant and sustained triglyceride reductions Substantial reduction in acute pancreatitis events Convenience of once-monthly self-administration $6 with a
Slide 19: Strong Commercial Execution and Compelling Product Profile Driving Robust Uptake
Strong Commercial Execution and Compelling Product Profile Driving Robust Uptake1-3 Strong Initial Robust Physician Positive Access Uptake Engagement Dynamics Effective patient Targeting over 3,000 physicians Coverage split: ~60% commercial, identification efforts ~40% government Leveraging omnichan
Slide 20: Building on TRYNGOLZA Early Launch Momentum for Sustained Success
Building on TRYNGOLZA Early Launch Momentum for Sustained Success1 Patient Finding Targeted HCP Establishing Broad, Durable is Critical Education is Essential Access is Key Most of the 3,000 estimated U.S. Targeting over 3,000 physicians to Majority of formal policies support FCS patients remain uni
Slide 21: Severe Hypertriglyceridemia: Prevalent Condition with Significant Unmet Medical Need
Substantial Unmet Need Fasting triglycerides ≥500 mg/dL and increased risk of potentially life-threatening acute pancreatitis Limited benefit from currently available treatments, including fibrates and omega-3s Market Poised for New Treatment Severe Hypertriglyceridemia: HCPs and patients dissatisfi
Slide 22: Strategy to Realize the Blockbuster Potential of Olezarsen in sHTG
Strategy to Realize the Blockbuster Potential of Olezarsen in sHTG1,2 Targeting Expanding Disease Building a Right-Sized Attractive Payer and Key HCPs Awareness3 Field Team Access Dynamics4 Specialty focused, Conducting sHTG disease ~200-person Payers recognize value in ~20,000 cardiologists, state
Slide 23: DAWNZERA Launch Off to Encouraging Start
Launch Underway DAWNZERA Launch FDA approval on August 21st Off to Encouraging First patient self-administered DAWNZERA within 10 days of Start1 approval Exceptional initial commercial execution Positive Physician Engagement Prescriptions written for all patient segments: switches from long- term pr
Slide 24: 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 25: IONIS EVERY STEP: Innovating to Meet the Needs of the HAE Community
IONIS EVERY STEP: Innovating to Meet the Needs of the HAE Community1 Dedicated personal support from Patient Education Managers Disease education, injection training and connection to additional resources DAWNZERA Direct digital companion TM Free trial program Financial support programs2 1. DAWNZERA
Slide 26: Zilganersen: Our First Anticipated Neurology Launch
Substantial Unmet Need Alexander disease is a rare, progressive and often fatal neurological condition No approved disease-modifying treatments Zilganersen: Our First Well-Established Patient Community Anticipated Neurology Strong partnership with the Alexander disease patient community Launch1,2 St
Slide 27: 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 Scalable Team Strong Initial Capabilities for Launch Execution Future Launches 27
Slide 28: Q3:2025 Financial Performance
Q3:2025 Financial Performance Beth Hougen Chief Financial Officer 28
Slide 29: Q3:2025 Financial Highlights
Q3:2025 Financial Highlights1 Commercial Revenue: $116M R&D Revenue: $41M Revenues $32M in TRYNGOLZA product sales Reflects the value Ionis’ technology $157M Royalty revenues increased ~13% YoY creates as partnered programs advance R&D Expenses2: $197M SG&A Expenses2: $87M Operating Expenses2
Slide 30: Increasing 2025 Financial Guidance
Increasing 2025 Financial Guidance1 Revenue Operating Cash Loss $875-$900 million $275-300 >$2.1 million2 billion Includes: $85-95 million of TRYNGOLZA net revenues Prior $825-850 million Prior $300-325 million Prior ~$2.0 billion 1. Based on current assumptions, subject to change. 2. Non-GAAP – ple
Slide 31: Conclusion
Conclusion Brett Monia, Ph.D. Chief Executive Officer 31
Slide 32: Well-Positioned to Build on Strong Momentum
Well-Positioned to Build on Strong Momentum Key Upcoming Catalysts1 2 NDA Submissions in 2 Independent Next Few Months Launches Next Year2 5 Phase 3 Data Readouts in 2026 Multiple Phase 2 Data ≥2 Phase 3 Study Readouts in 2026 Starts in 2026 1. Based on current assumptions, subject to change. 2. Ass
Slide 33: Q&A
Q&A IONIS
Slide 34: Transforming Human Health through RNA-Targeted Medicines
Transforming Human Health through RNA-Targeted Medicines 34
Slide 35: 2025 and 2026 Key Value-Driving Events
2025 and 2026 Key Value-Driving Events1 Phase 3 Clinical Events Regulatory Actions Product Launches 2025 2025 2025 Phase 2 ION582 Olezarsen Phase 2 DAWNZERA TRYNGOLZA WAINZUA Phase 2 TRYNGOLZA Clinical Data Events Study start CORE & CORE2 Data Clinical Data Events U.S. approval EU approval EU approv
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