Ionis Pharmaceuticals (IONS) investor relations material

Recent progress and upcoming milestones

• Launched two independent products in FCS and HAE last year, with two PDUFA dates for wholly-owned pipeline assets in 2026, including TRYNGOLZA for SHTG and zilganersen for Alexander disease.

• Five phase III readouts expected this year, including bepirovirsen, two cardiovascular outcome trials (CARDIO-TTRansform for ATTR-CM and HORIZON for Lp(a)), and robust midstage pipeline advancement.

• Biogen's tau program advancing to phase III after positive phase II data, with continued growth opportunities projected for 2026 and beyond.

Tau program and Alzheimer’s disease insights

• Tau-lowering oligonucleotide showed robust reductions in CSF tau and reversal of tau PET, with unprecedented cognitive benefits in phase II.

• Cognitive benefits were in line with or exceeded those seen with amyloid therapies, meeting pre-specified endpoints for phase III advancement.

• Placebo performed as expected, and all dose cohorts showed benefit, with further data to be presented at AAIC in July.

Severe hypertriglyceridemia (SHTG) and TRYNGOLZA

• Phase III data showed 85% reduction in acute pancreatitis events, leading to breakthrough therapy designation and confidence for June 30 PDUFA.

• Modest increase in liver fat observed, but not considered a safety signal; ongoing monitoring shows stabilization over time.

• Target population includes 1 million high-risk patients, with plans to expand access beyond those with acute pancreatitis history.

• Pricing set at $40,000 WAC based on data-driven demand and payer research, aiming for broad access.

• Peak revenue guidance evolved from $1B to $3B+ due to strong efficacy, demand research, and pricing strategy.