ALNYLAM PHARMACEUTICALS, INC.

Alnylam Pharmaceuticals, Inc. is a global commercial-stage biopharmaceutical company developing novel therapeutics based on ribonucleic acid interference, or RNAi, a naturally occurring biological pathway for sequence-specific silencing and regulation of gene expression. The company operates in the pharmaceutical industry, focusing on genetically validated genes implicated in human disease, with a pipeline spanning rare and prevalent diseases. The filing does not disclose overall market size or growth rate for the industry.

The filing names numerous competitors across therapeutic areas. For ATTR amyloidosis, competitors include Ionis and AstraZeneca (WAINUA/eplontersen), Pfizer (VYNDAQEL/VYNDAMAX), BridgeBio (ATTRUBY/acoramidis), Intellia and Regeneron (nexiguran ziclumeran), and others. For hypercholesterolemia, competitors include Amgen (REPATHA), Sanofi (PRALUENT), and LIB Therapeutics (LEROCHOL). For hemophilia, competitors include BioMarin (ROCTAVIAN) and various factor replacement products. The filing states the company believes it has a strong intellectual property position relevant to RNAi therapeutic products and delivery technologies, but does not provide a specific market share figure.

Alnylam generates revenue through net product revenues from sales of its four approved medicines (AMVUTTRA, ONPATTRO, GIVLAARI, OXLUMO), collaboration revenues including milestone payments and royalties from partners (Roche, Regeneron, Novartis, Sanofi, Vir), and royalty revenues. The company utilizes a N-acetylgalactosamine (GalNAc) conjugate approach or lipid nanoparticle (LNP) for hepatic delivery, and a hexadecyl (C16) moiety conjugate for CNS and ocular delivery. Primary customer segments are patients with genetically defined diseases and healthcare providers. Platform dynamics include the ESC+, IKARIA, and GEMINI technologies.

The company's TTR franchise includes AMVUTTRA (vutrisiran), a subcutaneously administered RNAi therapeutic targeting TTR, approved in the U.S. for hATTR amyloidosis with polyneuropathy and for ATTR amyloidosis with cardiomyopathy, and in the EU for both indications. ONPATTRO (patisiran) is an intravenously administered RNAi therapeutic targeting TTR, approved in the U.S. for hATTR amyloidosis with polyneuropathy. Nucresiran is a next-generation investigational RNAi therapeutic utilizing IKARIA technology, with Phase 3 trials initiated for hATTR polyneuropathy (TRITON-PN) and ATTR amyloidosis with cardiomyopathy (TRITON-CM). For the year ended December 31, 2025, net product revenues from AMVUTTRA were $2.99 billion ¹.

The Global Rare franchise includes GIVLAARI (givosiran) for acute hepatic porphyria (AHP), approved in the U.S. for adults and in the EU for adults and adolescents aged 12 years and older. OXLUMO (lumasiran) for primary hyperoxaluria type 1 (PH1) is approved in the U.S. to lower urinary and plasma oxalate levels in pediatric and adult patients, and in the EU for all age groups. Leqvio (inclisiran) for hypercholesterolemia is developed and commercialized by Novartis, approved in over 100 countries. Qfitlia (fitusiran) for hemophilia A and B is commercialized by Sanofi, approved by the FDA in March 2025 and by China's NMPA in December 2025.

In September 2025, the company issued $661.3 million ² aggregate principal amount of 0.00% Convertible Senior Notes due 2028. Concurrently, it repurchased approximately $637.8 million ³ aggregate principal amount of its 1.00% Convertible Senior Notes due 2027 for a total repurchase cost of approximately $1.11 billion ⁴. In December 2025, it repurchased an additional approximately $34.4 million ⁵ aggregate principal amount of the 2027 Notes for approximately $52.3 million ⁶. The company also entered into a $500.0 million ⁷ revolving credit agreement in September 2025. In December 2025, it announced a planned expansion of its Norton, Massachusetts manufacturing facility to add capabilities related to its siRELIS platform.

For the fiscal year ended December 31, 2025, total revenues were $3.99 billion ⁸, compared to $2.23 billion ⁹ in 2024. Net income was $1.03 billion ¹⁰ for 2025, compared to a net loss of $0.44 billion ¹¹ in 2024. Diluted earnings per share was $7.42 ¹² for 2025, compared to a diluted loss per share of $3.51 ¹³ in 2024. The company achieved profitability for the first time in fiscal year 2025. As of December 31, 2025, the company had an accumulated deficit of $6.70 billion ¹⁴.

A primary growth vector is the TTR franchise, with the company aspiring to lead the market in TTR revenue by 2030 and launch nucresiran, a next-generation silencer, in ATTR amyloidosis with polyneuropathy by 2028 and cardiomyopathy by 2030. The company initiated the TRITON-PN Phase 3 clinical trial for nucresiran in September 2025 and the TRITON-CM Phase 3 trial in June 2025. Another major growth vector is zilebesiran for hypertension, with a Phase 3 cardiovascular outcomes trial (ZENITH) initiated in September 2025, following a $300 million ¹⁵ development milestone payment from Roche in September 2025. The company also plans to deliver 2+ new transformative medicines beyond TTR with blockbuster potential.

The company aspires to achieve 25%+ total revenue growth compound annual growth rate through year-end 2030 and deliver sustained, profitable growth with approximately 30% non-GAAP operating margin.In December 2025, the company announced a planned expansion of its Norton, Massachusetts manufacturing facility to add capabilities related to its siRELIS platform, designed to substantially increase capacity and reduce production costs. The company expects to continue to add additional employees in 2026, with a focus on enhancing capabilities and increasing capacities, including the planned expansion of the Norton facility and expanded geographic reach for the global launch of AMVUTTRA for ATTR-CM.

The company aspires to reinvest approximately 30% of revenues in non-GAAP R&D. The filing does not provide specific R&D spending levels, capital expenditure plans, share repurchase authorization amounts, or dividend policy figures for the upcoming period.

The filing identifies several headwinds, including the risk that the marketing and sale of AMVUTTRA for ATTR-CM may be unsuccessful or less successful than anticipated. The company faces intense competition from other companies developing RNAi therapeutics, antisense technology, and other treatment modalities. The company also faces risks related to its dependence on third-party collaborators and manufacturers, and the potential for unfavorable pricing regulations, third-party reimbursement practices, or healthcare reform initiatives.

The company faces risks related to foreign currency exchange rate fluctuations, particularly movements in the U.S. dollar relative to the Japanese yen, Euro, and British pound. The company also faces risks related to changes in tax laws, including the OECD's Global Anti-Base Erosion Model rules, which could materially and adversely impact its effective tax rate or cash flows.

A significant portion of net product revenues is derived from AMVUTTRA, and if the company is unable to sustain and grow these revenues, its business would be materially harmed. The company has a history of losses with an accumulated deficit of $6.70 billion ¹⁶ as of December 31, 2025, and may not sustain profitability. The company relies on a limited number of third-party contract manufacturing organizations for the supply of drug substance and drug product, and any failure by these suppliers could disrupt clinical and commercial supply. The company faces intense competition from other companies developing RNAi therapeutics, antisense technology, and other treatment modalities for its approved products and product candidates. The company's dependence on collaborators such as Roche, Regeneron, Novartis, and Sanofi means that if any collaborator materially amends, terminates, or fails to perform its obligations, the development and commercialization of certain product candidates could be delayed or terminated.

Management's message emphasizes the launch of the 'Alnylam 2030' strategy to drive the company's next era of growth and patient impact. Key strategic priorities include building a durable TTR franchise to lead the market in TTR revenue by 2030, delivering therapies that prevent, halt, or reverse disease by expanding to 10 tissue types and more than 40 clinical programs, and scaling with discipline to achieve 25%+ total revenue growth compound annual growth rate through year-end 2030 and approximately 30% non-GAAP operating margin. Management also highlights the approval of AMVUTTRA for ATTR amyloidosis with cardiomyopathy in the U.S. and EU, the initiation of Phase 3 trials for nucresiran, and the achievement of profitability for the first time in fiscal year 2025.