Business Momentum and Pipeline Achievements - Ionis' first independent launch is exceeding expectations, with a second underway[13] - Olezarsen demonstrated statistically significant reductions of up to 72% in placebo-adjusted fasting triglycerides in sHTG patients[14, 18] - Olezarsen showed a highly statistically significant 85% reduction in adjudicated acute pancreatitis events compared to placebo[14, 21] - Zilganersen demonstrated statistically significant stabilization on the primary endpoint of gait speed in AxD patients[14] - ION582 showed consistent and meaningful improvements in key areas at 6 months in Angelman Syndrome patients[36] Commercial Performance and Strategy - TRYNGOLZA Q3 2025 net sales reached $32 million, with approximately 70% growth[13, 48] - DAWNZERA U S launch is underway with early excitement from physicians and patients[13] - The company is targeting over 3,000 physicians to increase FCS awareness[53] - DAWNZERA has a peak sales potential of over $500 million[65] Financial Highlights and Guidance - Q3 2025 commercial revenue was $116 million and R&D revenue was $41 million, totaling $157 million[75] - The company increased its 2025 revenue guidance to $875-$900 million, including $85-$95 million from TRYNGOLZA net revenues[77]

2 Ionis Leadership Here Today Innovation Day 2025: Accelerating Growth through Life-Changing Medicines OCTOBER 7, 2025 | Nasdaq: IONS Forward-Looking Statements This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis' goals, expectations, fina ...