1、42nd J.P.Morgan Healthcare ConferenceProf.Ugur Sahin,M.D.CEO&Co-founder9 January 20249:00 9:40 AM PSTThis Slide Presentation Includes Forward-Looking Statements2This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995,as amended

2、,including,but not limited to,statements concerning:planned next steps in BioNTechs pipeline programs,including,but not limited to,statements regarding timing or plans for initiation of clinical trials,enrollment or submission for,and receipt of product approvals with respect to BioNTechs product ca

3、ndidates;BioNTechs estimates of certain financial information,including financial guidance for full year 2024 revenue,which includes expected revenues related to sales of BioNTechs COVID-19 vaccine(referred to as COMIRNATY where approved for use under full or conditional marketing authorization)in t

4、erritories controlled by BioNTechs collaboration partners,particularly for those figures that are derived from preliminary estimates provided by BioNTechs partners;the rate and degree of market acceptance of BioNTechs COVID-19 vaccine and,if approved,BioNTechs investigational medicines;expectations

5、regarding anticipated changes in COVID-19 vaccine demand,including changes to the ordering environment and expected regulatory recommendations to adapt vaccines to address new variants or sublineages;the registrational potential of any trials BioNTech may initiate;the initiation,timing,progress,resu

6、lts,and cost of BioNTechs research and development programs,including statements regarding the timing of initiation and completion of studies or trials and related preparatory work,the availability of results,and characterization and timing of clinical data;BioNTechs targeted timing for a potential

7、oncology product launch,subject to approval,including expectations regarding the timing of commercial readiness activities;the potential safety and efficacy of BioNTechs product candidates;BioNTechs expectations with respect to its intellectual property;and BioNTechs ongoing relationships with Pfize

8、r,Inc.;Duality Biologics(Suzhou)Co.Ltd.;OncoC4,Inc.;Biotheus Inc.;Genmab S/A;Genentech Inc.,a member of the Roche Group;and others.In some cases,forward-looking statements can be identified by terminology such as“will,”“may,”“should,”“expects,”“intends,”“plans,”“aims,”“anticipates,”“believes,”“estim

9、ates,”“predicts,”“potential,”“continue,”or the negative of these terms or other comparable terminology,although not all forward-looking statements contain these words.The forward-looking statements in this presentation are neither promises nor guarantees,and you should not place undue reliance on th

10、ese forward-looking statements because they involve known and unknown risks,uncertainties,and other factors,many of which are beyond BioNTechs control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements.These risks and uncerta

11、inties include,but are not limited to:the uncertainties inherent in research and development,including the ability to meet anticipated clinical endpoints,commencement and/or completion dates for clinical trials,regulatory submission dates,regulatory approval dates and/or launch dates,as well as risk

12、s associated with preclinical and clinical data,including the data discussed in this release,and including the possibility of unfavorable new preclinical,clinical or safety data and further analyses of existing preclinical,clinical or safety data;the nature of the clinical data,which is subject to o

13、ngoing peer review,regulatory review and market interpretation;discussions with regulatory agencies regarding timing and requirements for additional clinical trials;the ability to produce comparable clinical results in future clinical trials;the timing of and BioNTechs ability to obtain and maintain

14、 regulatory approval for BioNTechs product candidates;the ability of BioNTechs mRNA technology to demonstrate clinical efficacy outside of BioNTechs infectious disease platform;BioNTechs pricing and coverage negotiations with governmental authorities,private health insurers and other third-party pay

15、ors after BioNTechs initial sales to national governments;the future commercial demand and medical need for initial or booster doses of a COVID-19 vaccine;competition from other COVID-19 vaccines or related to BioNTechs other product candidates,including those with different mechanisms of action and

16、 different manufacturing and distribution constraints,on the basis of,among other things,efficacy,cost,convenience of storage and distribution,breadth of approved use,side-effect profile and durability of immune response;the ability of BioNTechs COVID-19 vaccines to prevent COVID-19 caused by emergi

17、ng virus variants;BioNTechs and its counterparties ability to manage and source necessary energy resources;BioNTechs ability to identify research opportunities and discover and develop investigational medicines;the ability and willingness of BioNTechs third-party collaborators to continue research a

18、nd development activities relating to BioNTechs development candidates and investigational medicines;unforeseen safety issues and potential claims that are alleged to arise from the use of BioNTechs COVID-19 vaccine and other products and product candidates developed or manufactured by BioNTech;BioN

19、Techs and its collaborators ability to commercialize and market BioNTechs COVID-19 vaccine and,if approved,its product candidates;BioNTechs ability to manage its development and expansion;regulatory developments in the United States and other countries;BioNTechs ability to effectively scale BioNTech

20、s production capabilities and manufacture BioNTechs products,including BioNTechs target COVID-19 vaccine production levels,and BioNTechs product candidates;risks relating to the global financial system and markets;and other factors not known to BioNTech at this time.You should review the risks and u

21、ncertainties described under the heading“Risk Factors”in BioNTechs Report on Form 6-K for the period ended September 30,2023 and in subsequent filings made by BioNTech with the SEC,which are available on the SECs website at www.sec.gov.Except as required by law,BioNTech disclaims any intention or re

22、sponsibility for updating or revising any forward-looking statements contained in this presentation in the event of new information,future developments or otherwise.These forward-looking statements are based on BioNTechs current expectations and speak only as of the date hereof.Furthermore,certain s

23、tatements contained in this presentation relate to or are based on studies,publications,surveys and other data obtained from third-party sources and BioNTechs own internal estimates and research.While BioNTech believes these third-party sources to be reliable as of the date of this presentation,it h

24、as not independently verified,and makes no representation as to the adequacy,fairness,accuracy or completeness of,any information obtained from third-party sources.In addition,any market data included in this presentation involves assumptions and limitations,and there can be no guarantee as to the a

25、ccuracy or reliability of such assumptions.While BioNTech believes its own internal research is reliable,such research has not been verified by any independent source.In addition,BioNTech is the owner of various trademarks,trade names and service marks that may appear in this presentation.Certain ot

26、her trademarks,trade names and service marks appearing in this presentation are the property of third parties.Solely for convenience,the trademarks and trade names in this presentation may be referred to without the and TM symbols,but such references should not be construed as any indicator that the

27、ir respective owners will not assert,to the fullest extent under applicable law,their rights thereto.Our Vision:Harnessing the Power of the Immune System to Fight Human Disease3Innovative precision medicine pipeline targeting multiple product approvals in the coming yearsMulti-product immunotherapy

28、pioneer addressing medical need worldwidePowered by breakthrough science,disruptive technologies&AISustainable respiratory vaccine businessAI=artificial intelligence.BioNTechs key objectives for the next phase Elevating success beyond our historical achievementExecution in 20232023 accomplishmentsFr

29、anchise highlightsBuilding and Expanding a Long-term and Successful COVID-19 Franchise151.Partnered with Pfizer,2.Cumulative doses shipped in the years 2021-2023;3.COVID-19 Excess Mortality Collaborators:Lancet.2022.4.January to December 3,2023.5.September to December,as of January 8,2024.6.Company

30、assessment as of December 3,2023.400 million total vaccine doses distributed in 20234190 million XBB.1.5-adapted monovalent vaccine doses distributed in 20235Introduced single-dose vials and never-frozen prefilled syringes in the U.S.Maintained market leadership in the U.S.(54%),EU(90%),and Japan(85

31、%)6First approved mRNA vaccine4.5 billion doses shipped to 180 countries and territories2Millions of deaths averted3OncologyInfectious Disease7 clinical trials startedGrowing clinical stage pipeline6 clinical assets in-licensed3 first-in-human trials started 11 Phase 2&3 trials ongoingDeveloping an

32、Innovative Pipeline Focused on Oncology and Infectious Disease61.Partnered with Pfizer;2.In collaboration with Bill&Melinda Gates Foundation;3.Partnered with the Coalition for Epidemic Preparedness Innovations(CEPI).Tuberculosis2 Shingles1Mpox320clinical stage programs7clinical stage programsRigorou

33、s pipeline prioritization guided by clinical data and medical needBioNTechs pipelineClinical and scientific execution in 2023Progressing Innovation to Address a Broad Range of Unmet Needs71.Partnered with OncoC4;2.Partnered with DualityBio;3.Partnered with Genentech,member of Roche Group.NSCLC=non-s

34、mall cell lung cancer;HPV=human papillomavirus;PDAC=pancreatic ductal adenocarcinoma;CRC=colorectal cancer,HNSCC=head and neck squamous cell carcinoma.Plan to have 10+potentially registrational trials in 2024 and beyond Additional product candidates advancing to late-stage developmentBNT316/ONC-392(

35、gotistobart)1BNT323/DB-13032BNT323/DB-13032autogene cevumeran/BNT1223autogene cevumeran/BNT1223BNT113NSCLCEndometrial cancerBreast cancerPDACCRCHPV+HNSCCOngoing mid-&late stage trialsReinforcement learning&large language modelsSupporting R&D efforts and biology-focused generative AI.Building a Leadi

36、ng Biotechnology and AI Company at Scale8AI=artificial intelligence;ML=machine learning;GPU=Graphics Processing Unit;RL=reinforcement learning;LLM=large language models.Capabilities to leverage the power of computational medicine&AIAI drug design to develop next-generation products with a more effic

37、acious or safer profileSpeed up workflows to develop novel therapeutic&vaccine product candidatesCapability scale up with fully digitalized automation throughout the whole drug discovery and development processAI researchers,ML engineers and ML Operations experts Fully managed 500 Petaflop High Perf

38、ormance GPU Cluster in UK*2.Quantum computing R&D with multiple academic&commercial partnershipsPhysically realistic representations of complex environments,optimized for speed.300+AI ExpertsFrontier RL&LLMsSupercomputing Assets&Quantum Machine LearningSimulationExpertiseGrew team and expanded globa

39、l presence on 5 continents1,600 new employees joined in 2023Corporate Execution in 20231.Preliminary,unaudited figure;consists of cash,cash equivalents and security investments,as of December 31,2023.9Acquired InstaDeep and in-licensed 6 new clinical stage candidatesBuilding a multi-product,AI-power

40、ed,patient-centric company embedded in the biotech ecosystem Strengthened balance sheet with strong financial performance*17.5 bn Total cash plus security investments1*As of Dec.31,2023Infectious Disease OverviewVariant-adapted vaccinesDesigned to be effective against multiple variants of concern5Lo

41、ng-term healthconsequencesAccumulating evidence demonstrates that COVID-19 vaccination reduces long-COVID4Continuous evolutionOngoing antigenic evolution of SARS-CoV-21,2Risk remains high For severe COVID-19 in vulnerable populations3Long-Term Need for Annually Adapted Vaccines Anticipated 111.World

42、 Health Organization Tracking SARS-CoV-2 variant www.who.int/en/activities/tracking-SARS-CoV-2-variants accessed 30 October 2023;2.Global Initiative on Sharing All Influenza Data https:/gisaid.org/accessed 30 October 2023;3.FDA Briefing Document Vaccines and Related Biological Products Advisory Comm

43、ittee Meeting June 15,2023;4.Brannock et al.Nature Comm.2023;5.Stankov M.V.et al.medRxiv pre-print.2023.Annual and/or SEASONAL VACCINATION Variant-adapted COVID-19&respiratory pathogen combination vaccines in foreseeable futureCombination vaccines have the potential to provide optimized protection a

44、gainst multiple pathogens in at-risk populationCollaborative work with Pfizer to develop combination vaccines for various respiratory diseases*Seasonal Covid-Flu Combination Vaccine Could Address Dual Disease Burden In Overlapping Populations121.Investigators Brochure Version 5.0.BNT162/PF-07302048.

45、Available at:https:/www.tga.gov.au/sites/default/files/foi-2183-09.pdf;2.Kirchdoerfer R,et al.Nature.2016;3.Verbeke R,et al.J Control Release 2021;4.Vogel AB,et al.Nature.2021;5.Sahin U,et al.Nature.2021;6.Chaudhary N,et al.Nat Rev Drug Discov.2021;7.Vogel AB,et al.Nature.2021;8.Pfizer.Press release

46、.Available at:https:/ LM,et al.J Pharm Sci.2023;10.Financial Times.Available at:https:/ activities relate to the development of respiratory combination vaccine candidates utilizing the companies COVID-19 vaccine in various combinations with further approved and investigational respiratory vaccines.T

47、arget population:Healthy individuals 18-64 years oldTrial design:Single-dose mRNA influenza and COVID-19 vaccine candidates vs.SoC influenza and COVID-19 vaccinesPrimary endpoints:Safety,tolerability and immunogenicityInduction of neutralizing antibodies and T-cell responses4,5Easily adaptable and r

48、apid production time6-9Effective multi-antigen targeting10Intrinsic adjuvanticity and generation of high&robust antigen-specific adaptive immune responses1-3COVID-19FluPhase 3mRNA technology is optimally suited for combinationsvaccinesCOVID-19 Franchise1:Adaptable Approach in the Face of Dynamic Vir

49、us Evolution for Continued Success131.Partnered with Pfizer.Launch of seasonal adapted vaccineIf approved,earliest potential introduction of combination respiratory vaccinesExpect continued shift to single dose vials and pre-filled syringesImprove Comirnaty properties,e.g.,extend shelf half-life2023

50、 20242025Shift to commercialization model in key markets14HSVMalariaTuberculosisMpox3.7 billion people under age 50 globally infected with HSV-2491 million people aged 15-49 infected with HSV-1 worldwide249 million cases in 2022608,000 deaths in 2022 in 85 countriesChildren under 5 accounted for 80%

51、of all malaria deaths10.6 million cases globally in 20221.3 million deaths globally in 20222nd leading infectious killer after COVID-1991,000 cases during 22/23 outbreak2WHO warning about risk of international spread of current outbreak in DRCInfectious Diseases:Important Growth Area Addressing High

52、 Medical and Global Health Need1 1.All figures are from World Health Organization fact sheets unless otherwise referenced https:/www.who.int/news-room/fact-sheets(accessed January 04 2024);2.WHO 2022-23 Mpox outbreak:global trends.2023.accessed October 19,2023.https:/worldhealthorg.shinyapps.io/mpx_

53、global 3.Pan CX,et al.Ther Adv Vaccines Immunother.2022;4.Piot P.et al.Nature.2019.WHO=World Health Organization;HSV=Herpes Simplex Virus;DRC=Democratic Republic of the Congo.Individuals who live to 85 years old have50%riskof developing shingles3Incidence and severity of shingles rise with age,with

54、a marked increase after age 504ShinglesAdditional preclinical programs to start clinical trials in 2024/2025Healthcare and Social Responsibility 151.Tuberculosis program run in collaboration with the Bill&Melinda Gates Foundation,Mpox partnered with the Coalition for Epidemic Preparedness Innovation

55、s(CEPI),Malaria wholly owned program;2.Partnered with Pfizer,3.As of December,2023.Inaugurated manufacturing facility in Kigali,Rwanda in December 2023,which could become the first commercial-scale mRNA manufacturing facility in AfricaAdvanced mRNA-based vaccine candidates into the clinic to address

56、 global health threats135%of doses of COVID-19 vaccine delivered to low-and middle-income countries in 20232,3Contributing to democratizing access to novel medicines around the globeOncologyOverviewIntraindividual variability&intratumoral heterogeneity drivingevasion and secondary resistance mechani

57、smRoot Cause of Cancer Treatment FailureCancer cellsGenetically diverse&adaptable5-20 Years up to 10,000 mutationsMutationsDNAMutationHealthyCellMutationsMutationsMutationsMutationsIndividual patients17TumorCellOur Oncology Approach 18StrategyPortfolio strategy covering compound classes with synergi

58、stic mechanism of actionsImmunomodulatorsTargeted therapiesPersonalized mRNA vaccinesPrograms across a wide range of solid tumors and stages of treatmentPrograms with first-in-class and/or best-in-class potentialUnique therapeutic combinationsGoalsAddress the continuum of cancer treatmentBring novel

59、 therapies to cancer patients and establish new treatment paradigmsOpen up novel options to combine platforms and therapiesTowards a Potentially Curative Approach to Cancer:Differentiated Combinations of Multiplatform Assets Space for curative approachesImmunomodulatorsNovel checkpoint inhibitors,cy

60、tokines,immune agonistsmRNAvaccinesTargetedtherapyADCs,CAR-T,TCR-T,small moleculesSynergySynergySynergy19CAR=chimeric antigen receptor;ADC=antibody-drug conjugate;IO=immuno-oncology;TCR-T=T-cell receptor engineered T cell.ImmunomodulatorsOur modality agnostic armamentarium aims to focus on the most

61、relevant and crucial IO pathways Targeting different but complementary players in the complex cancer immunity cycle may promote a thorough and durable anti-tumoral effectmRNA cancer vaccinesCould eliminate polyclonal residual disease with individualized vaccines for potential long-term impactPolyspe

62、cific activity by targeting multiple antigens at onceTargeted therapyPotent and precise therapies could rapidly reduce tumor burdenEfficacy across the entire disease continuum including late linesTowards a Potentially Curative Approach to Cancer:Differentiated Combinations of Multiplatform Assets Sp

63、ace for curative approachesImmunomodulatorsNovel checkpoint inhibitors,cytokines,immune agonistsmRNAvaccinesTargetedtherapyADCs,CAR-T,TCR-T,small moleculesSynergySynergySynergy20CAR=chimeric antigen receptor;ADC=antibody-drug conjugate;IO=immuno-oncology;TCR-T=T-cell receptor engineered T cell.Immun

64、omodulatorsOur modality agnostic armamentarium aims to focus on the most relevant and crucial IO pathways Targeting different but complementary players in the complex cancer immunity cycle may promote a thorough and durable anti-tumoral effectmRNA cancer vaccinesCould eliminate polyclonal residual d

65、isease with individualized vaccines for potential long-term impactPolyspecific activity by targeting multiple antigens at onceTargeted therapyPotent and precise therapies could rapidly reduce tumor burdenEfficacy across the entire disease continuum including late lines21Therapeutic IO Candidates wit

66、h Novel Mode of Action Across Multiple Solid TumorsBNT313/GEN10531Clinical status Ph1/2 in multiplesolid tumorsBNT316/ONC-3922(gotistobart)Clinical status Ph1/2 in multiplesolid tumors Ph2 in PROC Ph3 in 2L+mNSCLC.BNT311/GEN10461(acasunlimab)Clinical status Ph1/2 in multiplesolid tumors Ph2 in mNSCL

67、C Ph2 in 2L mECBNT312/GEN10421Clinical status Ph1/2 trials in multiplesolid tumorsBNT314/GEN10591Clinical status IND approved FIH plannedBNT327/PM80023Clinical status Several Ph2/3 in patients in China ongoing Investigational New Drug Application accepted for further studies in the U.S.Anti-CD27Anti

68、-CTLA4Anti-4-1BBAnti-PD-L1Anti-4-1BBAnti CD40Anti-4-1BBAnti-EpCAMAnti-VEGFAnti-PD-L1 VHHInert FcOptimized FcBNT315/GEN10551Clinical status IND approved FIH plannedAnti-OX40Multiple trial starts and data readouts planned in 2024Inert FcInert FcInert FcInert FcInert Fc1.Partnered with Genmab;2.Partner

69、ed with OncoC4;3.Partnered with Biotheus.CTLA4=Cytotoxic T-Lymphocyte-Associated Protein 4;CD27,CD40,4-1BB=members of the tumor necrosis factor receptor superfamily;PDL-1=Programmed cell death ligand 1;HER2=human epidermal growth factor receptor 2;ADCC=Antibody dependent cell-mediated cytotoxicity;A

70、DCP=Antibody dependent cellular phagocytosis;PROC=platinum-resistant ovarian cancer;NSCLC=non-small cell lung cancer;EC=endometrial cancer APC=antigen presenting cells;VEGF=vascular endothelial growth factor;TME=tumor microenvironment;CTx=chemotherapy;IND=investigational new drug application;FIH=fir

71、st in human.PM80021Combined with Nab-Paclitaxel:Antitumor Activity as First Line Therapy in Patients with TNBC221.Partnered with Biotheus;TNBC=triple negative breast cancer;ORR=objective response rate;DCR=disease control rate,DoR=duration of response;PFS=progression free survival;PD=progressive dise

72、ase;SD=stable disease;PR=partial response;CR=complete response-8900-20-40-60-80Phase 2(NCT05879068):clinical activity of BNT327/PM8002 in combination with nab-paclitaxelJiong Wu et al.Presented at SABCS 2023.Poster#PS08-06PRSDPDCRNon-CR/Non-PD On TreatmentStudy MonthsChange fro

73、m Baseline(%)Change from Baseline(%)-10060400-20-40-8020-60PRSDPDCRAnti-tumor activity observed in patients with locally advanced or metastatic triple-negative breast cancer(n=42)Manageable adverse eventsORR:78.6DCR:95.2%Towards a Potentially Curative Approach to Cancer:Differentiated Combinations o

74、f Multiplatform Assets Space for curative approachesImmunomodulatorsNovel checkpoint inhibitors,cytokines,immune agonistsmRNAvaccinesTargetedtherapyADCs,CAR-T,TCR-T,small moleculesSynergySynergySynergy23CAR=chimeric antigen receptor;ADC=antibody-drug conjugate;IO=immuno-oncology;TCR-T=T-cell recepto

75、r engineered T cell.ImmunomodulatorsOur modality agnostic armamentarium aims to focus on the most relevant and crucial IO pathways Targeting different but complementary players in the complex cancer immunity cycle may promote a thorough and durable anti-tumoral effectmRNA cancer vaccinesCould elimin

76、ate polyclonal residual disease with individualized vaccines for potential long-term impactPolyspecific activity by targeting multiple antigens at onceTargeted therapyPotent and precise therapies could rapidly reduce tumor burdenEfficacy across the entire disease continuum including late lines24ADCs

77、:The Innovation Cycle is Just BeginningDifferentiated ADC linker technologyStability improving safety profileHigher efficacyNovel mechanisms of actionsTumor specific activationImproved and novel payloadsNovel targets and novel epitopesTargeting broader spectrum of tumorsHigher specificityBioNTech pl

78、ans to develop ADCs againstnovel targetsLinker Conjugates the payload to the antibodyAntibody Binds to a specific antigen on the surface of cancer cellsPayload Highly potent cytotoxic compounds BioNTech is driving the development of next-generation ADCsADC=antibody-drug conjugate.Our deep understand

79、ing of ADC targets and immunology distinctively positions us to consolidate and maximize the substantial therapeutic window offered by the next-gen ADC technologyADC Portfolio Constructed with Thoughtful Considerations251.RNAseq data from AACR Project GENIE;2.Partnered with DualityBio.*The completio

80、n of the agreement with MediLink is subject to customary closing conditions,including clearance under the Hart-Scott-Rodino Antitrust Improvements Act.ADC=antibody-drug conjugate;IO=immuno-oncology;MoA=mode of action;HR=hormone receptor;HER=human epidermal growth factor receptor;TROP2=trophoblast ce

81、ll-surface antigen;UC=uretherial cancer;EC=endometrialcancerTargetProgramStageIndicationsPartnerPh1/2Ph3HER2BNT323/DB-1303HR+HER2-low mBCDualityBioSolid tumors with HER2 expressionTROP2BNT325/DB-1305Solid tumorsDualityBioB7H3BNT324/DB-1311Solid tumorsDualityBioHER3BNT326/YL202Solid tumorsMediLink*Ta

82、rgetNSCLCSCLCHER2+BCHR+BCTNBCCRCGastricOvarianPDACHNSCCProstateHER2TROP2B7-H3HER3HighMedium/LowVery low/No-expressionADC combinations that are based on non-overlapping tumor antigens and different payload MoAsADC+IO to advance towards(neo)adjuvant and frontline settingsFour clinical stageADCs with b

83、road,yetminimal overlapping,indication opportunitiesInnovative trial design to open leapfrog pathFast-follower potential in large indicationsBNT323/DB-13032in multiple pivotalstudiesExpression level by indication1Unique indication selection strategyWider therapeutic window may enablenovel combinatio

84、ns in earlier linesAdvanced asset on path to registrationTowards a Potentially Curative Approach to Cancer:Differentiated Combinations of Multiplatform Assets Space for curative approachesImmunomodulatorsNovel checkpoint inhibitors,cytokines,immune agonistsmRNAvaccinesTargetedtherapyADCs,CAR-T,TCR-T

85、,small moleculesSynergySynergySynergy26CAR=chimeric antigen receptor;ADC=antibody-drug conjugate;IO=immuno-oncology;TCR-T=T-cell receptor engineered T cell.ImmunomodulatorsOur modality agnostic armamentarium aims to focus on the most relevant and crucial IO pathways Targeting different but complemen

86、tary players in the complex cancer immunity cycle may promote a thorough and durable anti-tumoral effectmRNA cancer vaccinesCould eliminate polyclonal residual disease with individualized vaccines for potential long-term impactPolyspecific activity by targeting multiple antigens at onceTargeted ther

87、apyPotent and precise therapies could rapidly reduce tumor burdenEfficacy across the entire disease continuum including late linesmRNA Cancer Vaccines May Become the Next Tangible Transformation in Oncology27Individual patient samples(blood and tissue)AI-drivenneoantigen predictionOn-demand tailored

88、 RNA manufacturingIndividualized immuno-therapyMapping of mutationsFixed combination of shared tumor antigens*Multi-antigen approach tailored to each indicationNeo-antigensIndividualized therapyMultiple sharedantigensOff-the-shelf therapyCancer vaccine platformsiNeST1,*FixVacindividualized Neoantige

89、n-Specific immunoTherapyFixed AntigenVaccineANTIGEN 1ANTIGEN 2ANTIGEN 3ANTIGEN 41.iNeST is being developed in collaboration with Genentech,a member of the Roche Group.*autogene cevumeran/BNT122;*Amount of tumor antigens varies across programs.AI=artificial intelligence.Personalized mRNA Cancer Vacci

90、nes:Key Takeaways28Aim to bring personalized cancer vaccines into the adjuvant setting in multiple indications including tumors with low mutational burden and cold tumor typesLow tumor mass,with residual cancer cellsTumor resistance mechanisms not fully establishedHealthier immune system allows for

91、functional T-cell responsesHigh unmet need,not addressed by approved immunotherapiesDemonstrated ability to generate durable de novo neoantigen specific polyepitope T-cell responses in multiple cold tumor typesColorectal Cancer 20-35%relapse rate within 4 years after adjuvant therapy 5-year survival

92、 rates of locoregional disease are 70%ctDNA is a potential marker for minimal residual disease and is under evaluation to identify patients at high risk of disease recurrence1-3Randomized Phase 2 trial in adjuvant setting initiated and recruitingAdjuvant SettingLow Mutational Burden1.Kotani et al.Na

93、t Med.2023,2.Vesterman Henriksen et al.Clin Cancer Res.2022;3.Chidharla et al.Int J Mol Sci.2023;4.Oettle,H.et al.JAMA 2013;5.Neoptolemos,J.P.et al.NEJM 2004.CPI=checkpoint inhibitor.Pancreatic Ductal Adenocarcinoma6975%relapse rate within 5 years after adjuvant therapy Expected to become the 2nd le

94、ading cause of cancer-related death in the US by 2030 5-year survival rates after resection alone are 10%4,5 CPI resistant due to low mutation burden and consecutively few mutation-derived neoantigensPhase 1 trial completed&randomized Phase 2 trial in adjuvant setting recruitingContribute to a Poten

95、tially Curative Approach to Cancer:Differentiated Combinations of Multiplatform Assets 29CAR=chimeric antigen receptor;ADC=antibody-drug conjugate;IO=immuno-oncology;TCR-T=T-cell receptor engineered T cell.Space for curative approachesImmunomodulatorsNovel checkpoint inhibitors,cytokines,immune agon

96、istsmRNAvaccinesTargetedtherapyADCs,CAR-T,TCR-T,small moleculesSynergySynergySynergyImmunomodulatorsOur modality agnostic armamentarium aims to focus on the most relevant and crucial IO pathways Targeting different but complementary players in the complex cancer immunity cycle may promote a thorough

97、 and durable anti-tumoral effectmRNA cancer vaccinesCould eliminate polyclonal residual disease with individualized vaccines for potential long-term impactPolyspecific activity by targeting multiple antigens at onceTargeted therapyPotent and precise therapies could rapidly reduce tumor burdenEfficac

98、y across the entire disease continuum including late linesOur Pipeline Holds Potential for Synergistic Drug Combinations1.Reinhard,K.et al.Science.2020.CAR=chimeric antigen receptor;IO=immuno-oncology;ADC=antibody-drug conjugates;MoA=mechanism of action.30CARCancervaccine+IOCancervaccine+IOADC+Cance

99、rvaccineADC+IOIO+ADCs deliver cytotoxic drugs directly to cancer cells while immunomodulators activate the immune system to recognize and destroy cancer cellsPotentially converging checkpoint inhibition and improved immune cell trafficking and ADC penetrationImmunomodulators could activate the immun

100、e system supporting vaccine-induced tumor-specific T cell responsesComplementary and/or potentially synergistic MoA of immunomodulators could enhance T cell priming and sustain activationmRNA cancer vaccine mediates in vivo stimulation and controlled expansion of CAR-T cells,induces a memory T cell

101、phenotype,increases target sensitivity1ADCs could quickly debulk tumors while cancer vaccines potentially boost the immune system to eradicatemulti-clonal micrometastases;hence potentially lifting the long-term survival curveBNT211 A Potentially First-in-Class Approach for CLDN6+Solid Tumors1.Kranz

102、LM,et al.Nature.2016;2.ahinU,et al.Nature.2020;3.Reinhard K,et al.Science.2020.CLDN6=Claudin 6;CAR=chimeric antigen receptor;scvf=single-chain variable fragment;CD=cluster of differentiation;EMA=European Medicines Agency;PRIME=PRIority MEdicines;R/R=relapsed refractory;PoC=proof of concept.CLDN6 CAR

103、 THighly sensitive and specific 2nd generation CAR against CLDN6 CLDN6 is absent from healthy adult tissue,but expressed in a variety of cancers1Amplification and persistence of CAR-T cells by repeated administration of CARVac3Clinically proven RNA-lipoplex vaccine for body-wide delivery of antigens

104、 to dendritic cells1,2CLDN6 CARVacSecond generation CAR targeting CLDN6XXXXCAR-T cell strategyAchievements:Presented PoC data for BNT211 in CLDN6+indicationsNear-term strategy:Aim to establish CLDN6 as proven target in solid tumorsAim to establish first CAR T-cell therapy in first solid tumor indica

105、tion(R/R germ cell tumors)Mid-to long-term strategy:Explore expansion into other solid tumor indicationsA pivotal trial in R/R germ cell tumors is planned to be initiated in 2024EMA PRIME designation in testicular cancerBNT211-01:Antitumoral Activity at Dose Level 232Data cut-off:10 Sep 2023.Waterfa

106、ll plot showing best percent change from baseline in sum of target lesion diameters and spider plot showing percent change in target sum from baseline over time for patients treated with CLDN6 CAR-T CLDN6 CARVac at DL2(N=22).*Patient had non-measurable disease per RECIST 1.1 and BOR was assessed by

107、tumor marker response.*Patient achieved complete response after surgical removal of tumors.Response data was pending for 5 patients at the data cut-off.Dotted lines show standard response evaluation criteria used to determine objective tumor response for target lesions per RECIST 1.1(CR=100%,PR=30 t

108、o 100%,SD=30 to 20%,and PD=20%or higher).Graphs contains additional data entered manually into the database following the data cut-off date that was not available in formal outputs.BOR=best overall response;CR=complete response;DCR=disease control rate;DL=dose level;EOC=epithelial ovarian cancer;GCT

109、=germ cell tumor;PD=progressive disease;ORR=objective response rate;PR=partial response;SD=stable disease.CLDN6 CAR-TDL2TotalSafety evaluable patients,n1027744Efficacy evaluable patients,n922738Patients with PR/CR,n113317Patients with SD,n18211Patients with PD,n71210ORR,%11.159.142.944.7DCR,%22.295.

110、571.473.7Days post-infusionGCTEOCOthersChange in target sum%Change in target sum%60300-30-60-90*60400-20-60-10020-40-80050100150200Best response and change in target sum(DL2 only CLDN6 CARVac)Phase 1/2 FIH study(NCT04503278):Efficacy at all dose levelsHaanen J.et al.Presented at ESMO 2023.Abstract#L

111、BA35.BNT211-01:CARVac Improves CAR-T Persistence at Dose Level 2Data cut-off:1 Sep 2023.BioNTech data on file derived from peripheral blood applying semi-quantitative PCR directed against CAR transgene.Displayed as copies of transgene per g of DNA input of isolated PBMC.Pending data up to day 50:2 p

112、atients each in monotherapy and combination cohort.Pending data up to day 90:3 patients for monotherapy,and 4 patients for combination cohort.CAR=chimeric antigen receptor;CARVac=CAR T-cell amplifying RNA vaccine;DL=dose level;EOC=epithelial ovarian cancer;GCT=germ cell tumor;LLOQ=lower limit of qua

113、ntification;PBMC=peripheral blood mononuclear cells.Phase 1/2 FIH study(NCT04503278):Pharmacokinetic dataHaanen J.et al.Presented at ESMO 2023.Abstract#LBA35.1 x 108(DL2)CAR T only1 x 108(DL2)CAR T+CARVacCLDN6 CAR T Conc.(copies/g)Time(Day)GCTEOCOthers35507500LLOQLLO

114、Q33Our Achievements in 2023 Pave Way for the Next Stage of Growth in Oncology34NSCLC=non-small cell lung cancer;HR=hormone receptor;HER=human epidermal growth receptor;BC=breast cancer;CRC=colorectal cancer;PDAC=pancreatic ductal adenocarcinoma.Prioritizing lead late-stage programs to accelerate pat

115、h-to-marketPlan to build fully integrated global oncology organization to discover,develop,and commercialize a multi-product portfolio by the end of 2025Accessed and continue to access external innovation to accelerate pipeline maturation in a capital-efficient manner2023 20242025Ongoing mid-&late-s

116、tage trials in multiple indications,including NSCLC,HR+/HER2-low BC,CRC,PDAC10+potentially registrational trials running for at least 6 programs,plan to start combination trials Advancing Our Vision:A Once In a Generation Opportunity to Transform Medicine.1.Partnered with Pfizer.IND=Investigational

117、new drug.Infectious diseasesGlobally marketed COVID-19 vaccine franchise1Maintain and deepen COVID-19 vaccine leadershipLaunch multiple oncology products from 2026 onwardsMid-term goals 2025-2029Driving transformation todayLong-term vision 2030Launch next-generation and combination COVID-19 vaccines

118、Approved products across oncology and infectious disease portfolioCardiovascular diseasesNeurodegenerative diseasesAutoimmune diseasesOncologyInitiating additional potentially registrational trialsWe aim to be a multi-product global biotechnology leader,working to address the worlds most pressing he

119、alth challenges with pioneering,disruptive technologies delivered at scale359 Phase 2 trials2 Phase 3 trials7 programs in9 clinical trials20 programs in30 clinical trialsInnovation engine producing multiple INDs per yearPotential new disease areasThank youAppendixAdvancing our Pipeline:Select Data M

120、ilestones in 2024381.Partnered with Genmab;2.Partnered with OncoC4;3.Partnered with DualityBio;4.Partnered with Biotheus;5.Partnered with Pfizer.NSCLC=non-small cell lung cancer,R/R=relapsed/refractors.ProgramIndicationTargeted MilestoneOncologyBNT311/GEN1046(acasunlimab)1R/R met.NSCLC,+/-pembrolizu

121、mabPhase 2 dataBNT312/GEN10421Multiple solid tumorsPh1/2 expansion cohort dataBNT316/ONC-392(gotistobart)2Multiple solid tumorsPh1/2 expansion cohort dataBNT323/DB-13033Multiple solid tumorsPh1/2 expansion cohort dataBNT325/DB-13053Multiple solid tumorsPh1/2 dataBNT327/PM80024Multiple solid tumorsPhase 2 dataInfectious DiseaseBNT162b25COVID-19,Omicron XBB.1.5 monovalent vaccinePhase 2/3 dataBNT1675ShinglesPhase 1 trial update