− Product and Pipeline Goals Detail Execution across Four Commercial Brands, Including One Potential Label Expansion, and Ten Clinical Data Readouts From Proprietary and Partner Programs –

− Pipeline Programs and Scientific Innovation Highlighted at R&D Day Exemplify Strength of RNAi Platform and Organic Product Engine –

− Alnylam to Webcast its R&D Day Event Today at 8:30 a.m. ET –

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, is hosting a virtual R&D Day today. During the event, the Company plans to showcase its R&D progress and platform innovation, as well as its product and pipeline goals for 2023 focused on continued commercial execution of four RNAi therapeutic products, and advancement of early-, mid-, and late-stage investigational programs.

“Throughout 2022, Alnylam has continued to demonstrate the strength of RNAi therapeutics, including the commercial launch of the fifth Alnylam-discovered product within four years, while advancing an organic pipeline of potentially transformative investigational medicines in both rare and common diseases,” said Akshay Vaishnaw, M.D., Ph.D., President of Alnylam. “We expect our track record of strong execution will continue in 2023, with plans to deliver strong commercial performance across four commercial brands, achieve one label expansion, and report ten clinical datasets across Alnylam- and partner-led programs. We believe these milestones will help advance us toward achieving our ‘Alnylam P⁵x25’ goals of becoming a top tier biotech company over the coming years.”

2023 Product and Pipeline Goals

Alnylam plans to provide guidance on 2023 combined net product revenue for ONPATTRO^®, AMVUTTRA^®, GIVLAARI^®, and OXLUMO^® with its fourth quarter and full year 2022 results.

Patisiran, a commercial-stage RNAi therapeutic for the treatment of polyneuropathy in patients with hATTR amyloidosis, and in development for the treatment of the cardiomyopathy of ATTR amyloidosis. Alnylam plans to:

• Achieve approval from the U.S. Food and Drug Administration (FDA) in late 2023, for the treatment of the cardiomyopathy of ATTR amyloidosis

Vutrisiran, a commercial-stage RNAi therapeutic for the treatment of polyneuropathy in patients with hATTR amyloidosis, and in development for the treatment of the cardiomyopathy of ATTR amyloidosis. Alnylam plans to:

• Report data from the evaluation of a biannual dosing regimen in early 2023
• Submit a Supplemental New Drug Application (sNDA) for a biannual dosing regimen in early 2023

ALN-TTRsc04, an investigational RNAi therapeutic in development for the treatment of ATTR amyloidosis. Alnylam plans to:

• Report topline Phase 1 results in late 2023

Zilebesiran, an investigational RNAi therapeutic in development for the treatment of hypertension. Alnylam plans to:

• Complete enrollment in the KARDIA-2 Phase 2 study in early 2023
• Report topline results from the KARDIA-1 Phase 2 study in mid-2023
• Report topline results from the KARDIA-2 Phase 2 study at or around year-end 2023

ALN-APP, an investigational RNAi therapeutic in development for the treatment of Alzheimer’s Disease and Cerebral Amyloid Angiopathy. Alnylam plans to:

• Report topline Phase 1 results in early 2023

ALN-KHK, an investigational RNAi therapeutic in development for the treatment of Type 2 Diabetes. Alnylam plans to:

• Initiate a Phase 1 study in early 2023
• Report topline Phase 1 results in late 2023

The Company also plans to continue advancement of its preclinical portfolio of investigational RNAi therapeutics targeting genes expressed in multiple tissue types, and plans to advance between 2-4 new Investigational New Drug (IND) applications from its organic product engine in 2023.

Partnered Program Milestones

Fitusiran, an investigational RNAi therapeutic in development for the treatment of hemophilia A and B, with or without inhibitors. Alnylam’s partner Sanofi plans to:

• Report Phase 3 results from the ATLAS-OLE-005 Phase 3 study evaluating a revised dose and dose regimen in late 2023

ALN-HBV02, an investigational RNAi therapeutic in development for the treatment of chronic hepatitis B and D virus infection. Alnylam’s partner Vir Biotechnology plans to:

• Report additional results from Part A of the MARCH trial, evaluating the combination of ALN-HBV02 (VIR-2218) and VIR-3434, an anti-HBV monoclonal antibody, for the treatment of patients with chronic HBV infection, in early 2023
• Report initial results from Part B of the MARCH trial in late 2023
• Report additional results from the Phase 2 study evaluating the combination of ALN-HBV02 (VIR-2218) and PEG-IFN alpha in early 2023
• Report initial results from the Phase 2 study evaluating the combination of ALN-HBV02 (VIR-2218) and VIR-3434, an anti-HBV monoclonal antibody, in viremic patients, in late 2023
• Report initial results from the Phase 2 study evaluating the combination of ALN-HBV02 (VIR-2218) and VIR-3434 in patients with Hepatitis Delta Virus (HDV) infection, in late 2023

ALN-PNP, an investigational RNAi therapeutic in development for the treatment of non-alcoholic steatohepatitis (NASH). Alnylam’s Partner Regeneron plans to:

• Initiate a Phase 1 study in early 2023

R&D Day Webcast Information

The Company’s R&D Day event will be held today, Thursday, December 15th, from 8:30 a.m. to 12:30 p.m. ET and will include a video stream on the Investors section of the Company’s website, investors.alnylam.com/events. A replay will be available on the Alnylam website within 48 hours after the event. Presentations showcased during the event will be featured on Capella (https://capella.alnylam.com/2022/12/15/alnylam-rd-day-2022).

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

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 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO^® (patisiran), GIVLAARI^® (givosiran), OXLUMO^® (lumasiran), AMVUTTRA^® (vutrisiran) and Leqvio^® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P⁵x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.

Alnylam Forward Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations beliefs, goals, plans or prospects, including without limitation expectations regarding Alnylam’s aspiration to become a top tier biotech company, the potential for Alnylam to identify new potential drug development candidates and advance its research and development programs, Alnylam’s ability to obtain approval for new commercial products or additional indications for its existing products, and Alnylam’s projected commercial and financial performance, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam’s business, results of operations and financial condition and the effectiveness or timeliness of Alnylam’s efforts to mitigate the impact of the pandemic; the potential impact of the January 2022 leadership transition on Alnylam’s ability to attract and retain talent and to successfully execute on its “Alnylam P⁵x25” strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches, including using Alnylam’s IKARIA and GEMINI platforms, and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, including ALN-APP, patisiran and vutrisiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, including patisiran and vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the indication for ONPATTRO or AMVUTTRA in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam’s ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of a current government investigation and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval.

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