Financial Data and Key Metrics Changes - Ionis Pharmaceuticals reported a revenue increase of 34% year-over-year, reaching $944 million in 2025, with commercial products contributing $436 million and R&D collaborations $508 million [30][31] - The company exceeded its financial guidance across all metrics, driven by strong execution and disciplined financial management [30][32] - Non-GAAP operating expenses increased modestly year-over-year, primarily due to investments related to the U.S. launch of TRYNGOLZA and DAWNZERA [32][39] Business Line Data and Key Metrics Changes - TRYNGOLZA generated $108 million in product sales in 2025, with a 56% increase in Q4 revenues compared to Q3 [19][31] - DAWNZERA achieved $8 million in product sales from its initial months of launch, with strong participation in a free trial program leading to 100% conversion to paid therapy [31][36] - Olezarsen is projected to exceed $2 billion in peak annual revenue, reflecting strong prescriber demand and positive Phase 3 data [24][66] Market Data and Key Metrics Changes - The payer mix for TRYNGOLZA is approximately 60% commercial and 40% government, with broad access for both clinically diagnosed and genetically confirmed patients [22][31] - The company anticipates a meaningful decline in TRYNGOLZA revenues throughout 2026 ahead of the sHTG launch, followed by accelerating growth post-approval [35][48] Company Strategy and Development Direction - Ionis is focused on maximizing the potential of its marketed medicines while preparing for multiple upcoming launches, including Olezarsen for sHTG and Zilganersen for Alexander disease [29][39] - The company aims to achieve cash flow breakeven by 2028, supported by a diversified revenue stream and disciplined investment strategy [30][39] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to deliver transformational medicines and create shareholder value, citing strong commercial momentum and an advancing pipeline [41][43] - The company is actively engaging with payers to ensure broad access for its products while balancing long-term value realization [48][56] Other Important Information - Ionis received breakthrough therapy designation from the FDA for Olezarsen, which is currently under review [17][72] - The company is preparing for the anticipated U.S. approval of high-dose Spinraza, with a PDUFA date set for April 3rd [18] Q&A Session Summary Question: Guidance on sHTG sales and pricing dynamics - Management clarified that current guidance assumes standard review for Olezarsen, with sales from the sHTG patient population expected in Q4 [46][47] - Discussions with payers are ongoing to ensure broad access for TRYNGOLZA prior to the sHTG launch, with a meaningful decline in revenues anticipated until then [48][49] Question: Reimbursement in FCS and pricing dynamics - The company reported no significant impact from competitors on TRYNGOLZA demand, with strong patient access maintained [56][59] Question: Peak revenue for Olezarsen - Management expressed increased confidence in the $2 billion peak revenue estimate for Olezarsen, driven by strong demand trends and positive Phase 3 data [63][66] Question: FDA interactions regarding sHTG filing - Management indicated that interactions with the FDA have been positive, and they believe Olezarsen deserves priority review designation [72][73] Question: European sites for Angelman syndrome program - The company is awaiting approval to open European sites for the Angelman syndrome program and plans to do so once approval is received [81][82]

Financial Data and Key Metrics Changes - Ionis generated $944 million in revenue for 2025, representing a 34% increase year-over-year [29] - Revenue from commercial products was $436 million (46% of total revenue), while R&D collaborations contributed $508 million (54% of total revenue) [29] - Royalty revenues increased by 11% to $285 million, driven by contributions from Spinraza and Waylivra [31] Business Line Data and Key Metrics Changes - TRYNGOLZA generated $108 million in product sales for 2025, with a 56% increase in Q4 sales compared to Q3 [30] - DAWNZERA achieved $8 million in product sales from its initial months of launch [30] - Olezarsen is projected to exceed $2 billion in annual peak revenue based on positive phase 3 data and strong prescriber demand [23][30] Market Data and Key Metrics Changes - The U.S. market for severe hypertriglyceridemia (sHTG) includes over 1 million individuals at high risk, indicating a significant patient population for Olezarsen [21] - The current payer mix for TRYNGOLZA is approximately 60% commercial and 40% government, with broad access for both clinically diagnosed and genetically confirmed patients [19] Company Strategy and Development Direction - Ionis aims to achieve cash flow breakeven by 2028 while expanding its commercial portfolio through multiple launches [39] - The company is focused on maximizing the potential of its marketed medicines and preparing for additional launches, including Olezarsen for sHTG and Zilganersen for Alexander disease [27][39] - Ionis is committed to maintaining broad patient access while maximizing long-term value realization for its products [46] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's trajectory, highlighting strong commercial momentum and a robust pipeline of innovative therapies [39] - The anticipated approval of Olezarsen is expected to drive significant revenue growth in the fourth quarter of 2026 [32] - Management noted that the company is actively engaging with payers to ensure continued access for patients [46] Other Important Information - The company has a well-capitalized balance sheet with approximately $1.6 billion in cash and investments projected by year-end [37] - Ionis plans to provide detailed revenue guidance for TRYNGOLZA and DAWNZERA at the first quarter earnings call [33] Q&A Session Questions and Answers Question: Can you clarify your guidance regarding sHTG sales and pricing dynamics? - Management confirmed that guidance does not assume significant sHTG sales initially and anticipates a decline in TRYNGOLZA revenues ahead of the sHTG launch, with growth expected post-approval [44][46] Question: What is the reimbursement landscape for FCS and how does it compare to competitors? - Management indicated that there has been no meaningful impact from competitors on TRYNGOLZA demand, and they are focused on maximizing value while ensuring broad access [56][58] Question: What is the expected timeline for the GSK partnered HBV program? - Management stated that GSK plans to present data at EASL in May, with peak sales estimates around $2.5 billion, and Ionis expects to earn tiered royalties from this program [87] Question: How does the launch strategy for Zilganersen compare to other rare diseases? - Management highlighted strong community interest and a focused launch strategy for Zilganersen, with a modest-sized team targeting major leukodystrophy centers [94]

Brett Monia, Ph.D. Chief Executive Officer Holly Kordasiewicz, Ph.D. Chief Development Officer YE:2025 Business Update and Financial Results February 25, 2026 Nasdaq: IONS 1 On Today's Earnings Call Beth Hougen Chief Financial Officer Eugene Schneider, M.D. Chief Clinical Development Officer 2 Eric Swayze, Ph.D. Executive Vice President, Research Forward-Looking Statements This presentation includes forward-looking statements regarding our business, financial guidance and the therapeutic and commercial pote ...

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 ...

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] - The company raised its 2025 financial guidance, now expecting total revenue between $875 million and $900 million, an increase of $50 million from previous guidance [25][26] - Operating loss is anticipated to be between $275 million and $300 million for the full year, with a cash balance expected to exceed $2.1 billion [25][26] Business Line Data and Key Metrics Changes - Tringolsa reported $32 million in net product sales, a nearly 70% increase quarter over quarter [14][23] - Royalty revenues increased by approximately 13% to $76 million in Q3, driven by contributions from Spinraza and Waylivra [24] - Donzera's launch is showing strong early adoption, with initial prescriptions being filled shortly after approval [19][20] 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 Donzera [20] - The severe hypertriglyceridemia (SHTG) market is estimated to have over 1 million high-risk patients in the U.S., with Olzarsen positioned to address unmet needs in this population [16][17] Company Strategy and Development Direction - The company is focused on executing its strategy with two independent launches underway and plans for two additional launches next year [27][22] - The advancing wholly owned late-stage pipeline and a robust partnered portfolio are expected to drive sustained growth [7][26] - The company aims to achieve cash flow breakeven by 2028, emphasizing long-term value creation [26] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the continued success of Tringolsa and the upcoming launches of Olzarsen and Zilganersen, highlighting the strong momentum across the business [5][27] - The management team is optimistic about the potential for multi-billion dollar revenue from the new product launches and the overall pipeline [7][25] Other Important Information - Richard Geary, Chief Development Officer, will retire at the end of the year, marking his last earnings call with the company [28] Q&A Session Summary Question: Thoughts on the launch curve for Olzarsen in SHTG - Management indicated strong interest from healthcare providers and plans to target approximately 20,000 HCPs covering around 360,000 patients [30][32] Question: Concerns regarding acute pancreatitis events in Olzarsen studies - Management reassured that the data is groundbreaking and that the acute pancreatitis outcomes will be detailed at the upcoming AHA presentation [36][38] Question: Peak revenue potential for Donzera and Olzarsen - Management expects peak sales for Donzera to exceed $500 million and for Olzarsen to exceed $1 billion [39] Question: Pricing strategy for Olzarsen - Management is still working on pricing and expects to provide more clarity next year [44][45] Question: Early prescriptions for Donzera - The launch is going well, with both switching patients and newly diagnosed patients contributing to early prescriptions [70][72]

Financial Data and Key Metrics Changes - In Q3 2025, the company generated $157 million in revenue, a 17% increase year over year, and $740 million for the first nine months, reflecting a 55% increase compared to the prior year [23][24] - Tringolsa reported $32 million in net product sales, representing a nearly 70% increase quarter over quarter [13][23] - Royalty revenues increased by approximately 13% to $76 million in Q3, driven by contributions from Spinraza and Waylivra [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 - Tringolsa's launch is gaining momentum, with a significant increase in prescribers and patient identification efforts [15][16] - Donzera, approved for hereditary angioedema, is seeing strong early adoption, with patients switching from prior therapies and treatment-naive patients starting on Donzera [18][19] - Olzarsen showed a significant reduction in triglycerides and acute pancreatitis events, positioning it for a strong launch next year [9][10] - Zilganersen demonstrated a disease-modifying effect in Alexander disease, with plans for an independent launch next year [10][11] Market Data and Key Metrics Changes - The company anticipates targeting approximately 20,000 healthcare providers (HCPs) for Olzarsen, covering around 360,000 patients with severe hypertriglyceridemia (SHTG) [32] - The U.S. prophylactic HAE market is well established, with many patients dissatisfied with current therapies, indicating a significant opportunity for Donzera [19][66] Company Strategy and Development Direction - The company is focused on executing its commercial strategy for Tringolsa and Donzera while preparing for upcoming launches of Olzarsen and Zilganersen [22][28] - The pipeline includes multiple late-stage programs, with expectations for four key launches from the partnered pipeline by the end of 2027 [6][12] - The company aims to achieve cash flow breakeven by 2028, driving long-term value creation [26][28] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing momentum across the business, with strong performance from independent launches and a robust pipeline [4][28] - The company is optimistic about the potential of Olzarsen and Zilganersen to address significant unmet medical needs [10][11] - Management highlighted the importance of patient identification and education efforts to maximize the impact of new therapies [15][16] Other Important Information - The company plans to submit a new drug application for Zilganersen in Q1 2026 and is initiating an expanded access program in the U.S. [11] - The company has a strong balance sheet, expecting to end the year with over $2.1 billion in cash [26] Q&A Session Summary Question: Thoughts on the launch curve for Olzarsen in SHTG - Management indicated strong interest from HCPs and plans to target approximately 20,000 HCPs covering 360,000 patients, expecting strong uptake based on phase 3 data [32] Question: Concerns regarding acute pancreatitis events in Olzarsen studies - Management reassured that the data is groundbreaking and will be presented at AHA, with no significant concerns regarding acute pancreatitis events [36] Question: Peak revenue potential for Donzera and Olzarsen - Management expects peak sales for Donzera to exceed $500 million and for Olzarsen to exceed $1 billion [38] Question: Pricing strategy for Olzarsen - Management is still working on pricing and expects to provide more clarity next year [40] Question: Early prescriptions for Donzera - Management reported strong early adoption, with switches from existing therapies and newly diagnosed patients [66]

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]

Core Insights - Ionis Pharmaceuticals released topline results from a pivotal study of zilganersen for Alexander disease, a rare neurological condition [1] - Zilganersen showed statistically significant stabilization in gait speed, with a mean difference of 33.3% compared to control at week 61 [2] - The drug demonstrated a positive disease-modifying impact, marking a first in AxD treatment [3] Efficacy and Safety - Zilganersen exhibited consistent benefits across key secondary endpoints, indicating slowed disease progression and stabilization [3] - Key secondary endpoints included various patient and clinician global impression scores, showing favorable trends [4] - The safety profile of zilganersen was favorable, with most adverse events being mild or moderate, and serious adverse events were numerically lower in the treatment group [4] Regulatory and Market Impact - Ionis plans to submit a new drug application to the FDA in Q1 2026 and is considering an Expanded Access Program in the U.S. [5] - Following the news, Ionis stock rose by 4.88% to $63.99 in premarket trading [5]

Q2:2025 Business Update and Financial Results July 30, 2025 Nasdaq: IONS 1 On Today's Earnings Call Eugene Schneider, M.D. Chief Clinical Development Officer Eric Swayze, Ph.D. Executive Vice President, Research 2 Brett Monia, Ph.D. Chief Executive Officer Kyle Jenne Chief Global Product Strategy Officer In this presentation, unless the context requires otherwise, "Ionis," "Company," "we," "our," and "us" refers to Ionis Pharmaceuticals and its subsidiaries. Ionis Pharmaceuticals® is a registered trademark ...