Financial Data and Key Metrics Changes - Total global net product revenues for 2025 were nearly $3 billion, representing an 81% growth compared to 2024, driven by a more than doubling of revenue in the TTR franchise [25][26] - GAAP profitability was achieved for the full year 2025, with non-GAAP operating income of $850 million, a $755 million increase compared to last year [29] - Gross margin on product sales was 77% for the full year, a 4% decrease compared to 2024, primarily due to increased royalties on AMVUTTRA [27] Business Line Data and Key Metrics Changes - The TTR franchise generated $858 million in Q4, up 151% year-over-year, and $4.4-$4.7 billion in total TTR revenue guidance for 2026, representing an 83% growth at the midpoint [11][31] - The rare disease portfolio generated $136 million in Q4, up 26% year-over-year, with GIVLAARI and OXLUMO together becoming a $500 million franchise in 2025 [11][12] Market Data and Key Metrics Changes - U.S. TTR net revenues grew 20% compared to Q3 2025 and 222% compared to Q4 2024, while international revenues grew 13% quarter-over-quarter and 47% year-over-year [13][14] - The company anticipates a mid-single-digit net price decrease for AMVUTTRA in 2026, with international TTR revenue growth expected to be consistent with 2025 [31][32] Company Strategy and Development Direction - The company aims to achieve global TTR leadership and launch nucresiran in 2028 for polyneuropathy and 2030 for cardiomyopathy as part of its Alnylam 2030 goals [8][9] - The strategy includes investing approximately 30% of revenues in non-GAAP R&D to accelerate organic innovation and selectively access external innovation [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth potential of the TTR franchise, citing strong fundamentals and early momentum from the AMVUTTRA launch [41][44] - The company is focused on building a durable growth foundation through education, awareness, and diagnosis enablement to expand the ATTR-CM category [18][19] Other Important Information - The company initiated three Phase 3 studies in 2025 and expanded its clinical pipeline with four proprietary CTAs [19][20] - The proprietary enzymatic ligation manufacturing platform, Syrelis, was launched to enhance capacity and reduce costs [7][22] Q&A Session Summary Question: Insights on new patient adds and first-line mix for patisiran versus tafamidis - Management highlighted strong AMVUTTRA launch fundamentals and improved first-line access, supporting confidence in 2026 guidance [40][43] Question: Addressing choppiness in scripts and pricing dynamics - Management noted strong access for patients and a mid-single-digit net price decline integrated into the outlook [47][49] Question: Seasonality impact on Q1 and potential tailwind - Management acknowledged typical industry seasonality but emphasized that underlying momentum remains strong [52][54] Question: Gross to net pattern expectations for 2026 - Management expects a gradual mid-single-digit net price decrease throughout the year, with access discussions largely completed [59][61] Question: External innovation strategy and potential partnerships - Management indicated a focus on complementary technologies that enhance internal innovation, with a high bar for external opportunities [66][68] Question: Impact of nucresiran on operating margin - Management expressed high conviction in nucresiran's potential to drive margins to the mid-40s post-2030 due to its best-in-class profile [70][71] Question: Insights on Huntington's program and trial initiation - Management is optimistic about the Huntington's program and aims to accelerate it responsibly based on target engagement data [78][79] Question: Prioritization of ACVR1C asset in obesity pipeline - Management prioritized ACVR1C due to its potential for more potent effects compared to other targets, with results expected by year-end [86][87]

Financial Data and Key Metrics Changes - Total global net product revenues for 2025 were nearly $3 billion, representing an 81% growth compared to 2024, driven by a more than doubling of revenue in the TTR franchise [24][25] - The company achieved GAAP profitability for the full year 2025 and expects to sustain profitability going forward [5][27] - Non-GAAP operating income for the full year was $850 million, a $755 million increase compared to the previous year [26] Business Line Data and Key Metrics Changes - The TTR franchise generated $858 million in net revenues in Q4 2025, up 151% year-over-year [11] - The rare disease portfolio generated $136 million in net revenue in Q4, reflecting a 26% increase compared to the same period last year [10] - GIVLAARI and OXLUMO together became a $500 million franchise in 2025, showing continued growth more than five years post-launch [10] Market Data and Key Metrics Changes - U.S. net revenues for the TTR franchise grew 20% compared to Q3 2025 and 222% compared to Q4 2024 [11] - International revenues grew 13% quarter-over-quarter and 47% year-over-year, indicating strong global momentum [12] - The company anticipates launching AMVUTTRA for ATTR cardiomyopathy in additional international markets throughout 2026 [12] Company Strategy and Development Direction - The company has set new five-year goals, Alnylam 2030, focusing on achieving global TTR leadership, sustainable innovation, and disciplined growth [6][9] - Plans include launching nucresiran in 2028 for polyneuropathy and 2030 for cardiomyopathy, with aspirations to deliver RNAi to 10 tissue types and expand the pipeline to over 40 clinical programs by 2030 [7][8] - The company aims for over 25% revenue CAGR through 2030 and a non-GAAP operating margin of approximately 30% [9] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the size and growth of the ATTR-CM category, noting that the majority of patients remain untreated [14] - The early momentum of AMVUTTRA is encouraging, with strong customer demand and broad access expected to drive growth [16] - The company is focused on improving diagnosis and treatment rates to expand the category further [17] Other Important Information - The company initiated three Phase 3 studies in 2025 and expanded its clinical pipeline with four proprietary CTAs [18] - The proprietary enzymatic ligation manufacturing platform, Syrelis, was launched to enhance capacity and reduce costs [20] - The company ended 2025 with cash, cash equivalents, and marketable securities of $2.9 billion, an increase from $2.7 billion at the end of 2024 [27] Q&A Session Summary Question: Can you comment on new patient adds and the mix of first-line for patisiran versus tafamidis switches? - Management highlighted strong AMVUTTRA launch momentum and improved first-line access, supporting confidence in 2026 guidance [38][41] Question: Can you speak to the choppiness in scripts for the first quarter and pricing dynamics? - Management noted that the majority of patients have first-line access and expect a mid-single-digit net price decline in 2026, which is integrated into their outlook [44][47] Question: Have you seen any seasonality during the fourth quarter? - Management acknowledged typical industry seasonality but emphasized that underlying momentum remains strong [50][51] Question: What is the rationale for prioritizing the ACVR1C asset over others in your pipeline? - Management indicated that ACVR1C appears to be a more potent target based on preclinical work and emerging data [81][85] Question: How should we think about the impact of nucresiran on operating margins once available? - Management expects nucresiran to have a best-in-class profile, potentially driving margins to the mid-40s post-2030 [68][69]

© 2026 Alnylam Pharmaceuticals, Inc. 1 Agenda Fourth Quarter and Full Year 2025 Financial Results Welcome February 12, 2026 • Christine Akinc Chief Corporate Communications Officer Overview • Yvonne Greenstreet, M.D. Chief Executive Officer Commercial Highlights • Tolga Tanguler Chief Commercial Officer Pipeline • Pushkal Garg, M.D. Chief Research & Development Officer Financial Summary • Jeff Poulton Chief Financial Officer Q&A Session 2 Alnylam Forward-Looking Statements This presentation contains forward ...

Financial Performance - The company achieved profitability for the first time in 2025, with full-year net product revenues of approximately $3.0 billion, primarily driven by strong growth in the TTR franchise [524]. - Total revenues for 2025 were $3,713,937, representing a 65% increase from $2,248,243 in 2024 [529]. - Net product revenues increased by 81% to $2,986,549 in 2025, up from $1,646,228 in 2024, largely due to growth from AMVUTTRA [530]. - AMVUTTRA generated $2,313,836 in total revenues in 2025, with a significant increase of 138% compared to 2024 [531]. - Collaboration revenues increased by 8% to $553,366 in 2025, with Roche contributing $394,881, a 230% increase from the previous year [533]. - Royalty revenue surged by 90% to $174,022 in 2025, driven by increased sales of Leqvio by Novartis [534]. - The operating income for 2025 was $501,578, a significant turnaround from a loss of $176,885 in 2024 [529]. - The company anticipates fluctuations in operating results for the foreseeable future, making period-to-period comparisons less predictive [527]. Expenses and Costs - Total operating costs and expenses for 2025 were $3,212.4 million, a 32% increase from $2,425.1 million in 2024 [538]. - Cost of goods sold increased to $677.2 million in 2025, representing a 121% increase from $306.5 million in 2024, with a cost of goods sold percentage of net product revenues rising to 22.7% [538][539]. - Research and development expenses rose to $1,319.8 million in 2025, a 17% increase from $1,126.2 million in 2024, primarily due to increased clinical trial expenses and employee compensation [543][544]. - Selling, general and administrative expenses increased to $1,210.7 million in 2025, a 24% increase from $975.5 million in 2024, driven by higher employee compensation and marketing investments [546]. Cash Flow and Financing - Net cash provided by operating activities was $524.1 million in 2025, a significant increase from a cash outflow of $8.3 million in 2024, attributed to stronger product sales [551]. - Net cash provided by investing activities for the year ended December 31, 2025, was $436.3 million, compared to a net cash used of $116.8 million in 2024 [552]. - Net cash used in financing activities was $305.2 million in 2025, a significant change from the $294.2 million provided in 2024, primarily due to $1.15 billion paid for the repurchase of 2027 Notes [553]. Deficit and Future Outlook - The company reported an accumulated deficit of $6.70 billion as of December 31, 2025, despite achieving profitability [524]. - The company expects net revenues from collaborations to decrease in 2026 compared to 2025, primarily due to the recognition of $300.0 million milestone revenue from the Roche Collaboration in 2025 [535]. - Royalty revenue is anticipated to increase in 2026 compared to 2025, driven by the growth of royalties from global net sales of Leqvio by Novartis [535]. - The company may require significant additional funds earlier than expected to continue commercializing existing products and developing new candidates [558]. Assets and Liabilities - As of December 31, 2025, the accumulated deficit reached $6.70 billion, while cash, cash equivalents, and marketable securities totaled $2.91 billion, up from $2.69 billion in 2024 [557]. - Future lease payments for operating lease obligations totaled $366.3 million as of December 31, 2025, with $48.1 million expected to be paid within the next 12 months [562]. - Capital expenditures increased to $58.7 million in 2025 from $34.3 million in 2024, with expectations for further increases in 2026 to support manufacturing capacity [562]. - The carrying value of convertible debt was $1.01 billion as of December 31, 2025, with no principal payments expected in the next 12 months [562]. Interest and Taxation - Interest expense increased to $252.6 million in 2025, a 78% rise from $141.9 million in 2024 [548]. - The company recorded a provision for income taxes of $9.4 million in 2025, compared to a benefit of $99.2 million in 2024 [549]. - Total other expense, net decreased to $178.4 million in 2025, an 11% improvement from $200.5 million in 2024, mainly due to reduced losses related to the change in fair value of the development derivative liability [548]. Risk Factors - The estimated impact of a 10% change in the interest rate would result in a liability adjustment of approximately $42.1 million related to future royalties and development funding [569]. - The company is exposed to foreign currency exchange risks primarily from operations in Japan, Europe, and the UK, which may affect financial results as international sales grow [572].

Financial Performance - Achieved global net product revenues of $995 million for Q4 2025 and $2,987 million for the full year 2025, representing 121% and 81% growth compared to the same periods in 2024[1] - Total TTR revenues for Q4 2025 reached $859 million, a 151% increase compared to Q4 2024, with AMVUTTRA contributing $827 million[3] - Full year 2025 total TTR revenues were $2,487 million, reflecting a 103% growth year-over-year[15] - Total revenues for the year ended December 31, 2025, were $3.71 billion, up 65% from $2.25 billion in 2024[47] - The company reported a net income of $111.5 million for Q4 2025, compared to a net loss of $83.8 million in Q4 2024[47] - Non-GAAP net income for full year 2025 was $683.6 million, compared to a loss of $3.1 million in 2024[13] - Non-GAAP net income for the twelve months ended December 31, 2025, was $683,644,000, compared to a loss of $3,051,000 in 2024[48] - GAAP net income for Q4 2025 was $111,543,000, compared to a loss of $83,763,000 in Q4 2024[48] Revenue Growth - GIVLAARI and OXLUMO generated Q4 2025 revenues of $87 million and $50 million, respectively, marking a 26% total Rare growth compared to Q4 2024[4] - Royalty revenue increased by 90% for the full year 2025, attributed to higher royalties from global net sales of Leqvio by Novartis[18] - AMVUTTRA net product revenue growth was reported at 189% for Q4 2025, with a constant currency growth of 187%[49] - Total TTR net product revenue growth was 151% for Q4 2025, with a constant currency growth of 149%[49] - ONPATTRO net product revenue growth decreased by 44% in Q4 2025, with a constant currency decline of 45%[49] - GIVLAARI net product revenue growth was 34% for Q4 2025, with a constant currency growth of 32%[49] - Total net product revenue growth was reported at 121% for Q4 2025, with a constant currency growth of 119%[49] - Total revenue growth for the twelve months ended December 31, 2025, was reported at 85%, with a constant currency growth of 83%[49] Expenses and Costs - Cost of goods sold increased by 161% to $267,723 thousand for the three months ended December 31, 2025, compared to $102,649 thousand in 2024, and by 121% to $677,166 thousand for the twelve months ended December 31, 2025, compared to $306,513 thousand in 2024[20] - GAAP research and development expenses rose by 24% to $372,218 thousand for the three months ended December 31, 2025, and by 17% to $1,319,775 thousand for the twelve months ended December 31, 2025, compared to the same periods in 2024[22] - GAAP selling, general and administrative expenses increased by 10% to $325,374 thousand for the three months ended December 31, 2025, and by 24% to $1,210,713 thousand for the twelve months ended December 31, 2025, compared to the same periods in 2024[23] - Interest expense for the three months ended December 31, 2025, was $65 million, including $38 million related to future Leqvio royalties, and for the twelve months, it was $253 million, including $150 million for the same[24] Strategic Initiatives - Launched "Alnylam 2030" strategy aimed at achieving global TTR leadership and sustainable innovation[2] - Announced plans to invest $250 million in a new siRNA enzymatic-ligation manufacturing facility to enhance production capacity[10] - The planned $250 million investment in the expansion of Alnylam's manufacturing facility aims to enhance production capacity and reduce costs[42] - Expected to initiate three Phase 2 clinical trials and announce clinical de-risking data from several pipeline programs in 2026[8] - The company is focused on expanding its pipeline with ongoing clinical trials for zilebesiran and nucresiran, contributing to increased R&D expenses[22] - The company has a strategic focus on addressing unmet medical needs globally, aiming for long-term sustainable innovation[42] Cash and Assets - Cash, cash equivalents, and marketable securities increased to $2.91 billion as of December 31, 2025, from $2.69 billion as of December 31, 2024, due to improved operating performance and proceeds from stock options[26] - Alnylam's cash and cash equivalents increased to $1.66 billion as of December 31, 2025, up from $966.4 million in 2024[45] - Alnylam's total assets grew to $4.97 billion in 2025, compared to $4.24 billion in 2024[45] - Alnylam's accumulated deficit decreased to $6.70 billion in 2025 from $7.29 billion in 2024[45] Future Guidance - Full-year 2026 financial guidance for total net product revenues is projected to be between $4,900 million and $5,300 million, representing a growth of 64% to 77% compared to 2025[28] - Non-GAAP R&D and SG&A expenses for 2026 are expected to be between $2,700 million and $2,800 million, excluding $300 million to $400 million of stock-based compensation expense[28] - The company expects TTR net product revenues to contribute significantly to its financial performance in 2026[42]

Core Viewpoint - Alnylam Pharmaceuticals, Inc. is considered a strong healthcare stock for 2026, with RBC Capital maintaining an Outperform rating but lowering the price target to $465 from $500 [1]. Group 1: Analyst Views - Alnylam Pharmaceuticals aims for a revenue target of $5.1 billion, surpassing the consensus estimate of $4.7 billion, with a long-term goal of a 25% compound annual growth rate through 2030, leading to projected revenue of $11.2 billion [2]. - Cantor Fitzgerald has a Neutral rating on Alnylam Pharmaceuticals, citing a slowdown in Amvuttra cardiomyopathy sales in November, although sales rebounded in December. The firm anticipates a mid-single-digit decline in Amvuttra's net price by 2026 [3]. Group 2: Company Overview - Alnylam Pharmaceuticals specializes in developing innovative medicines using RNA interference (RNAi) technology to target and silence disease-causing genes, focusing on treatments for rare and common genetic, metabolic, cardiovascular, and neurological diseases [4].

Core Viewpoint - Alnylam Pharmaceuticals Inc. has shown a mixed short-term performance with a 9.67% decrease over the past month, but a significant 45.26% increase over the past year, prompting long-term shareholders to consider the company's price-to-earnings (P/E) ratio for investment decisions [1]. Group 1: P/E Ratio Analysis - The P/E ratio is a critical metric for long-term shareholders to evaluate the company's market performance against historical earnings and industry standards [3]. - Alnylam Pharmaceuticals has a notably high P/E ratio of 1222.87, compared to the biotechnology industry's aggregate P/E ratio of 83.2, which may suggest that shareholders expect better future performance or that the stock is overvalued [4][5]. - While a lower P/E can indicate undervaluation, it may also reflect a lack of expected future growth, highlighting the need for a comprehensive analysis that includes industry trends and business cycles [7].

Core Viewpoint - Alnylam is entering a new chapter in its history, emphasizing its unique position in the biotech industry with a strong focus on RNAi technology and sustainable innovation [2][3]. Group 1: Company Leadership and Structure - The presentation features key executives including the CEO, Chief R&D Officer, Chief Commercial Officer, and Chief Financial Officer, highlighting the collaborative leadership within the company [2]. - The company has established a leadership position in RNAi, which is central to its business strategy and innovation [3]. Group 2: Innovation and Growth Strategy - Alnylam possesses a sustainable innovation engine that has contributed to its success and will continue to drive long-term growth [3]. - The company aims to leverage its proven organic product engine to maintain its competitive edge in the biotech sector [3].

Group 1 - The article discusses the importance of enabling Javascript and cookies in browsers to prevent access issues [1] - It highlights that users with ad-blockers may face restrictions when trying to access content [1]

Core Insights - Alnylam Pharmaceuticals Inc. has launched a new five-year strategic plan called "Alnylam 2030," focusing on scaling operations and building on the success of its previous P5x25 plan [1] - The company aims to establish global leadership in transthyretin (TTR) diseases, targeting market leadership in revenue by 2030 [2] - Alnylam plans to introduce nucresiran, a next-generation RNAi therapy, for polyneuropathy by 2028 and cardiomyopathy by 2030 [2] Financial Performance - Preliminary net product revenue for Amvuttra and Onpattro reached approximately $827 million and $32 million in Q4, resulting in a 151% year-over-year growth for the TTR franchise [4] - For the full year 2025, revenues for Amvuttra and Onpattro were about $2.3 billion and $173 million, respectively, more than doubling from 2024 [4] - Rare disease products Givlaari and Oxlumo generated combined fourth-quarter revenues of roughly $137 million, with full-year sales of about $499 million [4] Future Guidance - Alnylam projects combined net product revenue for 2026 to be between $4.9 billion and $5.3 billion, indicating a 71% growth at the midpoint [5] - The TTR franchise is expected to generate revenues of $4.4 billion to $4.7 billion, reflecting 83% growth at the midpoint [6] - The rare disease franchise is anticipated to achieve revenues of $500 million to $600 million, showing a 10% growth at the midpoint [6]