Successfully transitioned into a fully integrated commercial-stage company following the first two independent launches of TRYNGOLZA and DAWNZERA.

Performance attribution for TRYNGOLZA was driven by a compelling clinical profile and strong execution, exceeding expectations with $108 million in full-year revenue.

Achieved breakthrough Phase III results for olezarsen in severe hypertriglyceridemia, demonstrating an unprecedented 85% reduction in acute pancreatitis events.

Strategic positioning in neurology was bolstered by positive Phase III data for zilganersen, the first therapy to show disease-modifying benefits in Alexander disease.

Revenue growth of 34% year-over-year was supported by a diversified model where marketed medicines provide recurring income while R&D collaborations act as financial accelerators.

Maintained disciplined investment strategies, enabling the company to exceed financial guidance while expanding the commercial field organization to 200 members.

Anticipating three additional launches in 2026, including the first broad-market launch for olezarsen in sHTG, which has a projected peak sales potential exceeding $2 billion.

Financial guidance assumes a standard FDA review for olezarsen with a Q4 approval, though management notes that a priority review designation would improve the outlook.

Expects a meaningful decline in TRYNGOLZA revenues throughout the year as the company transitions its pricing and reimbursement strategy to align with the broader sHTG market launch.

Projecting five late-stage data readouts from the partnered pipeline, including high-impact cardiovascular outcome trials for pelacarsen and eplontersen.

Remains on track to achieve the long-term strategic goal of reaching cash flow breakeven by 2028 through accelerating commercial revenue and operating leverage.

Management is actively managing evolving pricing dynamics in the FCS market to preserve broad access ahead of the planned sHTG price adjustment.

The 2026 cash balance projection includes a $433 million earmark specifically to repay remaining convertible notes due that year.

Operating loss for 2026 is projected to remain at a similar level to 2025 when excluding the one-time $280 million Sapablursen license fee.

Inventory build-up for the anticipated sHTG launch is cited as a primary driver for near-term strategic investment and cash usage.

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Management confirmed they expect a meaningful revenue decline for TRYNGOLZA ahead of the sHTG launch as they engage with payers on a new reimbursement strategy.

The goal is to balance broad patient access with long-term value, using a $20,000 net price assumption for the broader sHTG population in their $2 billion peak sales model.

Management stated that while they believe the medicine deserves priority review based on breakthrough designation, they are currently guiding based on a standard 10-month review for conservatism.

They clarified that the supplemental NDA is currently within the filing review period and they expect a decision on the review status shortly.

The study has a well-balanced mix of patients who were treatment-naive and those already on stabilizers like tafamidis at baseline.

Management noted that while there were some 'drop-ins' (patients starting other therapies during the trial), the numbers were not considered meaningful to the study's integrity.

Ionis is advancing siRNA technology to extend dosing intervals for Lp(a) and other targets to six months or even once-yearly.

The follow-on Lp(a) program is currently in IND-supporting toxicology studies, aiming to build on the first-mover advantage of pelacarsen.

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