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]

Financial Performance - Total Q2 Net Product Revenues reached $672 million, a 64% increase year-over-year[17, 24] - Total TTR Net Revenues in Q2 were $544 million, representing a 77% year-over-year growth[17] - Rare Franchise Net Product Revenues in Q2 totaled $128 million, a 24% increase year-over-year[28] - Alnylam increased its 2025 Total Net Product Revenue Guidance to a range of $2650 million to $2800 million[17, 74] - The company's Q2 Non-GAAP Operating Income was $95 million[70] Commercial Highlights - U S ATTR-CM launch contributed approximately $150 million in revenue during Q2[33, 34] - There are approximately 1,400 ATTR-CM patients receiving AMVUTTRA as of June 30, 2025[17, 37, 45] - U S TTR franchise experienced 125% year-over-year growth in Q2[32] - GIVLAARI saw a 30% year-over-year growth, driven by an approximately 18% increase in global patients on therapy[29] - OXLUMO experienced a 15% year-over-year growth, driven by an approximately 16% increase in global patients on therapy[29] Pipeline Development - The TRITON-CM Phase 3 study for nucresiran in ATTR-CM has been initiated, with a targeted launch around 2030[17, 60] - Phase 1 multidose results for mivelsiran in Alzheimer's Disease were announced[17] - A Phase 1 study for ALN-4324 in Type 2 Diabetes was initiated[17]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [8][40] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [41] - Non-GAAP operating profit for the quarter was $75 million, reflecting a $73 million improvement year-over-year [43] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase compared to Q1 2024, with U.S. sales growing by 45% year-over-year [15][16] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, representing an 8% growth year-over-year [14] Market Data and Key Metrics Changes - In the U.S., the TTR franchise saw a 32% increase in demand driven by ongoing ONPATTRO patient uptake, with Ambutra capturing approximately 70% of new patient starts in Q1 2025 [16][19] - Internationally, the TTR franchise grew by 24% compared to Q1 2024, primarily due to increased demand for Ambutra [17] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [7][10] - The company is committed to achieving sustainable non-GAAP profitability in 2025 and emphasizes a disciplined approach to capital allocation [9][11] Management's Comments on Operating Environment and Future Outlook - Management acknowledged uncertainties related to potential policy changes, including tariffs and FDA personnel reorganization, but expressed confidence in Alnylam's positioning to mitigate impacts [9][45] - The management reiterated guidance for continued growth and a strong launch in ATTR cardiomyopathy, projecting a robust 36% year-over-year growth in TTR franchise revenues [27][39] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR Centimeters, with a successful launch underway [20][30] - The company is advancing its pipeline with several pivotal studies planned, including TRITON Centimeters and TRITON PN [47] Q&A Session Summary Question: Initial patients starting treatment and prescriber base - Management noted a broad uptake among both experienced and new prescribers, indicating strong early momentum in the cardiomyopathy launch [51][53] Question: Revenue benchmarks for ATTR cardiomyopathy - Management clarified that the revenue contribution from ATTR cardiomyopathy was not included in Q1 results, as the approval came late in the quarter [57][62] Question: Commercial strategies to capture market share - Management highlighted the unique mechanism of action of Ambutra and its potential as a first-line treatment, which is driving physician interest [64][66] Question: Use of Quick Start program and formulary access - Management reported limited use of the Quick Start program, with most patients paying zero copay, and confirmed no price difference between indications [70][72] Question: Impact of TrueBee on Ambutra's launch - Management indicated no headwinds from TrueBee's launch, emphasizing the growing and unsatisfied market for ATTR treatments [76][78] Question: Metrics on health systems and patient initiation - Management confirmed that over half of the 170 priority health systems have Ambutra on formulary, with many already initiating treatments [97][99]

Financial Data and Key Metrics Changes - In Q1 2025, Alnylam Pharmaceuticals reported total product revenues of $469 million, representing a 28% year-over-year growth, driven by a 36% increase in the TTR franchise revenues [6][37] - Collaboration revenue decreased by 16% to $99 million compared to the previous year, primarily due to a milestone achieved in Q1 2024 [38] - Gross margin on product sales remained at 85%, consistent with Q1 2024, but is expected to decrease for the remainder of the year due to escalating royalty rates [39][41] Business Line Data and Key Metrics Changes - The TTR franchise generated $359 million in global net revenues, a 36% increase year-over-year, with U.S. sales growing by 45% [14][15] - The rare disease franchise, including GIVLAARI and OXLUMO, delivered $109 million in combined product sales, reflecting an 8% growth year-over-year [13] - The TTR franchise's growth was primarily driven by increased demand for ONPATTRO and Ambutra, with a 32% increase in demand noted [15][16] Market Data and Key Metrics Changes - In the U.S., Ambutra captured approximately 70% of new patient starts in the first quarter of 2025, indicating strong market leadership despite new competition [18] - Internationally, the TTR franchise grew by 24% compared to the first quarter of 2024, driven by robust patient uptake [16] - The company noted that about 80% of the global addressable population remains untreated, presenting significant growth opportunities [19] Company Strategy and Development Direction - Alnylam aims to become the global leader in TTR, focusing on broad access, driving awareness, and supporting treatment initiation for patients [5][9] - The company is committed to achieving sustainable non-GAAP profitability in 2025 while continuing to advance its high-value pipeline [7][10] - Alnylam's strategy includes leveraging its innovative pipeline with multiple multibillion-dollar opportunities and maintaining strong financial performance through disciplined capital allocation [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning despite uncertainties related to potential policy changes, tariffs, and FDA reorganizations [7][8] - The management highlighted the strong early progress in the launch of Ambutra for ATTR cardiomyopathy and reiterated guidance for continued growth [6][37] - The company remains optimistic about achieving its 2025 goals, which include expanding access to its therapies and enhancing patient outcomes [10][26] Other Important Information - Alnylam received FDA approval for Ambutra as the first and only silencer approved in the U.S. for ATTR cardiomyopathy, with positive opinions from regulatory bodies in Brazil and the EU [20][29] - The company is advancing its pipeline with new clinical programs targeting various diseases, including a Phase I study for ALN434 targeting Type 2 diabetes [34][35] Q&A Session Summary Question: What is the profile of prescribers for Ambutra? - Management noted a broad uptake among both experienced prescribers and new doctors, indicating strong initial engagement with the product [48][51] Question: How does the revenue from ATTR cardiomyopathy compare to previous products? - Management clarified that the revenue from ATTR cardiomyopathy did not contribute to Q1 results, as the approval came late in the quarter [55][60] Question: What strategies are being employed to compete with tafamidis? - Management emphasized the unique mechanism of action of Ambutra and its compelling clinical data, which positions it as a first-line treatment option [62][64] Question: What are the dynamics of reimbursement for Ambutra? - Management explained that Ambutra has a single price across indications and highlighted the effectiveness of their patient support programs in facilitating access [68][70] Question: What are the expectations for formulary inclusion? - Management aims to complete formulary inclusion for all priority health systems by year-end, with encouraging early results already seen [81][82] Question: How is the early uptake of Ambutra characterized? - Management indicated that early uptake includes both switch patients and new patients, reflecting a strong initial market response [100][102]