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View the full Nov 10, 2026 version

Price: $39.42 → $28.33(−28.1%)
Discount category: Far below intrinsic value → Deep below intrinsic value
Next earnings: Nov 9, 2026 → Feb 9, 2027
Next earnings is estimate: No → Yes
About: Ionis Pharmaceuticals discovers and develops RNA-targeted medicines, mostly antisense drugs that stop the production of a disease-causing protein. It sells three medicines on its own in the US: TRYNGOLZA (olezarsen) for very high triglycerides, DAWNZERA (donidalorsen) for hereditary angioedema, and ZANVASTRO (zilganersen) for Alexander disease, approved on September 3, 2026. It also earns royalties and milestone payments from partners that sell or develop its drugs, such as Biogen (SPINRAZA for spinal muscular atrophy), AstraZeneca (WAINUA for a hereditary nerve disease), GSK (bepirovirsen for chronic hepatitis B), Novartis and Roche. In removed: Q2 added: Q3 2026, revenue was removed: $268 added: $243 million, and royalty revenue was removed: $76 added: $81 million. Ionis still loses money, because it spends on research and on new launches, and it targets cash flow breakeven in 2028.
Thesis: The market lowered its view of Ionis's pipeline after two large partnered heart trials failed in 2026. On July 9, 2026, AstraZeneca's eplontersen trial in transthyretin amyloid cardiomyopathy missed its primary endpoint. On September 4, 2026, Novartis said that pelacarsen lowered Lp(a) but did not reduce cardiovascular events in the HORIZON trial. Both trials were possible sources of large royalties. Investors now value Ionis mostly on its own launches, which are still removed: small: TRYNGOLZA sales were $5 million in Q2 2026 after a price cut, added: small, and Ionis still has an operating loss. The added: first full quarter of the TRYNGOLZA launch in severe hypertriglyceridemia was weak: sales were $9 million in Q3 2026, and on November 9, 2026, Ionis cut its 2026 TRYNGOLZA guidance to about $50 million from $100 million to $110 million. The market doubts that TRYNGOLZA can reach the multi-billion-dollar removed: potential added: peak sales that management removed: sees in severe hypertriglyceridemia, which the FDA approved in June 2026. added: still expects. For the gap to close, four things must be true. TRYNGOLZA sales must grow removed: fast added: clearly each quarter from removed: Q3 2026 in severe hypertriglyceridemia, with added: Q4 2026, and the EU decision for removed: this use added: severe hypertriglyceridemia, expected in Q4 removed: 2026. added: 2026, must be positive. DAWNZERA must reach its 2026 guidance of $110 million to $120 million of removed: sales. added: sales, after $37 million in Q3 2026. GSK must removed: launch bepirovirsen (Hibsago), added: grow HIBSAGO (bepirovirsen), which removed: the FDA added: is approved removed: for chronic hepatitis B on October 20, 2026, added: in the US, Japan and added: Canada, and win approvals in removed: other countries. Roche added: the EU and China. Partners must file sefaxersen in IgA nephropathy added: and ulefnersen in FUS-ALS after removed: the added: their positive Phase 3 removed: interim data of September and October 2026. added: results. Ionis must added: also stay on its path to cash flow breakeven in 2028. The removed: Q3 added: Q4 2026 report removed: on November 9, 2026 gives added: and the removed: first evidence of the TRYNGOLZA launch added: 2027 guidance, expected in removed: severe hypertriglyceridemia. added: February 2027, give the next evidence. If the launches grow, the gap can close over the next four to eight quarters. If TRYNGOLZA removed: grows added: keeps growing slowly, the market can keep a low value on the pipeline.
Risks: Ionis's value depends on new launches. TRYNGOLZA sales were only removed: $5 added: $9 million in removed: Q2 added: Q3 2026, and added: Ionis cut its added: 2026 TRYNGOLZA guidance to about $50 million from $100 million to $110 million. Its growth in severe hypertriglyceridemia is not yet proven. Other drugs that lower triglycerides can compete, and payers can limit use. Clinical trials can fail. Two partnered Phase 3 heart trials, of eplontersen and pelacarsen, missed their primary endpoints in 2026. Results for obudanersen in Angelman syndrome are due in the second half of 2027, and other pipeline drugs also depend on trial results. Ionis still loses money: its loss from operations was removed: $220 added: $350 million in the first removed: half added: nine months of 2026. It targets cash flow breakeven in 2028. If launches are slow, it can need more capital. Partners decide on development and sales of many Ionis drugs. GSK's removed: bepirovirsen won FDA approval on October 20, 2026, added: HIBSAGO (bepirovirsen) is approved in the US, Japan and Canada, but added: it still needs approvals in removed: other countries added: the EU and added: China and a good launch, and Roche's sefaxersen still needs its full two-year results. A partner can delay or stop a program. Ionis sold part of its SPINRAZA and pelacarsen royalties to Royalty Pharma, so it keeps less of these royalties. SPINRAZA also faces competition from other treatments for spinal muscular atrophy.
Balance sheet: Cash: removed: $2.1B added: $1.9B Debt: $1.3B Net cash: removed: $710M added: $539M Debt due within 12 months: $0.0M Last debt due: 2030 Ionis has net cash. At removed: June added: September 30, 2026, it had removed: $2,055 added: $1,884 million of cash, cash equivalents and short-term investments, down from $2,677 million at December 31, 2025, removed: mainly because it repaid its 0% convertible notes on April 1, removed: 2026. added: 2026, and used cash to fund operations. Debt is the principal of two convertible note issues: $770.0 million of 0% notes due 2030 and $575.0 million of 1.75% notes due 2028. Ionis can settle conversions in cash, shares or both. Debt does not include a removed: $562.6 added: $566.0 million liability for the sale of future SPINRAZA and pelacarsen royalties to Royalty Pharma in 2023, which Ionis pays from those removed: royalties added: royalties. After the pelacarsen trial failed, Ionis expects no pelacarsen royalty payments to Royalty Pharma, and removed: records at an added: the effective interest rate removed: of 12.0%. added: on this liability fell to 10.0%. Ionis has no EBITDA to compare with debt, because it had an operating loss of removed: $220 added: $350 million in the first removed: half added: nine months of 2026. It added: expects more than $1.6 billion of cash at the end of 2026 and targets cash flow breakeven in 2028. No removed: debt is added: convertible notes are due within 12 months of removed: June added: September 30, 2026, and the first notes are due in 2028. As of removed: Jun added: Sep 30, 2026.
Checkpoints: Oct 26, 2026: FDA decision on GSK's bepirovirsen in chronic hepatitis B. Passed. Watch: FDA approval on time passes; a rejection or a long delay fails. Outcome: The FDA approved bepirovirsen as Hibsago on October 20, 2026, six days before the target date. Nov 9, 2026: Q3 2026 results: first quarter of the TRYNGOLZA sHTG launch. removed: Pending. added: Failed. Watch: Fast growth in TRYNGOLZA sales after the June approval and DAWNZERA on track for $110 million to $120 million pass; flat TRYNGOLZA sales or a cut to 2026 guidance fail. added: Outcome: TRYNGOLZA sales were only $9 million in Q3 2026, and Ionis cut its 2026 TRYNGOLZA guidance to about $50 million from $100 million to $110 million, although DAWNZERA stayed on track. Q4 2026 (estimate): EU decision on TRYNGOLZA in severe hypertriglyceridemia. Pending. Watch: European Commission approval in Q4 2026 passes; a delay into 2027 or a rejection fails. Feb added: 9, 2027 (estimate): Full-year 2026 results and 2027 outlook. Pending. Watch: A 2027 outlook with strong growth in product added: sales, TRYNGOLZA sales added: that grow each quarter and a clear path to cash flow breakeven in 2028 removed: passes; added: pass; a later breakeven or slow launch growth fails.
Recent events: Nov added: 9, 2026: Ionis reported Q3 2026 results. Revenue rose to $243 million from $157 million, and the loss from operations was $130 million. TRYNGOLZA sales were $9 million, DAWNZERA sales were $37 million and ZANVASTRO sales were $2 million. SPINRAZA royalties were $69 million. Cash and short-term investments were $1.9 billion. Ionis cut its 2026 guidance for TRYNGOLZA sales to about $50 million from $100 million to $110 million, because the launch in severe hypertriglyceridemia grows more slowly than it expected. It kept its 2026 guidance for total revenue of $875 million to $900 million, DAWNZERA sales of $110 million to $120 million, a non-GAAP operating loss of $425 million to $475 million and more than $1.6 billion of cash. Ionis also said that GSK's HIBSAGO is now approved in the US, Japan and Canada. Nov 2, 2026: Ionis said it will discuss its Q3 2026 results in a webcast on Monday, November 9, 2026, at 9:00 a.m. Eastern Time. Oct 23, 2026: Ionis's partner Roche presented full interim Phase 3 IMAgINATION data for sefaxersen in IgA nephropathy. Sefaxersen reduced proteinuria by 43.1% against placebo at 37 weeks (p<0.0001), with no new safety signals. The study continues to week 105 to measure kidney function, and Roche will share the data with health authorities. Oct 20, 2026: The FDA approved GSK's Hibsago (bepirovirsen) for chronic hepatitis B in adults without cirrhosis, with suppressed virus and low surface antigen levels, together with standard antiviral therapy. Ionis discovered bepirovirsen and licensed it to GSK, and it earns milestone payments and royalties. GSK expects more regulatory decisions in other countries in the coming months. Oct 16, 2026: The CHMP of the European Medicines Agency recommended the extension of the EU approval of TRYNGOLZA to adults with severe hypertriglyceridemia and triglycerides of 880 mg/dL or more. Ionis expects the European Commission decision in Q4 2026, earlier than it had planned. Ionis works with its partner Sobi on TRYNGOLZA in Europe. Sep 23, 2026: Ionis and Roche said that sefaxersen met its primary endpoint at a prespecified interim analysis of the Phase 3 IMAgINATION study in IgA nephropathy, with a significant reduction in proteinuria at 37 weeks. The study continues to measure kidney function at week 105. Sep 22, 2026: Ionis and its partner Otsuka said that ulefnersen met the primary endpoint of the Phase 3 FUSION study in FUS-ALS, a rare genetic form of ALS (p=0.0005). The companies plan to discuss fast approval paths with the FDA and other regulators. Otsuka holds the license, and Ionis can receive milestone payments and royalties. Sep 4, 2026: Novartis said that its Phase 3 Lp(a)HORIZON trial of pelacarsen did not meet its primary endpoint of fewer cardiovascular events, although pelacarsen lowered Lp(a) as in earlier studies. Ionis discovered pelacarsen and earns royalties from Novartis, and it sold part of these royalties to Royalty Pharma in 2023. Sep 3, 2026: The FDA approved ZANVASTRO (zilganersen) as the first disease-modifying treatment for Alexander disease, an ultra-rare neurological disorder. Ionis received a Priority Review Voucher with the approval. This is its first independent launch in neurology. Jul 29, 2026: Ionis reported Q2 2026 results. Revenue was $268 million, and the loss from operations was $102 million. TRYNGOLZA sales were $5 million, after a lower net price from April 1, 2026, and DAWNZERA sales were $26 million. Cash and short-term investments were $2.1 billion. Ionis said it is on track for its 2026 guidance and for cash flow breakeven in 2028. Jul 9, 2026: Ionis and AstraZeneca said that the Phase 3 CARDIO-TTRansform trial of eplontersen in transthyretin amyloid cardiomyopathy missed its primary endpoint of cardiovascular death and recurrent cardiovascular events. A prespecified subgroup on eplontersen alone showed a nominally significant result. Jun 24, 2026: The FDA approved TRYNGOLZA to reduce triglycerides and the risk of acute pancreatitis in adults with severe hypertriglyceridemia. This is Ionis's first independent launch in a common condition. May 28, 2026: GSK reported that bepirovirsen gave a functional cure rate of 19% in chronic hepatitis B in the pivotal B-Well studies, against 0% with standard of care. In Q2 2026, Ionis and GSK amended their agreement, with higher milestones and royalty terms that exclude China, Hong Kong and Macau.