Ionis Pharmaceuticals — Third Quarter 2026 Earnings Summary

Financial Performance:

• Total revenue for the three months ended September 30, 2026, was $243 million, a 55% increase compared to $157 million in the same period in 2025; for the nine months ended September 30, 2026, revenue was $757 million, a 64% increase compared to $740 million in the prior year period.
• Commercial revenue increased 18% year-over-year to $136 million in Q3 2026 and 23% to $363 million for the nine months ended September 30, 2026.
• Research and development revenue was $107 million for Q3 2026 and $394 million for the nine months ended September 30, 2026, driven by collaborative agreement payments.
• Operating expenses were $373 million for Q3 2026 and $1,107 million for the nine months ended September 30, 2026, compared to $317 million and $907 million, respectively, in the prior year periods.
• Loss from operations was $130 million for Q3 2026 and $350 million for the nine months ended September 30, 2026, compared to losses of $160 million and $167 million, respectively, in the prior year periods.
• Non-GAAP loss from operations was $87 million for Q3 2026 and $218 million for the nine months ended September 30, 2026, compared to $129 million and $76 million, respectively, in the prior year periods.
• Net loss was $110 million for Q3 2026 and $317 million for the nine months ended September 30, 2026, compared to $129 million and $152 million, respectively, in the prior year periods.
• Non-GAAP net loss was $67 million for Q3 2026 and $185 million for the nine months ended September 30, 2026, compared to $98 million and $61 million, respectively, in the prior year periods.
• Cash, cash equivalents, and short-term investments totaled $1.9 billion as of September 30, 2026, down from $2.7 billion as of December 31, 2025.
• Contracts receivable were $88 million as of September 30, 2026, compared to $66 million as of December 31, 2025.

Guidance and Future Outlook:

• Reaffirmed 2026 total revenue guidance of $875–$900 million.
• Reaffirmed 2026 non-GAAP operating loss guidance of $425–$475 million.
• Reaffirmed 2026 cash, cash equivalents, and short-term investments guidance of greater than $1.6 billion.
• Lowered 2026 TRYNGOLZA product sales guidance to approximately $50 million from the previous $100–$110 million range due to a more gradual launch ramp.
• Reaffirmed 2026 DAWNZERA product sales guidance of $110–$120 million.
• Management remains confident in TRYNGOLZA's long-term growth potential and multi-billion-dollar peak sales.
• Full-year operating expenses are expected to grow in the low-teens percentage year-over-year.

Business Segments and Product Lines:

• TRYNGOLZA (olezarsen): Generated U.S. net product sales of $9 million in Q3 2026 and $41 million for the nine months ended September 30, 2026. FCS launch outside the U.S. is underway; received a positive CHMP opinion for sHTG with a final approval decision expected in Q4 2026.
• DAWNZERA (donidalorsen): Generated U.S. net product sales of $37 million in Q3 2026 and $79 million for the nine months ended September 30, 2026. Launch is underway outside the U.S. with new market approvals in Europe and Canada.
• ZANVASTRO (zilganersen): First independent neurology launch underway with first patients dosed; commercializing outside the U.S. with Recordati assuming approval.
• SPINRAZA (nusinersen): Generated global sales of $461 million in Q3 2026, a 23% increase year-over-year, resulting in $69 million in royalty revenue.
• WAINUA (eplontersen): Generated global sales of $68 million in Q3 2026, resulting in $7 million in royalty revenue. Phase 3 CARDIO-TTRansform study results for ATTR-CM were presented, showing nominal significance in the monotherapy population despite missing the primary composite endpoint in the overall population.
• HIBSAGO (bepirovirsen): Approved in the U.S., Japan, and Canada; under regulatory review in the EU and China.
• Sefaxersen: Phase 3 IMAgINATION study for IgAN met its primary endpoint with a 43.1% reduction in proteinuria relative to placebo.
• Ulefnersen: Phase 3 study in FUS-ALS met its primary endpoint with a favorable safety profile.
• Obudanersen: Completed enrollment in the Phase 3 REVEAL study for Angelman syndrome; data expected in the second half of 2027.
• ION775: Entered Phase 2 study for sHTG based on Phase 1 results showing robust triglyceride lowering.
• Sapablursen: Received Orphan Drug Designations in the U.S., EU, and Japan.

Market and Competitive Landscape:

• TRYNGOLZA is the first FDA-approved treatment to reduce triglycerides and acute pancreatitis risk in adults with severe hypertriglyceridemia (sHTG) and is establishing a new treatment paradigm for the underserved sHTG population.
• DAWNZERA is the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older.
• ZANVASTRO is the first and only disease-modifying treatment approved for children and adults with Alexander disease.
• HIBSAGO is a first-in-class treatment for chronic hepatitis B (CHB).
• Sefaxersen is the first RNA-targeted potential treatment for Immunoglobulin A Nephropathy (IgAN).

Risks and Challenges:

• TRYNGOLZA sales progress has been more gradual than anticipated due to early dynamics of establishing a new treatment paradigm.
• The Phase 3 CARDIO-TTRansform study for eplontersen missed the primary composite endpoint in the overall population.
• The Pelacarsen Phase 3 Lp(a) HORIZON data was not achieved in 2026.
• Forward-looking statements involve assumptions that may not materialize, including risks inherent in discovering, developing, and commercializing medicines.

Management Commentary and Tone:

• CEO Brett P. Monia stated the company continues to advance innovative medicines, noting three approvals in 2026, including two Ionis-owned medicines.
• CFO Elizabeth L. Hougen expressed confidence in achieving full-year DAWNZERA guidance and the company's 2026 total revenue, operating loss, and cash guidance.
• Management remains confident in TRYNGOLZA's potential to deliver sustained, long-term revenue growth despite the lower near-term guidance.
• The tone reflects commitment to achieving sustained positive cash flow and long-term value creation.

Other Key Points:

• Repayment of 0% convertible notes due April 2026 contributed to the decrease in cash and short-term investments from $2.7 billion to $1.9 billion.
• The 2025 sapablursen upfront payment of $280 million is excluded from current revenue comparisons.
• Management will host a conference call and webcast on November 9, 2026, at 9:00 a.m. Eastern time.
• Key 2027 value-driving events include Sefaxersen and Ulefnersen U.S. submissions and approvals, and the initiation of Phase 3 studies for Diranersen (Alzheimer's disease).