Alnylam Pharmaceuticals (NASDAQ:ALNY) used its presentation at the JPMorgan Healthcare Conference to outline what CEO Yvonne Greenstreet called the company’s “next exciting chapter,” highlighting a breakout commercial year in 2025, new long-term targets through 2030, and a pipeline that management said is designed to extend its leadership in RNA interference (RNAi) therapeutics.
2025 performance and near-term financial outlook
Greenstreet said 2025 was “transformational,” led by the “landmark approval of Amvuttra for ATTR cardiomyopathy.” In a press release the company issued the day before the conference presentation, Alnylam pre-announced fourth-quarter and full-year 2025 results, reporting nearly $3 billion in combined net product revenue across its four wholly owned products, representing 81% year-over-year growth.
Looking ahead, Alnylam guided to 2026 combined product sales of $4.9 billion to $5.3 billion, driven by TTR franchise guidance of $4.4 billion to $4.7 billion, which management characterized as 83% growth at the midpoint.
Alnylam 2030: three pillars and long-term targets
Greenstreet introduced a new five-year framework, “Alnylam 2030, accelerating innovation and scaling impact,” built around three strategic pillars:
- Global TTR leadership: The company said it intends to lead the market in TTR revenue by 2030 and cumulatively across the five-year period, and to launch its next-generation TTR silencer, nucresiran, first in polyneuropathy by the end of 2028 and then in cardiomyopathy by the end of 2030 (assuming positive phase 3 results and regulatory approvals).
- Growth through sustainable innovation: Alnylam aims to deliver “two or more new transformative medicines beyond TTR” with blockbuster potential, expand to 10 tissue types, and build a pipeline of more than 40 clinical programs. Management said it plans to invest about 30% of revenues in non-GAAP R&D.
- Scale with discipline and agility: The company targets 25% or greater total revenue CAGR through the end of 2030 and an approximately 30% non-GAAP operating margin across the period.
In the Q&A, Greenstreet and CFO Jeff Poulton emphasized the company’s history of setting multi-year targets and said the framework is intended to create internal focus and accountability. Poulton added that the goals are “almost more important for internal purposes than they are for external.”
Amvuttra launch dynamics and market access
Greenstreet said most patients with ATTR cardiomyopathy remain untreated despite improving diagnosis rates, describing the category as large, growing, and underserved. She said early launch performance suggests “the potential for a truly breakout launch,” supported by customer demand and Alnylam’s commercial execution as it expands into ex-U.S. markets.
She added that, within a few quarters, Amvuttra had “approached parity to tafamidis in share of new starts,” while noting the figures are estimates due to evolving data sources. Greenstreet also described Amvuttra as the “clear leader” in the “stabilizer progressor segment,” citing its orthogonal mechanism of action.
Management highlighted access and affordability metrics, including broad payer coverage heading into 2026, first-line access for most patients without step edits, and “most patients pay $0 in out-of-pocket costs.” Greenstreet also said 90% of patients can receive treatment within 10 miles of home due to the company’s network of health systems and alternate sites of care.
Asked about the potential impact of tafamidis generics (which the moderator noted Pfizer has said could occur in the U.S. in 2028), Greenstreet said it was “not really a big deal” for Alnylam and suggested generic availability could increase combination use. She pointed to HELIOS-B data showing benefits of Amvuttra in combination with tafamidis, noting that combination data are reflected on the label.
On international pricing, Poulton said ex-U.S. launches are not expected to have split indication pricing, and price “will likely come down,” impacting the existing polyneuropathy business. He said cardiomyopathy volume growth should more than offset that over time, but that in 2026 the company does not expect an acceleration of growth outside the U.S. compared with 2025.
Nucresiran and margin discussion
Management positioned nucresiran as a next-generation TTR silencer intended to offer rapid TTR knockdown “on the order of 95%” with twice-yearly dosing. Chief R&D Officer Pushkal Garg contrasted that with Amvuttra’s “about 85%” knockdown and said the higher knockdown and less variability could benefit both polyneuropathy and cardiomyopathy patients, alongside the convenience of biannual dosing.
Poulton also discussed margins, saying the company’s 30% non-GAAP operating margin target through 2030 does not assume a meaningful transition from Amvuttra to nucresiran because the cardiomyopathy launch is targeted for 2030. He said a successful nucresiran launch could enhance margins after 2030, adding that nucresiran would avoid the “royalty burden” associated with Amvuttra and citing an expected “high 20%” average royalty rate.
Pipeline highlights and platform updates
Greenstreet said Alnylam ended 2025 with more than 25 programs in active clinical development. She also highlighted a new manufacturing platform, an enzymatic ligation-based RNAi process called Cyrellus, which she said is designed to expand capacity and reduce cost of goods.
Among pipeline programs, management pointed to several assets it described as having multi-billion-dollar potential, including:
- Zilebesiran (angiotensinogen) for hypertension, with a proposed twice-yearly dosing approach.
- ALN-4324 (Grb14) and ALN-2232 (ACVR1C) in metabolic disease, including fat-specific weight loss potential for ALN-2232.
- Mivelsiran (amyloid precursor protein) in cerebral amyloid angiopathy, with plans to outline an Alzheimer’s disease strategy “shortly,” according to Garg.
- ALN-HTT02 (Huntingtin) for Huntington’s disease; management said initial phase 1 data are expected in the second half of the year, with safety and deep knockdown as key early priorities.
- ALN-6400 (plasminogen) for bleeding disorders, with a phase 2 trial underway in hereditary hemorrhagic telangiectasia and plans to start a phase 2 study in a second bleeding disorder later in the year.
For 2026, Greenstreet said the company expects four clinical data readouts, advancement of three phase 3 studies, initiation of three phase 2 studies, and filing of three to four new INDs.
In closing remarks, Greenstreet said Alnylam’s long-term aspiration is to generate “well over $10 billion in annual revenues” by 2030, supported by multiple blockbuster products, expanded manufacturing capacity, and continued pipeline reinvestment.
About Alnylam Pharmaceuticals (NASDAQ:ALNY)
Alnylam Pharmaceuticals, Inc (NASDAQ: ALNY) is a biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics. Founded to translate the scientific discovery of RNAi into new medicines, Alnylam applies small interfering RNA (siRNA) technology to silence disease-causing genes. The company develops therapies designed to provide durable disease modification by targeting underlying genetic drivers across a range of rare and more prevalent conditions.
Alnylam has advanced multiple siRNA-based products into commercialization, initially using lipid nanoparticle delivery and more recently employing GalNAc-conjugate chemistry to enable targeted delivery to the liver with subcutaneous dosing.
