Ionis Pharmaceuticals, Inc. · NASDAQ:IONS
Ionis Pharmaceuticals — Q2 2025 Earnings Presentation
30 slides from Ionis Pharmaceuticals's earnings presentation, Jul 30, 2025
Slide 1: Q2 2025 Business Update and Financial Results
Q2:2025 Business Update and Financial Results July 30, 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. Any statement describing Ionis’ goals, expectati
Slide 4: Introduction
Introduction Brett Monia, Ph.D. Chief Executive Officer 4
Slide 5: Q2 2025: Strong Momentum Across the Business
Q2:2025: Strong Momentum Across the Business Providing multi-billion revenue potential for Ionis1 First Independent On Track for Second 2025 Phase 3 Launch Exceeding Independent Launch Readouts Expectations Donidalorsen Olezarsen Potential to transform the treatment paradigm Positioned to transform
Slide 6: Inflection 2025: Poised to Deliver a Steady Cadence of New Medicines
Inflection 2025: Poised to Deliver a Steady Cadence of New Medicines Numerous Near-Term Growth Drivers1,2 3 ION582 4 (Angelman syndrome) ION582 Additional medicines (Angelman Additional Sefaxersen syndrome) Independent Key partner (IgAN) launches by launches by Eplontersen end of 2026 end of 2027 Pe
Slide 7: Building on the Early Commercial Success of TRYNGOLZA
Building on the Early Commercial Success of TRYNGOLZA Kyle Jenne Chief Global Product Strategy Officer 7
Slide 8: TRYNGOLZA: First and Only FDA-Approved Treatment for FCS
TRYNGOLZA: First and Only FDA-Approved Treatment for FCS1 TYRYNGOLZA Product Sales, net (millions) $19 Robust efficacy and safety Significant and sustained triglyceride reductions $6 Substantial reduction in acute pancreatitis events Convenience of once-monthly self- Q1:2025 Q2:2025 administ
Slide 9: TRYNGOLZA Continued to Surpass Expectations
TRYNGOLZA Continued to Surpass Expectations1,2 Strong Patient Favorable Physician Positive Access Uptake Engagement Dynamics Effective patient identification Targeting over 3,000 physicians Coverage split: ~60% efforts Leveraging omnichannel commercial, ~40% government Breadth and depth of
Slide 10: Ionis Every Step Designed to Meet the Unique Needs of the FCS Community
Ionis Every Step Designed to Meet the Unique Needs of the FCS Community Suite of services offering personal support for patients and HCPs Disease & nutrition education, injection training & other resources through dedicated patient education managers TM Authorization and reauthorization assistance,
Slide 11: Building on TRYNGOLZA Early Launch Momentum for Sustained Success
Building on TRYNGOLZA Early Launch Momentum for Sustained Success1 Patient Finding Targeted HCP Establishing Broad, is Critical Education is Essential Durable Access is Key Targeting over 3,000 Most of the 3,000 physicians to increase FCS awareness and Important that formal estimated U.S. FCS diagno
Slide 12: Olezarsen: Advancing Toward a Potential Blockbuster Opportunity in sHTG
Olezarsen: Advancing Toward a Potential Blockbuster Opportunity in Severe Hypertriglyceridemia1,2 Blockbuster potential3 • >1 million high-risk sHTG people in the U.S.4 First mover advantage5 Positive data in FCS reinforce our confidence to address sHTG Phase 3 data coming soon5 • Reported positive
Slide 13: Donidalorsen for HAE: Our Second Planned Independent Launch
Donidalorsen for HAE: Our Second Planned Independent Launch Compelling Product Profile + HAE Landscape Dynamics Underscore Donidalorsen’s Potential1-3 Robust Well Clinical New People with Defined Data Set Treatment HAE Opportunity including Options Have Shown Switch Needed Willingness ~7K in U.S.5 D
Slide 14: Ongoing and Upcoming Independent Launches to Power Growth
Ongoing and Upcoming Independent Launches to Power Growth1,2 3 Additional independent Additional launches by Medicines end of 2026 ION582 (Angelman syndrome) Zilganersen (Alexander disease) Donidalorsen Olezarsen (sHTG) (HAE) TODAY 2028 14 1. Assuming approval. 2. Timing expectations are based on cu
Slide 15: Bringing a Steady Cadence of Transformational Medicines to People with Serious Diseases
Bringing a Steady Cadence of Transformational Medicines to People with Serious Diseases Richard Geary, Ph.D. Chief Development Officer 15
Slide 16: Donidalorsen: Robust Data Supports Potential Preferred Treatment for HAE Prophylaxis
Donidalorsen: Robust Data Supports Potential Preferred Treatment for HAE Prophylaxis1,2 Hereditary Angioedema Phase 2 • Positive Phase 2 OLE data in • Substantial reductions in HAE • OLE cohort: long-term treatment up to 4 years of treatment + attack rates + favorable safety and continued to improve
Slide 17: Olezarsen sHTG Development Program Designed to Support Blockbuster Market Opportunity
Olezarsen sHTG Development Program Designed to Support Blockbuster Market Opportunity1 Severe Hypertriglyceridemia (sHTG) • Pivotal study in patients w/ • Pivotal study in patients w/ • Reported positive topline efficacy TG ≥500 mg/dL (sHTG) TG ≥500 mg/dL (sHTG) and safety data • Registrational stud
Slide 18: Essence Study Topline Results: Robust Efficacy and Favorable Safety
Essence Study Topline Results: Robust Efficacy and Favorable Safety Innovative • Largest study ever conducted for an RNA-targeted treatment to reduce triglycerides Study • Opportunity to fully explore the lipid benefits of olezarsen in people with Design hypertriglyceridemia and support the exposure
Slide 19: Severe Hypertriglyceridemia (sHTG): A Serious, Prevalent Condition with High Unmet Need
Severe Hypertriglyceridemia (sHTG): A Serious, Prevalent Condition with High Unmet Need1-7 Defined by triglyceride levels over 500 mg/dL and increased risk of acute, potentially fatal pancreatitis >1 million high-risk sHTG people in the U.S. High unmet need: Poorly managed with current treatments, “
Slide 20: Zilganersen for the Treatment of Alexander Disease
Zilganersen for the Treatment of Alexander Disease Devastating Neurological Disease with No Approved Disease-Modifying Treatments Rare leukodystrophy of significant unmet need • Prevalence: ~1 in 1-3 million1 • Accounts for ~2-8% of leukodystrophies, although likely underreported2 • No approved dise
Slide 21: ION582: A Promising New Investigational Medicine for Angelman Syndrome
ION582: A Promising New Investigational Medicine for Angelman Syndrome Robust Pivotal Phase 3 Study Now Underway1 • Full enrollment expected next year2 • Children and adults and both deletion and mutation genotypes • Global, randomized (2:1), 40mg and 80mg ION582 quarterly vs. placebo Positive Early
Slide 22: Extending the SMA Franchise
Extending the SMA Franchise Nusinersen High Dose • High dose nusinersen regulatory submissions under review globally • September 2025 PDUFA1 Salanersen • Designed with a novel Ionis chemistry to achieve strong efficacy & once-yearly dosing • Interim Phase 1 data showed that once-yearly dosing with b
Slide 23: 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 Zilganersen Phase 2 Donidalorsen TRYNGOLZA WAINZUA Phase 2 TRYNGOLZA Clinical Data Events Data Study start Clinical Data Events U.S. approval EU approval EU approval Clin
Slide 24: Q2 2025 Financial Performance
Q2 2025 Financial Performance Beth Hougen Chief Financial Officer 24
Slide 25: Q2 2025 Financial Highlights
Q2:2025 Financial Highlights1 Increased 2025 Financial Guidance Supported by the Early Launch Excellence of TRYNGOLZA Commercial Revenue: $103M R&D Revenue: $349M $452M Revenue • Over $19M in TRYNGOLZA product sales • Reflects the value Ionis’ technology • Royalty revenues increased ~10% YoY creates
Slide 26: Increased 2025 Financial Guidance
Increased 2025 Financial Guidance1 Driven by Strong YTD Financial Results & Improved Full Year Outlook Revenue Operating Cash Loss $825-$850 ~$2.0 million $300-325 billion Includes: $75-80 million of million2 TRYNGOLZA net revenues Prior $725-750 million Prior <$375 million Prior $1.9 billion 1. Bas
Slide 27: Conclusion
Conclusion Brett Monia, Ph.D. Chief Executive Officer 27
Slide 28: Inflection 2025: Poised to Deliver a Steady Cadence of New Medicines
Inflection 2025: Poised to Deliver a Steady Cadence of New Medicines Numerous Near-Term Growth Drivers1,2 3 ION582 4 (Angelman syndrome) ION582 Additional medicines (Angelman Additional Sefaxersen syndrome) Independent Key partner (IgAN) launches by launches by Eplontersen end of 2026 end of 2027 Pe
Slide 29: Q&A
Q&A IONIS
Slide 30: Innovation Day 2025
Innovation Day 2025 October 7, 2025 | Nasdaq: IONS
Ionis Pharmaceuticals — Q2 2025 Earnings Presentation on 6ix