Core Insights - Alnylam Pharmaceuticals is projecting combined product sales of $4.9 billion to $5.3 billion for 2026, primarily driven by the TTR franchise, which is expected to generate $4.4 billion to $4.7 billion, indicating an 83% growth at the midpoint [1] - The company reported nearly $3 billion in combined net product revenue for 2025, reflecting an 81% year-over-year growth, largely attributed to the successful launch of Amvuttra for ATTR cardiomyopathy [2][5] - Alnylam's long-term strategy, termed "Alnylam 2030," aims for global leadership in TTR revenue by 2030, with a target of over $10 billion in annual revenues supported by multiple blockbuster products [5][16] Financial Performance - The TTR franchise generated approximately $2.5 billion in 2025, doubling from the previous year and exceeding original guidance by over $800 million [1] - The company anticipates a total revenue compound annual growth rate (CAGR) of 25% or greater through 2030, with a target of approximately 30% non-GAAP operating margin [5][7] Product Pipeline and Innovation - Alnylam is expanding its pipeline with over 25 clinical programs, including the next-generation TTR silencer, nucresiran, which aims for rapid TTR knockdown with biannual dosing [4][12] - The company plans to deliver two or more new transformative medicines beyond TTR and expand its pipeline to over 40 clinical programs [7][14] Market Dynamics - Amvuttra is achieving parity with tafamidis in new starts and has broad payer access, with most patients paying $0 out-of-pocket [4][9] - The company is focusing on expanding its market presence, particularly in ex-U.S. markets, despite potential challenges from generic competition for tafamidis expected in 2028 [10][11] Strategic Framework - The "Alnylam 2030" framework is built around three strategic pillars aimed at accelerating innovation and scaling impact, emphasizing internal focus and accountability [6] - Management highlighted the importance of access and affordability metrics, ensuring that 90% of patients can receive treatment within 10 miles of home [9]

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]

Alnylam Pharmaceuticals FY Conference Summary Company Overview - **Company**: Alnylam Pharmaceuticals (NasdaqGS:ALNY) - **Industry**: Biotechnology, specifically RNA interference (RNAi) therapeutics Key Highlights Company Performance and Achievements - Alnylam has established a unique position in the biotech industry with a sustainable innovation engine and commercial excellence, leading to significant growth and success [2][3] - The company has six approved RNAi medicines generating multi-billion dollar annual revenues, treating approximately 500,000 patients globally [5][3] - In 2025, Alnylam achieved nearly $3 billion in combined net product revenues, an 81% year-over-year growth, largely driven by the launch of Amvuttra for ATTR cardiomyopathy [6][8] Strategic Goals - Alnylam has set ambitious five-year goals termed "Alnylam 2030," focusing on: 1. Achieving global TTR leadership and building a durable TTR franchise 2. Growing through sustainable innovation, including delivering transformative medicines beyond TTR 3. Scaling with discipline and agility to drive sustained, profitable growth [9][10] - The company aims for a total revenue CAGR of 25% or greater through 2030 and a Non-GAAP operating margin of approximately 30% [10][23] Pipeline and Innovation - Alnylam has over 25 programs in active clinical development, with plans to expand to 40 clinical programs and 10 tissue types by 2030 [5][9] - Key pipeline programs include: - **Nucresiran**: A next-generation TTR silencer expected to launch in polyneuropathy by 2028 and cardiomyopathy by 2030, offering a biannual dosing regimen [15][39] - **Zilebesiran**: Targets angiotensinogen for blood pressure control, addressing over 60 million patients with uncontrolled hypertension [17] - **Mivelsiran**: Targets amyloid precursor protein for treating cerebral amyloid angiopathy and Alzheimer's disease [18] - **ALN-HTT02**: Targets the Huntingtin gene for Huntington's disease, with a potential multi-billion dollar market opportunity [19] Market Dynamics and Competitive Position - Alnylam is positioned to challenge existing standards of care, with Amvuttra showing strong early market performance and approaching parity with Tafamidis in new starts [11][12] - The company anticipates that the introduction of Tafamidis generics in 2028 may unlock opportunities for combination therapies, enhancing Amvuttra's market position [33] - Alnylam's strategy includes significant investments in R&D, aiming to reinvest about 30% of revenues to accelerate innovation [9][10] Financial Guidance - For 2026, Alnylam expects total combined product sales between $4.9 billion and $5.3 billion, driven by the TTR franchise guidance of $4.4 billion to $4.7 billion, reflecting an 83% growth at the midpoint [20][23] - The company is focused on maintaining strong commercial execution and expanding its market share in both academic and community settings [30][31] Future Outlook - Alnylam aims to generate over $10 billion in annual revenues by 2030, driven by multiple blockbuster products and a best-in-class commercial organization [23] - The company is committed to social responsibility and plans to enhance manufacturing capacity while lowering production costs to support its expanding pipeline [23] Additional Insights - Alnylam's leadership emphasizes the importance of setting ambitious goals to create focus and accountability within the organization, which has historically led to exceeding expectations [25][26] - The company is actively working on initiatives to improve diagnosis rates and treatment access for patients with ATTR amyloidosis, recognizing the significant number of undiagnosed patients [14][13] This summary encapsulates the key points from Alnylam Pharmaceuticals' FY Conference, highlighting the company's strategic direction, performance metrics, and future aspirations in the biotechnology sector.

Core Viewpoint - Alnylam Pharmaceuticals has announced a new five-year strategy called "Alnylam 2030," aimed at scaling operations, achieving leadership in ATTR amyloidosis, driving long-term growth through sustainable innovation, and delivering exceptional financial results with discipline and agility [1] Group 1: Strategic Focus - The strategy emphasizes achieving leadership in ATTR amyloidosis, a key area for the company [1] - The company aims to drive long-term growth through sustainable innovation, indicating a commitment to research and development [1] - Financial discipline and agility are highlighted as essential components for delivering exceptional results [1] Group 2: Financial Performance - Alnylam reported preliminary fourth quarter and full year 2025 global net product results, although specific figures were not disclosed in the announcement [1]

Core Viewpoint - The article discusses the revolutionary shift in small nucleic acid drugs, highlighting their potential to transition from symptomatic treatment to addressing root causes, marking a significant advancement in the pharmaceutical industry [4]. Group 1: Small Nucleic Acid Drug Technology - Small nucleic acid drugs (siRNA, ASO, etc.) are considered the "third wave" of drug development, following small molecules and antibody drugs [4]. - These drugs are not limited by their molecular structure and can target a broader range of disease pathways, significantly increasing the probability of successful drug development [4]. - Current advancements in delivery technologies and chemical modifications have led to extended half-lives for these drugs, improving patient compliance in chronic disease management [4]. Group 2: Market Growth and Commercialization - The global small nucleic acid drug market is projected to reach $20.6 billion by 2029 and $54.9 billion by 2034, with a compound annual growth rate (CAGR) of 21.6% [5]. - Major players like Alnylam, Ionis, and Arrowhead are leading the market, with multinational corporations (MNCs) such as Novartis and Roche investing heavily in this sector [5]. - Alnylam's core product, Amvuttra, is expected to exceed $2 billion in sales by 2025, indicating strong market performance [6]. Group 3: Technological Breakthroughs - Arrowhead has developed RNAi therapies targeting various diseases through its TRiM platform, expanding the application of small nucleic acid drugs beyond liver diseases [7]. - Avidity Biosciences has made significant progress in muscle tissue delivery using antibody-oligonucleotide conjugates (AOC) technology, indicating a broader therapeutic potential [7]. Group 4: China's Small Nucleic Acid Drug Industry - The Chinese small nucleic acid drug industry is experiencing a qualitative leap, overcoming delivery patent barriers and demonstrating global competitiveness in target selection and molecular design [8]. - A complete industrial chain has emerged in China, with domestic raw materials achieving localization, thus reducing R&D costs [8]. - Significant business development (BD) transactions have occurred, including a record $5 billion deal between Wobang Pharmaceutical and Novartis, showcasing the global recognition of Chinese innovation [8].

About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision ...

Core Insights - Oligonucleotide therapies are emerging as a significant breakthrough in the treatment of rare diseases, with over a dozen therapies approved globally and hundreds in clinical research, promising to benefit more patients in the future [1][14][15] Industry Developments - The global landscape has seen more than ten oligonucleotide therapies approved for rare diseases, providing new treatment options for conditions such as Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), and Hemophilia [1][14] - There are currently over a hundred oligonucleotide therapies in clinical development targeting various rare diseases, including siRNA and antisense oligonucleotide (ASO) therapies [2][14] Recent Approvals and Innovations - In August, Ionis Pharmaceuticals received FDA approval for the LICA drug Dawnzera (donidalorsen) for preventing hereditary angioedema (HAE) attacks in patients aged 12 and older, marking it as the first RNA-targeted drug for HAE [4][18] - Ionis Pharmaceuticals and Sobi announced the approval of ASO drug Tryngolza (olezarsen) in the EU for treating genetically confirmed familial chylomicronemia syndrome (FCS) [4][19] - Alnylam Pharmaceuticals' siRNA therapy Amvuttra (vutrisiran) was approved by the FDA in March for treating patients with transthyretin amyloidosis with cardiomyopathy [5][19] Clinical Trial Progress - NS Pharma reported positive results from the long-term extension study of ASO therapy brogidirsen for DMD, showing effective exon 44 skipping and stable maintenance of motor function in patients [7][21] - RIBOMIC's umedaptanib pegol showed promising results in a Phase 2 trial for achondroplasia in children, with many patients experiencing improved height growth rates [7][21] - Ionis Pharmaceuticals' ASO therapy zilganersen demonstrated significant results in stabilizing walking speed in Alexander disease patients, with plans for a new drug application to the FDA in 2026 [8][22] WuXi TIDES Platform - WuXi TIDES has established an integrated solution for oligonucleotide and peptide therapies, covering custom synthesis, conjugation, process development, and CMC, facilitating the transition of innovative projects into clinical stages [1][11][26] - The platform offers comprehensive CRDMO services from drug discovery to commercial production, supporting high-throughput synthesis and custom synthesis for various oligonucleotides [11][26][27] Future Outlook - The company aims to continue leveraging its integrated CRDMO model to empower the development of various new drugs, including oligonucleotide therapies, to bring more effective treatments to patients [12][27]

Core Viewpoint - The biotech sector is experiencing a rebound in 2023, with expectations for continued recovery into 2026, despite initial pressures and a rough start to the year [1]. Group 1: Market Dynamics - Stocks of pharmaceutical companies that recently engaged in deals with the administration have traded higher, indicating a positive market response despite price reductions to align with global standards [2]. - The removal of uncertainty regarding drug pricing has allowed companies to adjust their business models accordingly, leading to potential revenue upside [3][4]. - The stabilization of negative earnings revisions after nearly three years suggests a potential upside for the biotech sector as it approaches 2026 [7]. Group 2: Regulatory Environment - Agreements signed with the Trump administration regarding drug pricing have provided clarity for companies, enabling them to better navigate their business models [8]. - There is ongoing uncertainty in the vaccine sector, particularly regarding regulatory frameworks, which may impact stock performance [8]. Group 3: Investment Opportunities - For large-cap stocks, Amgen and Regeneron are identified as having upside potential, while Biogen is seen as a laggard [9]. - The focus for small to mid-cap stocks includes innovation in cardiovascular disease, obesity treatments, and mergers and acquisitions (M&A) as key themes for the upcoming year [9]. - Cancer treatment is highlighted as a significant area of focus for future investments [10].

Core Insights - Brown Advisory Mid-Cap Growth Strategy underperformed its benchmark, the Russell Midcap® Growth Index, which increased approximately 3% in the third quarter of 2025 [1] Company Overview - Alnylam Pharmaceuticals, Inc. (NASDAQ:ALNY) focuses on discovering and commercializing therapeutics based on ribonucleic acid interference [2][3] - As of December 18, 2025, Alnylam's stock closed at $396.04 per share, with a market capitalization of $52.322 billion [2] Performance Metrics - Alnylam Pharmaceuticals experienced a one-month return of -9.24% but gained 61.36% over the last 52 weeks [2] - The product revenue for Alnylam grew 103% year-over-year to $851 million in the third quarter of 2025 [3] Investment Sentiment - Alnylam Pharmaceuticals was held by 72 hedge fund portfolios at the end of the third quarter, an increase from 58 in the previous quarter [3] - Despite acknowledging Alnylam's potential, the company believes certain AI stocks offer greater upside potential and less downside risk [3]

Core Insights - Alnylam Pharmaceuticals is investing $250 million to expand its facility in Norton, Massachusetts, to meet the increasing global demand for RNA interference (RNAi) therapeutics [1] - The expansion will create the first fully dedicated small-interfering RNA (siRNA) enzymatic-ligation manufacturing facility, aimed at increasing capacity and lowering production costs [1][4] - The siRELIS platform, accepted into the US FDA's Emerging Technology Program, will facilitate discussions on manufacturing approaches for oligonucleotide-based medicines [2][3] Facility Expansion - The Norton facility will expand to 200,000 square feet, allowing for local production of both clinical and commercial supplies of siRNA oligonucleotide drug substances [4] - Construction is currently underway, with the new offerings expected to be operational by late 2027 [5] - The facility has been operational since 2021 and has contributed to the growth of Alnylam's clinical pipeline, supporting early-stage programs targeting various tissue types [4] Manufacturing Technology - The siRELIS platform enables RNAi therapeutic manufacturing with reduced material and plant resource requirements, supporting sustainable, large-scale production [3] - This advancement is crucial for scaling the pipeline to include potential treatments for diseases such as hypertension, type 2 diabetes, and obesity [6] - The platform's acceptance follows pilot-scale production of zilebesiran and nucresiran, which are under investigation for cardiovascular events and amyloidosis, respectively [3]