Ionis Pharmaceuticals Inc.: Q4 FY2025 earnings call

What management said about Q4 FY2025, from the documents filed with the SEC on 25 February 2026: press release. Guidance figures: 1 raised, 4 new. The quarter’s numbers.

Read the filing

Key takeaways

• Revenue rose on commercial sales: Total revenue was $944 million for 2025, up from $705 million. Commercial revenue rose 49%, mainly from TRYNGOLZA product sales. Source
• Sapablursen upfront lifted R&D revenue: Research and development revenue was $508 million for 2025. It included a $280 million upfront payment from Ono Pharmaceutical for the global license of sapablursen in the second quarter. Source
• TRYNGOLZA sales reached $108 million: TRYNGOLZA net product sales were $50 million in the fourth quarter, up 56% on the prior quarter, and $108 million for the year, its first year of launch. Source
• Olezarsen sHTG sNDA awaiting acceptance: The olezarsen sHTG sNDA has been submitted. The company is awaiting acceptance, and 2026 guidance assumes a standard review timeline. Source
• Bepirovirsen met Phase 3 endpoint: Bepirovirsen achieved its primary endpoint in the B-Well 1 and B-Well 2 Phase 3 studies in chronic hepatitis B. Global filings are planned from Q1 2026. Source
• Launch spending lifted operating expenses: GAAP operating expenses rose to $1,326 million in 2025 from $1,180 million. SG&A rose to $394 million from $267 million, reflecting launch investment. Source
• Cash rose on convertible refinancing: Cash, cash equivalents and short-term investments were $2.7 billion at December 31, 2025, up from $2.3 billion, mainly from fourth-quarter convertible debt refinancing proceeds. Source
• Two independent launches planned 2026: Management named olezarsen for severe hypertriglyceridemia, its first launch in a broad population, and zilganersen for Alexander disease as 2026 independent launches. Source

“2025 was a defining year for Ionis, marked by the successful execution of our first two independent launches and multiple positive data readouts across our pipeline, positioning Ionis for continued success in 2026”

Brett P. Monia, Ph.D., chief executive officer of Ionis

Guidance

What changed from last quarter

• New guidance: Full-year 2026 guidance for revenue, non-GAAP operating loss and cash was issued. The January release had no 2026 revenue or operating loss range. Source
• New: The zilganersen NDA was planned for Q1 2026 in the January release. The company now reports it submitted, with an approval decision expected in H2 2026. Source
• New: Ulefnersen for FUS-ALS received U.S. Fast Track designation. The January release did not mention this designation. Source
• New: Management reported a recent expansion of the top-tier sales force ahead of the expected olezarsen sHTG launch. Source

Full-year results and growth drivers

• Revenue rose on commercial sales: Total revenue was $944 million for 2025, up from $705 million. Commercial revenue rose 49%, mainly from TRYNGOLZA product sales. Source
• Sapablursen upfront lifted R&D revenue: Research and development revenue was $508 million for 2025. It included a $280 million upfront payment from Ono Pharmaceutical for the global license of sapablursen in the second quarter. Source
• Fourth quarter revenue declined: Fourth quarter total revenue was $203 million, against $227 million a year earlier. Research and development revenue fell to $62 million from $141 million. Source
• Operating loss narrowed for year: GAAP loss from operations was $382 million for 2025, against $475 million. Non-GAAP loss from operations was $248 million, against $345 million. Source

Commercial products and royalties

• TRYNGOLZA sales reached $108 million: TRYNGOLZA net product sales were $50 million in the fourth quarter, up 56% on the prior quarter, and $108 million for the year, its first year of launch. Source
• DAWNZERA first full quarter sales: DAWNZERA net product sales were $7 million in the fourth quarter, its first full quarter on the market, and $8 million for 2025. Management said prescriptions were written for all patient segments. Source
• Royalty revenue rose on WAINUA: Total royalty revenue was $285 million for 2025, against $257 million. WAINUA royalties were $49 million, up from $20 million. SPINRAZA royalties were $212 million, down from $216 million. Source
• Partner product sales reported: SPINRAZA global sales were $356 million in the fourth quarter and $1.5 billion for 2025. WAINUA sales were $69 million in the fourth quarter and $212 million for the year. Source

“In 2025 we exceeded our revenue guidance, driven by growing commercial revenue from our independent launches and substantial R&D revenue from continued pipeline success”

Elizabeth L. Hougen, chief financial officer of Ionis

Pipeline and regulatory milestones

• Olezarsen sHTG sNDA awaiting acceptance: The olezarsen sHTG sNDA has been submitted. The company is awaiting acceptance, and 2026 guidance assumes a standard review timeline. Source
• Zilganersen NDA submitted, decision H2: The zilganersen NDA for Alexander disease has been submitted. An FDA approval decision is anticipated in the second half of 2026, and an expanded access program is underway in the U.S. Source
• Bepirovirsen met Phase 3 endpoint: Bepirovirsen achieved its primary endpoint in the B-Well 1 and B-Well 2 Phase 3 studies in chronic hepatitis B. Global filings are planned from Q1 2026. Source
• Four more Phase 3 readouts in 2026: After bepirovirsen, four further 2026 Phase 3 data readouts are listed: pelacarsen HORIZON, eplontersen CARDIO-TTRansform, sefaxersen IMAGINATION and ulefnersen FUSION. Source
• Opemalirsen Fast Track designation granted: Opemalirsen for APOL1-mediated chronic kidney disease received U.S. Fast Track designation. Source

Regional approvals and launches

• TRYNGOLZA launched in European Union: TRYNGOLZA was approved and launched in the EU as an adjunct to diet for genetically confirmed FCS in adults. Source
• DAWNZERA approved in EU in January: DAWNZERA was approved in the EU in January and recently launched for routine prevention of recurrent HAE attacks in patients 12 and older. Source
• SPINRAZA high dose approved in EU: High-dose SPINRAZA was approved and launched in the EU. Its U.S. review is under way. Source
• WAINUA approved in China: WAINUA was recently approved in China. Additional submissions are in progress to expand global access. Source

“We anticipate growth in product revenues, together with additional royalties, to position Ionis to achieve cash flow breakeven in 2028”

Elizabeth L. Hougen, chief financial officer of Ionis

2026 guidance basis

• Guidance reflects independent launch model: Management said the 2026 guidance reflects the company's evolution into a fully integrated commercial-stage biotechnology company, with revenue expected from several sources. Source
• Non-GAAP expenses to rise modestly: Non-GAAP operating expenses are expected to increase modestly in 2026, in line with plans to invest in independent launches and the wholly owned pipeline. Source
• Operating loss comparison excludes upfront: Management said the non-GAAP operating loss is expected to be similar to 2025, excluding the one-time sapablursen upfront payment recognized in 2025. Source

Costs and operating expenses

• Launch spending lifted operating expenses: GAAP operating expenses rose to $1,326 million in 2025 from $1,180 million. SG&A rose to $394 million from $267 million, reflecting launch investment. Source
• Equity compensation excluded from non-GAAP: Non-GAAP operating expenses were $1,192 million for 2025 after excluding $134 million of equity award compensation, which the company describes as non-cash. Source
• R&D expense near prior year: Research, development and patent expense was $916 million for 2025, against $902 million. Fourth quarter expense was $280 million, against $245 million. Source

Cash, debt and share count

• Cash rose on convertible refinancing: Cash, cash equivalents and short-term investments were $2.7 billion at December 31, 2025, up from $2.3 billion, mainly from fourth-quarter convertible debt refinancing proceeds. Source
• Convertible notes carried at year-end: The balance sheet carries 0% convertible notes due 2026 at $432 million current, 0% notes due 2030 at $751 million, and 1.75% notes due 2028 at $568 million. Source
• Weighted share count increased: Shares used in computing basic and diluted net loss per share were 160 million for 2025, against 150 million in 2024. Source

Strategy and partnered programs

• Two independent launches planned 2026: Management named olezarsen for severe hypertriglyceridemia, its first launch in a broad population, and zilganersen for Alexander disease as 2026 independent launches. Source
• Sapablursen moves to Phase 3 with Ono: Sapablursen showed positive Phase 2 results in polycythemia vera, presented at ASH. Ono is advancing sapablursen into Phase 3 development. Source
• Sales force expanded ahead of launch: The company expanded its top-tier sales force ahead of the expected olezarsen sHTG launch. Source
• Phase 2 readouts listed for 2026: Phase 2 data readouts are listed for 2026 for IONIS-MAPT Rx (BIIB080) in Alzheimer's disease, tominersen in Huntington's disease, and tonlamarsen in uncontrolled hypertension. Source

Coming up, as management said on 25 February 2026

• Olezarsen sHTG launch expected this year: Management expects olezarsen for sHTG to launch in 2026, subject to approval. Source
• Product guidance at Q1 earnings: Once the olezarsen sNDA is accepted, the company expects to give TRYNGOLZA and DAWNZERA product-level guidance at first quarter 2026 earnings. Source
• SPINRAZA high dose U.S. decision: High-dose SPINRAZA is under review for U.S. marketing approval, with a PDUFA date of April 3, 2026. Source
• Pelacarsen and eplontersen readouts timed: The pelacarsen HORIZON readout is expected mid-year 2026. The eplontersen CARDIO-TTRansform readout is expected in the second half of 2026. Source
• EASL presentation of bepirovirsen: Full bepirovirsen data are planned for presentation at the EASL Congress 2026, subject to acceptance. Source

Figures management reported

Risks management discussed

• Regulatory: Management noted that timing expectations for key events rest on current assumptions and may change. Source
• Regulatory: QALSODY is approved under accelerated approval, and continued approval may depend on verifying clinical benefit in confirmatory trials. Source
• Operational: Management said it will keep investing in go-to-market activities to support current and upcoming launches. Source

Earlier plans management reported on

• Ahead: Management said 2025 revenue substantially exceeded expectations. Source
• On track: Management described olezarsen sHTG launch preparations as on track, with the sNDA submitted. Source
• On track: Management said the partnered pipeline is on track for multiple Phase 3 readouts, beginning with bepirovirsen. Source
• On track: Management said zilganersen is on track for launch this year, assuming approval. Source
• Met: The January release expected EU approval and launch in Q1 2026. This release reports EU approval in January and a recent launch.
• Met: The January release planned the zilganersen NDA submission in Q1 2026. This release reports the NDA submitted.
• Met: The 2026 key events table marks the bepirovirsen B-Well data as achieved. Source

Other quarters

• Q3 FY2026 earnings call
• Q2 FY2026 earnings call
• Q1 FY2026 earnings call
• Q3 FY2025 results

Summarised with AI from the documents the company filed with the SEC. Every point is checked against the filing before it is shown: management’s own words word for word, figures against the line or table row they come from. A point that fails the check is left out. Source opens the filing at that line.