Financial Data and Key Metrics Changes - In Q2 2025, Ionis Pharmaceuticals reported revenue of $452 million, a twofold increase year over year, and $584 million for the first half of 2025, representing a nearly 70% increase compared to the prior year [30][31] - Non-GAAP net income for the quarter was $154 million, reflecting strong financial performance [31] - The company raised its 2025 revenue guidance by $100 million, now expecting between $825 million and $850 million in revenue for the year [34] Business Line Data and Key Metrics Changes - The launch of Trincolza generated $19 million in net product sales for Q2, marking a threefold increase quarter over quarter [10][32] - Royalty revenues increased by approximately 10% to $70 million in Q2, supported by contributions from SPINRAZA and WAYNUA [32] - Ionis anticipates $75 million to $80 million in Trincolza product sales for the full year [34] Market Data and Key Metrics Changes - The coverage mix for Trincolza patients is approximately 60% commercial and 40% government, with over 90% of patients paying $0 out of pocket since launch [12] - The company is targeting over 3,000 physicians and has reached more than 30,000 healthcare providers through its marketing efforts [14] Company Strategy and Development Direction - Ionis is focused on expanding its pipeline with multiple upcoming launches, including Donavolorsen for hereditary angioedema, which is expected to receive FDA approval soon [7][9] - The company aims to leverage its first-mover advantage in both familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) markets [15][71] - Ionis plans to continue investing in its late-stage programs while maintaining disciplined capital management [35] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the continued commercial success of Trincolza and the upcoming launch of Donavolorsen, highlighting the strong therapeutic profiles and unmet needs these products address [5][9] - The company anticipates a steady cadence of independent and partnered launches over the next few years, contributing to sustained revenue growth and positive cash flow [37] Other Important Information - Ionis is preparing for an innovation day on October 7 to highlight its pipeline and advancements in drug discovery [38] - The company is also set to initiate a quiet period starting July 31, which will be lifted upon data announcement from the CORE and CORE II studies [39] Q&A Session Summary Question: How is the TRINGOZA FCS launch progressing? - The company reported strong execution with a threefold increase in Q2 sales, effective patient identification efforts, and favorable reimbursement trends [41][43] Question: What triglyceride lowering is expected in the upcoming SHTG readout? - The company expects a reduction of 58% to 62% in triglyceride levels, which is considered clinically meaningful for physicians [48][49] Question: What is the status of Donavolorsen's launch preparations? - The company confirmed that everything is in place for the launch following the expected FDA approval on August 21 [50][54] Question: How does the company view competition in the market? - Management believes that patients are willing to switch to Donavolorsen due to its strong profile and ease of use compared to existing treatments [78] Question: What is the expected acute pancreatitis (AP) event rate in the CORE and CORE II studies? - The company confirmed that there will be more AP events in the CORE and CORE II studies combined than in the FCS BALANCE study, but specific numbers were not disclosed [64][104]

Financial Data and Key Metrics Changes - Ionis Pharmaceuticals reported revenue of $452 million for Q2 2025, a twofold increase year over year, and $584 million for the first half of 2025, an increase of nearly 70% compared to the prior year [29][30] - Non-GAAP net income for Q2 was $154 million, reflecting strong financial performance [29] - The company raised its 2025 revenue guidance by $100 million, now expecting between $825 million and $850 million in revenue for the year [32][34] Business Line Data and Key Metrics Changes - Trincolza generated $19 million in net product sales for Q2, representing a threefold increase quarter over quarter [8][30] - Royalty revenues increased by approximately 10% to $70 million in Q2, supported by contributions from SPINRAZA and WAYNUA [30] - Ionis anticipates $75 million to $80 million in Trincolza product sales for the full year [33] Market Data and Key Metrics Changes - The coverage mix for Trincolza patients is approximately 60% commercial and 40% government, with over 90% of patients paying $0 out of pocket since launch [10][11] - The company is targeting over 3,000 physicians and has reached more than 30,000 healthcare providers to increase awareness and patient identification for Trincolza [12][70] Company Strategy and Development Direction - Ionis is focused on launching multiple independent therapies, with Trincolza being the first and Donadolorsen expected to follow shortly after FDA approval [5][6] - The company aims to leverage its first-mover advantage in both familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG) markets [12][70] - Ionis plans to continue investing in its pipeline, with expectations of four potential launches by 2027 targeting serious conditions [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing commercial success of Trincolza and the upcoming launch of Donadolorsen, highlighting the strong therapeutic profiles and unmet needs being addressed [4][5] - The company anticipates continued revenue growth and positive cash flow in the coming years, supported by a robust pipeline and disciplined capital management [34][35] Other Important Information - Ionis is preparing for an innovation day on October 7 to highlight its pipeline and advancements in drug discovery [37] - The company is actively engaging with payers to ensure smooth market access for its upcoming products [15] Q&A Session Questions and Answers Question: Can you provide more details on the Trincolza FCS launch and expectations for the second half of the year? - Management highlighted strong early momentum with $19 million in Q2 sales and effective patient identification efforts, expecting continued growth through the second half of the year [44][46] Question: What level of triglyceride lowering is expected in the upcoming SHTG readout? - The company anticipates a triglyceride reduction of 58% to 62%, which is considered clinically meaningful for physicians managing these patients [48][49] Question: How is the launch readiness for Donadolorsen progressing? - Management confirmed that all preparations are in place for the anticipated launch following the August 21 PDUFA date, with a strong regulatory and clinical data foundation [56][57] Question: What insights can you provide regarding competition in the HAE market? - Management noted that existing prophylactic treatments are not fully satisfying patients, indicating a strong willingness to switch to Donadolorsen due to its favorable profile and self-administration convenience [78][80] Question: Can you clarify the expected acute pancreatitis (AP) event rates in the CORE and CORE II studies? - Management confirmed that the cumulative AP event rate in the CORE and CORE II studies is expected to be higher than in the FCS BALANCE study, but specific numbers will be provided in the upcoming data release [65][66]