The HELIOS-B study was designed to evaluate the safety and efficacy of investigational vutrisiran, an RNAi therapeutic subcutaneously administered once every three months for the potential treatment of cardiomyopathy in ATTR amyloidosis patients. The primary endpoint will evaluate the efficacy of vutrisiran versus placebo on the composite endpoint of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent heart failure visits) at 30 months in ATTR amyloidosis patients with cardiomyopathy. ?Today?s milestone represents another exciting step forward as we advance the investigation of RNAi therapeutics like vutrisiran in ATTR amyloidosis patients with cardiomyopathy. We reached full study enrollment for HELIOS-B, our largest clinical trial to date, approximately 20 months from study initiation, reflecting the high interest from patients and physicians in a potential treatment option with subcutaneous administration, quarterly dosing, and potent and reversible serum TTR reduction,? said Rena Denoncourt, Vice President, TTR Franchise Lead. ?If positive, the HELIOS-B study would support our efforts to advance the development of an industry leading franchise of RNAi therapeutics for the treatment of ATTR amyloidosis.? Topline full results from HELIOS-B are expected in early 2024. The HELIOS-B protocol includes an optional interim analysis which, if pursued, would be conducted following the data readout from Alnylam?s APOLLO-B Phase 3 clinical study of patisiran in patients with ATTR amyloidosis with cardiomyopathy. The APOLLO-B study completed enrollment in June 2021 and is expected to have topline data available in mid-2022. Based on those data and subsequent regulatory interactions, the potential path forward for a HELIOS-B interim analysis will be further refined, including potential for an earlier readout of topline results. About the HELIOS-B Phase 3 Study HELIOS-B is a global, Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy, which enrolled more than 600 adult patients with ATTR amyloidosis (including both hATTR and wtATTR amyloidosis) with cardiomyopathy. Patients were randomized on a 1:1 basis to receive either 25 mg of vutrisiran or placebo administered as a subcutaneous injection once every three months for up to 36 months. The primary endpoint will evaluate the efficacy of vutrisiran versus placebo on the composite endpoint of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent heart failure (HF) visits) at 30 months. For more information on HELIOS-B (NCT04153149) please visit?www.clinicaltrials.gov. About Vutrisiran Vutrisiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hereditary ATTR (hATTR) and wild-type ATTR (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, with the goal of blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. Quarterly, and potentially biannual, administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylam?s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability that may allow for infrequent subcutaneous injections. The U.S. Food and Drug Administration is currently evaluating the New Drug Application (NDA) for vutrisiran for the treatment of the polyneuropathy of hATTR amyloidosis. The safety and efficacy of vutrisiran for this indication or for the treatment of cardiomyopathy of ATTR amyloidosis have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency, or any other health authority. About ATTR Amyloidosis Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal (GI) tract. There are two different types of ATTR amyloidosis ? Hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, while wtATTR amyloidosis is estimated to impact 200,000 ? 300,000 people worldwide. 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 silencing messenger RNA (mRNA) ? the genetic precursors ? that encode for disease-causing 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) is leading 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 genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the potential treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam?s commercial RNAi therapeutic products are ONPATTRO^??(patisiran), GIVLAARI^??(givosiran), OXLUMO^??(lumasiran), and Leqvio^??(inclisiran) being developed and commercialized by Alnylam?s partner Novartis. Alnylam has a deep pipeline of investigational medicines, including six 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 Various statements in this release concerning Alnylam?s expectations, plans, aspirations, and goals, including those related to the investigational therapeutic vutrisiran and its potential as a low-dose, once quarterly, subcutaneously administered treatment option with reversible serum TTR reduction for patients with hATTR amyloidosis with cardiomyopathy, the expected timing for topline results from the HELIOS-B Phase 3 study of vutrisiran and the APOLLO-B Phase 3 study of patisiran, the potential for an optional interim analysis in HELIOS-B following the data readout from the APOLLO-B study, progress toward building an industry leading franchise of RNAi therapeutics for the treatment of ATTR amyloidosis, our aspiration to become a leading biotech company, and the planned achievement of our ?Alnylam P⁵x25? strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. 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; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates; actions or advice of regulatory agencies and Alnylam?s ability to obtain and maintain regulatory approval for its product candidates, 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 vutrisiran, if approved) 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, Regeneron and Vir; the outcome of litigation; the risk of 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 is not intended to convey conclusions about efficacy or safety as to any investigational uses or dosing regimens of any investigational RNAi therapeutics. There is no guarantee that any investigational therapeutics or dosing regimens for such therapeutics will successfully complete clinical development or gain health authority approval.