Vera+Tx_JPM+Jan+2025_vF2.pdf

《Vera+Tx_JPM+Jan+2025_vF2.pdf》由會員分享，可在線閱讀，更多相關《Vera+Tx_JPM+Jan+2025_vF2.pdf（26頁珍藏版）》請在三個皮匠報告上搜索。

1、 2025 VERA THERAPEUTICS,INC.J.P.Morgan Healthcare ConferenceJanuary 13,20252 2025 VERA THERAPEUTICS,INC.Forward-looking statementsDisclaimerThis material has been made available to you with the consent of Vera Therapeutics,Inc.(we,us,our,or the Company).Statements in this presentation that are not s

2、tatements of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.Such forward-looking statements include,without limitation,atacicepts potential to be a transformational treatment for patients with IgAN and a best-in-class and fir

3、st-in-class therapy,the Companys expectations regarding completing the pivotal Phase 3 ORIGIN 3 trial and the Phase 2 extension study in participants who completed the Phase 2b or Phase 3 ORIGIN trials,atacicepts potential to be a transformational treatment for additional patient cohorts beyond thos

4、e with IgAN,the Companys expectations regarding initiating clinical trials of atacicept for additional indications,the design and management of the Companys clinical trials,expectations regarding reporting results from such clinical trials and regulatory matters,including the timing and likelihood o

5、f success in obtaining drug approvals,atacicepts projected launch and Veras potential research and development plans for VT-109.Words such as“anticipate,”“plan,”“expect,”“will,”“may,”“potential”and similar expressions are intended to identify forward-looking statements,though not all forward-looking

6、 statements necessarily contain these identifying words.These forward-looking statements are based on the beliefs of the Companys management as well as assumptions made by and information currently available to the Company.Such statements reflect the current views of the Company with respect to futu

7、re events and are subject to known and unknown risks,including business,regulatory,economic and competitive risks,uncertainties,contingencies and assumptions about the Company,including,without limitation,risks related to the regulatory approval process,the potential that results of earlier clinical

8、 trials may not be obtained in later clinical trials,risks and uncertainties associated with the Companys business in general,the impact of macroeconomic and geopolitical events,and the other risks described in the Companys filings with the Securities and Exchange Commission.In light of these risks

9、and uncertainties,the events or circumstances referred to in the forward-looking statements may not occur.The actual results may vary from the anticipated results and the variations may be material.These forward-looking statements should not be taken as forecasts or promises nor should they be taken

10、 as implying any indication,assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or,in the case of the assumptions,fully stated in this presentation.You are cautioned not to place undue reliance on these forward-looking stateme

11、nts,which speak only as of the date of this presentation,and are based on managements assumptions and estimates as of such date.The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made,except as req

12、uired by law.Certain data in this presentation are based on cross-study comparisons and are not based on any head-to-head clinical trials.Cross-study comparisons are inherently limited and may suggest misleading similarities or differences.This presentation does not constitute an offer to sell or th

13、e solicitation of an offer to buy any securities,or a solicitation of any vote or approval,nor shall there be any sale of securities in any jurisdiction in which such offer,solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such jurisdictio

14、n.Investment in any securities described herein has not been approved or disapproved by the Securities and Exchange Commission or any other regulatory authority nor has any authority passed upon or endorsed the merits of the offering or the accuracy or adequacy of the information contained herein.An

15、y representation to the contrary is a criminal offense.This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S.Food and Drug Administration.No representation is made as to the safety or effectiveness of these product

16、candidates for the use for which such product candidates are being studied.The trademarks included herein are the property of the owners thereof and are used for reference purposes only.Such use should not be construed as an endorsement of such products.3 2025 VERA THERAPEUTICS,INC.eGFR normalizatio

17、n may suggest functional cure;FDA Breakthrough Therapy Designation awarded 2024 Only program with 2-year data in Phase 2 potential for commercial differentiation,if approved Only investigational drug with at home self admin of 1 mL SC QW and 90%patient retention at 2 years B cell modulation represen

18、ts a treatment paradigm shift for autoimmune diseases Progressive expansion in addressable patients:initial autoimmune kidney disease opportunity 200K Strong clinical potential in hematologic,rheumatologic,and other indications Currently$677M pro forma cash,cash equivalents and marketable securities

19、 as of September 30,20241 Management focused on potential for successful commercial launch Phase 3 read out on track for Q2 2025;if successful,anticipated PDUFA date 2026APRIL=A proliferation inducing ligand;BAFF=B cell activating factor;eGFR=estimated glomerular filtration rate;IgAN=immunoglobulin

20、A nephropathy;PDUFA=Prescription Drug User Fee Act;QW=once weekly;SC=subcutaneous.1.Includes$353M of cash,cash equivalents and marketable securities as of September 30,2024 and additional$324M in net proceeds from October 2024 follow-on equity offering.This estimate of the Companys cash,cash equival

21、ents and marketable securities as of September 30,2024 has not been audited.IgAN Potential Best-in-ClassPotential Indication ExpansionResourced for Potential LaunchAtacicept potentially first and best-in-class dual BAFF/APRIL B cell modulator in IgAN,with pipeline-in-a-product opportunity4 2025 VERA

22、 THERAPEUTICS,INC.Cumulative Atacicept data to date supports best-in-class potentialThis data is based on a cross-trial comparison and not a head-to-head clinical trial;such data may not be directly comparable due to differences in study protocols,conditions and patient populations.Atacicept 150 mg

23、data from Phase 2b ORIGIN trial shown for urine protein-creatinine ratio(UPCR),galactose-deficient immunoglobulin A1(Gd-IgA1),and hematuria.1.Phase 2 4 mg/kg IV Gd-IgA1 data from Mathur M,et al.NEJM 2023,Phase 2 4 mg/kg IV hematuria data from Barratt J,et al.WCN 2024,WCN24-AB-1799,Phase 2 pooled sib

24、eprenlimab UPCR data from Kooienga ASN 2022,TH-PO991,and eGFR data from Barratt J,et al.ASN 2023,abstr TH-PO1124;2.Phase 1b 80 mg data from Madan A,et al.ASN 2024,FR-PO854;3.Barratt J,et al.ASN 2024,FR-PO856.AtaciceptSibeprenlimab1Povetacicept2Zigakibart3MechanismBAFF/APRIL inhibitionAPRIL inhibitio

25、n onlyBAFF/APRIL inhibitionAPRIL inhibition onlyDosing&Administration25/75/150 mg SC QW(Phase 2)150 mg SC QW(Phase 3)1x1 mL self-administered2/4/8 mg/kg IV(Phase 2)400 mg SC QM(Phase 3)1x2 mL in-clinic injection80/240 mg SC QM(Phase 1b)80 mg SC QM(Phase 3)1xTBD mL in-clinic injection450 mg IV Q2W(Ph

26、ase 2)600 mg SC Q2W(Phase 3)2x2 mL in-clinic injectionDevelopment StagePhase 3Phase 3Phase 3Phase 3Randomized Controlled Trial DataGd-IgA1 Reduction64%at W36vs 7%placebo60%at W52vs+20%placeboNo placebocontrolled dataNo placebocontrolled dataHematuria80%resolution at W36Reductions at W36(nonquantifia

27、ble)Not reportedNot reportedUPCR Reductionvs Placebo 43%(p=0.003)at W36 43%at W36No placebocontrolled dataNo placebocontrolled dataeGFR Duration Data24 months,n=10212 months,n=14512 months,n=819 months,n=33Projected Commercial Launch20262026202720275 2025 VERA THERAPEUTICS,INC.$677MCash,cash equival

28、ents,and marketable securities(pro forma unaudited as of 9.30.24)163.4MShares outstanding(as of 11.21.24)Strong Financial Position1.Includes$353M of cash,cash equivalents and marketable securities as of September 30,2024 and additional$324M in net proceeds from October 2024 follow-on equity offering

29、.This estimate of the Companys cash,cash equivalents and marketable securities as of September 30,2024 has not been audited.6 2025 VERA THERAPEUTICS,INC.and Expanded IgANNon-IgAN autoimmunekidney disease PMN,FSGS,MCDVera optionality to expand in autoimmune kidney disease&beyondVera Therapeutics corp

30、orate estimates for peak year prevalence based on 1.ClearView Healthcare Partners Analysis;2.US Census 2023;3.McGrogan A.Nephrol Dial Transplant 2011;4.Couser ASN 2017;5.Beck LH.N Engl J Med 2009;6.Filler G.Am J Kidney Dis 2003;7.Troyanov S.J Am Soc Nephrol 2005.8.Hommos MS.Mayo Clin Proc 2017;9.Hen

31、gel FE.N Engl J Med 2024;10.Vivarelli M.Clin J Am Soc Nephrol 2017.PMN=primary membranous nephropathy;FSGS=focal segmental glomerulosclerosis;MCD=minimal change disease;ITP=immune thrombocytopenia;AIHA=autoimmune hemolytic anemia;CAD=cold agglutinin disease;APS=antiphospholipid syndrome;SLE=systemic

32、 lupus erythematosus;COVID=Coronavirus disease 2019;MG=myasthenia gravis;DM=diabetes mellitus.BAFF/APRILinhibition+70K1-10230K160K1US prevalence estimatesPotential Future IndicationsHematology ITP,AIHA,CAD,APSRheumatology SLE,Sjogrens,Long COVID Neurology MG Metabolism DM Type 17 2025 VERA THERAPEUT

33、ICS,INC.Atacicept Projected CatalystsBased on managements current assumptions.1.Subject to US approval.Catalyst20252026IgANPhase 3 full enrollmentPhase 3 primary endpointBLA submissionProjected US launch1IgANInitial dataIgAN,PMN,FSGS,MCDInitiationInitial dataVera holds worldwide,exclusive rights to

34、develop and commercialize atacicept2Q2H2Q8 2025 VERA THERAPEUTICS,INC.Dual BAFF/APRIL inhibition has broad therapeutic potential to address multiple autoimmune diseasesImmunity in healthAntibodies bind to foreign antigensAutoimmune diseaseAutoantibodies bind to autoantigensB cellBAFFAPRILB cellBAFFA

35、PRILAtacicept:Rationally designed therapeutic of modern biotechnology that binds BAFF and APRIL with nanomolar potency offers the promise of precision modulation of B cells and autoantibodiesB cells source of autoantibodies target cell of interest for therapeutic interventionAutoantigens and autoant

36、ibodies mediate autoimmune diseaseB cells fueled by two cytokines,BAFF and APRIL9 2025 VERA THERAPEUTICS,INC.Atacicept is an example of rational drug designFc=fragment crystallizable;IgG1=immunoglobulin G1;Kd=dissociation constant;TACI=transmembrane activator and calcium-modulator and cyclophilin li

37、gand.1.Willen D,et al.Eur J Drug Metab Pharmacokinet 2020;45(1):27-40;2.Vera data on file.TACI receptorBAFFAPRILBAFFAPRILKd1.45 nM2Kd0.672 nM2AtaciceptTACIreceptorFc domainof IgG1t1/2=35 days1Native TACI-Fc fusion:Soluble protein binds both BAFF and APRIL with nanomolar potencyB cellB cell10 2025 VE

38、RA THERAPEUTICS,INC.ORIGIN Phase 2b long-term data revealed in late breaking oral presentation at ASN Kidney Week and JASN manuscriptET=end of treatment;RAASi=renin-angiotensin-aldosterone system inhibitor;SGLT2i=sodium-glucose cotransporter-2 inhibitor.Week 0241 Endpoint362 EndpointAtacicept 150 mg

39、 QWn=30Atacicept 75 mg QWn=30Atacicept 25 mg QWn=15Placebon=30Atacicept 150 mg QWDouble-Blind TreatmentOpen-label Extension96EndpointsPrimary efficacy:UPCR-24h at week 24Key secondary:UPCR-24h at week 36eGFR change up to week 96Gd-IgA1 changeHematuria changeSafetyInclusion CriteriaParticipants 18 ye

40、ars old with biopsy-proven IgAN and high risk of disease progressionStable and optimized RAASi for 12 weeksUse of SGLT2i allowedUPCR-24h 0.75 g/g or UP 0.75 g per 24heGFR 30 mL/min/1.73 m2Blood pressure 150/90 mmHg72Interim AnalysisLongest duration B cell modulator data to date11 2025 VERA THERAPEUT

41、ICS,INC.90%of participants completed atacicept treatment through 2 yearsOLE=open-label extension.1.Full analysis set and safety population.2.Discontinued to pursue elective surgery(n=1),and discontinued due to positive hepatitis B DNA and adverse event(n=1).3.Initiated prohibited medication for conc

42、omitant disease(n=1),discontinued due to plan to start prohibited medication for concomitant disease(n=1)and adverse event(n=1).4.Discontinued due to investigator decision(n=1),pregnancy(n=2),participant withdrawal(n=2),surgery(n=1),serious adverse event of pneumonia in a heavy smoker,resolved(n=1),

43、adverse event of worsening alanine aminotransferase and aspartate aminotransferase(n=1),and medical monitor criteria(n=1).5.90%=102/113(out of the 116 randomized and treated participants,3 discontinued placebo prior to week 36).Randomizeddouble-blind treatment periodOLE period90%completed atacicept

44、treatment5232 screened116 randomized and treated116 failed screening2 discontinued treatment23 discontinued treatment382 atacicept134 placebo1111 entered OLE102 completed week 9680(98%)31(91%)9 discontinued treatment4Completed week 36 and entered OLE12 2025 VERA THERAPEUTICS,INC.We believe an ideal

45、IgAN disease modifying therapy would be expected toStabilize eGFRResolve hematuriaReduce proteinuriaReduce Gd-IgA113 2025 VERA THERAPEUTICS,INC.Stabilization of eGFRResolution of hematuriaReduction in proteinuriaReduction in Gd-IgA1ORIGIN Phase 2b 96-week results consistent with IgAN disease modific

46、ationAtacicept group includes all participants receiving any atacicept dose at each timepoint,with baseline(BL)defined as the last available measurement prior to the first dose of atacicept.Data from weeks 0 to 60 includes participants who switched from placebo to atacicept.1.Percentage changes from

47、 BL computed using FDA-endorsed mixed-effects modeling;2.Percentages represent change from BL in number of participants with hematuria at each visit divided by number with BL hematuria;3.Changes from BL in eGFR were analyzed using MMRM analysis and LS estimation and SE were estimated from the model

48、directly;eGFR slope was analyzed using mixed-effects model with random intercept and random slope and mean slope and SE were estimated from the model directly.Including eGFR profile consistent with the general population of-1 mL/min/year-10-5051001224364860728496-100-80-60-40-20001224364860728496-75

49、-60-45-30-150Mean SE Change fromBL in eGFR,3 mL/min/1.73m2Mean SE%Change from BL in Gd-IgA11-0.6-66%-60-40-20001224364860728496Mean SE%Change from BL in UPCR1-52%Mean Change from BLin%Participants(95%CI)2-75%1137511174n=10979SlopeWeek from First Atacicept DoseWeek from First Atacicept DoseMean eGFR

50、change from baselineAnnualized eGFR slope of-0.6 mL/min/1.73 m2 per yearn=1101081077810910710829787774112756340n=10961n=1106210860108601086178437641Week from First Atacicept DoseWeek from First Atacicept DosemL/min/year967260483624120Set thestandardin IgAN14 2025 VERA THERAPEUTICS,INC.This data is b

51、ased on a cross-trial comparison and not a head-to-head clinical trial;such data may not be directly comparable due to differences in study protocols,conditions and patient populations.Projected eGFR trajectories for general population and IgAN natural history do not represent clinical data and assu

52、me a constant eGFR slope over time.CKD=chronic kidney disease.1.Slope estimate from Baba M,et al.PLOS ONE 2015;2.Average historical placebo slope from 9 clinical trials3-11;3.Lafayette R,et al.Lancet 2023;4.Rovin BH,et al.Lancet 2023;5.Li PK-T,et al.Am J Kidney Dis 2006;6.Manno C,et al.Nephrol Dial

53、Transplant 2009;7.Lv J,et al.JAMA 2017;8.Wheeler DC,et al.Kidney Int 2021;9.Lv J,et al.JAMA 2022;10.Zhang H,et al.ASN Kidney Week 2023,poster TH-PO1123;11.Mathur M,et al.N Engl J Med 2023.Atacicept treated participants have eGFR slope profile consistent with general population without kidney disease

54、-12-8-40401224364860728496Change from Baseline in eGFR,mL/min/1.73m2Week-1-6-0.6General population estimate1Atacicept IgAN natural history including supportive CKD therapy2Slope,mL/min/y15 2025 VERA THERAPEUTICS,INC.2024 Draft KDIGO IgAN guidelines call for target eGFR slope -1 mL/min/year1.Adapted

55、from Pitcher D,et al.CJASN 2023.eGFR slope data from approved therapies:2.Rovin BH,et al.Lancet 2023;3.Wheeler DC,et al.Kidney Int 2021;4.Lafayette R,et al.Lancet 2023;5.Average historical placebo(including chronic kidney disease standard of care)data from 9 clinical trials:Li PK-T,et al.Am J Kidney

56、 Dis 2006;Manno C,et al.Nephrol Dial Transplant 2009;Lv J,et al.JAMA 2017;Wheeler DC,et al.Kidney Int 2021;Lv J,et al.JAMA 2022;Zhang H,et al.ASN Kidney Week 2023,poster TH-PO1123;Mathur M,et al.N Engl J Med 2023;Lafayette R,et al.Lancet 2023,Rovin BH,et al.Lancet 2023.Annual eGFR slope,mL/min/1.73m

57、2-0.1002211-0.52517191568-1564038402316-21008980786026-3100100100918546-510010010010095590 1818 3030 4040 5050 90%power at week 36Key secondary:eGFR change up to week 104 90%power for eGFR 4 mL/min at week 104SafetyKey Inclusion CriteriaPatients 18 years old with biopsy-proven IgAN and high risk of

58、disease progressionStable and optimized RASi for 12 weeks,use of SGLT2i allowedUPCR-24h 1.0 g/g or UP 1.0 g per 24heGFR 30 mL/min/1.73 m2Blood pressure 150/90 mmHgWeek 015636104Fully enrolled2 EndpointeGFR:n=376Full enrollment expected Q2 2025RASi=renin-angiotensin system inhibitor.18 2025 VERA THER

59、APEUTICS,INC.Phase 2 extension study in participants who complete ORIGIN 2b/3 Objectives:1.Provide patients with extended access to atacicept prior to commercial availability in their country/region2.Capture longer-term data for research purposes3.Generate data from reinitiation of atacicept treatme

60、nt following off-treatment periodWeek 0Atacicept 150 mg QW156/BeyondGroup 1Group 2ORIGIN 2bORIGIN 3Off treatmentORIGIN Extend:Commitment to providing long-term access to atacicept for all ORIGIN participants19 2025 VERA THERAPEUTICS,INC.1.Willen D,et al.Eur J Drug Metab Pharmacokinet 2020;45(1):27-4

61、0.vs Biologic therapies utilizing at home,self-administered,SC 1 mL QW dosing have shown high compliance This dosing paradigm has the potential to support atacicept as a foundational therapy for IgAN Atacicepts half life also supports evaluation of extended dosing QM dose finding study in 2025t1/235

62、 days1Atacicept at home,self-administered QW dosing highly attractive;QM program under way in 2025 20 2025 VERA THERAPEUTICS,INC.Targeting B cell production of autoantibodies against glomerular antigens offers the potential of additional kidney indications Immune Complex Deposition Leading to Glomer

63、ulonephritis and Kidney DamageAutoantibody ProductionB Cell ActivationBAFFAPRILAtaciceptAnti-nephrin podocytopathyAnti-nephrin antibodiesAnti-PLA2R podocytopathyAnti-PLA2R antibodiesIgANAnti-Gd-IgA1 antibodiesOther autoimmune kidney diseases Antibodies associated withB cellPLA2R=phospholipase A2 rec

64、eptor.21 2025 VERA THERAPEUTICS,INC.PIONEER:Phase 2 basket trial in expanded IgAN and anti-PLA2R&anti-nephrin podocytopathies 1.6 cohorts:adult IgAN with eGFR 20 to 30 mL/min/1.73 m2,n 20;adult IgAN with UPCR 1.0 g/g,n 50;adult IgAN with UPCR 5.0 g/g,n 20;adolescent(15 y)IgAN with UPCR 0.3 g/g,n 10;

65、Adult recurrent IgAN post kidney transplant,n 10;adolescent and adult IgA vasculitis nephritis,n 10.361 EndpointAtacicept 150 mg QW522 EndpointWeek 0Population 1,n 120Expanded IgAN populations1Population 3,n 20Anti-nephrin podocytopathy(Minimal Change Disease/FSGS)Population 2,n 20Anti-PLA2R podocyt

66、opathy(Membranous Nephropathy)Key EndpointsPrimary:UPCR change at week 36Key secondary:eGFR change at weeks 36,52Exploratory:Gd-IgA1 change at weeks 36,52Change in percentage of participants with hematuria at weeks 36,52Change in anti-PLA2R antibodiesChange in anti-nephrin antibodiesSafety22 2025 VE

67、RA THERAPEUTICS,INC.Established leadership in B cell modulation and expanded breadth of expertise positions Vera for further innovation1.Unaudited as of September 30,2024.Includes$353M of cash,cash equivalents and marketable securities as of September 30,2024 and additional$324M in net proceeds from

68、 October 2024 follow-on equity offering.This estimate of the Companys cash,cash equivalents and marketable securities as of September 30,2024 has not been audited.Study initiatedERA best abstractJan 25 R&D Day:72-week resultsFDA BTD for atacicept in IgAN96-week disease modification presented in ASN

69、LB oral and JASN manuscriptPrimary endpoint cohort enrolledAtacicept indication expansion to broader IgAN cohort,PMN,FSGS,MCDTwo transformative financings leading to$677M pro forma cash position12024R&D AccomplishmentsCorporate Growth2024Clinical pharmacologyResearch&discoveryBioassay and biomarkers

70、Translational medicinePreclinical developmentPharmacovigilanceField Medical DirectorsHealth economics&outcomes researchCommercialPIONEERStrong financialpositionORIGIN3ORIGIN2bNew talent&functionalexpertiseORIGINExtend23 2025 VERA THERAPEUTICS,INC.Opportunity to innovate and extend leadership in B ce

71、ll modulationBCMA=B cell maturation antigen.Monoclonal antibodies binding either BAFF or APRIL aloneFc fusion proteins containing TACI or TACI variants Novel BCMA constructs represent an innovative B cell modulatory unlockTACIBCMABAFFAPRILAtaciceptLongest duration of B cell modulator data to date sh

72、owing eGFR stabilizationB cell receptors that bind both cytokinesB cell productionof pathogenic antibodiesCurrent landscape of B cell modulators24 2025 VERA THERAPEUTICS,INC.Novel,next-generation dual BAFF/APRIL inhibitorPotential for additional patient benefit across diseases and populationsTACIBCM

73、ABAFFAPRILAtaciceptB cell receptors that bind both cytokines Novel molecule engineered by team at Stanford University Picomolar binding affinity for BAFF and APRIL,attractive PK and half-life Novel composition may offer differentiation onFrequency of administrationRoute of administrationOther charac

74、teristics of moleculeVT-109B cell productionof pathogenic antibodies25 2025 VERA THERAPEUTICS,INC.Vera PipelineResearch&DiscoveryPreclinicalClinicalMarketedAtaciceptIgANPMN,FSGS,MCDPotential future autoimmune indicationsVT-109Potential future autoimmune indicationsMAU868BK virusVera holds worldwide,exclusive rights to develop and commercialize atacicept,VT-109,and MAU868Phase 3Phase 2Phase 2 2025 VERA THERAPEUTICS,INC.