葆元-Corporate-Presentation-January-2025-_vJPM_vF.pdf

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1、DRIVEN BY SCIENCE,FOCUSED ON LIFEDavid Hung,M.D.Founder,President,&CEOJ.P.Morgan Healthcare ConferenceJanuary 2025Forward looking statementsCertain statements included in this presentation(this“Presentation”)that are not historical facts are forward-looking statements for purposes of the safe harbor

2、 provisions under the United States Private Securities Litigation Reform Act of 1995.Forward-looking statements are sometimes accompanied by words such as“believe,”“may,”“will,”“estimate,”“continue,”“anticipate,”“intend,”“expect,”“should,”“would,”“plan,”“predict,”“potential,”“seem,”“seek,”“future,”“

3、outlook”and similar expressions that predict or indicate future events or trends or that are not statements of historical matters.These forward-looking statements include,but are not limited to,our expectations the timing of FDA approval and commercial launch,expectations and timing of establishing

4、a commercial organization,a full NDA approval for taletrectinib for the treatment of advanced ROS1+NSCLC(line agnostic),the potential for taletrectinib to become a new therapeutic option for ROS1+NSCLC,taletrectinibs and safusidenibs best-in-class therapeutic potential,potential therapeutic benefit

5、of Nuvation Bios product candidates and planning and advancement of clinical studies for such product candidates,sufficiency of Nuvation Bios current cash balance to support operations in the near term,clinical study design,or the potential of the DDC platform.These statements are based on various a

6、ssumptions,whether or not identified in this Presentation,and on the current expectations of the management team of Nuvation Bio and are not predictions of actual performance.These forward-looking statements are subject to a number of risks and uncertainties that may cause actual results to differ f

7、rom those anticipated by the forward-looking statements,including but not limited to the challenges associated with conducting drug discovery and initiating or conducting clinical studies due to,among other things,difficulties or delays in the regulatory process,enrolling subjects or manufacturing o

8、r acquiring necessary products;the emergence or worsening of adverse events or other undesirable side effects;risks associated with preliminary and interim data,which may not be representative of more mature data;and competitive developments.Risks and uncertainties facing Nuvation Bio are described

9、more fully in its Form 10-Q filed with the SEC on November 6,2024 under the heading“Risk Factors,”and other documents that Nuvation Bio has filed or will file with the SEC.You are cautioned not to place undue reliance on the forward-looking statements,which speak only as of the date of this Presenta

10、tion.Nuvation Bio disclaims any obligation or undertaking to update,supplement or revise any forward-looking statements contained in this Presentation.2Nuvation Bio is tackling some of the greatest unmet needs in oncology3Taletrectinib is a 3rd generation,potentially best-in-class ROS1 inhibitor app

11、roved for advanced ROS1+NSCLC in China;NDA accepted by U.S.FDA for priority review(line agnostic)with PDUFA date of 6/23/25Global oncology company aimed at making best-in-class drugs by improving validated mechanisms that have encountered safety liabilities or limitations in efficacy NUV-1511,the Co

12、mpanys first clinical-stage drug-drug conjugate(DDC),is being evaluated in a Phase 1/2 study;NUV-868 is a BD2-selective BET inhibitor that has completed Phase 1 and Phase 1b studiesRobust cash balance of$549 million as of 9/30/24 and taletrectinib PDUFA date of 6/23/25 position Nuvation Bio to poten

13、tially become a U.S.commercial stage organization as early as June 2025Safusidenib is a potentially best-in-class,brain penetrant,mIDH1 inhibitor entering pivotal studies for diffuse IDH1-mutant gliomaNuvation Bio has four differentiated oncology programs ranging from China approval/U.S.NDA under re

14、view,to Phase 1 ongoing4ProgramPotential Indication(s)Current Stage of Development Anticipated Milestones&Recent UpdatesPreclinicalPhase 1Phase 2PivotalNDA ReviewTaletrectinib1(ROS1)Advanced ROS1+NSCLC(treatment line agnostic)NDA accepted by U.S.FDA for priority review(line agnostic)Approved by Chin

15、as NMPA for advanced ROS1+NSCLC5 Pooled data from pivotal TRUST-I&TRUST-II studies presented at ESMO in September 2024Safusidenib2(mIDH1)Diffuse IDH1-mutant gliomaEntering pivotal studies in 2025Phase 2 study ongoingNUV-1511(DDC)Advanced solid tumors3Phase 1/2 dose escalation study ongoingNUV-868(BE

16、T)Currently under internal evaluation4Completed Phase 1 monotherapy and Phase 1b combination studies in advanced solid tumorsBET:Bromodomain and Extra-Terminal motif;ESMO:European Society of Medical Oncology Congress;mIDH1:mutant isocitrate dehydrogenase 1;NSCLC:Non-small cell lung cancer;PDUFA:Pres

17、cription Drug User Fee Act;ROS1+:c-ros oncogene 1-positive;1.Taletrectinib has been granted Orphan Drug Designation from the U.S.FDA for the treatment of patients with ROS1+NSCLC and other NSCLC indications,and Breakthrough Therapy Designations by both the U.S.FDA and Chinas NMPA for the treatment o

18、f patients with locally advanced or metastatic ROS1+NSCLC;worldwide development and commercial rights in-licensed from Daiichi Sankyo;rights to taletrectinib have been out-licensed in China and Japan.2.Worldwide development and commercial rights in-licensed from Daiichi Sankyo,excluding Japan where

19、Daiichi Sankyo retains development and commercial rights.3.Includes patients with advanced solid tumors who previously received and progressed on or after treatment with Enhertu and/or Trodelvy per approved U.S.FDA labeling,human epidermal growth factor receptor 2-negative(HER2-)metastatic breast ca

20、ncer,metastatic castration-resistant prostate cancer(mCRPC),advanced pancreatic cancer,and platinum-resistant ovarian cancer.4.Nuvation Bio has decided not to initiate a Phase 2 study of NUV-868 as a monotherapy or in combination with olaparib or enzalutamide in the advanced solid tumor indications

21、that were part of the Phase 1 and Phase 1b study designs.The Company is evaluating next steps for the NUV-868 program,including further development in combination with approved products for indications in which BD2-selective BET inhibitors may improve outcomes for patients.5.Based on results of the

22、TRUST-I clinical study,Chinas NMPA approved taletrectinib for the treatment of adult patients with locally advanced or metastatic ROS1+NSCLC who have or have not previously been treated with ROS1 TKIs.Approved for advanced ROS1+NSCLC in China;NDA accepted for priority review in U.S.with PDUFA date o

23、f 6/23/25Taletrectinib|ROS1i5Advanced ROS1+NSCLCNDA accepted by U.S.FDA for priority review in December 2024Taletrectinib has the highest overall response rate and median progression-free survival of any ROS1 inhibitor in the first line(TKI-nave)settingTaletrectinib2Repotrectinib3Entrectinib4Crizoti

24、nib5ncORRMedian DORMedian PFSIC-cORR1Pooled TRUST-I&TRUST-IITRIDENT-1ALKA-372-001,STARTRK-1,STARTRK-2PROFILE 100116089%44 months46 months77%(13/17)7179%34 months36 months89%(8/9)16868%21 months16 months80%(20/25)5372%25 months19 monthsN/AStudyNote:These data are derived from different clinical studi

25、es,with differences in study design and patient populations.No head-to-head studies have been conducted.Comparisons in a head-to-head study may yield different results.cORR:confirmed Overall response rate;DOR:Duration of response;IC-cORR:Intracranial confirmed overall response rate;PFS:Progression f

26、ree survival.1.Reflects IC-cORR in patients with measurable CNS tumors.2.Perol et al.,ESMO Presentation,2024.3.AUGTYRO prescribing information and Drilon et al.,New England Journal of Medicine,2024.4.Drilon et al.,JTO Clinical Research Reports,2022.5.XALKORI prescribing information and Shaw et al.,A

27、nnals of Oncology,2019.6Few drugs in oncology have matched the 89%ORR and 46-month mPFS seen with taletrectinib in the first line(TKI-nave)settingTaletrectinib189%46 months44 monthsRETEVMO(selpercatinib)284%22 months20 monthsAUGTYRO(repotrectinib)379%36 months34 monthsALECENSA(alectinib)479%26 month

28、s1%):First Line TherapyPD-L1 Positive(1%):First Line TherapyCONTRAINDICATIONS for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents;some oncogenic drivers(ie,EGFR exon 19 deletion or L858R;ALK,RET,or ROS

29、1 rearrangements)have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.CONTRAINDICATIONS for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents;some oncogenic drivers(ie,EGFR exon

30、19 deletion or L858R,ALK rearrangements)have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors.13Taletrectinib has greater numerical benefits over its competitors than the leaders of the EGFR and ALK markets over their nearest competitorsPrecedent NSCLC markets(1L)1ROS1+NSCLC(

31、1L)2ALK+NSCLCNote:These data are derived from different clinical studies,with differences in study design and patient populations.No head-to-head studies have been conducted.Comparisons in a head-to-head study may yield different results.ORR:Overall response rate;mPFS:median Progression-free surviva

32、l.1.ALECENSA prescribing information(ALEX study results comparing alectinib to crizotinib);LORBRENA prescribing information;TAGRISSO prescribing information.2.Perol et al.,ESMO Presentation,2024;AUGTYRO prescribing information and Drilon et al.,New England Journal of Medicine,2024;Drilon et al.,JTO

33、Clinical Research Reports,2022;XALKORI prescribing information and Shaw et al.,Annals of Oncology,2019.EGFR+NSCLCmPFSORRmPFS(2nd gen.)36 mo.46 mo.10 mo.26 mo.26 mo.NR 5-yrs10 mo.19 mo.46 mo.19-16 mos.mPFS(1st gen.)72%79%79%76%69%77%79%89%89%72-68%ORR(2nd gen.)ORR(1st gen.)TaletrectinibTaletrectinibT

34、aletrectinibTaletrectinib14$80$139$195$231$251$223$158$149$138$102$105$100$85$199$327$378$394$421$521$537$18$31$34$38$44$52$60$77$112$141$177$224$80$139$195$231$336$440$516$638$683$707$855$921 201220132014201520162017201820192020202120222023Good,but not great drugs(neither alectinib or lorlatinib ha

35、ve best-in-class efficacy and safety),have still increased the ALK market 4xSource:Evaluate Pharma,Earning Reports from Pfizer(crizotinib,lorlatinib),Roche(alectinib),Takeda(brigatinib)from 2012 to 2023.Notes:Total U.S.crizotinib net revenue shown for illustrative purposes(approved for ALK-positive

36、NSCLC in 2011 and ROS1-positive NSCLC in 2016).Net revenue of ceritinib in ALK+NSCLC is minimal and not broken out by U.S.only therefore not included in this analysis.Total Net U.S.Revenue(ALK+NSCLC TKIs)AlectinibCrizotinibBrigatinibLorlatinibAlectinib approved in 1L settingLorlatinib approved in 2L

37、 settingAlectinib approved in 2L setting post-crizotinibLorlatinib approved in 1L setting$in millionsAlectinib TKIMarket Share:Y1Y2Y3Y4Y5Y6Y7Y80%19%37%54%55%56%55%57%15$15$254$405$869$1,268$1,566$1,780$2,007$2,276$689$731$727$638$521$266$6$23$39$26$17$14$11$9$3$689$731$748$915$965$1,161$1,285$1,580$

38、1,791$2,016$2,279 20132014201520162017201820192020202120222023Osimertinib captured 90%market share after only increasing mPFS by 9 months and ORR by 8%;US EGFR market has grown 3x since its launchSource:Evaluate Pharma,Earning Reports from AstraZeneca(Osimertinib,erlotinib)and Roche(gefitinib)from 2

39、013 to 2023.Notes:Net revenue of afatinib are not available as Boehringer Ingelheim is a private company.Net revenue of dacomitinib in EGFR+NSCLC is minimal and therefore not included in this analysis.Total Net U.S.Revenue(EGFR+NSCLC TKIs)OsimertinibErlotinibGefitinibOsimertinib approved in 1L setti

40、ngErlotinib patent expiryOsimertinib approved in 2L settingOsimertinib approved in adjuvant setting$in millionsOsimertinib TKIMarket Share:Y1Y2Y3Y4Y5Y6Y7Y81%21%32%61%83%92%95%95%16Safusidenib|mIDH1i17DiffuseIDH1-mutant gliomaEntering pivotal studies in 2025IDH mutations in glioma lead to accumulatio

41、n of oncometabolite 2-HG,which drives cancer growth and creates an immunosuppressive tumor microenvironment Gain-of-function mutation confers novel enzymatic activity,which convert-KG to 2-HG Epigenetic dysregulation with genome-wide hypermethylation(G-CIMP)2-HG impairs cellular differentiation 2-HG

42、 creates an immunosuppressive tumor microenvironment Grade 2 and 3 glioma:95-97%IDH1 mutations 3 5%IDH2 mutationsMechanism of Action:IDH mutationsSource:Carosi,et al.,Cancers,2024.18Safusidenib crosses the blood-brain-barrier,inhibits mIDH1,and suppresses 2-HG levelsSource:Whittle et al.,Neuro-Oncol

43、ogy,2024.*Asterix denotes normal brain sample for patient A-04.19The diffuse IDH1-mutant glioma market represents a sizeable commercial opportunity,particularly because patients can remain on drug for years2013.3K 18.3Kpeople living with diffuse IDH1-mutant glioma in the U.S.Grade 2:63%Grade 337%Sou

44、rce:CBTRUS Statistical Report:U.S.Cancer Statistics NPCR and SEER,2018-2020.Royalty Pharmas acquisition of rights to Agios Pharmaceuticals royalty on U.S.net sales of vorasidenib validates safusidenibs market potential21 In May 2024,Royalty Pharma announced it acquired an interest in Agios Pharmaceu

45、ticals royalty on U.S.net sales of Serviers vorasidenib Royalty Pharma paid Agios$905 million in cash upon FDA approval of vorasidenib for a 15%royalty on annual U.S.net sales up to$1 billion Will receive a 12%royalty and Agios will retain a 3%royalty on potential U.S.net sales$1 billion Royalty Pha

46、rma forecasts vorasidenib peak U.S.net sales of$1 billion Implies vorasidenib valuation of$6 billionSource:Royalty Pharma plc press release,Royalty Pharma investor presentation,and Agios Pharmaceuticals press release.Transaction Overview0%18%ORR0%20%40%17%33%0%20%40%ORRSafusidenib early-stage data s

47、howed higher response rates than vorasidenib in low-grade(non-enhancing)and high-grade(enhancing)diffuse mIDH1 glioma22Enhancing glioma n=35 Non-enhancing glioma n=12 Enhancing glioma n=30 Non-enhancing glioma n=22 ORR:Overall response rate.Note:Information depicts response rates with IDH inhibitor

48、in IDH1-mutant gliomas in Phase 1 studies;Enhancing and non-enhancing glioma was assessed by Response Assessment in Neuro-Oncology(RANO)and RANO-LGG,respectively.Contrasting enhancement is generally associated with a higher degree of malignancy.These data are derived from different clinical studies,

49、with differences in study design and patient populations.No head-to-head studies have been conducted.Comparisons in a head-to-head study may yield different results.1.Natsume et al.,Neuro-Oncology,2023.2.Mellinghoff et al.,Clinical Cancer Research,2021 and Mellinghoff et al.,New England Journal of M

50、edicine,2023.EnhancingNon-enhancingSafusidenib1Vorasidenib211%Phase 1 studyPivotal study(INDIGO)Two complete responses observed lasting 174 weeks(grade 4 astrocytoma)and 95 weeks(grade 3 oligodendroglioma),with patients still on treatment at data cutoff23Enhancing glioma n=35 Non-enhancing glioma n=

51、12 Note:Information depicts response rates with IDH inhibitor in IDH1-mutant gliomas in Phase 1 studies;Enhancing and non-enhancing glioma was assessed by Response Assessment in Neuro-Oncology(RANO)and RANO-LGG,respectively.Minor response not applicable in enhancing glioma patients assessed by RANO.

52、Contrasting enhancement is generally associated with a higher degree of malignancy.These data are derived from different clinical studies,with differences in study design and patient populations.No head-to-head studies have been conducted.Comparisons in a head-to-head study may yield different resul

53、ts.1.Natsume et al.,Neuro-Oncology,2023.2.Two complete responses represent one complete response in a grade 4 astrocytoma and one complete response in the target lesions of a grade 3 oligodendroglioma(with stable disease in non-target lesions).3.Mellinghoff et al.,Clinical Cancer Research,2021.Safus

54、idenib1Vorasidenib3RANO responsesEnhancingn=35Non-enhancingn=12Overall response6(17%)4(33%)Complete response22(6%)0(0%)Partial response4(11%)1(8%)Minor responseN/A3(25%)Stable disease11(31%)8(67%)Progressive disease17(49%)0(0%)Not evaluable1(3%)0(0%)RANO responsesEnhancingn=30Non-enhancingn=22Overal

55、l response0(0%)4(18%)Complete response0(0%)0(0%)Partial response0(0%)1(5%)Minor responseN/A3(14%)Stable disease17(57%)16(73%)Progressive disease12(40%)2(9%)Not evaluable1(3%)0(0%)Another IDH1 inhibitor(ivosidenib)blocks 2-HG synthesis and increases tumor infiltrating CD8+T cells,demonstrating augmen

56、tation of immunityivosidenibivosidenib+anti-CD8vehicleSource:Wu et al.,Cancer Discovery,2022.1.IHC staining for CD8 in CKIR132Csubcutaneous allograft ICCs after 6 days treatment with vehicle or AG120;right:quantification.Data represents mean SD;*P0.01;unpaired t-test.2.Analysis of serial changes in

57、tumor volume.N=6 mice per group.Data represent means SEM;*P0.001;unpaired t-test.Ivosidenib promotes tumor CD8+T-cell infiltration1Depletion of CD8+T-cells blocks anti-tumor activity of ivosidenib224Safusidenib,unlike vorasidenib,shows far greater activity in mice with an intact immune system rather

58、 than immunocompromised mice,suggesting immune MOAvehiclevehiclevehicleSafusidenib 50 mg/kg BIDSafusidenib150 mg/kg BIDSafusidenib200 mg/kg BIDSafusidenib 200 mg/kg BIDDoxorubicinSafusidenib400 mg/kg QDXenografts in immunocompetent miceSurvivalTumor VolumeTumor Volume(mm3)Tumor Volume(mm3)Days after

59、 start of treatmentDays after start of treatment2,5000501,0001,5002,00002468101214020030040050010007142128Xenografts in immunodeficient miceSource:Nuvation internal preclinical research.25Vorasidenib 50 mg/kg QDTEAE:n(%);Preferred Term1,2All gradesGrade 3Skin hyperpigmentation25(53)N/ADiarrhea22(47)

60、2(4)Pruritus14(30)0Alopecia13(28)0Arthralgia13(28)1(2)Nausea12(26)0Headache11(23)1(2)Rash11(23)0Source:Natsume et al.,Neuro-Oncology,2023.1.Safety analysis set(n=47).2.Patients were only counted once even if the same adverse event was reported more than once.Five of the top eight adverse events seen

61、 in a Phase 1 study of safusidenib are consistent with an immune-related MOA26Committed team tackling the greatest unmet needs in oncologyBroad pipeline across multiple stages of developmentTaletrectinib|ROS1 inhibitor:NDA accepted for priority review(line agnostic,full approval)in December 2024Safu

62、sidenib|mIDH1 inhibitor:Phase 2 study ongoingNUV-1511|Drug-drug conjugate:Phase 1 dose escalation study ongoingNUV-868|BD2-selective BET inhibitor:Completed Phase 1 and Phase 1b studiesStrong cash position to support operations in near term$549.1 million as of September 30,2024Experienced biotech le

63、adership teamFounded by Dr.David Hung,previously the founder and CEO of Medivation,who successfully developed and commercialized XTANDIPotentially best-in-class candidates leveraging and improving validated mechanismsPotential for better efficacy and tolerability27Potential to become a commercial stage organization in the U.S.as early as mid-2025NDA for taletrectinib accepted for priority review with PDUFA goal date of June 23,2025Taletrectinib has been approved in China for the treatment of advanced ROS1+NSCLCPDUFA:Prescription Drug User Fee Act.