Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][37] - The TTR franchise generated $544 million in revenues, reflecting a 77% increase year-over-year [8][11] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, a 27% increase at the midpoint [9][42] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined sales of ONPATTRO and Ambutra rise by 80% compared to Q1 2025, driven primarily by the launch of Ambutra [14][16] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][11] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the demand from the ATTR Centimeters launch [15][11] Market Data and Key Metrics Changes - International markets are expected to contribute to Ambutra's revenues in the second half of 2025, with launches in Germany and Japan [15][27] - The U.S. TTR franchise achieved $383 million in Q2 2025, indicating robust growth dynamics [16][11] - The company has yet to recognize any ATTR Centimeters revenue internationally, but anticipates strong growth as international launches commence [15][11] Company Strategy and Development Direction - Alnylam focuses on three core elements: TTR leadership, growth through innovation, and strong financial performance [6][7] - The company aims to establish long-term leadership in TTR and expand its pipeline of RNAi therapeutics [6][9] - Alnylam is committed to disciplined capital allocation and sustainable growth, with a focus on patient and customer centricity [28][9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early performance of Ambutra and its potential for sustainable growth [9][28] - The company highlighted the importance of real-world evidence generation and the development of next-generation RNAi therapeutics [27][9] - Management remains optimistic about achieving its Alnylam Pizza Fit by 25 goals, reinforcing its position as a top-tier biotech company [10][9] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, enhancing its development prospects [9][31] - Alnylam's gross margin on product sales was 79% for the quarter, down from 84% in 2024, primarily due to increased royalties [39][37] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.9 billion, an increase from $2.7 billion at the end of 2024 [41][37] Q&A Session Summary Question: Can you provide details on the patient profiles for Ambutra? - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy mix emerging [48][49] Question: How are you thinking about net price for Ambutra moving forward? - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [56][57] Question: Was there any bolus effect in cardiomyopathy scripts in Q2? - Management confirmed solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [60][61] Question: Can you comment on the criteria physicians are using for stabilizer progressors? - Clinical evidence suggests that 30% to 50% of patients on stabilizers may progress, and physicians are using a variety of factors to determine treatment [81][82] Question: How should we think about the rate of new patient starts per quarter? - Management expects both categories of patients to continue growing, with a balanced uptake between new patients and stabilizer progressors [97][98]

Financial Data and Key Metrics Changes - Alnylam reported total net product revenues of $672 million for Q2 2025, representing a 64% year-over-year growth [9][35] - The TTR franchise generated revenues of $544 million, reflecting a 77% increase year-over-year [7][35] - The company increased its total net product revenue guidance for 2025 from a range of $2.05 billion to $2.25 billion to a revised range of $2.65 billion to $2.8 billion, marking a $575 million or 27% increase at the midpoint [9][39] Business Line Data and Key Metrics Changes - The TTR franchise in the U.S. saw combined Q2 sales of ONPATTRO and Ambutra rise by 80% compared to Q1, driven primarily by the Ambutra launch [13][35] - The rare franchise, including GIVLAARI and OXLUMO, delivered $128 million in combined Q2 sales, up 24% year-over-year [12][35] - The U.S. TTR franchise grew 125% compared to 2024, primarily due to the ATTR Centimeters launch [14] Market Data and Key Metrics Changes - Approximately 1,400 cardiomyopathy patients were receiving Ambutra by the end of Q2, contributing an estimated $150 million in revenue [13][23] - International markets are expected to begin contributing to Ambutra sales in the second half of the year, with launches in Germany and Japan [8][26] - The U.S. TTR franchise achieved $383 million in Q2, representing an 80% quarter-over-quarter growth [15] Company Strategy and Development Direction - Alnylam is focusing on TTR leadership, growth through innovation, and strong financial performance as key strategic pillars [4][6] - The company aims to establish itself as a top-tier biotech firm by delivering sustainable innovation and value creation [5][10] - The launch of Ambutra is seen as a flagship commercial franchise with robust long-term growth potential [6][27] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strong early launch performance of Ambutra and the potential for continued growth [9][39] - The company remains committed to advancing care through real-world evidence generation and the development of next-generation RNAi therapeutics [26][34] - Management highlighted the importance of disciplined execution and patient-centricity in driving long-term growth [27][39] Other Important Information - The FDA granted fast track designation to nucrisiran for ATTR Centimeters, which is expected to streamline the review process [9][31] - The gross margin on product sales was reported at 79%, down from 84% in the previous year, primarily due to increased royalties on Ambutra [37] Q&A Session Summary Question: Details on patient profiles for Ambutra - Management noted broad uptake across first-line patients and stabilizer progressors, with a healthy share of first-line patients emerging [45][46] Question: Thoughts on net price for Ambutra - The expectation is for a mid-single-digit reduction in net price for Ambutra in 2025 compared to 2024 [50][52] Question: Bolus effect in cardiomyopathy scripts - Management indicated solid commercial execution and emphasized that results are not just a flash in the pan, expecting continued sustainable growth [56][57] Question: Assumptions underpinning updated TTR franchise guidance - Management expects steady growth in both first-line and second-line patient flows, with a healthy trend in first-line use observed [65][70] Question: Criteria for stabilizer progressors - Clinical evidence suggests that one-third to half of patients on stabilizers progress, and physicians are using a variety of factors to determine eligibility for Ambutra [76][82] Question: Rate of new patient starts per quarter - Management is pleased with the initial uptake and expects both categories of patients to continue growing, though specific numbers will not be reported [91][94] Question: Payer requirements for Ambutra treatment - Broad coverage is reported across Medicare and commercial payers, with minimal step edits required for access [98][102]