BIOHAVEN JPM 2025JAN12 FINAL.pdf

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1、 2025 Biohaven,Ltd.All rights reserved.43rd Annual J.P.Morgan Healthcare ConferenceJanuary 13,2025Vlad Coric,M.D.Chairman and Chief Executive OfficerJENNIFER Living with SCA3Participant in the Troriluzole Clinical Study Forward-Looking StatementThis presentation includes forward-looking statements w

2、ithin the meaning of the Private Securities Litigation Reform Act of 1995,including statements about Biohaven Ltd.(the“Company”)and our planned and ongoing clinical trials for our taldefgrobep alfa,troriluzole,BHV-2100,BHV-7000,BHV-8000,BHV-1300,BHV-1310,BHV-1510 and BHV-1530 development programs,th

3、e timing of and the availability of data from our clinical trials,the timing and our decisions to proceed with our planned regulatory filings,the timing of and our ability to obtain regulatory approvals for our product candidates,the clinical potential utility of our product candidates,alone and as

4、compared to other existing potential treatment options,and the potential advancement of our early phase programs including BHV-1400,BHV-1500,and BHV-1600.The use of certain words,including“continue”,“plan”,“will”,“believe”,“may”,“expect”,“anticipate”and similar expressions,is intended to identify fo

5、rward-looking statements.Investors are cautioned that any forward-looking statements,including statements regarding the future development,timing and potential marketing approval and commercialization of our development candidates,are not guarantees of future performance or results and involve subst

6、antial risks and uncertainties.Actual results,developments and events may differ materially from those in the forward-looking statements as a result of various factors including:the expected timing,commencement and outcomes of Biohavens planned and ongoing clinical trials;the timing of planned inter

7、actions and filings with the Food and Drug Administration;the timing and outcome of expected regulatory filings;complying with applicable US regulatory requirements;the potential commercialization of Biohavens product candidates;the potential for Biohavens product candidates to be first-in-class or

8、best-in-class therapies;and the effectiveness and safety of Biohavens product candidates.You should,therefore,not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation.Additional important factors to be considered in connection

9、with forward-looking statements are described in the Companys filings with the Securities and Exchange Commission,including within the sections titled“Risk Factors”and“Managements Discussion and Analysis of Financial Condition and Results of Operations”.This presentation also contains market data an

10、d other information based on industry publications,reports by market research firms or published independent sources.Some market data and information is also based on the Companys good faith estimates,which are derived from managements knowledge of its industry and such independent sources referred

11、to above.January 13,2025J.P.Morgan Healthcare Conference2IntegratedDISCOVERY ENGINEADVANCING CANCER TREATMENTSwith strategic partnershipsPIONEERING therapies for rare diseases including SMA&SCAFocused on Days MatterCOMMERCIALIZATION OF NOVEL TXs POSITIONED FOR FUTURE VALUE CREATIONDIVERSIFIED into t

12、op areas of INNOVATIONINCREASED MARKET CAP 10XTWO YEARSSINCE SPIN-OFFCLINICALLY VALIDATEDNEXT-GEN TRAPDEGRADERS Targeted removal of aberrant proteinsRARE DISEASERENALCARDIOVASCULARONCOLOGYOBESITYNEUROLOGYIMMUNOLOGY&INFLAMMATIONARIA,Amyloid-related imaging abnormalities;AAb,Autoantibody.PRECLINICALPH

13、ASE 1PHASE 2PHASE 3MARKETGLUTAMATETroriluzoleBHV-4157Spinocerebellar AtaxiaObsessive-Compulsive DisorderMYOSTATINTaldefgrobep AlfaBHV-2000Spinal Muscular AtrophyObesityION CHANNELKv7 ActivatorBHV-7000Focal EpilepsyGeneralized EpilepsyBipolar Disorder Major Depressive Disorder TRPM3 AntagonistBHV-210

14、0Migraine&Pain DisordersINFLAMMATION&IMMUNOLOGYTYK2/JAK1 Inhibitor(brain-penetrant)BHV-8000Prevention of Amyloid Therapy Induced ARIAParkinsons Disease Alzheimers DiseaseMultiple SclerosisIgG DegraderBHV-1300Common Disease(Graves,RA)BHV-1310Rare Disease(Myasthenia Gravis)Gd-IgA1 DegraderBHV-1400IgA

15、Nephropathy1AR AAb DegraderBHV-1600Peripartum CardiomyopathyONCOLOGYTrop2 ADC+/-PD1BHV-1510Advanced or Metastatic Epithelial TumorsFGFR3 ADCBHV-1530Urothelial CancerCD30 ADCBHV-1500Hodgkin LymphomaUndisclosed TargetsMerus and GeneQuantum CollaborationsDEGRADATION TARGETBIFUNCTIONAL MoDE DEGRADERASGP

16、R RECEPTOR ON HEPATOCYTEEXTRACELLULAR DEGRADERSRAPID AND SELECTIVE REMOVAL OF DISEASE-CAUSING PROTEINSJanuary 2025J.P.Morgan Healthcare Conference6DEGRADERSMoDE Platform:Degraders Designed for Real-life and to Preserve Healthy Immune Functioning Maximizes selectivity to treat disease while minimizin

17、g side effects Short half-life enables concomitant administration with Fc-biologics Allows for subcutaneous and autoinjector formulationsAdvancing Next-Generation TRAP(Targeted Removal of Aberrant Proteins)Degraders:Only degrades specific disease-causing targets while leaving healthy immune system c

18、ompletely intact New Phase 1 clinical trial data demonstrates deep,rapid,and selective lowering of very specific targeted species3 Exciting New IndicationsIgA Nephropathy|Peripartum Cardiomyopathy|Graves Disease Emerging clinical data with BHV-1400 shows rapid,deep,and selective removal of only gala

19、ctose-deficient IgA1 while preserving healthy immune functionNEWSBREAKINGTSHR AUTOANTIBODY DEGRADERGraves diseasePLA2R AUTOANTIBODY DEGRADERMembranous nephropathy(MN)Other indicationsMoDEDegrader Platform1AR AUTOANTIBODY DEGRADERDilated cardiomyopathy(DCM)IgG4 DEGRADERMembranous nephropathy(MN)Pemph

20、igus vulgarisAutoimmune encephalitis(AE)Muscle-specific kinase(MuSK)myasthenia gravis(MG)Chronic inflammatory demyelinating polyneuropathy(CIDP)PROINSULIN AUTOANTIBODY DEGRADERDiabetes1AR AUTOANTIBODY DEGRADERPeripartum cardiomyopathy(PPCM)Gd-IgA1 DEGRADERIgA VasculitisIgG DEGRADERMyasthenia gravis(

21、MG)IgG DEGRADERRheumatoid arthritis(RA)IgG DEGRADERGraves diseaseMoDE Degrader Platform Technology:Driving Toward Targeted Removal of Disease-Causing ProteinsJanuary 2025J.P.Morgan Healthcare Conference7Gd-IgA1 DEGRADERIgA NephropathyNext-Gen TRAP DegradersPATIENTCENTRICLIFEALTERINGFAST AND DEEPRemo

22、ves disease-causing proteins within hoursEASY-TO-USEEasy-to-use autoinjector for self-administrationAllows for concomitant use of biologicsTUNABLELevel of degradation carefully modulated by dose level and frequencyEmploys bodys natural mechanism for removal of senescent proteinsSELECTIVEDesigned to

23、target specific pathogenic species for maximal efficacy and minimal side effectsDegrader Platform TechnologyIgA NEPHROPATHY BHV-1400:Potential to treat by removing pathogenic species without chronic immunosuppression Robust science indicating disease is galactose-deficient IgA1-driven Biomarker endp

24、oint with well-established accelerated approval pathwayJanuary 2025J.P.Morgan Healthcare Conference9BHV-1400IgA Nephropathy Is Caused by Excess Production of Galactose-Deficient IgA1(Gd-IgA1)January 2025J.P.Morgan Healthcare Conference10Gd-IgA1 immune complexes deposit into the kidney,recruiting imm

25、une cells and causing the release of pro-inflammatory and profibrotic mediatorsNo therapy selectively targets the pathogenic nidus of disease,Gd-IgA1.UNTIL NOWKEY POINTS Y S T E M I C C I R C U L AT I O NAberrant form of immunoglobulin,galactose-deficient IgA1 forms in excess Immunoglobulin(IgG or I

26、gA)target Gd-IgA1 to form circulating immune complexesG d-I g A 1I g GR E N A L C O R P U S C L EBHV-1400 Rapidly Removes Galactose-Deficient IgA1 from Circulation and from the Renal Glomerular Mesangium in vivo in Pre-Clinical StudiesJanuary 2025J.P.Morgan Healthcare Conference11BHV-1400 Rapidly Cl

27、ears Galactose-Deficient IgA11 HOUR6 HOURGd-IgA1+VehicleGd-IgA1+BHV-1400R E N A L C O R P U S C L EIn the Absence of BHV-1400,Galactose-Deficient IgA1(red)Accumulates in the Renal GlomerulusPreliminary Phase 1:Selective and Deep Removal of Gd-IgA1 Within HoursJanuary 2025J.P.Morgan Healthcare Confer

28、ence12BHV-1400 at the lowest SAD cohort rapidly and selectively removes 60%of Gd-IgA1 while preserving normal immunoglobulins(IgG,IgE,IgA,IgM)NEWSBREAKING-80-60-40-200Hours Post Dose 04824487296Gd-IgA1%Change from BaselineBHV-1400 125 mg Single doseIgGIgAIgEIgMGd-IgA1 60%Gd-IgA1 LOWERING within 4 ho

29、ursBHV-1400 SELECTIVELY DEGRADES ONLY Gd-IgA1Targeting the pathogenesis of disease without immunosuppressionTARGET B CELLSwith global immunoglobulin suppressionPovetaciceptAtaciceptSibeprenlimabZigakibartFelzartamabBHV-1400:Selective Removal of Disease-Causing Gd-IgA1 without Immunosuppression Compa

30、red to Market CompetitorsJanuary 2025J.P.Morgan Healthcare Conference13IgDIgMIgEIgAIgGGd-IgA1 autoantibodyB C E L L SB C E L L SRavulizumab(Ultomiris)INHIBITS COMPLEMENTSYSTEMWith broad immunosuppressionFabhaltaRO7434656TARGETENDOTHELIN RECEPTORAstrasentanFilspariBROADIMMUNOSUPPRESSIONTarpeyoTRAP De

31、graderBHV-1400 Degrades Gd-IgA1 Rapidly:Timeline of Earliest Reported Gd-IgA1 Lowering Across Key Market CompetitionJanuary 2025J.P.Morgan Healthcare Conference14Lowest dose of BHV-1400 tested shows deep reductions of Gd-IgA1 within hoursKEY POINT1.Lowering numbers reported for the median from the f

32、irst and lowest BHV-1400 SAD cohort and for mean lowering for the highest dose SAD cohorts for Sibeprenlimab(12.0 mg/Kg)and Povetacicept(960 mg)2.Davies et al.A first-in-human,randomized study of the safety,pharmacokinetics and pharmacodynamics of povetacicept,an enhanced dual BAFF/APRIL antagonist,

33、in healthy adults.Clin Transl Sci.2024 Nov;17(11):e70055.doi:10.1111/cts.70055.PMID:39494621;PMCID:PMC11532938.3.Mathur et al.Safety,tolerability,pharmacokinetics,and pharmacodynamics of VIS649(sibeprenlimab),an APRIL-neutralizing IgG2 monoclonal antibody,in healthy volunteers.Kidney In Rep.2022 Feb

34、 8;7(5):993-1003.doi:10.1016/j.ekir.2022.01.1073.PMID:35570983;PMCID:PMC9091613.0200400600Time to Lowering Achieved(Hours)4 4 DAYS4 4 WEEKSPovetacicept210%10%Gd-IgA1 loweringSibeprenlimab360%$15B*Market Potential of Biohavens Degrader PlatformFUTURE DEGRADERSAND INDICATIONSIgG DEGRADERSGd-IgA1 DEGRA

35、DER1AR AUTOANTIBODY DEGRADERIgG4 DEGRADERPROINSULIN AUTOANTIBODY DEGRADERIgG DEGRADERSGd-IgA1 DEGRADERIgA NephropathyIgA Vasculitis1AR AUTOANTIBODY DEGRADERDilated cardiomyopathy(DCM)Peripartum cardiomyopathy(PPCM)*Biohaven Internal Analysis:Peak US Gross SalesAntibodyCancer cellMATEPayloadTargeted

36、cancer cell antigenOncology:Next-Generation ADCsNovel mAbs Validated and emerging targets Merus collaboration leverages differentiateddual-targeting antibody platformExclusivity to TopoIx payload Superior preclinical anti-PD/L1 synergy and immunogenic cell death GeneQuantum collaboration provides br

37、oad target exclusivity to the payloadfor 18 oncology targetsSingle-step chemistry,native mAbsModular,efficient,and scalable MATE technologydeveloped from Yale University Spiegel LabIrreversible,Site-Specific ConjugationMinimize payload-associated tox,DAR homogeneityCombination I/O Therapies Supply a

38、greement:BHV-1510 with LibtayoBiohavens Novel ADC Conjugation Technology and Strategic Collaborations Driving Next-Generation Cancer Therapies Collaborate to generate highly differentiated ADCsJ.P.Morgan Healthcare Conference29January 13,2025BHV-1510(Trop2 TopoIx)in Phase 1(mono and anti-PD1 combina

39、tion)MULTIPLE DC/INDs planned 20252026Novel ADCs and De-Risked Fast-Followers in Clinic BHV-1500(CD30 MMAE)IND planned 2025BHV-1530(FGFR3 TopoIx)in Phase 1 startup FPI early 2025Broad and flexible platform applicabilitySTRATEGIC COLLABORATIONS AND CLINICAL SUPPLY AGREEMENTSBHV-1510 is a Highly Diffe

40、rentiated Trop2 ADCIdeally positioned for fast-to-market strategy with anti-PD-1 comboNovel TopoIx Payload Synergy with Anti-PD-1 In VivoInduces immunogenic cell death and complete tumor regressionsSuperior to datopotamab deruxtecan(DS-1062)plus anti-PD-1Fully Optimized Next-generation ADC Novel and

41、 highly stable linker-payload(DAR4)Differentiated Pre-clinical Safety Profile Datopotamab deruxtecan(DS-1062):interstitial lung disease(ILD)Sacituzumab tirumotecan(MK2870/SKB264):hematological toxicitiesTRODELVY:neutropenia,diarrheaMilestones AchievedFirst-in-human trial initiated April 2024Anti-PD-

42、1 combo cohorts with Libtayo initiated 4Q 2024J.P.Morgan Healthcare Conference30BHV-1510TROP2 ADC Clinical activity and no ILD with TopoIx observed in early cohorts Target exclusivity expanded for up to 18 ADC targets incorporating TopoIx payload NEWSBREAKINGJanuary 13,2025BHV-1510(Trop2 ADC with To

43、polx)with Early Clinical Activity in Phase 1 Clinical activity across doses starting at the lowest dose(2 mg/kg,Q3W)Tumor reduction observed in tumor types including ovarian,SCLC,NSCLC Favorable preliminary safety and PK profile No payload-associated ILD,diarrhea,or significant hematological toxicit

44、y Main toxicity observed is on-target Trop2 ADC class mucositis;an expected and manageable effect Very low free payload in serum,demonstrates high ADC stability Dose escalation(mono and Libtayo combo)and dose/schedule optimization ongoingJanuary 13,2025J.P.Morgan Healthcare Conference31Observed clin

45、ical activity and safety supports broad investigation of ADCs incorporating novel TopoIx payload and highly stable linker KEY POINTCase 1:71 y/o,Platinum-resistant ovarian cancer,2 mg/kg,Q3W25%tumor reduction at week 18 with dramatic drop in CA-125BaselineWeek 18BaselineWeek 12Case 2:70 y/o,SCLC pos

46、t carboplatin+durvalumab and lurbinectedin,4 mg/kg Q3WPR(60%reduction)at week 12TopoIx Payload Is a Novel Topoisomerase 1 InhibitorWith a Superior Pre-clinical Profile Compared to DXd and SN-38January 13,2025J.P.Morgan Healthcare Conference32SN-38DXdTopoIxIn vitro cytotoxicity+ICD*+Transported by AB

47、CG2n/aYNBystander killingn/a+In vivo efficacy+Superior Pre-clinical ProfileSuperior Immunogenic Cell DeathSynergy with anti-PD1 CombinationBiohaven retains broad target exclusivity with GeneQuantum for up to 18 ADC targets incorporating TopoIx to leverage unique profile as monotherapy and in anti-PD

48、1-based combinationsKEY POINTAdvancing TopoIx Payload in Next-Gen ADC to Target Urothelial Cancer and Other Solid TumorsNovel and proprietary FGFR3 mAbEnzymatic,site-specific conjugationFavorable nonclinical tox profileValidated target with limited competitionNo ADCs approved or in advanced developm

49、entCore opportunity in FGFR3-altered metastatic urothelial cancer(mUC)only 1 Tyrosine Kinase Inhibitor approvedPotential extension into other FGFR3-driven solid tumors$400M to$1B peak US gross sales potentialSynergistic Efficacy With Checkpoint Inhibitors In VivoBHV-1530/anti-PDL1 combination showed

50、 synergy similar to BHV-1510PD1 synergy with PADCEV(Nectin-4 ADC with MMAE payload)showed dramatically improved survival in mUC Milestones AchievedUS FDA IND May Proceed Letter grantedJ.P.Morgan Healthcare Conference33BHV-1530CLINIC-READY FGFR3 ADCFirst-in-Human study planned to initiate in 1H 2025N

51、EWSBREAKINGJanuary 13,2025Probability of Survival(%)Days after cell implantationBHV-1530:Potential to Address Unmet Need in Metastatic Urothelial Cancer(mUC)and other FGFR3-driven TumorsBHV-1530 shows synergistic activity in vivo with anti-PD-L1 combinationG1.vehicle G2.anti-PD-L1 G3.BHV-1530 G4.BHV

52、-1530+anti-PD-L1hFGR3-GL261Group%Increased Life Span(ILS)Median Survival(days)G1-15G227%19G3107%31G4300%63J.P.Morgan Healthcare Conference34January 13,202562K new mUC cases,14K deaths/year in US(2023)Multiple opportunities for BHV-1530 across therapy linesSynergistic CPI combinations in FGFR3+biomar

53、ker-selected 1LLimited efficacy of current 2L optionsSeveral tumor types beyond mUC also driven by FGFR3FGFR3 mutation/fusion in 20%mUCFGFR3 overexpression 35%mUCFGFR3 overexpression,mutation,or fusion leads to excessive pathway activation and increased tumorigenicityA leader in developing different

54、iated bispecificmAbs for oncologyClinically validated platformLead program(Zenocutuzumab)granted US FDA accelerated approval in December 2024Next-generation ADC conjugation and payloadplatform technologiesBiohaven-Merus Collaboration Represents a Leading-Edge Approach to Developing Highly Optimized

55、Bispecific ADCsJ.P.Morgan Healthcare Conference35January 13,2025Multi-target collaboration,leveraging each companys innovative tech for ADC co-developmentNEWSBREAKINGPotential advantages of dual-target bispecific ADCsPreferential bindingImproved internalizationOptimal tumor penetrationMultiple MOA o

56、f tumor cell killingPotential for superior specificity andbenefit/risk profile vs.single target ADCsCo-development maximizesexpertise and efficienciesBHV-7000 Kv7.2/7.3 ActivatorPotassium(K+)Ion ChannelIon Channel PlatformsBHV-7000,Potential Best-in-Clinic Selective Kv7 Activator,Nears Completion of

57、 Pivotal Trials with Blockbuster PotentialJanuary 13,2025J.P.Morgan Healthcare Conference37Epilepsy3.5M PatientsClinically validated MOA for epilepsyGlobal Phase 2/3 program ongoing in focal epilepsy(2 trials)and idiopathic generalized epilepsy(1 trial)Major Depressive Disorder21M PatientsClinically

58、 validated MOA for MDDDifferentiated profile vs.SSRIsBipolar Disorder7M PatientsNovel MOA for bipolar disorderDifferentiated profile vs.antipsychotics,lithium,and ASMsAcute bipolar mania topline results expected in 1H 2025Topline results expected in 2H 20251st focal epilepsy study topline results ex

59、pected in 1H 2026Pivotal topline results for BHV-7000 development program expected withinthe next yearNEWSBREAKINGBHV-2100:Proof of Concept Pain Study Demonstrates AntiNociceptive and AntiHyperalgesic EffectsEfficacyLowering in self-reported VAS pain rating scaleClinically meaningful reductions in l

60、aser-evoked potentials in normal and UVB-inflamed skinSafetyWell-toleratedNo effects observed on core temperatureNo change on heat pain thresholdJanuary 13,2025J.P.Morgan Healthcare Conference384647484950515253545556575801:0002:0003:0004:00Visual Analog Scale(VAS)Time(hours)BHV-2100 150mgPlaceboLase

61、r-Induced Paradigmp 0.05Preliminary Data up to Tmax;p-value out to 8 hour test period First indication of potential clinical efficacy in pain with the novel TRPM3 mechanismKEY POINTLASER STIMULATION AND EVALUATION UNITPain ScorePRESYNAPTIC NEURONPOSTSYNAPTIC NEURONGLUTAMATETRORILUZOLETroriluzole SCA

62、January 13,2025J.P.Morgan Healthcare Conference40TRORILUZOLEGLUTAMATE MODULATOR Submitted NDA for treatment of all SCA genotypes(potential Priority Review)Preparing for commercial launch in 2025NEWSBREAKINGTroriluzole Is First Treatment to Slow SCA Disease ProgressionLong-term RWE study confirmed be

63、nefit over 3 years in all SCA genotypesSCA Represents Significant Commercial OpportunityEst.15,000 patients in the US and 24,000 in UK and EUNo currently approved SCA treatmentsMilestones AchievedSubmitted NDA after pre-NDA meeting in 4Q 2024(potential Priority Review)EMA MAA for all SCA genotypes u

64、nder reviewBiohaven Pioneered Clinical Trials for Spinocerebellar Ataxia0.00.51.01.52.02.50123f-SARA(SE)Years*TROUS1012029017775656143*1.5 yeardelay in progression*p-values .05TroriluzoleCRC-SCACRC-SCA,Clinical Research Consortium for SCA;EUROSCA,European registry of SCA;f-SARA,Functional Scale for

65、the Assessment and Rating of Ataxia;LSM,least squares mean;PSM,Propensity Score MatchingBHV-8000January 13,2025J.P.Morgan Healthcare Conference42BHV-8000TYK2/JAK1 INHIBITOR(brain-penetrant)First-in-Clinic,Oral,Selective,Brain-Penetrant TYK2/JAK1 InhibitorUniquely potent,TYK2/JAK1 selective,brain-pen

66、etrant inhibitorSelectivity profile avoids class risks associated with JAK2/3 inhibitionBreaks the Cycle of NeuroinflammationReduces inflammatory impacts of microglia,astrocytes and infiltrating T-lymphocytesPotential to Treat Multiple Neuroinflammatory DisordersSupported by a broad range of clinica

67、l,translational,and epidemiological evidenceIndications include Parkinsons disease,anti-amyloid therapy induced ARIA,Alzheimers disease,and multiple sclerosisEncouraging Results from Completed Phase 1 TrialSafe and well-tolerated Evidence of target engagementRobust brain penetrationMilestone Achieve

68、dFDA meetings successfully completed enabling registrational programs for Parkinsons disease and prevention of ARIAPivotal study in Parkinsons disease planned to initiate in 1H 2025NEWSBREAKINGARIA,Amyloid-related imaging abnormalities;SAD,single ascending dose;MAD,multiple ascending dose;TYK,tyrosi

69、ne kinase;JAK,Janus kinase.Real-World Analytics of Large Healthcare Database ShowParkinsons Disease Risk Reduction With TNF/IL-17 Targeting Therapies Biohaven conducted analysis using Komodo Health database(over 320 million patients since 2012)examining treatment with anti-TNF or anti-IL17 and incid

70、ence of PD Millions of patients over 8+years of dosing captured key epidemiologic confirmation of the neuroinflammatory hypothesis Results support rationale for the effectiveness of BHV-8000 in treating PDTreatmentPD EventsPerson-yearsRate(per 100 person-years)Adjusted IRR(95%CI)P-valueAnti-TNF or A

71、nti-IL-17 exposure2,957393,1140.660.77(0.74 0.80)0.0001No Treatment50,5625,328,3070.95Anti-TNF exposure2,471371,8670.660.64(0.52 0.80)0.0001 No Treatment50,5625,328,3070.95Anti-IL-17 exposure8115,5980.520.77(0.78 0.81)0.0001 No Treatment50,5625,328,3070.95IRR,incidence rate ratio;TNF,tumor necrosis

72、factor.January 13,2025J.P.Morgan Healthcare Conference43BHV-8000 Demonstrates a Promising Phase 1 ProfileSTUDY COMPLETED:3 SAD cohorts and 3 MAD cohorts SAD dose cohorts(10,20 and 30 mg);MAD dose cohorts(6,10 and 20 mg)8 healthy subjects per cohort(6 active:2 placebo)SAFETY PROFILE:Safe and well-tol

73、erated to date No SAEs or severe AEs;only mild AEs observed that resolved spontaneously No adverse laboratory trends related to study drugPHARMACODYNAMIC EFFECTShs-CRP,IFN-beta,and IP-10 showed drug-related changes in plasmaPHARMACOKINETICSApproximately 50%CNS penetration in humansJanuary 13,2025J.P

74、.Morgan Healthcare Conference44AE,adverse event;hs-CRP,high-sensitivity C-reactive protein;IFN-beta,Interferon beta;MAD,multiple ascending dose;SAD,single ascending dose;SAE,serious adverse event.BHV-8000 is safe and well-tolerated at doses showing evidence of CSF penetration and target engagementKE

75、Y POINTProvides a highly-sensitive supportive secondary efficacy endpointNovel Composite EndpointParkinsons Disease Composite Score(PARCOMS)Based on established methodology(i.e.,Alzheimers Disease Composite Score ADCOMS)Leverages PPMI and placebo-arm clinical trial data(C-Path)Comprises the most res

76、ponsive items from common endpoints in early PD trialsBHV-8000:Unique Phase 2/3 Study Design for Parkinsons DiseaseNovel Primary Efficacy EndpointTime-to-event(2-point worsening on MDS-UPDRS-Part II)Addresses FDA requirement for a functional endpoint in PD trialsMDS-UPDRS-Part II recommended,but dec

77、lines very slowly in early PD 300 fewer patients per trial versus a mean change on MDS-UPDRS-Part II Based on comprehensive analyses of PPMI and placebo-arm clinical trial data(C-Path)Provides a meaningful efficacy endpoint with a smaller sample sizePPMI,Parkinsons Progression Markers Initiative;MDS

78、-UPDRS,Movement Disorder Society Unified Parkinsons Disease Rating Scale.January 13,2025J.P.Morgan Healthcare Conference45Pivotal study planned to initiate in 1H 2025NEWSBREAKING48-Week Time-to-eventBHV-8000 High Dose(n183)BHV-8000 Low Dose(n183)Placebo(n183)56-Days48-WeeksOLEScreeningTALDEFGROBEP/M

79、YOSTATIN COMPLEXACTIVIN TYPE II RECEPTORACTIVIN TYPE IRECEPTORSKELETAL MUSCLE CELL SURFACEMyostatin SMA and ObesityEfficacy Results:Clinically Meaningful Improvements Enhanced In Myostatin-Positive Caucasian ParticipantsADDITIONAL SUPPORTIVE DATAResponder Analysis*50%of taldefgrobep-treated particip

80、ants responded vs.30%on placeboOpen-label Extension*Motor function continues to improveTaldefgrobep Significantly Reduced Fat Mass Gain in SMA Participants While Increasing Lean Muscle Mass and Bone Density(vs.Placebo)DXA prespecified outcome measures in overall study population at Week 48 demonstra

81、ted:Greater reduction in percent change in total body fat mass(p=0.008)Numerically larger increases in lean muscle mass Numerically larger increases in bone densityJanuary 13,2025J.P.Morgan Healthcare Conference47LS,least squares;MFM-32,32-Item Motor Function Measure;SE,standard error*response defin

82、ed as 3-point change from baseline improvement on MFM-32 at Week 48 *Preliminary dataPlacebo adjusted difference similar to what was seen with other SMA therapy(risdiplam)in registrational SUNFISH trial;magnitude of effect appears addictive since added to SOCKEY POINTMFM-32 Total Score Change from B

83、aselineTaldefgrobep alfa(N=72)Placebo(N=51)LS Mean Change(+/-SE)WeeksTaldefgrobep alfaPlacebo725168516849705068500122436480123=1.4p=0.02Optimal Management of Obesity Remains a Critical Unmet Medical Need By 2030,1 billion people worldwide will be living with obesity,including 50%of American adults1

84、Obesity is a disease of excess and/or abnormal adipose tissue,not excess mass Incretin mimetics have revolutionized management of obesity,but present liabilities Up to 40%of total body weight loss is lean mass2 Gastrointestinal side effects3 Reduced bone mass4 Two-thirds stop GLP-1 therapy within 1

85、year5 Two-thirds of lost body weight returns within 1 year of stopping GLP-1 therapy5,6January 13,2025J.P.Morgan Healthcare Conference48Endocrine Diabetes mellitus Hypothyroidism SubfertilityGI Hiatus hernia Gallbladder disease Inguinal herniaCarcinoma Breast Colorectal EndometrialMusculoskeletal Os

86、teoarthritis Back painCardiovascular Sudden death Cardiomyopathy Hypertension Ischemic heart disease Peripheral vascular disease Deep vein thrombosis Pulmonary embolismRespiratory Restrictive lung disease Obstructive sleep apnea Obesity hypoventilation syndrome Difficult intubationGenitourinary Mens

87、trual problems Female incontinence Renal calculiComplications of Obesity71 https:/www.worldobesity.org/resources/resource-library/world-obesity-atlas-2022;Accessed 9-JAN-2025.2.Wilding JPH et al,N Engl J Med.2021;384(11):989-1002.3.Wilding,et.al.,Diabetes Obes Metab.2022;24(8):1553-64.doi:10.1111/do

88、m.14725 4.Hansen MS,et al.,eClinicalMedicine.2024;72:102624 5.Scientific American.What happens when you quit Ozempic or Wegovy?APR 2024.https:/ 9-JAN-2025.6.Sikirica MV.Et al.,Diabetes Metab Syndr Obes.2017;10:403-12.7.UpToDate.Overweight and obesity in adults:health consequences.https:/ 9-JAN-2025.

89、Taldefgrobep Phase 2 Study in ObesityDESIGNRandomized,double-blind,placebo-controlled trialPOPULATION Male and female adults living with overweight or obesity(BMI 27-40)without comorbid diabetes mellitusSAMPLE SIZE 80 participants randomized 1:1(Sex M/F and BMI$5.25B,subject to annual cap($400M/year

90、)1$642M3101.1M2CGRPPATIENTSPATIENTS 1 1INDICATIONGd-IgA1 Degrader 140K 140K IgA NEPHROPATHYRARE DISEASERENALCARDIOVASCULARONCOLOGYOBESITYNEUROLOGYIMMUNOLOGY&INFLAMMATION1AR Degrader 200K200K DCM/PERIPARTUM CARDIOMYOPATHYTrop2316K316K EPITHELIAL TUMORSCD3095K95K HODGKIN LYMPHOMATaldefgrobep Alfa10K 1

91、0K SPINAL MUSCULAR ATROPHY10M10M OBESITYTRPM3 Antagonist 40M40M MIGRAINE 10M10M PAINKv7 Activator 2.4M 2.4M FOCAL EPILEPSY7M7M BIPOLAR DISORDER1.1M1.1M GENERALIZED EPILEPSY21M 21M MAJOR DEPRESSIVE DISORDERTYK2/JAK10.5M0.5M EARLY PARKINSONS DISEASE3.5M3.5M ARIA PREVENTION3950K950K MULTIPLE SCLEROSIS3

92、.5M3.5M EARLY ALZHEIMERS DISEASE4IgG DegradersBiohavens pipeline working to help millions of patients 130K 130K mAB PARTIAL RESPONDER RA2100K 100K MYASTHENIA GRAVIS350K 350K ATD REFRACTORY GRAVES DISEASE2Troriluzole15K15K SPINOCEREBELLAR ATAXIA3.2M3.2M OBSESSIVE-COMPULSIVE DISORDERFGFR3118K118K mUC and SOLID TUMORSTop Areas of Innovation52