KPTI JPM HC Conference 2023 Karyopharm.pdf

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1、12023 KARYOPHARM THERAPEUTICS INC.JP MORGAN 2023 HEALTHCARE CONFERENCE January 11,2023A Commercial-Stage Pharmaceutical Company Pioneering Novel Cancer Therapies22023 KARYOPHARM THERAPEUTICS INC.Richard PaulsonChief Executive OfficerOVERVIEW32023 KARYOPHARM THERAPEUTICS INC.Forward-looking Statement

2、s and Other Important InformationThis presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995.Such forward-looking statements include those regarding Karyopharms preliminary fourthquarter and full year 2022 financial results;Karyoph

3、arms expected cash runway;the ability of selinexor or eltanexor to treat patients with multiple myeloma,endometrial cancer,myelofibrosis,myelodysplastic neoplasms,diffuse large B-cell lymphoma,and other diseases;expectations related to future clinical development and potential regulatory submissions

4、 of selinexor or eltanexor;expectations with respect to commercialization efforts;submissions to,and the review and potential approval of selinexor,eltanexor or any of its other product candidates by,regulatory authorities,including the Companys regulatory strategy,the anticipated availability of da

5、tato support such submissions,timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways;the expected design of the Companys clinical trials;and thetherapeutic potential of and potential clinical development plans for Karyopharms

6、product candidates,especially selinexor and eltanexor.Such statements are subject to numerous important factors,risks anduncertainties,many of which are beyond Karyopharms control,that may cause actual events or results to differ materially from Karyopharms current expectations.For example,there can

7、 be no guarantee thatKaryopharm will successfully commercialize XPOVIO or that any of Karyopharms drug candidates,including selinexor and eltanexor,will successfully complete necessary clinical development phases or thatdevelopment of any of Karyopharms drug candidates will continue.Further,there ca

8、n be no guarantee that any positive developments in the development or commercialization of Karyopharms drug candidate portfoliowill result in stock price appreciation.Managements expectations and,therefore,any forward-looking statements in this press release could also be affected by risks and unce

9、rtainties relating to a number of other factors,including the following:the risk that the COVID-19 pandemic could disrupt Karyopharms business more severely than it currently anticipates,including by negatively impacting sales of XPOVIO,interrupting or delayingresearch and development efforts,impact

10、ing the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates,delaying ongoing or planned clinical trials,impedingthe execution of business plans,planned regulatory milestones and timelines,or inconveniencing patients;the adoption of

11、XPOVIO in the commercial marketplace,the timing and costs involved in commercializingXPOVIO or any of Karyopharms drug candidates that receive regulatory approval;the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharms drug candidates that receive regulatory approval;Kar

12、yopharms results of clinical trials and preclinical studies,including subsequent analysis of existing data and new data received from ongoing and future studies;the content and timing of decisions made by the U.S.Food and Drug Administration and other regulatory authorities,investigational review bo

13、ards at clinical trial sites and publication review bodies,including with respect to the need for additional clinical studies;the ability ofKaryopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the poten

14、tial future financial implications of such agreement;Karyopharms ability to enroll patients in its clinical trials;unplanned cash requirements and expenditures;development or regulatory approval of drug candidates by Karyopharms competitors for products or productcandidates in which Karyopharm is cu

15、rrently commercializing or developing;and Karyopharms ability to obtain,maintain and enforce patent and other intellectual property protection for any of its products or productcandidates.These and other risks are described under the caption Risk Factors in Karyopharms Quarterly Report on Form 10-Q

16、for the quarter ended September 30,2022,which was filed with the Securities andExchange Commission(SEC)on November 3,2022,and in other filings that Karyopharm may make with the SEC in the future.Any forward-looking statements contained in this press release speak only as of the datehereof,and,except

17、 as required by law,Karyopharm expressly disclaims any obligation to update any forward-looking statements,whether as a result of new information,future events or otherwise.Karyopharm regularlyuses its website to post information regarding its business,drug development programs and governance.Karyop

18、harm encourages investors to use ,particularly the information in the section entitled“Investors,”as a source of information about Karyopharm.References to in this presentation are not intended to,nor shall they be deemed to,incorporate information on intothis presentation by reference.Other than th

19、e currently approved indications of XPOVIO,selinexor and eltanexor are investigational drugs that have not been approved by the FDA or any other regulatory agency,and thesafety and efficacy of these drugs has not been established by any agency.XPOVIO(selinexor)and NEXPOVIO(selinexor)are registered t

20、rademarks of Karyopharm Therapeutics Inc.Any other trademarks referred to in this presentation are the property of their respective owners.All rightsreserved.42023 KARYOPHARM THERAPEUTICS INC.Innovation and Patient FocusedFounded in 2008,building on over a decade of research into selective inhibitio

21、n of nuclear export(SINE)as a novel mechanism of actionFocused Clinical Pipeline with One Planned and Two Ongoing Pivotal Studies;Optimizing Dose for Efficacy and TolerabilityPhase 3 selinexor+ruxolitinib in treatment nave MF(planned)2 Phase 3 SPd3in R/R MM post anti-CD38Phase 3 selinexor as mainten

22、ance in TP53 wildtype EC4Strong Financial PositionCash position of$279m at end of 2022*Cash runway until late 2025XPOVIO/NEXPOVIOApproved in Multiple Myeloma(MM)and DLBCL1Expanded global footprint with regulatory approvals in 40 countriesExpect total revenues to be$157.7m in 2022Moving into earlier

23、lines of therapy in MMPositioned for Next Stage of GrowthPassionately driven in its mission to positively impact lives and defeat cancer1.*Based on preliminary unaudited estimate1.1.DLBCL approved in the U.S.under accelerated approval pathway 2.MF:myelofibrosis;pending regulatory feedback 3.selinexc

24、or+pomalidomide+dexamethasone 4.Endometrial cancer52023 KARYOPHARM THERAPEUTICS INC.Grew U.S.XPOVIO net sales by 22%to$120.4m*Received full marketing authorization in the EU for NEXPOVIO;Approved in 40 countries Commercial launches by partners ex-US Initiated pivotal Phase 3 study evaluating lower d

25、ose selinexor,SPd1,an all oral regimen in R/R MMInitiated pivotal Phase 3 study of selinexor as a maintenance therapy in TP53 wild-type EC Partnership with Foundation Medicine to develop TP53 companion diagnostic Presented top-line and subgroup analysis data from SIENDO in ECCompleted recruitment fo

26、r interim analysis of Phase 2 study evaluating eltanexor in high-risk relapsed/refractory MDSEvaluating eltanexor,second SINE compound,in patients of high unmet needInitial results from Phase 1 evaluating selinexor+ruxolitinib in treatment nave MF Encouraging preliminary results across the three rel

27、evant endpoints of SVR35,TSS50 and hemoglobin stabilization Multiple MyelomaEndometrial CancerMyelofibrosisMyelodysplastic Neoplasms1.*Based on preliminary unaudited estimate;1.1.Selinexor+pomalidomide+dexamethasoneKey Program Accomplishments in 202262023 KARYOPHARM THERAPEUTICS INC.9-13 monthsT-cel

28、l re-directing therapiesProteasomeinhibitors(PIs)*Immuno-modulatory agents(IMiDs)*Anti-CD38 monoclonal antibodies(mAbs)*Selective Inhibitors of Nuclear Export(SINE)XPO1 inhibitors*NCCN*(SPd,SDd,SKd)USPI XVdXPOVIO Provides a Class Switch and Combinatorial OptionalityXPOVIO:Novel Class of Therapy and

29、Convenient Oral for 2L4L RRMM post anti-CD38 5L+2L-4L XPOVIO combinations other than XVd and Xd will not be promoted by Karyopharm,but may be considered for future indication updates.Safety and efficacy of selinexor in combinations other than XVd and Xd have not been established and have not been ap

30、proved by the US FDA or any other regulatory authority.*+dexamethasone*NCCN Guideline inclusion for SPd,SDd and SKdLines of Therapy72023 KARYOPHARM THERAPEUTICS INC.XPOVIO Update:4Q 2022 and FY 20224Q and FY 2022 Highlights Continued shift into earlier lines of therapy,approaching 55%of patients in

31、2-4L1,andincrease in duration of therapy YoYStrong YoY growth in Community contributing to 70%of selinexor revenuesin Q4Continued improvement in perception and intent-to-prescribe data in 2-4L2Increased pressure in Academic setting due to intensifying late line competition and ongoing trials1.1.Base

32、d on Komodo claims analysis,assessed as of October 2022.2.Based on internal KPTI Myeloma HCP ATU(healthcare professionals awareness,trial and usage)1.*Based on preliminary unaudited estimate$98.4M$120.4M2021202222%$29.8M$28.3M$29.0M$32.0M$31.1M4Q 20211Q 20222Q 20223Q 20224Q 20224%*Net Product Revenu

33、e up 22%YoY Driven by Growth in 2L4L 82023 KARYOPHARM THERAPEUTICS INC.Full EMA Approval Received for NEXPOVIOExpanding Indication to 2L+2L+multiple myeloma and R/R DLBCL*2L+multiple myelomaPenta-or triple-class-refractory multiple myeloma and R/R DLBCL*Penta-or triple-class-refractory multiple myel

34、omaCountry/RegionIndication(s)PartnerApprovalsUnited StatesEurope1MenariniUKMenariniMainland ChinaAntengeneSouth KoreaAntengeneAustraliaAntengeneSingaporeAntengeneCanadaForusIsraelNeopharmTaiwanAntengene1.The 27 countries comprising the European Union,plus Iceland,Norway,Northern Ireland and Lichten

35、stein.XPOVIO/NEXPOVIONow Approved in 40 Countries1.*DLBCL approved in the U.S.under accelerated approval pathway92023 KARYOPHARM THERAPEUTICS INC.Reshma Rangwala,MD,PhDChief Medical OfficerPIPELINE UPDATE102023 KARYOPHARM THERAPEUTICS INC.1.Increases nuclear levels of tumor suppressor proteins and t

36、heir activation4,52.Traps oncoprotein mRNA in the nucleus,leading to reduced oncoprotein levels63.Retains activated glucocorticoid receptor in the nucleus,leading to altered expression of genes involved in inflammatory pathways7NucleusXPO1RAN-GTPNuclear pore complexProtein cargoes:e.g.,tumor suppres

37、sor proteins and growth regulators like p53,p27,or FOXO family proteins1,2Selinexor and Eltanexor(SINE compounds)selectively inhibit nuclear export by binding XPO1Exportin 1(XPO1)transports proteins and protein-RNA complexes out of the nucleusCytoplasmRNA cargoes:e.g.,oncoprotein mRNA like MYC3RAN-G

38、DP(GTP hydrolysis)Adapted from Azizian NG,et al(2020)RNA binding adaptor(e.g.,elF4E)NucleusRAN-GDP(GTP hydrolysis)SINE compoundReduced proliferation and increased apoptosis of cancer cells8SINE:Selective inhibition of nuclear exportMYC,MYC proto-oncogene;eIF4E,Eukaryotic translation initiation facto

39、r 4E;FOXO,forkhead box,sub-group O;p27,cyclin-dependent kinase inhibitor 1B;p53,tumor protein 53;RAN,RAS-related nuclear protein;GDP,guanosine diphosphate;GTP,guanosine triphosphate 1.Azizian NG,et al.J Hematol Oncol.2020;13(1):61.doi:10.1186/s13045-020-00903-4;2.Das A,et al.Exp Hematol Oncol.2015;4

40、:7.doi:10.1186/s40164-015-0002-5.;3.Culjkovic-Kraljacic B.Cell Rep.2012;2(2):207-15.doi:10.1016/j.celrep.2012.07.007.4.Turner JG,et al.Biochem Pharmacol.2012 Apr 15;83(8):1021-32.doi:10.1016/j.bcp.2011.12.016.5.Azmi AS,et al.Nat Rev Clin Oncol.2021 Mar;18(3):152-169.doi:10.1038/s41571-020-00442-4.6

41、Kashyap T et al,Oncotarget.2018 Jul20;9(56):30773-30786.doi:10.18632/oncotarget.25637;7.Argueta C,et al.Oncotarget.2018 May 22;9(39):25529-25544.doi:10.18632/oncotarget.25368.doi:10.1016/j.clml.2018.03.003;8.Sun Q,et al.Signal Transduct Target Ther.2016;1:16010.doi:10.1038/sigtrans.2016.10112023 KAR

42、YOPHARM THERAPEUTICS INC.DLBCL,diffuse large B-cell lymphoma;MDS,myelodysplastic neoplasms;MM,multiple myeloma;XPO1,exportin 1.Assessed in three mammalian species(mouse,rat,and monkey);Not a substrate of permeability glycoprotein(P-gp).1.XPOVIO(selinexor)package insert.Newton,MA:Karyopharm Therapeut

43、ics Inc;2.Karyopharm Therapeutics.Drug pipeline.https:/ ZA,et al.Leukemia.2016;30(12):2364-2372.doi:10.1038/leu.2016.136;4.ClinicalTrials.gov.KCP-8602-801.https:/clinicaltrials.gov/ct2/show/NCT02649790.Published August 15,2022.SelinexorEltanexorFirst novel XPO1 inhibitorSecond novel XPO1 inhibitorBo

44、th oral compounds have been shown to bind and inhibit XPO1.1,2FDA-approved in MM and in DLBCL1Currently being investigated in both solid tumors and hematologic malignancies2Penetrates blood-brain barrier(BBB)3Dosing:once weekly in MM(XVd),twice weekly in MM(Xd)and in DLBCL1 Prioritization of clinica

45、l development in TP53 wild type endometrial cancer and myelofibrosisInvestigational compoundCurrently being investigated in relapsed/refractory(R/R)MDS2Compared to selinexor,lower BBB penetration observed in select animal models3,Dosing:5 times per week in Ph 1/24Strong rationale for further develop

46、ment in both solid tumors and hematologyTwo Differentiated,Complementary Novel SINE CompoundsFocused on areas where a highly potent XPO1 impact is neededFocused on areas where continuous XPO1 Inhibition needed122023 KARYOPHARM THERAPEUTICS INC.12RegimenIndicationStudy NameEarly StageMid StageLate St

47、ageCommercialw/dexamethasoneMultiple myeloma(penta-refractory)STORMw/bortezomib+dexamethasoneMultiple myeloma(2L+)BOSTONmonotherapyDLBCL(R/R)SADALSELINEXORw/R-GDPDLBCL(R/R)XPORT-DLBCL-0301monotherapyEndometrial cancer(maintenance)SIENDOmonotherapyEndometrial cancer(maintenance;TP53 wild-type)XPORT-E

48、C-042w/pomalidomide+dexamethasoneMultiple myeloma(2L+)XPORT-MM-0312,3w/multiple approved agentsMultiple myeloma(relapsed/refractory)STOMP4monotherapyMyelofibrosis(previously treated)XPORT-MF-035w/ruxolitinibMyelofibrosis(treatment nave)XPORT-MF-0345ELTANEXORmonotherapyMyelodysplastic neoplasms(refra

49、ctory)KCP-8602-8011.1.XPORT-DLBCL-030 is a Phase 2/3.2.Versus elotuzumab,pomalidomide,and dexamethasone.2.3.EMN29 Study:Sponsored by European Myeloma Network.4.STOMP has a total of 11 arms;enrollment complete in all arms5.XPORT-MF-034 is a Phase 1/2.Progressing Focused Pipeline Across Cancers With H

50、igh Unmet Needssolid tumor cancerhematologic cancer132023 KARYOPHARM THERAPEUTICS INC.13Endometrial Cancer60 mg QWXPORT-42Multiple Myeloma160 mg(80 mg BIW)STORM1Multiple Myeloma100 mg QWBOSTONMultiple Myeloma100-60*mg QWSTOMPEndometrial Cancer80 mg QWSIENDOMyelofibrosis80-60 mg QWXPORT-351Myelofibro

51、sis60-40 mg QWXPORT-34Optimizing Selinexor Dose to Improve Patient Experience and Overall Benefit Multiple Myeloma60-40 mg QWXPORT-31/EMN29July 2019:1st MM U.S.Commercial Approval DateDec 2020:2nd MM U.S.Commercial Approval DatePh 1/2 Study:Completed/OngoingOngoingPh 3 Study:OngoingPh 2 Study:Ongoin

52、gPh 1/2 Study:OngoingPh 3 Study:Ongoing1.1.Following 80mg weekly*2 cycles80-60 mg QW142023 KARYOPHARM THERAPEUTICS INC.ENDOMETRIAL CANCER152023 KARYOPHARM THERAPEUTICS INC.15Initiated Global Phase 3 Pivotal Study;TP53 Mutation Status Will Be Assessedby Companion Diagnostic Partner Foundation Medicin

53、e1Primary Endpoint PFS assessed by InvestigatorKey Secondary Endpoint OSSecondary Endpoints4 Safety HR-QoLPlacebo weekly until PD n=110Selinexor 60 mg orally QW until PDn=110R1:1Key EligibilityTP53 wild-type endometrial cancer1 Primary stage IV or recurrent EC Received at least 12 weeks of platinum-

54、based therapy+/-immunotherapy In partial response(PR)or complete response(CR)to chemotherapyXPORT-EC-042 Global Phase 3,Randomized,Double-Blind,Trial of Selinexor as Maintenance Therapy for Patients with TP53 Wild-type,Advanced or Recurrent Endometrial Cancer(N=220)HR-QoL,health-related quality of l

55、ife;OS,overall survival;PFS,progression-free survival;PD,progressive disease;QW,every week1.Utilizing Foundation Medicines tissue-based next generation sequencing test to identify TP53 status2.European Network for Gynaecological Oncological Trial groups;3.Gynecologic Oncology(GOG)Foundation 4.Select

56、ed secondary endpoints Study in Collaboration with ENGOT2and GOG3162023 KARYOPHARM THERAPEUTICS INC.Updated Exploratory Subgroup Analysis from SIENDO Study in Patients with TP53 Wild Type Endometrial Cancer1,2Further Supports Rationale for Evaluating Selinexor as Maintenance Therapy1.1.TP53 WT/MUT s

57、tatus of patients under continued evaluation.10%of patients on the selinexor arm and 7%of patients on the control arm have pending tumor TP53 status.2.2.Preliminary data from pre-specified exploratory subgroup analysis as of the database cut date of November 30,2022.Most common adverse events(AE)wer

58、e nausea,vomiting and diarrhea with no meaningful change in the AE profile since last data cutMost common Gr 3/4 AEs were neutropenia(18%),nausea(12%),thrombocytopenia(9%)and fatigue(8%).No Grade 5 events observedAEs were generally manageable with supportive care and dose modificationsMedian PFSSeli

59、nexor(n=77):20.8 monthsPlacebo(n=36):5.2 monthsThe safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S.FDA or any other regulatory authority.172023 KARYOPHARM THERAPEUTICS INC.17Supportive Mechanism of ActionForced retention of p53 in

60、the cell nucleus by inhibition of XPO1allows p53 to carry out its tumor suppressor and other regulatoryfunctionsPhase 3 SIENDO study Generated strong hypothesis in patientswith TP53 wild-typeECCurrently no FDA approvedtreatments in themaintenancesettingAddressing a significant unmet needSignificant

61、market opportunity14K patients diagnosed with advanced and recurrent endometrial cancer in the U.S.each year150%of these patients have TP53 wild-type EC2Potential for Significant Paradigm Shift for the Treatment of Women with Advanced or Recurrent TP53 Wild-Type Endometrial Cancer1.1.Clarivate/DRG E

62、ndometrial Carcinoma Epidemiology Dashboard(2022 figures,pub 2020 2.“Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer:An NRG Oncology study”,Leslie,Kimberly K.et al.Gynecologic Oncology,Volume 161,Issue 1,113 121The

63、safety and efficacy of selinexor in endometrial cancer has not been established and has not been approved by the U.S.FDA or any other regulatory authority.182023 KARYOPHARM THERAPEUTICS INC.MYELOFIBROSIS192023 KARYOPHARM THERAPEUTICS INC.19There are 17,000 Americans living with MF in the U.S.each ye

64、ar1What is Myelofibrosis(MF)?Bone marrow cancer that disrupts bodys normal production of blood cells Causes extensive scarring in bone marrow,leading to enlarged spleen,severe anemia and constitutional symptomsTreatment Landscape and Unmet Need Ruxolitinib is the standard of care for newly diagnosed

65、 MFApproximately 40%of patients respond2Responses last up to 4 yearsOnce patients stop responding,the median survival is only 14 months3 and 5-year survival is 18%4 No other approved class of therapies other than JAK inhibitors in the last 10 years1.Clarivate/DRG Epidemiology Data(2022 figures,pub 2

66、019).2.https:/ Nov 2021.3.Newberry KJ,et al.Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation.Blood.2017;130:11251131;Palandri F,et al.Life after ruxolitinib:reasons for discontinuation,impact of disease phase,and outcomes in 218 patients with myelofibrosis.Cancer.2019

67、;26:12431252;Kuykendall AT,et al.Between a rux and a hard place:evaluating salvage treatment and outcomes in myelofibrosis after ruxolitinib discontinuation.Ann Hematol.2018;97:435441.4.Price et al.PLoS One.2014;9(3):e902995 5.Internal assumption based on historical range of 2g/dL increase)at last f

68、ollow upSAFETY AND TOLERABILITYMost common TEAEs6(n=24):Nausea,anemia and fatigue(majority Grade 1-2)Most common Grade 3 TEAEs:Anemia(38%)and thrombocytopenia(21%)232023 KARYOPHARM THERAPEUTICS INC.23One patient received 20 mg for 3 cycles then 60 mg for 3 cycles and was included in the 40mg group f

69、or the purpose of this analysisAt Week 24,All Evaluable Patients had Reduction in Spleen Volume Relative to BaselineThe safety and efficacy of selinexor in myelofibrosis has not been established and has not been approved by the U.S.FDA or any other regulatory authority.242023 KARYOPHARM THERAPEUTICS

70、 INC.0%10%20%30%40%50%60%70%80%90%100%0 Weeks12 Weeks24 WeeksSpleen Volume Reduction1.One patient with missing TSS 50 score2.Assigned selinexor starting dose 0%10%20%30%40%50%60%70%80%90%100%0 Weeks12 Weeks24 WeeksTotal Symptom Score Reduction1Selinexor Dose2=60mgSelinexor Dose2=40mgEncouraging Evid

71、ence of Selinexor Activity in Retrospective,Exploratory Analysis from Phase 1 Selinexor+Ruxolitinib Study(034)in Patients with Treatment Nave Myelofibrosis Whose Ruxolitinib Dose Was Reduced to 5mg at Cycle 1 or 2Inhibition of XPO1 Is Potentially a Fundamental Mechanism in Myelofibrosisn=7SVR 35TSS

72、50n=6The safety and efficacy of selinexor in myelofibrosis has not been established and has not been approved by the U.S.FDA or any other regulatory authority.252023 KARYOPHARM THERAPEUTICS INC.Single-Agent Selinexor Resulted in Sustained Spleen Responses in Refractory MF Patients in Phase 2 ESSENTI

73、AL Study1,2-70-60-50-40-30-20-10010203040Spleen volume change(%)SVR35SVR25-62%-55%-43%-37%-32%-25%-3%-2.5%2%27%Two patients not evaluable:One patient died due to liver abscess after 9 weeks of treatment(unrelated)and one patient discontinued after 18 weeks due to grade 3 fatiguePresence of high-risk

74、 mutation(ASXL1,EZH2,IDH1/2,SRSF2 or U2AF1)SVR35 at week 24=30%;SVR35 at week 24=40%(4/10 pts)SVR25 at week 24=50%;SVR25 at week 24=60%(6/10 pts)%Week 12Week 24Week 241.Tantravahi,et al.ASH 202 2.Data cut-off as of November 20212.Preliminary data cut from investigator sponsored open label trialThe s

75、afety and efficacy of selinexor in myelofibrosis has not been established and has not been approved by the U.S.FDA or any other regulatory authority.SVR25,spleen volume reduction of at least 25%;SVR35,spleen volume reduction of at least 35%262023 KARYOPHARM THERAPEUTICS INC.*Pending regulatory feedb

76、ackInitial Data Suggest That Selinexor May Have the Greatest Benefit in Treatment Nave Myelofibrosis XPORT-MF-034 Ph 1/2 Initiate Ph 3*in 1H 2023XPORT-MF-035 Ph 2Combination with JAKi(ruxolitinib)Single AgentEvaluating evolving data to determine optimal and efficient developmental pathway that may i

77、nclude monotherapy and innovative combinations272023 KARYOPHARM THERAPEUTICS INC.MYELODYSPLASTIC NEOPLASMS282023 KARYOPHARM THERAPEUTICS INC.What is Myelodysplastic Neoplasms(MDS)?Blood-forming cells in marrow become abnormal and create immature blood cells that are not able to function properlyTrea

78、tment Landscape Hypomethylating agents(HMA)are the current standard of care for patients with newly diagnosed,higher-risk MDS Approximately 50%of patients respond;responses typically last 2 years2Opportunity and Unmet Need Prognosis in relapsed/refractory disease is poor,with an expected survival of

79、 4-6 months3,4 No currently approved therapies for HMA-refractory diseaseEltanexor Has the Potential to Improve Survival in High Risk Relapsed/Refractory Myelodysplastic Neoplasms15,000 patients diagnosed with intermediate-to-high risk MDS each year in the US11.Clarivate/DRG Myelodysplastic-Syndrome

80、-Epidemiology-Dashboard(2022 figures,pub 2020)2.Gil-Perez A.Ther Adv Hematol.2019 doi:10.1177/2040620719847059.3.Jabbour E,Cancer.2010;116(16):3830-4.4.Prbet T.J Clin Oncol.2011;29:3322-7.292023 KARYOPHARM THERAPEUTICS INC.1.Lee,Sangmin,et al.ASH 2021.2.n=15;10 patients on 20mg eltanexor and 5 patie

81、nts on 10mg eltanexor3.Clavio M,Cancer.2021;127(12):2015-24.Single-agent Eltanexor Demonstrated Promising Activity Among Patients WithHMA Refractory MDS in a Phase 1 Study1 Historical overall survival(OS)of 4-6 months in patients with relapsed/refractory MDS3 Single-agent eltanexor demonstrated medi

82、an OS of 9.9 months2The Grade 3/4 AEs across all patients were anemia(40%),leukopenia(20%),thrombocytopenia without bleeding(20%),decreased appetite/weight(20%),neutropenia(40%):no febrile neutropenia,1 case of sepsis.No severe bleeding events which is the corresponding clinical outcome for thromboc

83、ytopenia(as you have febrile neutropenia and sepsis as the clinical outcome for neutropenia.)The safety and efficacy of eltanexor in myelodysplastic syndrome not been established and has not beenapproved by the US FDA or any other regulatory authority.OS months150105Survival probability0.41.00.60.80

84、.20.0The safety and efficacy of eltanexor in MDS has not been established and has not been approved by the U.S.FDA or any other regulatory authority.302023 KARYOPHARM THERAPEUTICS INC.30Phase 2 Expansion of the Ongoing Phase 1/2 Study of Single-Agent Eltanexorin Relapsed/Refractory MDSPhase 2(PART F

85、)Enrollment(N=83)Relapsed/Refractory MDSPrimary Endpoint:ORRSecondary Endpoints:OS 6-month OS PFS DCR DOR Rate of transfusion independenceEltanexor 10 mg PO on days 1-5 of each week(28-day cycle)DCR,disease control rate;DOR,duration of response;MDS,myelodysplastic syndrome;ORR,overall response rate;

86、OS,overall survival;PFS,progression-free survival;PO,by mouth;Karyopharm Therapeutics Inc.Clinical Study Protocol.Version 7.0.KCP-8602-801.Data from planned interim analysis(n=30)expected in Q1 2023312023 KARYOPHARM THERAPEUTICS INC.FINANCIAL HIGHLIGHTS AND MILESTONES322023 KARYOPHARM THERAPEUTICS I

87、NC.32Financial Snapshot$279M$279MLate 2025Late 2025$120.4M$120.4MCASH,EQUIVALENTS&INVESTMENTS*31-Dec-20221EXPECTED CASH RUNWAYNET PRODUCT REVENUE20221$157.7M$157.7MNET TOTAL REVENUE202211.Preliminary unaudited estimates1.*Includes restricted cash332023 KARYOPHARM THERAPEUTICS INC.33MYELOFIBROSISENDO

88、METRIAL CANCERMULTIPLE MYELOMAUpcoming Milestones for 2023 and Beyond Leverage commercial capabilities and grow US XPOVIO sales(2023)Continuation of global launches(2023)Report top-line results from pivotal Phase 3 study evaluating SPd1(2H 2024)Present updated results from SIENDO study at a medical

89、conference(2023)Report top-line results from pivotal Phase 3 study EC-042 in TP53 wild-type EC(2H 2024)Report interim Phase 2 eltanexor data in relapsed/refractory MDS (1Q 2023)and top-line data(2024)Report updated results in Phase 1 trial of selinexor+ruxolitinib in treatment nave MF(1H 2023)Initiate pivotal Ph 3 selinexor+ruxolitinib study in treatment nave MF(1H 2023)Define optimal mono and innovative combo development plan(1H 2023)MYELODYSPLASTIC NEOPLASMS1.Selinexor+pomalidomide+dexamethasone342023 KARYOPHARM THERAPEUTICS INC.Thank you!