44th Annual J.P. Morgan Healthcare Conference 2026 Breakthrough Therapies Driving Accelerating Growth Brett Monia, Ph.D. Chief Executive Officer January 2026 | 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 desc ...

Core Viewpoint - Ionis Pharmaceuticals Inc. has received a positive opinion from the CHMP recommending the approval of DAWNZERA for the prevention of recurrent attacks of hereditary angioedema in adults and adolescents aged 12 years and older [1][6]. Group 1: Hereditary Angioedema (HAE) - HAE is a rare genetic condition affecting approximately one in 50,000 people globally, characterized by severe swelling in various body parts [2]. - The condition highlights the need for effective prevention therapies due to its potentially life-threatening nature [2]. Group 2: DAWNZERA Mechanism and Trials - DAWNZERA functions by inhibiting plasma prekallikrein (PKK), a protein involved in activating inflammatory mediators linked to HAE attacks [3]. - The CHMP's recommendation is based on Phase 3 data from the OASIS-HAE and OASISplus trials, which showed significant reductions in attack frequency [3][4]. - The pivotal trials included adults and adolescents aged 12 years and older, demonstrating DAWNZERA's efficacy and safety, including self-administration via an autoinjector [4]. Group 3: Safety and Approval Status - Safety data indicated that DAWNZERA was generally well tolerated during trials [5]. - DAWNZERA was previously approved in the U.S. in August 2025, becoming the first RNA-targeted prophylactic treatment for HAE [5]. - The positive opinion from CHMP is now referred to the European Commission, with a final decision expected in the first quarter of 2026, positioning DAWNZERA as a transformative therapy for HAE patients [6]. Group 4: Stock Performance - Ionis Pharmaceuticals' stock has traded between $23.95 and $76.78 over the past year, closing at $71.55 on November 14, 2025, reflecting a 2.45% increase [6].

Financial Data and Key Metrics Changes - In Q3 2025, the company generated $157 million in revenue, a 17% increase year-over-year, and for the first nine months, revenue totaled $740 million, reflecting a 55% increase compared to the prior year [23][24] - TRYNGOLZA product sales reached $32 million, representing a nearly 70% increase over the second quarter [23][24] - Royalty revenues increased by approximately 13% to $76 million in Q3, driven by contributions from SPINRAZA and WAINUA [24] - The company raised its 2025 financial guidance, now expecting total revenue between $875 million and $900 million, an increase of $50 million from prior guidance [25][26] Business Line Data and Key Metrics Changes - TRYNGOLZA, the FDA-approved treatment for familial chylomicronemia syndrome, continues to show strong momentum with significant sales growth [5][14] - DAWNZERA, approved for hereditary angioedema, has seen strong early adoption, with initial prescriptions being filled shortly after approval [19][20] - The company anticipates two additional independent launches next year, with olzarsen for severe hypertriglyceridemia and zilganersen for Alexander disease [6][10] Market Data and Key Metrics Changes - The U.S. prophylactic HAE market is well established, with approximately 20% of patients switching treatments annually, indicating a significant opportunity for DAWNZERA [20] - The severe hypertriglyceridemia (sHTG) patient population is estimated to exceed 1 million in the U.S., with many patients struggling to manage triglyceride levels with current treatments [16][17] Company Strategy and Development Direction - The company is focused on executing its commercial strategy for TRYNGOLZA and DAWNZERA while preparing for upcoming launches of olzarsen and zilganersen [22][27] - The company aims to achieve cash flow breakeven by 2028, driving long-term value creation [26][27] - The commercial team is expanding outreach to healthcare providers and enhancing patient identification efforts to maximize the potential of its therapies [15][17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the continued success of TRYNGOLZA and DAWNZERA, highlighting the strong early feedback from physicians and patients [19][20] - The company is optimistic about the upcoming data presentations and regulatory submissions, which are expected to further validate its pipeline and market potential [9][11] - Management emphasized the importance of addressing unmet needs in serious diseases and the potential for multi-billion dollar revenue from its pipeline [7][10] Other Important Information - The company announced the retirement of Richard Geary, Chief Development Officer, recognizing his contributions over the past 30 years [28] - The company is preparing for a significant data presentation at the American Heart Association (AHA) conference, which is expected to highlight the efficacy of olzarsen [38][39] Q&A Session Summary Question: What is the expected launch curve for olzarsen in sHTG? - The company anticipates strong interest from healthcare providers and plans to target approximately 20,000 HCPs covering around 360,000 patients with sHTG [31][33] Question: Any concerns regarding acute pancreatitis events in olzarsen studies? - Management expressed confidence in the groundbreaking results and emphasized that the data will be presented at AHA, with no significant concerns noted [37][38] Question: What are the peak revenue expectations for olzarsen and DAWNZERA? - Peak sales for DAWNZERA are expected to exceed $500 million, while olzarsen is anticipated to surpass $1 billion [39][40] Question: What is the pricing strategy for olzarsen? - The company is still evaluating pricing and will announce final pricing upon approval of the sHTG indication [44][45] Question: How is the early adoption of DAWNZERA progressing? - Early adoption is strong, with both switching patients and newly diagnosed patients starting treatment [72] Question: What is the source of revenue growth for WAINUA? - The revenue growth is primarily driven by new patient identification and the product's performance in improving quality of life [73]

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 ...

Company Highlights - Aurinia Pharmaceuticals Inc. (AUPH) has seen solid growth for its product LUPKYNIS, with expected net product sales for 2025 ranging from $250 million to $260 million, up from $216.2 million last year [2][3] - Arrowhead Pharmaceuticals Inc. (ARWR) is preparing for its first commercial launch in 2025, with its lead drug candidate Plozasiran under FDA review, decision expected on November 18, 2025 [4][5] - Beta Bionics Inc. (BBNX) reported a 54% growth in second-quarter net sales, with expectations for full-year 2025 net sales to range between $88 million and $93 million, compared to $65.1 million last year [7][8] - Kiniksa Pharmaceuticals International plc (KNSA) anticipates net product revenue for its drug Arcalyst to be between $625 million and $640 million for 2025, up from $417 million in 2024 [10][11] - Ionis Pharmaceuticals Inc. (IONS) generated net product sales of $19 million in Q2 2025, with a supplemental new drug application expected by year-end [12][14] - Stoke Therapeutics Inc. (STOK) is developing Zorevunersen for Dravet syndrome, with a 52-week high of $24.60 reached recently, representing an 82% gain in less than two months [16][17] - Fortress Biotech Inc. (FBIO) is awaiting an FDA decision on its investigational drug CUTX-101 for Menkes disease, expected on September 30, 2025 [18][21] Stock Performance - AUPH stock increased by 168% over 1.5 years, reaching a 52-week high of $12.87 [3] - ARWR stock gained 65% in less than 9 months, hitting a 52-week high of $31.13 [5] - BBNX stock rose nearly 55% in less than 4 months, reaching a 52-week high of $26.66 [8] - KNSA stock saw a 46% increase in less than four months, touching a 52-week high of $37.34 [11] - IONS stock gained 52% in less than two months, reaching a 52-week high of $64.72 [15] - STOK stock increased by 82% in less than two months, achieving a 52-week high of $24.60 [17] - FBIO stock rose by 61% in less than a month, reaching a 52-week high of $3.97 [21]