In 2025 Ionis executed its first two independent product launches as a commercial‐stage biotech company, with TRYNGOLZA® (olezarsen) generating $105 million in preliminary U.S. net sales in its inaugural full year on the market. This performance exceeded initial expectations for the first FDA‐approved treatment for familial chylomicronemia syndrome. Concurrently, DAWNZERA™ (donidalorsen), the company’s RNA‐targeted therapy for hereditary angioedema, achieved broad market penetration with prescriptions written across all patient segments and a growing base of repeat prescribers. These launches mark a critical inflection point in Ionis’s transition from R&D to fully integrated commercial operations.

Ionis is positioned for two additional independent launches in 2026: olezarsen for severe hypertriglyceridemia—its first therapy in a large patient population—and zilganersen for Alexander disease, representing the inaugural neurology franchise from its owned pipeline. The olezarsen supplemental NDA has been submitted following Phase 3 CORE/CORE2 studies that demonstrated up to a 72% placebo‐adjusted reduction in fasting triglycerides and an 85% reduction in acute pancreatitis events. Based on this robust profile, peak annual net sales guidance for olezarsen has been raised to over $2 billion. Zilganersen’s NDA is planned for Q1, supported by Breakthrough Therapy designation and an ongoing U.S. expanded access program.

Beyond its owned assets, Ionis expects five Phase 3 readouts and four NDA submissions in 2026 across partnered programs. Notable catalysts include topline data from Novartis’s HORIZON cardiovascular outcomes study of pelacarsen in lipoprotein(a)-driven disease, GSK’s pivotal CHB studies of bepirovirsen with planned global regulatory filings, and AstraZeneca’s CARDIO-TTRansform study of eplontersen in ATTR-CM. Additional Phase 3 results are anticipated from Roche’s IgA nephropathy program and Otsuka’s ALS asset, alongside multiple Phase 2 readouts in Alzheimer’s and new trial initiations. Management reaffirmed a goal of achieving cash‐flow breakeven by 2028, driven by these near‐term commercial and clinical milestones.