1、PRECISION GENETIC MEDICINES THROUGH BASE EDITINGJANUARY 2024 NASDAQ:BEAMCautionary note regarding forward-looking statementsThis presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.Such forward-looking statements include stateme

2、nts regarding:the initiation,timing,progress and results of preclinical studies and research and development programs,including the initiation and progress of clinical trials,including our BEACON trial and our BEAM-201 trial;the advancement of our pipeline,including the advancement of BEAM-101,BEAM-

3、201,BEAM-301,BEAM-302,and additional liver programs in multiple preclinical studies;our current expectations and anticipated results of operations,including our expected use of capital;the sufficiency of our capital resources to fund operating expenses and capital expenditure requirements and the pe

4、riod in which such resources are expected to be available;the potential activities and benefits under license and collaboration agreements and the formation of new collaborations;and the therapeutic applications and potential of our technology,including our potential to develop life-long,curative,pr

5、ecision genetic medicines for patients through base editing,including potential safety advantages,all of which are subject to known and unknown important risks,uncertainties and other factors that may cause our actual results,performance or achievements,market trends,or industry results to differ ma

6、terially from those expressed or implied by such forward-looking statements.Therefore,any statements contained herein that are not statements of historical fact may be forward-looking statements and should be evaluated as such.Without limiting the foregoing,the words anticipate,expect,suggest,plan,v

7、ision,believe,intend,project,forecast,estimates,targets,projections,potential,should,could,would,may,might,will,and the negative thereof and similar words and expressions are intended to identify forward-looking statements.Each forward-looking statement is subject to important risks and uncertaintie

8、s that could cause actual results to differ materially from those expressed or implied in such statement,including,without limitation,risks and uncertainties related to:our ability to develop,obtain regulatory approval for,and commercialize our product candidates,which may take longer or cost more t

9、han planned;our ability to raise additional funding,which may not be available;our ability to obtain,maintain and enforce patent and other intellectual property protection for our product candidates;the potential impact of pandemics and other health emergencies,including their impact on the global s

10、upply chain;that preclinical testing of our product candidates and preliminary or interim data from preclinical studies and clinical trials may not be predictive of the results or success of ongoing or later clinical trials;that initiation and enrollment of our clinical trials may take longer than e

11、xpected;that our product candidates may experience manufacturing or supply interruptions or failures;risks related to competitive products;and the other risks and uncertainties identified under the headings Risk Factors Summary and Risk Factors and elsewhere in our annual report on Form 10-K for the

12、 year ended December 31,2022,our Quarterly Report on Form 10-Q for the quarter ended March 31,2023,our Quarterly Report on Form 10-Q for the quarter ended June 30,2023,and in any subsequent filings with the Securities and Exchange Commission(the SEC)which are available on the SECs website at www.sec

13、.gov.Additional information will be made available by our annual and quarterly reports and other filings that we make from time to time with the SEC.These forward-looking statements speak only as of the date of this presentation.Factors or events that could cause our actual results to differ may eme

14、rge from time to time,and it is not possible for us to predict all of them.We undertake no obligation to update any forward-looking statement,whether as a result of new information,future developments or otherwise,except as may be required by applicable law.2.OUR VISION IS TO PROVIDE LIFE-LONG CURES

15、 for patients suffering from serious diseasesPOTENTIAL FOR one-time,curative therapies GENE EDITING FOR rare and common diseases PLATFORM FOR rapidly-programmable precision medicines Base editing is an efficient,predictable and potentiallybest-in-class gene editing technology4NUCLEASE CRISPR,ZFN,TAL

16、ENsDouble-stranded breaks Lack of control of gene sequence outcomesPrecision targetingwith CRISPRBASE EDITING BEAM THERAPEUTICSEnzymatic base conversionHighly efficientwith predictable gene sequence outcomesPrecision targetingwith CRISPRA C G-G C A TA C G T C G C T T A T G C A TA-T G C A TA C G T C

17、T A T G C A TA C-A TA C G T C A A C-G C A Tetc-DeletionsA G C T InsertionsBase editing technology has multiple,highly versatile applications5CRISPR ProteinDeaminaseGuide RNAActivate expressionSilence proteinsCorrect mutationsMultiplex editsModify proteinsTurns on genes to restore or increase functio

18、nTurns off any gene with disease-causing activity Repairs the most common type of gene mutation,single base changesTargets multiple pathways simultaneously with high efficiencyChanges how proteins bind or signal without disrupting their functionBEAM-101Multiple at Beam and partnersBEAM-302,BEAM-301B

19、EAM-201ESCAPEPROGRAMSWe have built a comprehensive,fully-integrated platform for precision genetic medicinesGuide RNADesignProductionBase EditingA and C base editorsSingle and multiplexmRNADesignProductionCell TherapyEx vivoHSC and T cellsLNPIn vivoLiver,HSCs and other tissuesGMP ManufacturingExtern

20、al CDMOIn-house at NC facilityFULLY INTEGRATED TECHNOLOGY AND CAPABILITIESMODULAR PLATFORM FOR RAPID DEVELOPMENT OF NEW BASE EDITING PROGRAMS6Advancing a diversified pipeline into the clinic7PROGRAM/DISEASEDELIVERYEDITING APPROACHRESEARCHLEAD OPTIMIZATIONIND ENABLINGPHASE I/IIPIVOTALBEAM-101Sickle C

21、ell Disease(SCD)Ex vivoHSCActivation of fetal hemoglobin(HbF)ESCAPESickle Cell DiseaseBeta ThalassemiaEx vivoHSCMultiplex HbF edit+CD117 edit-antibody pair BEAM-302Alpha-1 Antitrypsin Deficiency(AATD)In vivoLNPCorrection of E342K mutationBEAM-301Glycogen Storage Disease 1a(GSD1a)In vivoLNPCorrection

22、 of R83C mutationBEAM-201T-cell Leukemia/Lymphoma(T-ALL/T-LL)and CD7+AMLEx vivoT cellsMultiplex silenced CD7 CAR-TPfizer collaboration targetIn vivo LNPUndisclosedApellis collaboration targetIn vivo LNPUndisclosedLNP=Lipid Nanoparticle;HSC=Hematopoietic Stem Cell;T-ALL/TLL=T-Cell Acute Lymphoblastic

23、 Leukemia/T-Cell Lymphoblastic Lymphoma;AML=Acute Myeloid Leukemia;ESCAPE:Engineered Stem Cell Antibody Paired Evasion Highly differentiated priority programs with significant value creation potential8Sickle Cell DiseaseAlpha-1 Antitrypsin Deficiency Best-in-class potential for BEAM-101 Increased pr

24、obability of technical success for ex vivo gene editing and HbF upregulation Validated FDA regulatory pathway ESCAPE has potential to eliminate chemotherapy from transplant,expanding reach of base editing to more patients Platform for future hematology pipeline Best-in-class potential for BEAM-302 I

25、ncreased probability of technical success forin vivo LNP gene editing in liver Potential for rapid clinical proof of concept(change in functional AAT and PiZ AAT levels)Clinical-stage AATD program with potential to be a one-time treatment that benefits both lung and liver disease Platform for future

26、 liver pipelineHEMATOLOGYLIVER GENETIC DISEASEAAT=Alpha-1 Antitrypsin protein2023 was a transformative year for CRISPR gene editing,for base editing,and for Beam92023Highlights GENE EDITINGFirst in vivo gene editing INDs cleared by FDAFirst in vivo liver base editing clinical data First CRISPR-based

27、 product approved for SCDBEAM First patients dosed with base edited therapies in U.S.in multiple trials BEAM-201 dosed Q3BEAM-101 dosed and engrafted Q4Lilly acquisition of Beams rights to Verve programsPrioritized portfolio to focus on core value drivers in SCD and AATDExpected cash runway into 202

28、72024 is expected to be a year of significant catalysts for Beam102024 Anticipated Catalysts BEAM-101SCDComplete sentinel dosing and initiate expansion dosing in first half of 2024 Present clinical data on multiple patients in second half of 2024ESCAPESCDInitiate Phase 1-enabling preclinical studies

29、 in 2024BEAM-302AATDFile BEAM-302 CTA ex-U.S.Initiate clinical trial for BEAM-302 ex-U.S.in first half of 2024*BEAM-301GSD1aSubmit U.S.IND application in first half of 2024BEAM-201T-ALL/T-LLPresent clinical data in second half of 2024*assuming CTA acceptanceWhat if we could develop better one-time t

30、herapies for patients with SCD?SICKLE CELL DISEASE11Wave 3:100,000Beams multi-wave strategy is focused on developing safer,more effective,and more accessible treatments for patients with SCD12Eligible SCD Patient Population(U.S.)Wave 2:30-40,000Wave 1:10,000Wave 2 ESCAPE:Multiplex HbF edit+CD117 sel

31、ection editNon-genotoxic conditioning eliminates chemotherapy and broadens patient population for ex vivo gene therapyBroader range of disease severityIncreased willingness-to-treatWider age rangeWave 1 BEAM-101:Precise HbF upregulationPotentially best-in-class gene editing Non-cutting,non-viral the

32、rapy with busulfan conditioning to address severe SCD with high vaso-occlusive crisis(VOC)burdenWave 3 In vivo:Base editing with HSC-targeted LNPsIn vivo delivery would overcome need for transplantation,lower infrastructure requirements and unlock wider patient access and geographiesSource:Internal

33、Beam estimatesBEAM-101:Designed to be best-in-class genetic medicine for SCD13BEAM-101 PotentialSCD PatientHBBHBG1HBG2HBBHBG1HBG2Mutated hemoglobin gene(HBB)Direct reactivation of HbF genesHemoglobin genesSCD Unmet Need Sickle cell hemoglobin(HbS)polymerization is root cause of sickle cell pathophys

34、iology Affects millions of people worldwide and 100K in U.S.Median survival in the U.S.is 20 years shorterCurrent Available Treatments Disease-modifying therapies require ongoing treatment and do not prevent organ dysfunction Recently approved gene therapies reduce VOCs but residual HbS 50%suggests

35、room for improvementBEAM-101 Potential Precision editing without requirement of double-stranded DNA breaks or viral insertion More efficient editing leading to greater and more uniform induction of HbF and reduction of HbS and normalization of hemoglobin Investment in wholly owned manufacturing and

36、improved process and patient experienceHemoglobin expressionExpression of sickle-causing hemoglobinHbF expressed and HbS decreasedHbSHbFRBCs form and function normallyRBCs sickle and polymerize with hypoxiaImpact on red blood cells(RBCs)CDC Data&Statistics;Lancet Haematol 2023;10:e58599;DeBaun et al

37、.Blood.2019 Feb 7;133(6):615-617Precise,single base editing without need for double-stranded breaks or viral insertion results in highest editing efficiency in pre-clinical modelsBEAM-101:Potential for highest HbF induction and lowest residual HbS levels versus other approaches in the field14Preclin

38、ical data presented at ASGCT 2020;Edited human HSPCs analyzed 16 weeks after infusion in NBSGW mice(MeanSEM,n=4-6);1.Sorted human Lineage-CD34+bulk bone marrow;2.Sorted erythroid cells(GlyA+)00708090100UneditedEdited-globin/Total-like globins(%)00708090100UneditedEditedS-globin

39、/Total-like globins(%)Base editing at HBG1/2 promoters1HbF protein levels200708090100UneditedEditedBase Editing(%)HbS protein levels290%65%95%of severe AATD population that typically develop progressive lung and/or liver disease 100,000 PiZZ individuals in the U.S.;10%diagnosedCurrent Ava

40、ilable Treatments Lung disease:Medications for emphysema and possible weekly IV plasma-derived AAT(augmentation);lung transplant considered for severely affected patients Liver disease:Supportive care;liver transplant considered for end-stage diseaseBEAM-302 Potential One-time therapy that addresses

41、 both lung and liver disease,with corrected gene under normal regulation Reduction of mutant PiZ AAT in liver and restored circulating functional AATLiverLungAlpha-1 Antitrypsin(AAT)deficiency:SERPINA1 mutation(PiZZ)Mutant PiZ AAT aggregates in liver causing damageLack of AAT secretionleads to lung

42、damageAmerican Thoracic Society/European Respiratory Society statement:standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency Am J Respir Crit Care Med,200319Normal AAT:Wildtype SERPINA1 AAT protein is secreted from liver,protecting lungsBEAM-302:Corrected the

43、PiZ mutation and restored functional AAT with a single dose in AATD mouse model20Liver editing correlated with increased corrected serum AAT and decreased mutant PiZ AAT,at or below 0.75mpkLiver EditingSerum AAT LevelsVehicle0.1mpk0.25mpk0.5mpk0.75mpk1mpk050100150%Serum AAT isoformCorrected AATPiZ A

44、AT0.9%saline0.1mpk0.25mpk0.5mpk0.75mpk1mpk020406080Editing efficiency(%)Additional base-edited allelesCorrected allelesIndels10.928.037.348.749.2BEAM-302:Phase 1/2 trial designed to achieve clinical proof-of-concept in patients across the spectrum of AATD Opportunity to achieve first ever clinical p

45、roof-of-concept of in vivo base editing leading to correction of a disease-causal mutation CTA submitted to UK;additional filings to followPart A:AATD-associated Lung DiseasePart B:AATD-associated Lung and/or Liver DiseaseAssess early safety and efficacy and identify optimal dose for pivotal studyUp

46、 to 4 dose cohortsPatients included with mild to moderate liver diseaseUp to 4 dose cohortsPatients excluded with liver diseaseInitiate Phase 1/2 trial ex-U.S.in first half of 2024Dose ExplorationDose ExpansionDose ExplorationDose Expansion21Chou&Mansfield.2007.Curr.Gen.Ther.;Internal Beam estimates

47、 Wildtype G6PC geneG6PC R83C mutationBEAM-301:Aims to normalize glycogen metabolism in patients with GSD1a to prevent hypoglycemia and other disease manifestationsLiverUnmet Need in GSD1a Patients with Severe R83C Mutation:Inability to convert glycogen back to glucose to sustain blood sugar while fa

48、stingPatients at constant risk of hypoglycemia that can result in seizures,coma or deathEstimated 300 R83C patients in U.S.based on updated epidemiologyCurrent Standard of Care:Liquid cornstarch supplementation every 2-4 hours,even throughout the nightBEAM-301 Potential:Correct liver G6PC mutation t

49、o restore enzyme activity and enable normal glucose homeostasis,as well as eliminate chronic cornstarch supplementationAnimal studies suggest 11%editing sufficient for restoring fasting glucose and metabolic profileNon-functional G6PaseGlycogenGlucoseGlucose-6-phosphatePyruvateAcetyl-CoAFatty acids,

50、triglyceridesXX22U.S.IND filing expected in first half 2024BEAM-301:Treatment with a single dose significantly improved long-term survival in GSD1a mouse model23 Preclinical studies of BEAM-301 demonstrated a single dose significantly improved long-term survival out to a year in humanized R83C homoz

51、ygous mice Untreated homozygous R83C mice die within weeks of birth Given its rare nature and geographic distribution of patients,Beam will initially focus development of BEAM-301 in the U.S.0Probability of Survival20406080501x dose BEAM-301wild-typeUntreatedTime(weeks)0Creative pipeline

52、and platform partnerships unlock additional value and broaden therapeutic impact24Strategic Deals resulting in$675M upfront and more than$1B in potential milestonesInnovator Dealsgaining rights to innovative and complementary technologies$300M upfront for 3 base editing targets Beam option at end of

53、 Phase 1/2 for 35%WW cost/profit split on 1 program$75M upfront for base editing for complement-mediated diseases Beam option at end of Phase 1 for 50%of U.S.rights on one program$50M upfront for non-exclusive license to Cas12b nuclease for certain engineered cell therapies$250M in upfront/equity pl

54、us up to$350M in potential development-stage payments to acquire Beams cost/profit split options in 3 Verve cardiovascular programs Prime editing(PE)technology is complementary to base editing Beam exclusive PE rights for all A-G and C-T edits plus any edit for SCD Next-gen RNA and delivery technolo

55、gies Beam equity stake in Orbital plus IP access in gene editing and other fields2024 is expected to be a year of significant catalysts for Beam252024 Anticipated Catalysts BEAM-101SCDComplete sentinel dosing and initiate expansion dosing in first half of 2024 Present clinical data on multiple patie

56、nts in second half of 2024ESCAPESCDInitiate Phase 1-enabling preclinical studies in 2024BEAM-302AATDFile BEAM-302 CTA ex-U.S.Initiate clinical trial for BEAM-302 ex-U.S.in first half of 2024*BEAM-301GSD1aSubmit U.S.IND application in first half of 2024BEAM-201T-ALL/T-LLPresent clinical data in second half of 2024*assuming CTA acceptanceTHANK YOUJ.P.MORGAN HEALTHCARE CONFERENCE JANUARY 2024