Alnylam Forward Looking Statements

1 1 2022 Alnylam Pharmaceuticals, 2022 Alnylam PharmaceuticalsNathan (USA)Diagnosed with AHP2 Alnylam Forward Looking StatementsThispresentationcontainsforwar d-lookingstatementswithinthemeaningofSec tion27 AoftheSecuritiesActof1933andSection21 EoftheSecuritiesExchangeActof1934,includ ingexpectationsregardingouraspirationtob ecomealeadingbiotechcompanyandtheplanned achievementofour AlnylamP5x25 strategy,ourabilitytoattainfinancialself -sustainability,ourpreliminaryfourthquar terand2021fiscalyearglobalnetproductreve nueandpatientsontherapy,theprobabilityof successofourRNAitherapeuticsplatform.

2 Thedriversofourfuturegrowthpotential,inc ludingthepotentialofourTTRfranchise,ourc ontinuedconfidenceinthedesignandongoinge xecutionoftheAPOLLO-BPhase3studyandtheev idenceforinvestigationalRNAitherapeutics inATTR cardiomyopathy,thepotentialopportunityfo rRNAitherapeuticsinprevalentdiseases,and thepotentialofourengineforsustainableinn ovationincludingthepotentialforimprovedp roductprofilestoemergefromourIKARIAandGE MINI platforms, ,uncertaintiesandotherfactors,including, withoutlimitation:thedirectorindirectimp actoftheCOVID-19globalpandemicoranyfutur epandemiconourbusiness,resultsofoperatio nsandfinancialconditionandtheeffectivene ssortimelinessofoureffortstomitigatethei mpactofthepandemic;thepotentialimpactoft herecentleadershiptransitiononourability toattractandretaintalentandtosuccessfull yexecuteonour AlnylamP5x25 strategy;thefinalizationandauditofourfou rthquarterand2021fiscalyearfinancialresu ltswhichcouldpotentiallyresultinchangeso radjustmentstotheselectedpreliminaryfina ncialresultspresentedherein.

3 Ourabilitytodiscoveranddevelopnoveldrugc andidatesanddeliveryapproaches,including usingourIKARIAandGEMINI platforms,andsuccessfullydemonstratethee fficacyandsafetyofourproductcandidates;t hepre-clinicalandclinicalresultsforourpr oductcandidates;actionsoradviceofregulat oryagenciesandourabilitytoobtainandmaint ainregulatoryapprovalforourproductcandid ates,includingvutrisiran,aswellasfavorab lepricingandreimbursement;successfullyla unching,marketingandsellingourapprovedpr oductsglobally;delays,interruptionsorfai luresinthemanufactureandsupplyofourprodu ctcandidatesorourmarketedproducts;obtain ing,maintainingandprotectingintellectual property;ourabilitytosuccessfullyexpandt heindicationforOXLUMO,ONPATTRO(andpotent iallyvutrisiran,ifapproved)inthefuture;o urabilitytomanageourgrowthandoperatingex pensesthroughdisciplinedinvestmentinoper ationsandourabilitytoachieveaself-sustai nablefinancialprofileinthefuturewithoutt heneedforfutureequityfinancing;ourabilit ytomaintainstrategicbusinesscollaboratio ns.

4 Ourdependenceonthirdpartiesforthedevelop mentandcommercializationofcertainproduct s,includingNovartis,Sanofi,RegeneronandV ir;theoutcomeoflitigation;thepotentialim pactofcurrentandriskoffuturegovernmentin vestigations;andunexpectedexpenditures;a swellasthoserisksmorefullydiscussedinthe RiskFactors ,orifanyunderlyingassumptionsproveincorr ect,ouractualresults,performance,timelin esorachievementsmayvarymateriallyfromany futureresults, ,exceptasrequiredbylaw, Poised to Become a Top-Tier BiotechLeader in RNAi Therapeutics Pioneered new class of innovative medicines 4 medicines approved in < 3 years Robust clinical pipeline across rare and prevalent diseases Global footprint with strong commercial capabilities Leading IP estate with fundamental, delivery.

5 And product-specific patent protection Strong balance sheet, on path toward financial self-sustainabilityHighly differentiated with proven track record and deriskedplatform Modular and reproducible approach to drug development Historic probability of clinical success multiples higher than industry standards Organic product engine capable of sustaining innovation for future growth Track record of setting and exceeding 5-year goals4 Notable Accomplishments in 2021* Preliminary selected financial results are unaudited, subject to adjustment, and provided as an approximation in advance ofthe Company s announcement of complete financial results in February (vutrisiran, OXLUMO )Completed enrollment in two key Phase 3 studies in ATTR-CMCombined net product revenues of $662 million* (83% growth YoY)2 CTA filings(ALN-APP, ALN-XDH)

6 Maintained strong financial position $ billion in cashat year-end 2021* $100M+ YoY improvement in non-GAAP operating loss 9/30 YTD$Launched new 5-year strategyAdvanced multiple investigational products for prevalent diseases(zilebesiran, ALN-HBV02, ALN-HSD)Expanded commercial presence into>30 countries5 Continuing Strong Global Commercial ExecutionCombined Net Product Revenues ($662M) at Upper End of Guidance Range, with 83% YoY Growth* 2021Q2 2021Q3 2021Q4 2021>1,500>1,725>1,875>2,050Q1 2021Q2 2021Q3 2021Q4 2021~$475M2021 >2,050 patientsas of December 31, 2021Q2 2021Q3 2021Q4 2021~225>270>300>350Q1 2021Q2 2021Q3 2021Q4 2021~$128M2021 >350 patientsas of December 31, 2021Q2 2021Q3 2021Q4 2021~50~100>120>140Q1 2021Q2 2021Q3 2021Q4 2021~$60M2021 >140 patientsas of December 31, 2021* Preliminary selected financial results are unaudited, subject to adjustment.

7 And provided as an approximation in advance ofthe Company s announcement of complete financial results in February ~ ~ ~19$M$M$M6 Alnylam Clinical Development Pipeline1 Includes marketing application submissions; 2 Approved in the and Canada for the PN of hATTR amyloidosis in adults, and in the EU, Japan and other countries for the treatment of hATTR amyloidosis in adults with stage 1 or stage 2 polyneuropathy; 3 Approved in the , Brazil and Canada for the treatment of adults with acute hepatic porphyria (AHP), and in the EU and Japan for the treatment of AHP in adults and adolescents aged12years and older; 4 Approved in the , EU and Brazil for the treatment of primary hyperoxaluria type 1 in all age groups.

8 5 Approved in the for the treatment of heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) and in the EU for the treatment of hypercholesterolemia or mixeddyslipidemia; 6 Novartis has obtained global rights to develop, manufacture and commercialize inclisiran; 50% of inclisiran royalty revenue fromNovartis will be payable to Blackstone by Alnylam ; 7 Phase 3 study of vutrisiran in Stargardt Disease expected to initiate in late 2022; 8 Cemdisiran and pozelimab are each currently in Phase 2 development; Alnylam and Regeneron are evaluating potential combinationsof these two investigational therapeutics; 9 Dicerna is leading and funding development of belcesiran; 10 Vir is leading and funding development of ALN-HBV02.

9 * Not approved for any indication and conclusions regarding the safety or efficacy of the drug have not been of January2022 EARLY/MID-STAGE(IND/CTA Filed-Phase 2)LATE STAGE (Phase 2-Phase 3)REGISTRATION/COMMERCIAL1(OLE/Phase 4/IIS/registries)COMMERCIAL RIGHTShATTR Amyloidosis-PN2 GlobalAcute Hepatic Porphyria3 GlobalPrimary Hyperoxaluria Type 14 GlobalLeqvio (inclisiran)Hypercholesterolemia5 Milestones & up to 20% Royalties6 Vutrisiran*hATTR Amyloidosis-PNGlobalPatisiranATTR AmyloidosisGlobalVutrisiran*ATTR AmyloidosisGlobalVutrisiran7*Stargardt DiseaseGlobalFitusiran*Hemophilia15-30% RoyaltiesLumasiranSevere PH1 Recurrent Renal StonesGlobalCemdisiran (+/-Pozelimab)8*Complement-Mediated Diseases50-50.

10 Milestone/RoyaltyBelcesiran9*Alpha-1 Liver option post-Phase 3 ALN-HBV02 (VIR-2218)10*Hepatitis B Virus Infection50-50 option post-Phase 2 Zilebesiran (ALN-AGT)*HypertensionGlobalALN-HSD*NASH 50-50 ALN-APP*Alzheimer s Disease; Cerebral Amyloid Angiopathy50-50 ALN-XDH*GoutGlobalFocused in 4 Strategic Therapeutic Areas (STArs):Genetic MedicinesCardio-Metabolic DiseasesInfectious DiseasesCNS/Ocular Diseases7 High-Yield Productivity of Alnylam RNAi Therapeutics PlatformComparison of Historical Industry Metrics to Alnylam Portfolio11 Analysis as of November 2021; Past