JPM 2023 再生元.pdf

1、J.P.Morgan Healthcare ConferenceJ a n u a r y 9,2 0 2 3This non-promotional presentation contains investigational data as well as forward-looking statements;actual results may vary materially.J.P.Morgan Healthcare Conference 2023Strategy&Business Update2Leonard S.Schleifer,MD,PhDCo-Founder,President

2、&Chief Executive Officer3Note regarding forward-looking statements and non-GAAP financial measuresThis presentation includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals,Inc.(Regeneron or the Company

3、),and actual events or resultsmay differ materially from these forward-looking statements.Words such as anticipate,expect,intend,plan,believe,seek,estimate,variations of such words,and similar expressions are intended to identify such forward-lookingstatements,although not all forward-looking statem

4、ents contain these identifying words.These statements concern,and these risks and uncertainties include,among others,the impact of SARS-CoV-2(the virus that has caused the COVID-19pandemic)on Regenerons business and its employees,collaborators,and suppliers and other third parties on which Regeneron

5、 relies,Regenerons and its collaborators ability to continue to conduct research and clinical programs,Regenerons ability to manage its supply chain,net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees(collectively,Regenerons Products)

6、,and the global economy;the nature,timing,and possible success and therapeutic applications of Regenerons Products and product candidates being developed by Regeneron and/or its collaborators or licensees(collectively,Regenerons Product Candidates)and research andclinical programs now underway or pl

7、anned,including without limitation EYLEA(aflibercept)Injection,Dupixent(dupilumab)Injection,Libtayo(cemiplimab)Injection,Praluent(alirocumab)Injection,Kevzara(sarilumab)Injection,Evkeeza(evinacumab),Inmazeb(atoltivimab,maftivimab,and odesivimab-ebgn),aflibercept 8 mg,pozelimab,odronextamab,itepekima

8、b,fianlimab,garetosmab,linvoseltamab,REGN5713-5714-5715,Regenerons other oncology programs(including its costimulatory bispecific portfolio),Regenerons and its collaborators earlier-stage programs(including REGN14287,Regenerons“next generation”COVID-19 antibody discussed in this presentation),and th

9、e use of human geneticsin Regenerons research programs;uncertainty of the utilization,market acceptance,and commercial success of Regenerons Products and Regenerons Product Candidates and the impact of studies(whether conducted by Regeneron orothers and whether mandated or voluntary),including the s

10、tudies discussed or referenced in this presentation,on any of the foregoing or any potential regulatory approval of Regenerons Products and Regenerons Product Candidates;thelikelihood,timing,and scope of possible regulatory approval and commercial launch of Regenerons Product Candidates and new indi

11、cations for Regenerons Products,including without limitation those listed above;the likelihood and timing ofachieving any of the anticipated milestones described in this presentation;safety issues resulting from the administration of Regenerons Products and Regenerons Product Candidates in patients,

12、including serious complications or side effectsin connection with the use of Regenerons Products and Regenerons Product Candidates in clinical trials;determinations by regulatory and administrative governmental authorities which may delay or restrict Regenerons ability to continue todevelop or comme

13、rcialize Regenerons Products and Regenerons Product Candidates;ongoing regulatory obligations and oversight impacting Regenerons Products,research and clinical programs,and business,including those relating topatient privacy;the availability and extent of reimbursement of Regenerons Products from th

14、ird-party payers,including private payer healthcare and insurance programs,health maintenance organizations,pharmacy benefit managementcompanies,and government programs such as Medicare and Medicaid;coverage and reimbursement determinations by such payers and new policies and procedures adopted by s

15、uch payers;competing drugs and product candidates that maybe superior to,or more cost effective than,Regenerons Products and Regenerons Product Candidates;the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees(including

16、 those discussed or referenced in this presentation)may be replicated in other studies and/or lead to advancement of product candidates to clinical trials or therapeutic applications;the ability of Regeneron to manufacture and managesupply chains for multiple products and product candidates;the abil

17、ity of Regenerons collaborators,licensees,suppliers,or other third parties(as applicable)to perform manufacturing,filling,finishing,packaging,labeling,distribution,and othersteps related to Regenerons Products and Regenerons Product Candidates;unanticipated expenses;the costs of developing,producing

18、,and selling products;the ability of Regeneron to meet any of its financial projections or guidance andchanges to the assumptions underlying those projections or guidance;the potential for any license or collaboration agreement,including Regenerons agreements with Sanofi and Bayer(or their respectiv

19、e affiliated companies,as applicable),tobe cancelled or terminated;and risks associated with intellectual property of other parties and pending or future litigation relating thereto,other litigation and other proceedings and government investigations relating to the Company and/or itsoperations,the

20、ultimate outcome of any such proceedings and investigations,and the impact any of the foregoing may have on Regenerons business,prospects,operating results,and financial condition.A more complete description of theseand other material risks can be found in Regenerons filings with the U.S.Securities

21、and Exchange Commission.Any forward-looking statements are made based on managements current beliefs and judgment,and the reader is cautioned notto rely on any forward-looking statements made by Regeneron.Regeneron does not undertake any obligation to update(publicly or otherwise)any forward-looking

22、 statement,including without limitation any financial projection or guidance,whetheras a result of new information,future events,or otherwise.This presentation includes non-GAAP net income per diluted share,which is a financial measure that is not calculated in accordance with U.S.Generally Accepted

23、 Accounting Principles(“GAAP”).This non-GAAP financial measure is computedby excluding certain non-cash and/or other items from the related GAAP financial measure.The Company also includes a non-GAAP adjustment for the estimated income tax effect of reconciling items.The Company makes such adjustmen

24、tsfor items the Company does not view as useful in evaluating its operating performance.Management uses this and other non-GAAP measures for planning,budgeting,forecasting,assessing historical performance,and making financial andoperational decisions,and also provides forecasts to investors on this

25、basis.Additionally,such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Companys core business operations.However,there are limitations in the use of such non-GAAP financial measures as they exclude certain expenses that are recurring in nature.

26、Furthermore,the Companys non-GAAP financial measures may not be comparable with non-GAAPinformationprovided byothercompanies.Any non-GAAPfinancialmeasurepresented byRegeneronshouldbe considered supplementalto,andnot a substitute for,measuresof financial performance preparedin accordance with GAAP.20

27、22 progress across key strategic priorities positions Regeneron to deliver long-term shareholder value4Potential upcoming regulatory submissions,approvals and data readoutsPositive aflibercept 8 mg data position retinal franchise for prolonged leadershipExceptional Dupixent clinical profile and comm

28、ercial execution,now approved to treat five Type 2 allergic diseases and in AD patients as young as 6 monthsStrengthened immuno-oncology platform with Libtayo acquisition,advances for CD3 bispecifics,promising costimulatory bispecific data,and robust LAG-3 programPotential breakthrough advance for C

29、OVID-19 treatment and prevention with a novel monoclonal antibodyThis slide contains investigational drug candidates that have not been approved by any regulatory authority.Note:Definitions for all acronyms and abbreviations in this presentation can be found on page 37.Maintaining U.S.leadership wit

30、h 2022 revenue growth continuing to outpace anti-VEGF category growth5$0.0$0.8$1.4$1.7$2.7$3.3$3.7$4.1$4.6$4.9$5.8$6.32011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022U.S.Net Product Sales,in$Billions#1 anti-VEGF treatment for retinal diseases FY 2022 U.S.net product sales of$6.26B(+8%YoY)

31、*Q4 2022 U.S.net product sales of$1.50B(-3%YoY)*Negatively impacted by a short-term shift to off-label use of compounded Avastin Temporary closing in Q4 2022 of fund that provides patient co-pay assistance Most recent Q4 2022 market data suggests that shift to off-label Avastin is already beginning

32、to reverse75%branded category share in December 2022,consistent with prior 2022 quartersDemographic trends expected to drive future category growth*Based on preliminary,unaudited resultsSymphony Health,as of December 23,2022.*+8%Annual growthin 2022*Standard-of-care based on 11+years of safety and e

33、fficacy experience,breadth of indications,and flexible dosing regimensReducing treatment burden for patients with wAMDand DME remains a high unmet needIf approved,patients eligible for aflibercept 8 mg could benefit from extended dosing intervalsAflibercept 8 mg has potential to shift treatment para

34、digm;positions Regenerons retinal franchise for prolonged leadership6Aflibercept 8 mg is an investigational product and has not been approved for use by any regulatory authority.BLA submission completed in December 2022Using priority review voucher to expedite FDA reviewPre-launch planning underway

35、with potential FDA approval by late August 2023Aflibercept 8 mg has the potential to become the next-generation standard-of-care anti-VEGF treatmentAflibercept 8 mg is being jointly developed by Regeneron and Bayer AG.The lead sponsors of the trials were Regeneron for PHOTON and Bayer for PULSAR.Q8W

36、*7%Pooled Aflibercept 8 mg(N=456)Q8W*4%Q12W*7%Q16W89%Aflibercept 8 mg Q16W(N=156)93%of aflibercept 8 mg DME patients maintained dosing intervals 12 weeks through week 48 7Q8W*9%Q12W91%Aflibercept 8 mg Q12W(N=300)Safety of aflibercept 8 mg comparableto that of aflibercept 2 mg*Patients shortened base

37、d on dose-regimen modification assessments at some point through week 48.aflibercept 2 mg Q8W n=167,aflibercept 8 mg Q12W n=328,aflibercept 8 mg Q16W n=163.Patients completing week 48 Mean#of injections through week 48Aflibercept 2 mg(Q8W)7.7Aflibercept 8 mg(Q12W)5.7Aflibercept 8 mg(Q16W)4.9Afliberc

38、ept 8 mg is an investigational product and has not been approved for use by any regulatory authority.Q12W93%Aflibercept 8 mg 12-and 16-week dosing regimens achieved non-inferior vision gains compared to aflibercept 2 mg 8-week dosing regimenQ8W*13%Q12W*11%Q16W77%Aflibercept 8 mg Q16W(N=312)Q8W*17%Po

39、oled Aflibercept 8 mg(N=628)83%of aflibercept 8 mg wAMD patients maintained dosing intervals 12 weeks through week 48 8Q8W*21%Q12W79%Aflibercept 8 mg Q12W(N=316)Q12W83%Mean#of injections in first 48 weeksAflibercept 2 mg(Q8W)6.9Aflibercept 8 mg(Q12W)6.1Aflibercept 8 mg(Q16W)5.2*Patients shortened ba

40、sed on DRM assessments at some point through week 48.Patients completing 48 week;2 mg Q8W n=309,8 mg Q12W n=316,8 mg Q16W n=312.Patients completing week 48.Note:Percentages may not add to 100%due to rounding.Bayer AG is the lead sponsor of the PULSAR study.Safety of aflibercept 8 mg comparableto tha

41、t of aflibercept 2 mgAflibercept 8 mg 12-and 16-week dosing regimens achieved non-inferior vision gains compared to aflibercept 2 mg 8-week dosing regimenAflibercept 8 mg is an investigational product and has not been approved for use by any regulatory authority.7%remained on Q4W dosing throughout Y

42、ear 1Cross-trial comparison of aflibercept 8 mg and faricimab in DME patients9Dosing intervals of DME patients randomized to aflibercept8 mg Q16W arm(N=156)in PHOTON study,through 48 weeksDosing intervals of DME patients randomized to faricimab 6 mg PTI arm(N=286)in YOSEMITE study,through 52 weeks*A

43、flibercept 8 mg is an investigational product and has not been approved for use by any regulatory authority.No head-to-head data vs.faricimab available caution advised when comparing results of different clinical studies.For descriptive purposes only.048121620242832364044480 4 8 12 16 20 24 28 32 36

44、 40 44 48 52 52Only 2 in 10completed a full Q16W dosing cycleat the end of Year 1 Interval extension was permitted notwithstanding a CST increase or decrease of 10%with up to a 10-letter loss of vision 4 in 10unable to achieve or maintain dose extension(Q8W,Q12W,Q16W)89%maintained Q16W dosing throug

45、h week 48WeeksPatients3 initial monthly doses*Wycoff C et al.Efficacy,durability,and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema(YOSEMITE and RHINE):two randomised,double-masked,phase 3 trials.Lancet 2022;399:74155.Colors modifi

46、ed for consistency.Q8WQ12WQ16WQ4WInitial dosesWeeksPatientsdecision4 initial monthly doses1077%maintained Q16W dosing through week 4811%achieved Q12W dosing through week 4845%assigned to Q16W dosing at week 2433%assigned to Q12W dosing at week 2422%assigned to Q8W dosing at week 20Dosing intervals o

47、f wAMD patients randomized tofaricimab 6 mg in TENAYA and LUCERNE studies(n=665)*(Dose interval shortening was not permitted in Year 1 per studies protocols)Dosing intervals of wAMD patients randomized to aflibercept 8 mg Q16W arm(N=312)in PULSAR studyQ8WQ12WQ16WPost-initiation periodInitial doses*A

48、AO 2022.Colors modified for consistency.4 initial monthly doses3 initial monthly dosesAflibercept 8 mg is an investigational product and has not been approved for use by any regulatory authority.No head-to-head data vs.faricimab available caution advised when comparing results of different clinical

49、studies.For descriptive purposes only.Cross-trial comparison of aflibercept 8 mg and faricimab in wAMD patientsIn first 9 months of 2022,Dupixent global net product sales grew 41%and exceeded$6.2 billionIncremental market penetration,new indications,and younger populations represent significant oppo

50、rtunity for continued growth112022 regulatory progress across 5 diseases:Atopic DermatitisApproved by FDA as first biologic medicine for AD patients aged 6 months to 5 years;EU submission under reviewAsthmaApproved by EC for patients aged 6 to 11 years Eosinophilic EsophagitisApproved by FDA as firs

51、t and only treatment;recommended for EU approval by the CHMP Prurigo NodularisApproved by FDA and EC as first and only treatmentChronic Spontaneous Urticaria sBLA submitted to FDA for biologic-nave patients2022 approvals expected to make meaningful revenue growth contributions starting in 2023$3.4$4

52、.7$1.1$1.5First 9 Months of 2021First 9 Months of 2022U.S.ROW+41%Sanofi records global net product sales of Dupixent,$BillionsThis slide contains investigational indications for dupilumab that have not been approved by any regulatory authority.Delivering on“pipeline in a product”potential12This slid

53、e contains investigational indications for dupilumab that have not been approved by any regulatory authority.Under regulatoryreview/submittedInvestigationalindicationsApproved byFDA and/or ECDupixents differentiated mechanism of action can benefit patients suffering from multiple Type 2 allergic dis

54、easesDupixent clinical trials have demonstrated that IL-4 and IL-13 are key drivers of multiple Type 2 allergic diseasesAtopic DermatitisAdults 18+AsthmaAdults/Adol 12+Atopic DermatitisAdolescent 12+CRSwNPAdults 18+Atopic DermatitisPed 6-11AsthmaPed 6-11CIndU-COLDAdults/Adol 12+CSUAdults/Adol 12+EoE

55、Ped 1-11Prurigo NodularisAdults 18+EoEAdults/Adol 12+Atopic DermatitisInfant 6 mo-5YCOPDAdults 18+TodayBPAdults 18+CPUOAdults 18+CRSsNPAdults/Adol 12+AFRSAdults/Ped 6+Dupixent&itepekimab:two opportunities to address high unmet need in COPD13Potential to address Type 2 COPD in both current and former

56、 smokersTwo Phase 3 studies ongoing:BOREAS fully enrolled NOTUS enrollingBOREAS achieved pre-specified interim efficacy threshold,triggering initiation of NOTUS studyKey inclusion criteria:Eosinophils 300/lBOREAS pivotal data expected in 1H 2023,NOTUS in 1H 2024Potential to address COPD in former sm

57、okersTwo Phase 3 studies ongoing:AERIFY-1 enrolling AERIFY-2 enrollingDemonstrated 42%reduction in exacerbations vs.placebo in Phase 2 study of former smokersNo inclusion criteria for eosinophil countPivotal data from both AERIFY studies expected in 2024Itepekimab(anti IL-33)Itepekimab only600K pati

58、entsDupixent or itepekimab350K patientsDupixent only150K patientsType 2Non-Type 2Former Smokers(70%of COPD patients)Current Smokers(30%of COPD patients)This slide contains investigational drug candidates and indications that have not been approved by any regulatory authority.U.S.,EU and Japan addres

59、sable patient number estimates Tumor TypeInitial IndicationData Disclosures2H 2022HematologyLymphomaMultiple myelomaDermato-oncologyNeoadjuvant CSCCFirst-line advanced melanomaOther Solid TumorsMET-altered advanced NSCLCAdvanced NSCLCOvarian cancer(2L+)Metastatic castration-resistantprostate cancerM

60、eaningful advances in oncology in 202214Indicates pivotal or potentially pivotal studyThis slide contains investigational drug candidates and indications that have not been approved by any regulatory authority.OdronextamabLinvoseltamabCemiplimabCemiplimabPSMAxCD28UbamatamabMETxMETCemiplimabFianlimab

61、indicates data readoutCemiplimabFianlimabFDA approved in November 2022 for first-line use in combination with platinum-based chemotherapyOne of two PD-1/L1 antibodies FDA-approved for use in combination with chemotherapy irrespective of histology or PD-L1 expression levelsJ.P.Morgan Healthcare Confe

62、rence 2023Research&Pipeline Update15George D.Yancopoulos,MD,PhDCo-Founder,President&Chief Scientific OfficerEvolution of Regenerons turn-key technologies powering our science and pipelineBiologicals:Turn-Key Therapeutic PlatformsGenetic Medicines:Turn-Key Therapeutic PlatformsAntibodiesTrapsGene The

63、rapysiRNAGenome editing(insertion/knockout)CRISPR/Cas9 Tech|RNAi|Next-Gen Editing|Viral Vector Tech|AAVUNLOCKING POWER OF HUMAN GENETICSCD3 bispecificsCostimulatory bispecificsRegeneron is foundedCOMMITMENT TOMOUSE GENETICSMOUSE GENETICS VELOCIMMUNE MOUSE with humanized immune system Multiple approv

64、ed&clinicalstage antibodies&bispecificsRegeneron Genetics Center Over 2M Humans Sequenced Targets and Genetic Medicine Pipeline|16Meaningful advances across therapeutic areas in 202217OphthalmologyImmunologyOncologyBroader PipelineEYLEA(VEGF Trap)Received six months of pediatric exclusivity sBLA acc

65、epted for Priority Review in Retinopathy of PrematurityAFLIBERCEPT 8 MG(VEGF Trap)Positive pivotal data in wet Age-related Macular Degeneration and Diabetic Macular Edema BLA submitted,with priority review voucherDUPIXENT(anti-IL-4/IL-13)FDA and EC approval as first and only treatment indicated for

66、Prurigo Nodularis FDA approval as first treatment indicated for Eosinophilic Esophagitis;recommended for EU approval by the CHMP FDA approval as first biologicfor pediatric(6mos 5yrs)Atopic Dermatitis EC approval in pediatric(6 11yrs)Asthma sBLA submitted for Chronic Spontaneous UrticariaLIBTAYO(ant

67、i-PD-1)FDA approval in combination with chemotherapy for 1Ladvanced NSCLC EC and Japan approval in 2L Cervical CancerOTHER ONCOLOGY Positive data presented for fianlimab+Libtayo in advanced Melanoma and advanced NSCLC Initial data presented for novel bispecifics in solid tumors(METxMET,ubamatamab)Fi

68、rst data for PSMAxCD28+Libtayo showed encouraging anti-tumor activity in mCRPC Potentially pivotal Phase 2 data presented for odronextamab in B-NHL and linvoseltamab in Myeloma sBLA accepted for priority review for Evkeeza in pediatric HoFH BLA submitted for pozelimabin CHAPLE Reported rapid,deep,an

69、d sustained TTR reduction after single dose of NTLA-2001 Preliminary data reported for siRNA for HSD17B13 in NASH showing robust target knockdown Discovered rare mutations in CIDEB gene that protect against liver disease;published in NEJM Inmazeb won prestigious“Best Biotechnology Product”Prix Galie

70、n award for treatment of EbolaThis slide contains investigational drug candidates and indications that have not been approved by any regulatory authority.Tumor-Targeted BiparatopicsDesigned to disrupt cellular signaling and/or deliver a cytotoxic drug to tumor cellsUnique flexibility of internally d

71、eveloped pipeline drives potential for novel and differentiated combinations18CD3 Bispecifics:“Signal 1”Designed to bridge tumor-associated antigens on cancer cells with CD3-expressing T cells,resulting in potential local T-cell activation and cytotoxicityPD-1 Inhibitor CD28 Bispecifics:“Signal 2”De

72、signed to increase the activity of T cells that recognize tumor antigens by augmenting costimulatory signalsModulating immune responseDesigned to overcome the tumor suppressive microenvironment(e.g.,by inhibition of checkpoints,or targeted delivery of immuno-modulators)Unique flexibility of internal

73、ly developed pipeline drives potential for novel and differentiated combinations19Odronextamab(CD20 xCD3)Linvoseltamab(BCMAxCD3)MUC16xCD3(REGN4018)PSMAxCD3(REGN4336)R/R B-NHL,CLLR/R MultipleMyelomaMetastatic prostate cancerRecurrent ovarian cancerCemiplimab(PD-1)PSMAxCD3(REGN4336)Metastatic prostate

74、 cancerCemiplimab(PD-1)Ubamatamab(MUC16xCD3)Recurrent ovarian cancerCemiplimab(PD-1)EGFRxCD28(REGN7075)Cemiplimab(PD-1)MUC16xCD28(REGN5668)Cemiplimab(PD-1)PSMAxCD28(REGN5678)Solid tumorsRecurrent ovarian cancerMetastatic prostate cancerUbamatamab(MUC16xCD3)MUC16xCD28(REGN5668)Recurrentovarian cancer

75、PSMAxCD3(REGN4336)PSMAxCD28(REGN5678)Metastaticprostate cancerFianlimab(LAG3)Cemiplimab(PD-1)Melanoma&other advanced malignanciesHNSCCGITR(REGN6569)Cemiplimab(PD-1)CSCC,MCC,BCCvidutolimod(TLR9)Cemiplimab(PD-1)METxMET(REGN5093)METxMET ADC(REGN5093-M114)MET-altered advanced NSCLCMET over-expressing ad

76、vanced NSCLCTumor-Targeted BiparatopicsCD3 Bispecifics:“Signal 1”CD28 Bispecifics:“Signal 2”Modulating immune responseOdronextamab(CD20 xCD3)CD22xCD28(REGN5837)R/R B-NHLPD-1 Inhibitor This slide contains investigational drug candidates that have not been approved by any regulatory authority.Unique f

77、lexibility of internally developed pipeline drives potential for novel and differentiated combinationsOdronextamab(CD20 xCD3)Linvoseltamab(BCMAxCD3)MUC16xCD3(REGN4018)PSMAxCD3(REGN4336)R/R B-NHL,CLLR/R MultipleMyelomaMetastatic prostate cancerRecurrent ovarian cancerCemiplimab(PD-1)PSMAxCD3(REGN4336

78、)Metastatic prostate cancerCemiplimab(PD-1)Ubamatamab(MUC16xCD3)Recurrent ovarian cancerCemiplimab(PD-1)EGFRxCD28(REGN7075)Cemiplimab(PD-1)MUC16xCD28(REGN5668)Cemiplimab(PD-1)PSMAxCD28(REGN5678)Solid tumorsRecurrent ovarian cancerMetastatic prostate cancerUbamatamab(MUC16xCD3)MUC16xCD28(REGN5668)Rec

79、urrentovarian cancerPSMAxCD3(REGN4336)PSMAxCD28(REGN5678)Metastaticprostate cancerFianlimab(LAG3)Cemiplimab(PD-1)Melanoma&other advanced malignanciesHNSCCGITR(REGN6569)Cemiplimab(PD-1)CSCC,MCC,BCCvidutolimod(TLR9)Cemiplimab(PD-1)METxMET(REGN5093)METxMET ADC(REGN5093-M114)MET-altered advanced NSCLCME

80、T over-expressing advanced NSCLCTumor-Targeted BiparatopicsCD3 Bispecifics:“Signal 1”CD28 Bispecifics:“Signal 2”Modulating immune responseOdronextamab(CD20 xCD3)CD22xCD28(REGN5837)R/R B-NHLPD-1 Inhibitor 200800601003050070900105012090020200105006080010500205003055001050080800505009-100-80-60-40-2002

81、040608010001008170010700101007070020900305014090040100905016070030200402003-100-80-60-40-20020406080100Costim bispecifics may allow“cold”tumors to respond to immunotherapy21Signal 1Signal 2REGN5678(PSMAxCD28)+Libtayo(PD-1 antibody)Mechanism of Action PSMA is highly expressed on prostate tumors The c

82、ombination of REGN5678 and Libtayo(cemiplimab)is designed to further increase the antitumor activity of T cells that recognize cancer cells by augmenting costimulatory“Signal 2”and blocking cancer cells from using the PD-1 pathway to suppress T-cell activationREGN5678+Libtayo:Initial Phase 1/2 data

83、show dose-dependent anti-tumor activity for PSMAxCD28 when combined with LibtayoPatients from REGN5678 dose levels 1-5Patients from REGN5678 dose levels 6-8 REGN5678:Potential to overcome mCRPC resistance to PD-1 inhibition DL 1-5(n=17):Minimal anti-tumor activity and no Gr3 irAEs DL 6-8(n=16):Dose-

84、dependent responses observed with correlated irAEs Grade 3 immune-related adverse events only occurred in certain patients with anti-tumor activity*Aug 3,2022 press release,Sep 2022 ESMO REGN Investor Event.Preliminary data.DL3DL4DL5DL2DL1DL8DL7DL6Best PSA changefrom baseline(%)Best PSA changefrom b

85、aseline(%)Initial PSMAxCD28+Libtayo clinical data show responses in tumors resistant to anti-PD-1 monotherapyPSMAxCD28+Libtayo demonstrated profound anti-tumor activity in tumor type historically resistant to anti-PD-1 monotherapy22Key takeaways from initial PSMAxCD28 dataMinimal PSMAxCD28 anti-tumo

86、r activity at lower doses,as predicted by preclinical modelsAnti-tumor activity amplified with Libtayo initiationGr 3 immune-related adverse events only occurred in certain patients with anti-tumor activity“Index patient”(DL6)experiencing ongoing response 1.5 years after initial dosing*Maintained PS

87、A levels below the limit of detectionDisappearance of soft tissue diseaseNormalizing bone scan with negative PSMA PET scan*Patient discontinued therapy after 7 weeks due to due to a Gr3 irAE of the skin that resolved with treatment Per physician reportAt DL8,3 of 4 patients showed profound PSA respo

88、nses upon initiation combination therapy05001000W0W3W6W9HLHPSA(ng/ml)0204060W0W3W6W9W12Patient 1009Treatment held at W9 Patient 2004Patient passed away W13Initiate PSMAxCD28Initiate LibtayoPSA(ng/ml)0100200300W0W3W6W9W12W15PSA(ng/ml)Dosing schedule per protocolAIDPGr 3PRPRSDHepatitisGr 2Patient 7003

89、Treatment held for 1 week between W9 and W10Costimulatory bispecifics platform:status and next steps23*Skokos,D.,Wei,J.,et al.(2022).Science Translational Medicine.https:/doi.org/10.1126/scitranslmed.abn1082Prostate CancerOvarian CancerEGFR+Solid TumorsHematologyPSMAxCD28(REGN5678)+Libtayo Share ini

90、tial Phase 1 dataPresent Phase 1 data at a medical meeting in 1H23Select go-forward dose(s)in 2023PSMAxCD28(REGN5678)+PSMAxCD3(REGN4336)Phase 1 study plannedInitial data in 2024+MUC16xCD28(REGN5668)+Ubamatamab(MUC16xCD3)Initiate Phase 1(dose escalation)Initial data in 2024MUC16xCD28(REGN5668)+Libtay

91、oInitiate Phase 1(dose escalation)Initial data in 2023EGFRxCD28(REGN7075)+Libtayo Phase 1 early dose escalation data presented at SITC 2022Present updated data in 2023CD22xCD28(REGN5837)+Odronextamab(CD20 xCD3)Supportive preclinical data presented at SITC 2022*Phase 1/2 study in DLBCL to initiate 1H

92、 2023TAAxCD28+Linvoseltamab(BCMAxCD3)Phase 1 study in 3L+multiple myeloma to initiate in 2023Costimulatory bispecifics will be combined with both Libtayo and a growing list of CD3 bispecificsThis slide contains investigational drug candidates that have not been approved by any regulatory authority.D

93、ual LAG-3 and PD-1 blockade may provide enhanced immune activation vs.anti-PD-1 alone24This slide contains investigational drug candidates that have not been approved by any regulatory authority.Fianlimab(anti-LAG-3)+Libtayo(anti-PD-1)Melanoma Two metastatic melanoma cohorts showed a consistent and

94、strong efficacy signal Phase 3 studies in 1L advanced melanoma and adjuvant melanoma ongoing Phase 3 study in perioperative melanoma initiating in 1H 2023 NSCLC Promising early data presented from expansion cohort of the FIH study Phase 2/3 studies initiating in 1L advanced NSCLC(1H 2023)and periope

95、rative NSCLC(2H 2023)Exploring additional indications Neoadjuvant breast cancer:I-SPY study of fianlimab+Libtayo+paclitaxel,data presented in 2H 2022 Science-led development for potential additional indications Lymphocyte-activation gene 3(LAG-3)is an immune checkpoint receptor that delivers an inhi

96、bitory signal to activated T cells LAG-3 expression in melanoma biopsies has been shown to be associated with therapeutic resistance to antiPD-1,suggesting that inhibiting LAG-3 in addition to PD-1 may enhance the anti-tumor effectRobust clinical development program underwayFianlimab+Libtayo:competi

97、tive efficacy in 1L metastatic melanomaData from second anti-PD-(L)1-nave metastatic melanoma cohort confirmed strong efficacy signal observed in first cohort25Tumor response waterfall plot by investigator assessment(melanoma antiPD-(L)1-nave patients,cohorts 6 and 15)PDSDPRCR100Best percent change

98、from baseline80604020-1000-20-40-60-80123456789 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 4142 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 747675Patients(N=76)*AntiPD-1/PD-L1 nave cohorts,Fianlimab 16

99、00 mg+cemiplimab 350 mg IV every 3 weeks,for up to 51 weeks,Prior systemic therapies,including prior adjuvant therapies,excluded for cohort 15.Data cut-off date:1 Jul 2022 Long,G.(March 2022).Abstract 360385:Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable

100、 melanoma:Overall survival and response rates from RELATIVITY-047 Presentation.ASCO Plenary Series 2022.This slide contains investigational drug candidates that have not been approved by any regulatory authority.No direct head-to-head data available caution advised when comparing results of differen

101、t clinical studies.%(n),unless otherwise statedCohort 6*(N=40)Cohort 15*(N=40)Cohort 6+15(N=80)RELATIVITY-047(nivolumab&relatlimab-rmbw)(N=355)ORR,%(95%CI)62.5(45.8,77.3)65.0 (48.3,79.4)63.8(52.2,74.2)43(38,48)Complete response15.0(6)2.5(1)8.8(7)16(58)Partial response47.5(19)62.5(25)55.0(44)27(95)St

102、able disease17.5(7)15.0(6)16.3(13)17(61)Progressive disease15.0(6)15.0(6)15.0(12)30(105)NE/Unknown5.0(2)5.0(2)5.0(4)8(27)DCR80.0(32)80.0(32)80.0(64)62.8(223)KM-estimated PFS,median(95%CI),mos24(4.2,NE)NR(7.5,NE)24(9.9,NE)10.2(6.5,14.8)DOR,median(95%CI),mosNR(11.9,NE)NR(6.3,NE)NR(22.6,NE)NR(29.6,NR)O

103、S,HR(95%CI)-0.80(0.64,1.01)Safety profile of fianlimab+Libtayo combination similar to anti-PD-1 monotherapyTumor TypeInitial IndicationUpcoming Expected Data Disclosure20232024+HematologyLymphomaMultiple myelomaDermato-oncologyNeoadjuvant CSCCAdjuvant CSCCAdvanced CSCC(2L)Perioperative and adjuvant

104、melanomaFirst-line advanced melanomaOther Solid TumorsMET-altered advanced NSCLCPerioperative and advanced NSCLCOvarian cancer(2L+)Metastatic castration-resistant prostate cancerSCCHNEGFR+solid tumorsPoised to advance oncology pipeline in 2023 and beyond26CemiplimabCemiplimabUbamatamabCemiplimabMUC1

105、6xCD28UbamatamabMUC16xCD28CemiplimabEGFRxCD28CemiplimabGITRCemiplimabPSMAxCD3PSMAxCD3PSMAxCD28OdronextamabCemiplimabMETxMET ADCVidutolimodCemiplimabFianlimabCemiplimabLinvoseltamabindicates pivotal or potentially pivotal studyFianlimabCemiplimabThis slide contains investigational drug candidates tha

106、t have not been approved by any regulatory authority.CemiplimabPSMAxCD28FianlimabCemiplimabFianlimabCemiplimabNext-gen COVID antibody binds outside variable RBD and has demonstratedhigh neutralization activity against all known variants and lineages27Variant Lineage REGEN-COV*XevudyEvusheldBebtelovi

107、mabREGN14287D614G OmicronBA.2-BA.4/5BA.4.6BA.2.75-BQ.1BQ.1.1XBBDifferentiated vs.prior antibody approaches Binding site outside of immunodominant,highly variable RBD and NTD regions,lowering risk of losing activity against future variants Targeted epitope highly conserved,with over 99.9%conservation

108、 since beginning of the pandemic Demonstrated high neutralization potency against all known SARS-CoV-2 variants and lineages to dateTargeting treatment and prophylactic setting In the U.S.alone,millions of immuno-compromised people will not adequately respond to vaccination Antibodies can be dosed p

109、rophylactically to prevent infection and severe COVID-19 diseaseAnticipate initiating REGN14287 clinical trial in 2023,pending regulatory discussions High neutralizing activity(IC5010-10 M)Limited neutralizing activity(10-10 MIC5010-9 M)Low neutralizing activity(10-9 MIC5010-8 M)Not evaluated for ne

110、utralizing activity*REGEN-COV(casirivimab(REGN10933)and imdevimab(REGN10987)was developed by Regeneron Pharmaceuticals,Inc.REGEN-COV is currently not authorized for use.Xevudy(sotrovimab,also known as VIR-7831 and GSK4182136)was developed by GlaxoSmithKline plc and Vir Biotechnology,Inc.Evusheld(AZD

111、7442,combination of tixagevimab(AZD8895)and cilgavimab(AZD1061)was discovered by Vanderbilt University Medical Center and licensed to AstraZeneca.Bebtelovimab(LY-CoV1404;LY3853113)was discovered by AbCellera and the National Institute of Allergy and Infectious Diseases(NIAID)Vaccine Research Center

112、and was licensed to Eli Lilly and Company.NOTE:Neutralizing activity from published studies or measured by Regeneron using publicly available sequences.This slide contains investigational drug candidates that have not been approved by any regulatory authority.-Genetic Medicines:Turn-Key Therapeutic

113、PlatformsGene TherapysiRNAGenome editing(insertion/knockout)CRISPR/Cas9 Tech|RNAi|Next-Gen Editing|Viral Vector Tech|AAVBiologicals:Turn-Key Therapeutic PlatformsAntibodiesTrapsCD3 bispecificsCostimulatory bispecificsEvolution of Regenerons turn-key technologies powering our science and pipelineUNLO

114、CKING POWER OF HUMAN GENETICSRegeneron is foundedRegeneron Genetics Center Over 2M Humans Sequenced Targets and Genetic Medicine PipelineCOMMITMENT TOMOUSE GENETICSMOUSE GENETICS VELOCIMMUNE MOUSE with humanized immune system Multiple approved&clinicalstage antibodies&bispecificsBIOLOGICSTO TARGETGE

115、NETIC MEDICINES|28Optimizing genetic medicines with antibody-targeted deliveryImproving delivery technologies to create the next generation of genetic medicines 29Systemic delivery mostly targets the liver Local deliveryCurrent options for genetics medicines deliveryOur visionSpecifically target any

116、 cell typewith systemic deliveryorCapitalizing on Regenerons expertise in biologics by deploying antibody technologies that more efficiently deliver payloads to potentially address challenging genetic diseasesLiver“overloaded”when attempting to target other organsAchieved proof-of-concept innon-huma

117、n primatesRegeneron-discovered,approved and investigational medicines across a wide and diverse set of diseases30odronextamab(CD20 xCD3)linvoseltamab(BCMAxCD3)REGN5459(BCMAxCD3)REGN7257(IL-2Rg)REGN9933(Factor XI)REGN7999(TMPRS6)NTLA-2001#(TTR)REGN5381/REGN9035(NPR1)ALN-HSD(HSD17B13)ALN-APP (APP)ALN-

118、PNP (PNPLA3)“Next-Gen”COVID Antibodies(SARS-CoV-2)fianlimab(LAG-3)REGN4336(PSMAxCD3)REGN5093(METxMET)REGN5093-M114(METxMET ADC)REGN5668(MUC16xCD28)REGN5678(PSMAxCD28)REGN6569(GITR)REGN7075(EGFRxCD28)cemiplimab(PD1)vidutolimod(TLR9)ubamatamab(MUC16xCD3)odronextamab(CD20 xCD3)pozelimab(C5)linvoseltama

119、b(BCMAxCD3)sarilumab*(IL-6R)dupilumab*(IL-4R)mibavademab(LEPR)REGN5381/REGN9035(NPR1)aflibercept(VEGF)aflibercept 8 mg(VEGF)dupilumab*(IL-4R)itepekimab*(IL-33)REGN5713-5714-5715(Bet v 1)Over 30 product candidatescemiplimab(PD1)fianlimab(LAG-3)Collaboration with:*Sanofi;Roche;Alnylam;#Intellia;Ultrag

120、enyx;Bayer pozelimab+cemdisiran(C5xC5)Phase 1Phase 2Phase 3ApprovedAs of January 2023Regeneron received a CRL in December 2022 for the REGEN-COV BLA.This slide contains investigational drug candidates that have not been approved by any regulatory authority.alirocumab(PCSK9)garetosmab(Activin A)SOLID

121、 ORGAN ONCOLOGYHEMATOLOGYGENERAL MEDICINEI&IOPHTHALMOLOGYEYLEARetinopathy of PrematurityDUPIXENT*CINDU-Cold(2H)LIBTAYOAdjuvant CSCCItepekimab*COPDDUPIXENT*Eosinophilic EsophagitisDUPIXENT*Pediatric EoE(mid)DUPIXENT*Type 2 COPDFianlimab+LIBTAYOAdvanced MelanomaDUPIXENT*Prurigo NodularisPRALUENTPediat

122、ric HeFH(mid)DUPIXENT*CRSsNPPozelimab cemdisiran+C5-mediated diseasesDUPIXENT*Chronic Spontaneous UrticariaOdronextamabB-Cell NHL(2H)DUPIXENT*CPUOGaretosmabFOPEVKEEZAPediatric HoFHLinvoseltamabR/R Multiple Myeloma(2H)DUPIXENT*Bullous PemphigoidKEVZARA*Polymyalgia RheumaticaAflibercept 8 mgRVOAfliber

123、cept 8 mgWet AMD/DME PozelimabCHAPLE SyndromeMultiple potential FDA submissions:2022-2024+31*In collaboration with Sanofi.+In collaboration with Alnylam.An sBLA for an every 16-week dosing regimen for EYLEA(aflibercept 2 mg)in patients with diabetic retinopathy was withdrawn from FDA review in Janua

124、ry 2023.2024+20222023BLAsBLAThis slide contains investigational drug candidates that have not been approved by any regulatory authority.Submission complete,pending acceptanceAccepted submissionSubmission accepted and approved in 2022Using priority review voucher2023 key upcoming milestones32Ophthalm

125、ology FDA decision for EYLEA in ROP(Q1)BLA acceptance for aflibercept 8 mg in DME and wAMD(Q1)FDA decision and potential U.S.launch of aflibercept 8 mg(Q3)Two-year data for PHOTON(DME)and PULSAR(wAMD)(Q3)Dupixent sBLA acceptance for CSU(Q1)EC decision on pediatric AD(6mo 5yr)and EoE(1H)Report data f

126、or Phase 3 studies in CINDU-Cold and Type 2 COPD(1H)Submit sBLA for pediatric EoE(mid)and CINDU-Cold(2H)FDA decision on CSU(Q4)Pozelimab(anti-C5 antibody)BLA acceptance(1H)and FDA decision(2H)on CHAPLESolid Organ Oncology Initiate Phase 3 study for fianlimab+Libtayo in perioperative melanoma(1H)as w

127、ell as Phase 2/3 studies in 1L advanced NSCLC(1H)and perioperative NSCLC(2H)Report additional data for PSMAxCD28+Libtayo Report initial data across solid organ oncology,including for CD3 bispecifics and CD28 costimulatory bispecifics EC decision for Libtayo in combination with chemotherapy in 1L adv

128、anced NSCLC(1H)Odronextamab(CD20 xCD3)Initiate confirmatory studies in FL and DLBCL,including in earlier lines(1H)Initiate Phase 1 study in combination with REGN5837(CD22xCD28)in aggressive B-NHL(1H)Submit BLA in B-NHL(2H)Linvoseltamab(BCMAxCD3)Initiate confirmatory studies in MM,including in earlie

129、r lines(1H)Initiate Phase 1 study in combination with TAAxCD28 in MM(2H)Submit BLA in 3L+MM(2H)This slide contains investigational drug candidates that have not been approved by any regulatory authority.Three responsibility focus areas all reflect our“doing well by doing good”ethos33Our mission:Use

130、the power of science to repeatedly bringnew medicines to people with serious diseasesImprove the lives of peoplewith serious diseasesFoster a culture ofintegrity and excellenceBuild sustainable communities123 Product quality and safety Diverse,healthy and engaged workforce Ethics and integrity STEM

131、education-sponsorship of top science competitions:Regeneron Science Talent Search Regeneron International Science and Engineering Fair Environmental sustainability Pipeline innovation Access to medicine and fair pricing Patient advocacyQ&A34George D.Yancopoulos,MD,PhDCo-Founder,President&Chief Scien

132、tific OfficerMarion McCourtEVP,Head of CommercialLeonard S.Schleifer,MD,PhD Co-Founder,President&Chief Executive OfficerAllocated$3.4 billion*to business development and share repurchases in 202235$1.8 billion investment in Tarrytown R&D facilities announced in July 2021 Continued investments in res

133、earch and development and manufacturing capacity Deploy excess cash to opportunistically repurchase shares Approximately$9.8 billion*in share repurchases since November 2019,including$2.1 billion*in 2022 Libtayo acquisition provides flexibility on existing and future oncology collaborations involvin

134、g Libtayo combinations Acquisition of Checkmate Pharmaceuticals and collaboration with CytomX to expand immuno-oncology pipelineInternal Investmentin our world-class R&D capabilities and capital expenditures to support sustainable growthBusiness Developmentto expand pipeline and maximize commercial

135、opportunitiesRepurchaseShares*Based on preliminary,unaudited results.Recast GAAP Income Statement including IPR&D for Q4 202136In Q4 2022,Regeneron expects to record an acquired in-process research and development(IPR&D)charge of approximately$30 millionrelated to an up-front payment in connection w

136、ith the Companys collaboration with CytomXTherapeutics,Inc.which is expected to negatively impact each GAAP and non-GAAP diluted earnings per share by approximately$0.21 Beginning with the first quarter of 2022,the Company added a new line item,Acquired in-process research and development,to its Con

137、densed Consolidated Statements of Operations.This line item includes in-process research and development acquired in connection with asset acquisitions as well as up-front/opt-in payments related to license and collaboration agreements.Amounts recorded to Acquired in-process research and development

138、 would have historically been recorded to Research and development expenses.*IPR&D charge primarily related to$34 million aggregate up-front payments in connection with our collaboration agreement with Nykode Therapeutics.IPR&D charge primarily related to a$20 million opt-in payment in connection wi

139、th a product candidate under our collaboration agreement with Adicet Bio,Inc.IPR&D charge primarily related to a$195 million charge related to the Companys acquisition of Checkmate.Based on preliminary,unaudited results.Abbreviations and Definitions37AbbreviationDefinition1LFront line2L+Second line

140、and beyond3L+Third line and beyondADAtopic dermatitisAFRSAllergic fungal rhinosinusitis BCCBasal cell carcinomaBCMAB-cell maturation antigenBLABiologics license applicationB-NHLB-cell non-Hodgkins lymphomaBPBullous pemphigoidCHAPLECD55-deficient protein-losing enteropathyCHMPCommittee for medicinal

141、products for human useCIConfidence intervalCIndU-COLDChronic inducible urticaria coldCLLChronic lymphocytic leukemiaCOPDChronic obstructive pulmonary diseaseCPUOChronic pruritis of unknown originCRComplete responseCRLComplete response letterCRSsNPChronic sinusitis without nasal polyposisCRSwNPChroni

142、c sinusitis with nasal polyposisCSCCCutaneous squamous cell carcinomaCSUChronic spontaneous urticariaDCRDuration of complete responseDLDose levelDLBCLDiffuse large B-cell lymphomaDMEDiabetic macular edemaDORDuration of responseECEuropean CommissionEGRFEpidermal growth factor receptorEoEEosinophilic

143、esophagitisAbbreviationDefinitionFIHFirst in humanFLFollicular lymphomaFOPFibrodysplasia ossificans progressiveGAAPGenerally accepted accounting principlesGITRGlucocorticoid-induced TNFR-related proteinHeFHHeterozygous familial hypercholesterolemiaHNSCCHead and neck squamous cell carcinomaHoFHHomozy

144、gous familial hypercholesterolemiaHRHazard ratioIC50Half maximal inhibitory concentrationirAEImmune-related adverse eventLAG-3Lymphocyte-activation gene 3 MMolarmCRPCMetastatic castration-resistant prostate cancerMCCMerkel cell carcinomaMMMultiple myelomaMUC16Mucin 16NASHNon-alcoholic steatohepatiti

145、sNENot estimableNEJMNew England Journal of MedicineNRNot reachedNSCLCNon-small cell lung cancerNTDN-terminal domainOSOverall survivalPD-1/PD-(L)1Programmed cell death protein/(ligand)1PET scanPositron emission tomography scanPFSProgression-free survivalpMHCPeptide-major histocompatibility complex cl

146、ass IPMRPolymyalgia rheumaticaPNPrurigo nodularisPRPartial responseAbbreviationDefinitionPSAProstate-specific antigenPSMAProstate-specific membrane antigenPTIPersonalized treatment intervalRBDReceptor binding domainROPRetinopathy of prematurityROWRest of worldRVORetinal vein occlusion sBLASupplemental biologics license applicationSCCHNSquamous cell carcinoma of the head and neckSDStable diseaseTAATumor-associated antigenTCRT-cell receptorTTRTransthyretin proteinVEGFVascular endothelial growth factorwAMDWet age-related macular degeneration