Analyst Conference Summary

biotechnology

conference date: February 25, 2026 @ 8:30 AM Pacific Time
for quarter ending: December 31, 2025 (Q4, fourth quarter 2025)

Forward-looking statements

Overview: Putting a good face on Q4 results that were down y/y. Plenty of cash, though, and the big money would be in 2027 if approved to treate SHTG.

Basic data (GAAP):

Revenue was $203 million, up 29% sequentially from $157 million, and down 8% from $227 million year-earlier. However, drug revenue was up y/y.

Net income was negative $229 million, down sequentially from negative $104 million, and up from negative $110 million year-earlier.

EPS (diluted) was negative $1.41, down sequentially from negative $0.80, and down from negative $0.66 year-earlier,

Guidance:

For 2026 revenue expected between $800 and $825 million, down from 2025. Non-GAAP operating income negative $500 to $550 million. Cash ending near $1.6 billion. Revenue guidance could improve if obtains FDA priority review for Tryngolza for SHTG.

Conference Highlights:

CEO Brett Monia said "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. This year, we are poised for two additional independent launches of groundbreaking therapies: olezarsen for severe hypertriglyceridemia, our first launch in a broad patient population, and zilganersen for Alexander disease, our first launch from our leading neurology pipeline. Our partnered pipeline is also on track for multiple groundbreaking Phase 3 readouts, beginning with the recent positive data for bepirovirsen in chronic hepatitis B to be followed by two cardiovascular outcome trials — the pelacarsen Lp(a) Horizon trial mid-year 2026 and the eplontersen Cardio-TTRansform trial in the second half of 2026. Together, this progress positions Ionis to continue delivering a steady cadence of transformative medicines to people living with serious diseases, fueling substantial growth and long-term value creation."

Well positioned to achieve significant revenue growth and sustained positive cash flow in the next few years. Plans to use $433 million in 2026 to repay 2026 convertible notes.

Tryngolza (Olezarsen) for familial chylomicronemia syndrome (FCS) payer coverage is good and continues to grow. Most potential patients are undiagnosed; estimated U.S. total is just 3,000. EU CHMP issued a positive opinion in Q2 2025, approved in Q3 2025, with partner Sobi launch in Q4 2025. Licensed global rights ex U.S., Canada, and China to Sobi. Exceded sales expectations in first year on market. No significant effect in Q4 from the new competitor on the market.

In Tryngolza for SHTG (severe hypertriglyceridemia) the Phase 3 CORE data, and from 2 other Phase 3 trials, were positive. Showed pancreatitis reduction. Ionis submitted the sNDA in Q4 2025. Approval possible in late 2026. Estimated U.S. sHTG patients over 1 million. Will adjust price for this much larger population. Already has full field team in place in Q1 2026.

Zilganersen for Alexander disease Phase 3 study reported positive results in Q3 2025. NDA submitted in January 2026. Could launch in 2026.

Wainua revenue continues to grow. Believes royalties could add meaningfully to revenue in the growing ATTRv-PN market. ATTR Cardiomyopathy trial continues, with enrollment completed in Q3 2023, but data not expected until later in 2025. Launches for PN are underway in several nations. Received EU approval for PN in Q2 2025. [But competing drug for ATTR-CM now on market from Alnylam, in addition to older drugs like Tafamidis.]

Obudanersen (ION582) for Angelman syndrome reported positive Phase 2 data in Q3 2025. The Phase 3 study is expectd to fully enroll in 2026.

Donidalorsen (now Dawnzera) for hereditary angioedema (HAE) was approved by the FDA in August 2025. European approval in January 2026. HAE has over 7,000 patients in the US. Independent commercial launch is off to a good start. Believes peak sales could be $500 million per year. Sales ramp will mainly be in 2026.

Spinraza (nusinersen) for SMA higher dose now has a PDUFA of April 3, 2026 after receiving a CRL earlier in 2025. Approved in Q4 in EU. Salanersen for SMA had postive Phase 1 results, Biogen will take into registrational studies. Salanersen royalty rates would be higher than those for Spinraza, and of course would extend the patent coverage period.

Opemalirsen (ION532) to reduce APOL1 for APOL1-mediated kidney disease began a Phase 2b study in Q2 2025, triggering a $30 million milestone payment. Granted FDA Fast Track.

In Q4 2025 Bepirovirsen for chronic hepatitis B achieved its primary endpoint and demonstrated a statistically significant and clinically meaningful functional cure rate in 2 Phase 3 studies. Global filings began in Q1 2026.

In Q4 2025 Sapablursen for polycythemia vera (PV) had positive Phase 2 results, presented at American Society of Hematology (ASH) conference. Ono is advancing sapablursen into Phase 3 development.

Possible Phase 3 readouts in 2026 include Pelacarsen for Lp(a), Eplantersen for ATTR-CM, Ulefnersen for FUS-ALS, and Sefaxerson for IgAN.

Non-GAAP numbers: net income negative $186 million, sequentially down from negative $98 million, and down from negative $68 million year-earlier. No non-GAAP EPS given.

Cash ended at $2.7 billion, up sequentially from $2.2 billion from refinancing proceeds.

Ionis has a pipeline of about 45 potential drugs, with 12 in clinical development, and 8 in Phase 3 trials. A growing number are wholly-owned.

GAAP Operating expense was $418 million, consisting of $8 million for cost of goods sold; $280 million for R&D and $130 million for selling, general and administrative. Operating income was negative $215 million. Other income net was negative $13 million. Income tax $1 million.

Full year 2025 revenue was $944 million, up from $705 million in 2024. Net income was negative $381 million or negative $2.38 per share.

Q&A selective summary:

Guidance includes not SHTG sales or milestones, matching Redemplo price? Are assuming some SHTG sales, with standard review, in Q4 2026. Some potential for research collaboration revenue. Engaging with payers about pricing of Tryngolza, expecting some meaningful decline, to be compensated by growth with SHTG approval. Will announce pricing later this year.

Cardiomyopathy? We have a good trial balance of patients on and off Trafamidis. Working on our data presentation.

FCS reimbursement, competitor pricing? Patient demand is strong in 2026. No meaningful impact from competitor. Want to provide broad access for SHTG.

IO-532? Astrazeneca parnership, strong preclinical data, unmet need significant. They decided to go to Phase 2 after strong Phase 1 data. Timing of Phase 2 data release is upto Astrazeneca.

We believe SHTG deserves priority review, but it is up to the FDA.

Peak royalties for GSK CHB Bepirovirsen program? Data is impressive, unprecedented. GSK will present data in May. Peak sales $2.5 billion. We have tiered royalties from 10% to 12%, plus potiential milestone payments. Our peak royalty estimate is several billion dollars [???].

We believe about 300 people in the U.S. have Alexander Disease, with about 150 identified. Community is enthusiastic about our treatment. Peak revenue greater than $100 million. Potential approval in Q4.

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