1、1 2024 Alnylam Pharmaceuticals,Inc.January 8,2024Yvonne Greenstreet,MBChBChief Executive Officer42ndAnnual J.P.Morgan Healthcare Conference2Alnylam Forward Looking StatementsThis presentation contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Sect

2、ion 21E of the SecuritiesExchange Act of 1934.All statements other than historical statements of fact regarding Alnylams expectations,beliefs,goals,plans or prospects including,without limitation,expectations regarding Alnylams aspiration to become a top-tier biotech company and the planned achievem

3、ent of its“Alnylam P5x25”strategy,the potential for Alnylam to identify new potential drug development candidates and advance its research and development programs,Alnylamsability to obtain approval for new commercial products or additional indications for its existing products,and Alnylams projecte

4、d commercial and financialperformance,should be considered forward-looking statements.Actual results and future plans may differ materially from those indicated by theseforward-looking statements as a result of various important risks,uncertainties and other factors,including,without limitation,risk

5、s and uncertaintiesrelating to Alnylams ability to successfully execute on its“Alnylam P5x25”strategy;Alnylams ability to discover and develop novel drug candidates anddelivery approaches and successfully demonstrate the efficacy and safety of its product candidates;the pre-clinical and clinical res

6、ults for Alnylamsproduct candidates,including topline results from the Companys HELIOS-B Phase 3 study of vutrisiran;actions or advice of regulatory agencies andAlnylams ability to obtain and maintain regulatory approval for its product candidates,as well as favorable pricing and reimbursement;succe

7、ssfullylaunching,marketing and selling Alnylams approved products globally;delays,interruptions or failures in the manufacture and supply of Alnylams productcandidates or its marketed products;obtaining,maintaining and protecting intellectual property;Alnylams ability to successfully expand the appr

8、ovedindications for AMVUTTRA in the future;Alnylams ability to manage its growth and operating expenses through disciplined investment in operations andits ability to achieve a self-sustainable financial profile in the future without the need for future equity financing;the direct or indirect impact

9、 of the COVID-19 global pandemic or any future pandemic on Alnylams business,results of operations and financial condition and the effectiveness or timeliness ofAlnylams efforts to mitigate the impact of the pandemic;Alnylams ability to maintain strategic business collaborations;Alnylams dependence

10、on thirdparties for the development and commercialization of certain products,including Roche,Novartis,Sanofi,Regeneron and Vir;the outcome of litigation;thepotential risk of future government investigations;and unexpected expenditures;as well as those risks more fully discussed in the“Risk Factors”

11、filed withAlnylams most recent periodic report(Quarterly Report on Form 10-Q or Annual Report on Form 10-K)filed with the SEC and in its other SEC filings.Inaddition,any forward-looking statements represent Alnylams views only as of the date of this presentation and should not be relied upon as repr

12、esentingAlnylams views as of any subsequent date.Alnylam explicitly disclaims any obligation,except to the extent required by law,to update any forward-lookingstatements.3Leader in RNAi TherapeuticsOn Track to Become Top-Tier,Self-Sustainable Biotech by End of 2025LEADING COMMERCIAL CAPABILITIES$1 B

13、ILLION generated in annual product sales60 countries with commercial presence through direct or distributor salesUp toROBUST AND HIGH-YIELDING PIPELINE15 clinical programs across rare,specialty,and prevalent diseases 15 additional programs expected in clinic by end of 2025STRONG FINANCIAL POSITION$2

14、 BILLION cash balance On path toward financial self-sustainability$OUTSTANDING R&D PRODUCTIVITY new class of medicines5 medicines approved in 10.Positive zilebesiran Phase 2 results in patients with mild-to-moderate hypertension$Maintained strong financial position$2.4 billion in cash at year-end 20

15、23*Combined net product revenues of$1,241 million*(39%growth YoY)Landmark partnership to maximize global opportunity for zilebesiran in hypertensionContinued recognition of award-winning culturePreclinical delivery to new tissue types(adipose and muscle)Driving Robust Product GrowthExtending RNAi Le

16、adershipBuilding a Sustainable Business Human Proof of Concept for RNAi therapeutics in CNS Overpatients on Alnylamcommercial medicines5,00055 medical publications,including 14 in high-impact journals5ChenLiving with hATTR Amyloidosis(Brazil)ROBUST&HIGH-YIELD R&D PIPELINESUSTAINABLE INNOVATION ENGIN

17、ESTRONG COMMERCIAL GROWTH6ChenLiving with hATTR Amyloidosis(Brazil)ROBUST&HIGH-YIELD R&D PIPELINESUSTAINABLE INNOVATION ENGINESTRONG COMMERCIAL GROWTH7Transformational Medicines Delivering$1,241 Million in Annual Product Revenues in 2023*Strong Commercial Performance,Well Positioned for Exceptional

18、Growth*Preliminary selected financial results are unaudited,subject to adjustment,and provided as an approximation in advance of the Companys announcement of complete financial results in February 2024$166$306$475$651$912*$0$55$187$243$329*200222023Global Product Sales($M)65%CAGR*2018 Lau

19、nch2022 Launch2019 Launch2020 LaunchRobust 39%2023 YoY Growth*in Total Net Product Revenues40%*YoY growth in TTR franchise revenues35%*YoY growth in ultra-rare franchise revenuesPatients in ultra-rare franchise globally4,060Patients in TTR franchise globallyTTR FranchiseUltra-Rare Franchise1,0808Che

20、nLiving with hATTR Amyloidosis(Brazil)ROBUST&HIGH-YIELD R&D PIPELINESUSTAINABLE INNOVATION ENGINESTRONG COMMERCIAL GROWTH9Positioned to Deliver Strong Growth and Innovation Across Multiple Disease Areas and Indications Advancing a Robust and High-Yielding Pipeline of RNAi Therapeutics*Partnered,Alny

21、lam-led with profit split Partner-led with profit split Partner-led with Alnylam option for profit split Partner-led with Milestones/RoyaltiesALN-APP is awaiting CTA approval to begin Phase 2 in CAAIND-enablingALN-HTT02*Huntingtons DiseaseALN-SOD1Amyotrophic Lateral SclerosisALN-Gene ABleeding Disor

22、dersALN-Gene YType 2 Diabetes MellitusPhase 1ALN-TTRsc04ATTR AmyloidosisALN-KHKType 2 Diabetes MellitusALN-APP*Alzheimers DiseaseALN-PNPNASHALN-BCATHepatocellular CarcinomaPhase 2Zilebesiran*HypertensionALN-HSDNASHElebsiran(ALN-HBV02/VIR-2218)Hepatitis B Virus InfectionElebsiran(ALN-HBV02/VIR-2218)H

23、epatitis D Virus InfectionBelcesiranAlpha-1 Liver DiseaseALN-APP*Cerebral Amyloid AngiopathyPhase 3VutrisiranATTR Amyloidosis with CMFitusiranHemophiliaCemdisiran(pozelimab combo)Myasthenia GravisCemdisiran(pozelimab combo)Paroxysmal Nocturnal HemoglobinuriaApproved10Rare,Progressively Debilitating,

24、and Fatal DiseaseATTR Amyloidosis1.Coelho T,et al.N Engl J Med.2013;369(9):819-8292.Ando,et al.Orphanet J Rare Dis,2013;Ruberg,et al.Circulation,2012(includes hATTR amyloidosis patients with polyneuropathy and cardiomyopathy);Gertz,et al.Am J Manag Care.2017;23:S107-S1123.Information based on Alnyla

25、m modeling dataDescriptionCaused by a misfolded transthyretin(TTR)protein that accumulates as amyloid deposits in multiple tissues including heart,nerves,and GI tract1Hereditary ATTR(hATTR)Amyloidosis50,000patients worldwide2Wild-Type ATTR(wtATTR)Amyloidosis200,000300,000patients worldwide3Proteolys

26、is&dissociationMisfoldingAggregation&depositionProtein synthesisRNAi therapeutics target disease upstream via rapid knockdown of TTR11RNAi Therapeutics Deliver Rapid Knockdown of Disease-Causing TTR Protein TTR deposition in tissue of ATTR patients causes irreversible damage and premature death1 RNA

27、i mechanism drives rapid knockdown of TTR Majority of HCPs say that speed of reaching 80%mean serum TTR reduction impacts treatment consideration2Change from Baseline in Serum TTR Levels*Data from HELIOS-A Phase 3 study of vutrisiran;1.Hawkins et al.,Ann Med.2015;47(8):625-38;2.Market research with

28、U.S.HCPs(n=40)-100-80-60-40-20006248546066727884Mean(SE)Percent Change from Baseline in Serum TTRTime(weeks)VutrisiranPatisiran12Rapid Knockdown Results in Transformative Profile in hATTR Amyloidosis with PolyneuropathymNIS+7,modified Neuropathy Impairment Score+7;Norfolk QOL-DN,Norfolk Q

29、uality of Life-Diabetic Neuropathy;LS,least squares;SEM,standard error of the mean.The figures show LS mean change over time based on MMRM analysis in the overall populationAPOLLOPlaceboAPOLLOPlaceboStrong Commercial UptakeGROWTH Approaching$1 billion in annual revenues 4,060 patients on commercial

30、ONPATTRO or AMVUTTRA globallyLEADERSHIP 90%estimated U.S.market share 80%estimated market share in Japan and EuropemNIS+7Norfolk QoLONPATTRO(APOLLO study)AMVUTTRA(HELIOS-A study)PlaceboPatisiranPlaceboPatisiran13U.S.ATTR-CM prevalence of 150K expected to grow 3%annually as elderly population increas

31、es faster than overall population*Launch of multiple therapies and modalities 2426 expected to support continued category growthFirst approved therapy and new testing method driving increase in diagnosis rates since 20190k50k100k150k200k2002220232024202520262027202820292030Exceptional Gro

32、wth Potential in ATTR-CM MarketSource:Internal Market research *U.S.Census,elderly population defined as 65+#of U.S.ATTR-CM Patients PrevalenceDiagnosed Patients60%EstimatedDx in 3014Randomized,Double-Blind Outcomes Study in ATTR Amyloidosis Patients with CardiomyopathyVutrisiran Phase 3 StudyClinic

33、alTrials.gov Identifier:NCT04153149N=655Patient Population ATTR amyloidosis;wild-type or any TTR mutation Confirmed cardiomyopathy and medical history of symptomatic heart failure NYHA III;minimum walk and NT-proBNP limits at baseline1:1 RANDOMIZATIONPrimary Endpoint Composite outcome of all-cause m

34、ortality and recurrent CV events(when last patient reaches Month 30)Select Secondary Endpoints 6-MWT distance Kansas City Cardiomyopathy Questionnaire(KCCQ OS)score Echocardiographic parameters All-cause mortality&recurrent all-cause hospitalizations&urgent HF visits All-cause mortality Recurrent CV

35、 events NT-proBNPVutrisiranSC q3M25 mgPlaceboSC q3MorTopline results expected early 202415Positioned to Deliver Outcomes Benefit in ATTR-CM Designed and powered to deliver outcomes;2x as large and 3x as long as APOLLO-B Enriched for patients most likely to benefit,excluding advanced NYHA III and IV

36、Longest follow-up of any ATTR-CM study(36 months in most patients)Analyses planned to demonstrate consistency of effect across key subgroupsDesignExecution Overenrolled by 10%Tafamidis baseline sub-group lower than target of 50%Low rate of tafamidis drop-ins,well within expectationsSupportive Data f

37、rom Patisiran in APOLLO-BEvidence for Disease StabilizationEarly Separation of Mortality CurvesReduction in Disease Biomarkers6MWT,Mean Change from Baseline(SEM)MonthNo significant difference in mortality was observed in APOLLO-B.The FDA issued a Complete Response Letter to the sNDA for patisiran fo

38、r treatment of the cardiomyopathy of ATTR amyloidosis.Patisiran has not been approved by the FDA,EMA,or any other regulatory agency for cardiac manifestations of amyloidosis.No conclusions can or should be drawn regarding its safety or effectiveness in this population.NT-proBNP,Mean Fold Change(95%C

39、I)1.01.11.21.31.41.5603912MonthCumulative All-Cause Mortality(%)Month603924681012Double-blind PeriodOpen-label Extension16If Approved,Vutrisiran Expected to Have Market-Leading Profile in ATTR-CM1.Market research with U.S.HCPs(n=40).2.Market research with HCPs(n=530).3.Market research wit

40、h ATTR patients(n=205).Note:The safety and efficacy of AMVUTTRA(vutrisiran)for the treatment of the cardiomyopathy of ATTR have not been established or evaluated by the FDA,EMA or any other health authority.The information is intended to provide an overview of the potential clinical profile of vutri

41、siran in ATTR-CM Highly targeted RNAi-based mechanism enables rapid knockdown of TTR Reduces pathogenic protein production,acting upstream of approved medicinesUnique MOA Quarterly dosing that aligns with doctor visits and promotes strong adherence Only 4 Dosesper Year Reduction in mortality and CV

42、hospitalizations Halting decline in functional capacity and quality of life Well tolerated safety profilePotential for Impactful Clinical ProfileNearly twice as many patients indicated they would prefer quarterly HCP-administration vs.monthly self-administration3Majority of HCPs say that speed of re

43、aching 80%mean serum TTR reduction impacts treatment consideration1HCPs report that 75%of patients treated with tafamidis have only partial or no response2170k50k100k150k200k250k2002220232024202520262027202820292030203120322033PrevalenceDiagnosed PatientsProfile of Vutrisiran Expected to

44、Support First-Line Positioning in ATTR-CMNote:The safety and efficacy of AMVUTTRA(vutrisiran)for the treatment of the cardiomyopathy of ATTR have not been established or evaluated by the FDA,EMA or any other health authority.Pending positive HELIOS-B study results and regulatory approval.Source:Inte

45、rnal Market research.LOE:loss of exclusivity.Monotherapy Monotherapy orCombo therapyTafamidis LOE(Q428)AMVUTTRA Post-Taf LOE Tafamidis progressors Add-on therapy AMVUTTRA Pre-Taf LOE 1st line patients Tafamidis progressorsCost of combo is prohibitiveGeneric tafamidis could allow for combo therapy if

46、 data supportContinued evidence generation#of U.S.ATTR-CM Patients 18-100-80-60-40-200200306090120150180Mean Serum TTR Knockdown(percent,SEM)Time(days)Placebo(N=8)5 mg(N=6)25 mg(N=6)100 mg(N=6)300 mg(N=6)Phase 1 study ongoingPhase 3 study initiation in ATTR-CM expected at or around year-end 2024Init

47、ial Phase 1 Results Support Best-in-Class ProfileExpanding TTR Leadership with ALN-TTRsc04 Single 300mg dose resulted in rapid,deep,and durable knockdown of serum TTR:90%at Day 15 97%at Day 29 93%at Day 180 All doses of ALN-TTRsc04 well tolerated to date;no adverse events considered related to study

48、 drug by investigator Data support potential for annual subcutaneous dosing19Leading Preventable Risk Factor for Cardiovascular Morbidity and MortalityUncontrolled Hypertension is a Global Health Crisis*Ettehad D,et al.Lancet 2016;387:95767.Targeting Tonic BP Control to Reduce Cardiovascular and Ren

49、al RisksNumber of Patients(7 Major Markets)219M77M62MPrimaryHypertensionHypertension withHigh CV riskUncontrolledHypertension atHigh CV riskRisk Reduction per 10 mm Hg Decrease in SBP*Major CV Events20%CHD17%Stroke27%HF28%Renal Failure5%All Cause Mortality13%Circadian RhythmAdherence24-Hour BP Level

50、BP VariabilityCardiorenal ProtectionRestore normal nocturnal dippingBiannual dosing to improve adherenceAvoid exaggerated BP variability over 24h and long-termStrict 24-hourBP control20Phase 2 Results:Single Doses Reduced Blood Pressure Out to Six MonthsZilebesiran Data Support Potential to Transfor

51、m Treatment of Hypertension*p0.0001;Blood pressure assessments were censored if taken while patients were receiving or within 2 weeks after stopping any rescue medication.Data points are staggered for visualization;Zilebesiran is an investigational RNAi therapeutic for the treatment of hypertension;

52、1.Bakris et al.AHA Scientific Sessions 2023;aAdjusted 95%CIs and p values for the Month 3 primary analysis are based on Dunnetts test;BL,baseline;CI,confidence interval;LSM,least-squares mean;LSMD,LSM difference;Q3M,every 3 months;Q6M,every 6 months;SBP,systolic blood pressure;AEs,adverse events;ISR

53、,injection site reaction.Robust 24-hour Mean SBP Reduction24-hour Tonic BP Control Maintained Out to Month 6 Generally well tolerated Low incidence of AEs of ISR,hyperkalemia,and hypotension,which were mild or moderate in severity and transient;most did not require therapeutic intervention150 mg Q6M

54、(n=78)300 mg Q6M(n=73)300 mg Q3M(n=75)600 mg Q3M(n=76)Placebo(n=75)-25-20-15-10-50150 mgQ6M300 mgQ6M300 mgQ3M600 mgQ6MLSM(95%CI)Change from Baseline in 24-Hour Mean Ambulatory SBP(mmHg)3 Months6 Months*21Launch with label to reduce cardiovascular morbidity and mortalityExpected 2030Comprehensive Zil

55、ebesiran Development Plan to Reimagine Treatment of HypertensionExploring Benefits of Tonic BP Control to Reduce CV RiskThe safety and efficacy of zilebesiran have not been established or evaluated by the FDA,EMA or any other health authority.Launch assumes positive clinical trial results and regula

56、tory approval.MACE,major adverse cardiovascular event;1.Desai AS,et al.N Engl J Med.2023;389:228-238Phase 1Phase 2Phase 3Zilebesiran safety,tolerability,and PK/PD in patients with mild-to-moderate hypertension1Cardiovascular Outcomes Trial(CVOT)Study in patients with uncontrolled hypertension at hig

57、h CV risk,evaluating MACE-type endpointZilebesiran monotherapy in patients with mild-to-moderate hypertensionResults presented at AHA Nov 2023Zilebesiran in combination with single antihypertensive in patients with mild-to-moderate hypertensionTopline results expected early 2024Zilebesiran in combin

58、ation with 2 antihypertensives in high CV risk patients with uncontrolled hypertensionInitiation expected early 202422ALN-APP Has Potential to Address Multiple Patient Populations with High Unmet NeedExpanding Beyond Liver with First CNS Program in ClinicAPP:One target,two distinct pathological proc

59、essesGenetically validated target for CAA and ADUpstream of A42 and A40,pathogenic proteins involved in CAA and AD Significant patient population with high unmet need in both diseasesCAA:Second leading cause of intracerebral hemorrhageAD:Over 5M people affected in U.S.(over 30M worldwide)APP Protein

60、 Structure courtesy of David S.Goodsell and the RCSB Protein Data Bank;APP:amyloid precursor protein;ALN-APP is an investigational RNAi therapeutic for the treatment of CAA and AD.Alzheimers Disease(AD)APP mutations and duplications cause Early Onset ADAmyloid deposits in brain tissue,tau tangles in

61、 neurons,neurodegenerationCerebral Amyloid Angiopathy(CAA)APP mutations cause hereditary CAAAmyloid deposits in walls of vessels in CNS and results in cerebral hemorrhages and cognitive impairment23Phase 1 Results*Mark First Demonstration of Gene Silencing by RNAi Therapeutics in Human BrainALN-APP

62、Achieved Rapid and Durable Reductions in Key Biomarkers*Data presented at 16thClinical Trials on Alzheimers Disease(CTAD)conference,October 2023Dose escalation in Phase 1 Part A ongoingMulti-dose Part Binitiating in approved regionsPhase 2 CAA study initiationplanned for early 2024 Generally well to

63、lerated AEs generally mild to moderate in severity;most unrelated to study drug CSF safety biomarkers,routine lab assessments,and preliminary data for exploratory biomarker neurofilament light chain(NfL)all continued to show no concerning trendsMarked Reductions in CSF A42 and A40 at Month 2 Rapid a

64、nd Durable Reductionsin CSF sAPP-100-75-50-2502550750Median Change from Baseline (%)Time(months)PlaceboALN-APP 25 mgALN-APP 50 mgALN-APP 75 mg-80-60-40-200PlaceboALN-APP 25 mgALN-APP 50 mgALN-APP 75 mgMedian Change from Baseline(%)A42A4024Additional Value Creation Opportunities via Partne

65、red ProgramsELEBSIRAN(ALN-HBV02/VIR-2218)Hepatitis B/D Virus InfectionPotential for functional cure of chronic HBV infection and chronic suppressive therapy for HDV infectionDemonstrated robust reductions in HBsAg and potent antiviral activity in HDVAdditional Phase 2 readouts expected in 2024Alnyla

66、m opt-in right to elebsiran prior to Phase 3FITUSIRANHemophiliaInnovative approach to hemophilia A and B,with or without inhibitorsDemonstrated reduction in annualized bleed rate across multiple Phase 3 studiesNDA submission expected 2024CEMDISIRAN/POZELIMABComplement-Mediated DiseasesUnique siRNA/a

67、ntibody combination providing potent C5 inhibitionDemonstrated unprecedented LDH reduction in nave patients with Paroxysmal Nocturnal Hemoglobinuria(PNH)Phase 3 studies in Myasthenia Gravis and PNH ongoingPhase 3 in Geographic Atrophy initiating in 1H24ALN-HSD and ALN-PNPNonalcoholic Steatohepatitis

68、Novel approach to NASH leveraging genetically validated targetsDemonstrated improvement in biopsy-derived NAFLD Activity Score in NASH patients with ALN-HSDALN-HSD Phase 2 and ALN-PNP Phase 1 studies ongoing in NASH patients25ChenLiving with hATTR Amyloidosis(Brazil)ROBUST&HIGH-YIELD R&D PIPELINESUS

69、TAINABLE INNOVATION ENGINESTRONG COMMERCIAL GROWTH26Organic Product Engine Capable of Sustaining Innovation for Future Growth Derisked platform with highly differentiated features:Rapid knockdownClamped pharmacologyExtended durability Favorable safety profile Modular and reproducible approach to dru

70、g development Historical probability of clinical success multiples higher than industry standards,driven by human genetics27Multiple Sources of Sustainable Innovation Drive Robust PipelineGEMINIIKARIAReversir12 monthsExtrahepatic DeliveryPlatform DesignsHuman GeneticsTargeting Nine Alnylam-Led INDs

71、Across Four Tissues by End of 2025By End of 2025new tissues with INDs2new CNS INDs3+including partnered programs2new liver INDs10+including partnered programs528Alnylam 2024 Goals*Not approved for any indication and conclusions regarding the safety or effectiveness of these drugs have not been estab

72、lished.Early is Q1-Q2,Mid is Q2-Q3,and Late is Q3-Q4 EarlyMidLateCombined Net Product Revenue Guidance to be Provided at Q4/YE 2023 EarningsVUTRISIRANATTR AmyloidosisHELIOS-B Topline ResultssNDA SubmissionALN-TTRsc04*ATTR AmyloidosisInitiate Phase 3 ATTR-CM StudyZILEBESIRAN*HypertensionKARDIA-2 Phas

73、e 2 Topline ResultsInitiate KARDIA-3 Phase 2 StudyALN-APP*Alzheimers DiseaseInterim Phase 1 Part B Multi-Dose ResultsInitiate Phase 2 StudyCerebral Amyloid AngiopathyInitiate Phase 2 StudyALN-KHK*Type 2 DiabetesInitiate Phase 1 Part BALN-BCAT*Hepatocellular CarcinomaInitiate Phase 1 StudyADDITIONAL

74、PROGRAMSFile 3 New INDsKEY PARTNER-LED PROGRAM MILESTONESFITUSIRAN*(Sanofi)HemophiliaSubmit NDA Filing2024ELEBSIRAN*(Vir)Chronic HBV/HDV InfectionPhase 2 ResultsQ2,Q429EarlyMidLateCombined Net Product Revenue Guidance to be Provided at Q4/YE 2023 EarningsVUTRISIRANATTR AmyloidosisHELIOS-B Topline Re

75、sultssNDA SubmissionALN-TTRsc04*ATTR AmyloidosisInitiate Phase 3 ATTR-CM StudyZILEBESIRAN*HypertensionKARDIA-2 Phase 2 Topline ResultsInitiate KARDIA-3 Phase 2 StudyALN-APP*Alzheimers DiseaseInterim Phase 1 Part B Multi-Dose ResultsInitiate Phase 2 StudyCerebral Amyloid AngiopathyInitiate Phase 2 St

76、udyALN-KHK*Type 2 DiabetesInitiate Phase 1 Part BALN-BCAT*Hepatocellular CarcinomaInitiate Phase 1 StudyADDITIONAL PROGRAMSFile 3 New INDsKEY PARTNER-LED PROGRAM MILESTONESFITUSIRAN*(Sanofi)HemophiliaSubmit NDA Filing2024ELEBSIRAN*(Vir)Chronic HBV/HDV InfectionPhase 2 ResultsQ2,Q4Alnylam 2024 Goals*

77、Not approved for any indication and conclusions regarding the safety or effectiveness of these drugs have not been established.Early is Q1-Q2,Mid is Q2-Q3,and Late is Q3-Q4 Phase 3 resultsVutrisiran sNDA filing(assuming positive study)Phase 2 resultscommercial products(4 wholly owned)5clinical study

78、 starts6new INDs330Patients:Over 0.5 million on Alnylam RNAi therapeutics globallyProducts:6+marketed products in rare and prevalent diseasesPipeline:Over 20 clinical programs,with 10+in late stages and 4+INDs per yearPerformance:40%revenue CAGR through YE 2025Profitability:Achieve sustainable non-GAAP profitability within periodAmbitious Five-Year Strategy to Drive Growth31Thank You!