Core Insights - Alnylam Pharmaceuticals reported $1.1 billion in revenue for Q4 2025, marking an 84.9% year-over-year increase, with an EPS of $1.25 compared to $0.06 a year ago [1] - The revenue fell short of the Zacks Consensus Estimate of $1.14 billion by 3.35%, while the EPS exceeded the consensus estimate of $1.16 by 8.16% [1] Financial Performance Metrics - Net Product Revenue for Onpattro in the U.S. was $12.02 million, significantly below the estimated $5.37 million, reflecting a year-over-year decline of 39.7% [4] - Net Product Revenue for Oxlumo in the U.S. was $17.61 million, lower than the estimated $23.94 million, showing a 6.1% decrease year-over-year [4] - Net Product Revenue for Givlaari in the U.S. reached $56.34 million, surpassing the estimated $47.24 million, with a year-over-year increase of 25.1% [4] - Net Product Revenue for Amvuttra in the U.S. was $641.57 million, exceeding the estimated $619.86 million, representing a substantial year-over-year increase of 250.1% [4] - Total product revenues netted $994.72 million, slightly below the estimated $1.01 billion, but reflecting a 120.6% increase compared to the previous year [4] - Net revenues from research collaborators were $40.94 million, significantly lower than the estimated $94.22 million, indicating a year-over-year decline of 61.7% [4] - Royalty revenue was reported at $61.37 million, exceeding the estimated $55.64 million, with a year-over-year increase of 73.4% [4] Stock Performance - Alnylam's shares have returned -12.2% over the past month, contrasting with the Zacks S&P 500 composite's -0.3% change, indicating underperformance relative to the broader market [3] - The stock currently holds a Zacks Rank 3 (Hold), suggesting it may perform in line with the market in the near term [3]

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] - The company achieved GAAP profitability for the full year 2025 and expects to sustain profitability going forward [7][29] - Non-GAAP operating income for 2025 was $850 million, a $755 million increase compared to the previous year [28] Business Line Data and Key Metrics Changes - The TTR franchise generated $858 million in net revenues in Q4 2025, up 151% year-over-year [12] - The rare disease portfolio generated $136 million in net revenue in Q4, up 26% year-over-year [11] - GIVLAARI and OXLUMO together became a $500 million franchise in 2025, reflecting continued growth more than five years post-launch [11] 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 [12] - International revenues grew 13% quarter-over-quarter and 47% year-over-year, indicating strong global momentum [14] - The company anticipates launching AMVUTTRA for ATTR cardiomyopathy in additional international markets throughout 2026 [14] 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 [8][9] - Plans include launching nucresiran in 2028 for polyneuropathy and 2030 for cardiomyopathy, with an aim for over 25% revenue CAGR through 2030 [10] - The company expects to invest approximately 30% of revenues in non-GAAP R&D to accelerate organic innovation and selectively access external innovation [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 [15] - The early momentum of AMVUTTRA is encouraging, with strong customer demand and broad access expected to drive future growth [17] - Management highlighted the importance of improving diagnosis and treatment rates to expand the category further [18] Other Important Information - 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 [29] - Collaboration revenue for 2025 was $553 million, an 8% growth compared to 2024, including a significant milestone payment [26] Q&A Session Summary Question: Insights on new patient additions and first-line mix for patisiran versus tafamidis - Management expressed satisfaction with the AMVUTTRA launch and noted strong fundamentals supporting continued growth [41][43] Question: Addressing choppiness in scripts and pricing dynamics - Management indicated confidence in access and pricing, with a mid-single-digit net price decline expected in 2026 [49][61] Question: Seasonality effects in Q4 and potential tailwinds for Q1 2026 - Management acknowledged typical industry seasonality but emphasized that underlying momentum remains strong [53][54] Question: Gross to net pattern over 2026 - Management confirmed a gradual mid-single-digit net price decrease expected throughout the year [59][61] Question: External innovation strategy and potential partnerships - Management highlighted a focus on complementary technologies that enhance the existing portfolio and pipeline [66][98] Question: Impact of nucresiran on operating margins - Management anticipates significant positive margin impacts post-2030 if nucresiran demonstrates a best-in-class profile [70][71] Question: Updates on the Huntington's program and trial initiation - Management is optimistic about the Huntington's program and plans to accelerate it responsibly based on initial data [78][79] Question: Prioritization of ACVR1C asset in obesity pipeline - Management explained the prioritization based on preclinical data indicating ACVR1C's potential for greater efficacy compared to other targets [86][87]

Alnylam Pharmaceuticals (NasdaqGS:ALNY) Q4 2025 Earnings call February 12, 2026 08:30 AM ET Company ParticipantsChristine Lindenboom - Chief Corporate Communications OfficerJeff Poulton - CFOPushkal Garg - Chief Research and Development OfficerTolga Tanguler - Chief Commercial OfficerYvonne Greenstreet - CEOConference Call ParticipantsAlexander Canani - AnalystCory Kasimov - AnalystEllie Merle - AnalystJames Sheehan - AnalystKostas Theodoslou - AnalystLuca Issi - AnalystMaury Raycroft - AnalystMike Ulz - An ...

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 Insights - The global MCE (Myeloid Cell Engager) market has surpassed $9 billion in cumulative transaction value from 2022 to 2025, with major pharmaceutical companies like Novartis, Eli Lilly, and GSK actively entering the field through collaborations and acquisitions [1][20] - The year 2025 is anticipated to be a pivotal year for MCE, with significant deals such as Sanofi's $1.9 billion acquisition of Dren Bio and GSK's collaboration with LTZ Therapeutics valued at over $1.5 billion [1][19][12] - Despite the enthusiasm from large pharmaceutical companies, there are only a handful of biotech firms with a clear focus on MCE, raising questions about the early-stage technology and the limited number of players in the field [1][20] Industry Dynamics - The bottleneck in immunotherapy has led to a renewed focus on myeloid cell therapies, as traditional T-cell therapies face limitations in solid tumors [2][22] - Research indicates that myeloid cells, such as macrophages and dendritic cells, play a crucial role in the immune response within the tumor microenvironment, prompting a shift towards targeting these cells for therapeutic purposes [2][3] - The MCE approach utilizes bispecific antibodies to bridge tumor cells and myeloid cells, enhancing the immune response against tumors while addressing the limitations of T-cell therapies [5][7] Competitive Landscape - The MCE market is characterized by a three-tier structure: core biotech firms with proprietary technology, multinational corporations (MNCs) accelerating development through partnerships, and companies with foundational immunology expertise poised to enter the market [9][10] - Key players in the biotech sector include Dren Bio, which focuses on Dectin-1 activation, and LTZ Therapeutics, which employs a dual-pathway activation strategy involving myeloid and NK cells [10][11] - Companies like Elpiscience and Glenmark are also exploring innovative approaches to enhance myeloid cell engagement, indicating a diverse range of strategies within the MCE landscape [14][17] Market Potential - The demand for MCE therapies is driven by the substantial market size in oncology and autoimmune diseases, with the global solid tumor treatment market projected to reach $272 billion by 2032 [22] - MCE therapies are expected to address unmet needs in solid tumors, offering a differentiated mechanism compared to traditional therapies, which often face safety and efficacy challenges [22][23] - The potential for MCE to complement existing therapies like CAR-T and PD-1 inhibitors highlights its strategic importance in the evolving landscape of immunotherapy [23][24] Future Outlook - The success of MCE as a next-generation immunotherapy will depend on clinical trial outcomes and the ability to overcome technical challenges related to safety and efficacy [22][24] - The next 3-5 years will be critical for MCE, as clinical data will determine its viability and potential to reshape treatment paradigms in oncology and beyond [24]

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. 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, influencing their cautious outlook [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].