Karyopharm Therapeutics Inc. · NASDAQ:KPTI

Karyopharm Therapeutics — Investor Presentation (November 2015)

32 slides from Karyopharm Therapeutics's investor presentation, Nov 10, 2015

  1. Slide 1: Corporate Presentation: Targeting Disease at the Nuclear Pore

    Exhibit 99.1 NASDAQ: KPTI Corporate Presentation November 2015 Targeting Disease at the Nuclear Pore

  2. Slide 2: Forward-looking Statements

    Forward-looking Statements This presentation contains forward-looking statements within the meaning of the “safe harbor” provisions of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the therapeutic potential of and potential clinical dev

  3. Slide 3: Karyopharm: At the Nucleus of Cancer Care

    Karyopharm: At the Nucleus of Cancer Care Karyopharm’s wholly owned, lead SINE™ compound selinexor offers an entirely new approach to cancer therapy that restores the ability of a cell to detect cancerous changes and commit suicide Novel mechanism Tumor Suppressor Protein First in class (TSP) activa

  4. Slide 4: Selinexor: SINE Compound with Broad Clinical Development Strategy

    Selinexor: SINE™ Compound with Broad Clinical Development Strategy DRUG CANDIDATE AREA OF THERAPY PRECLINICAL PHASE 1 & PHASE 2 PHASE 2 or 3 AML (SOPRA) Richter’s (SIRRT) DLBCL (SADAL) Hematological Malignancies Multiple Myeloma (STORM) Multiple Myeloma (STOMP) Sel+Pom+Dex; Sel+Bort+Dex; Sel+Len+Dex

  5. Slide 5: Karyopharm's Broad Therapeutic Pipeline

    Karyopharm’s Broad Therapeutic Pipeline DRUG CANDIDATES AREA OF THERAPY PRECLINICAL PHASE 1 & PHASE 2 REGISTRATION Topical Selinexor (KPT-330) Wound Healing Diabetic Foot Ulcers Hematological Malignancies Canine Lymphoma – NADA Submission in Progress (MUMS designation received) Oral Verdinexor (KPT-

  6. Slide 6: Selinexor: Novel Anti-Cancer Agent: Restores Tumor Suppressors & Reduces Oncoproteins

    Selinexor: Novel Anti-Cancer Agent: Restores Tumor Suppressors & Reduces Oncoproteins CYTOPLASM Cell Membrane Tumor Suppressors XPO-1 Tumor Suppressors p53 Par-4 PP2A pRB Nuclear Pore Complex p21 Nuclear Envelope SINE IkB BRCA1 p27 Tumor Suppressors elF4E (myc,bcl2 mRNA) 6 ©2015 – Karyopharm Therape

  7. Slide 7: Initial Focus for Single-Agent Approval of Selinexor

    Initial Focus for Single-Agent Approval of Selinexor in: • DLBCL • Acute Myeloid Leukemia • Multiple Myeloma • Richter’s Transformation 7 ©2015 –Karyopharm Therapeutics Inc.

  8. Slide 8: Selinexor's Broad and Durable Oral Single-Agent Anti-Tumor Activity

    Selinexor’s Broad and Durable Oral Single-Agent Anti-Tumor Activity SelinexorBroad and durable single-agent anti-tumor activity in a pill 1,250+ Patients treated to date with single agent or in combination up to 50%Disease control across hematologic and solid tumor malignancies >6 month Durability –

  9. Slide 9: Diffuse Large B-Cell Lymphoma: The Opportunity

    Diffuse Large B-Cell Lymphoma: The Opportunity Aggressive form of Non-Hodgkin’s Lymphoma (NHL) Incidence: 25,000 new cases annually in the US • ~40%of incidentpatientswill succumbto their disease • ~10,000deathsper yearin USA(~22,500worldwide) Greatest unmet need currently in GCB and Double-Hit Subt

  10. Slide 10: Best Responses in DLBCL Patients

    Best Responses in DLBCL Patients Total Category ORR CR PR SD PD DCR Evaluable All Patients 39* 31% 4 (10%) 8 (21%) 8 (21%) 19 (49%) 51% Patientsonstudy> 1 Month 28 43% 4 (14%) 8 (29%) 8 (29%) 8 (29%) 71% De novo 28 25% 3 (11%) 4 (14%) 6 (21%) 15 (54%) 46% Origin Transformed 11 45% 1 (9%) 4 (36%) 2 (

  11. Slide 11: Selinexor in DLBCL: Promising Responses in Single Hit and Double Hit Patients (ICML)

    Selinexor in DLBCL: Promising Responses in Single Hit and Double Hit Patients (ICML) 11 ©2015 – Karyopharm Therapeutics, Inc.

  12. Slide 12: Phase 1 DLBCL Data: Response Correlates with Overall Survival (EHA 2015)

    Phase 1 DLBCL Data: Response to Selinexor Correlates with Overall Survival (EHA 2015) OS (CR/PR vs SD/PD) PFS (CR/PR vs SD/PD) Patients at risk Data as of May 16, 2015 Presentedat the20th Congress ofthe EuropeanHematology Association, Vienna,Austria2015 12 ©2015 – Karyopharm Therapeutics, Inc.

  13. Slide 13: SADAL: Randomized Phase 2 Trial in DLBCL

    SADAL: Randomized Phase 2 trial in DLBCL SADAL: Selinexor Against Diffuse Aggressive Lymphoma Ongoing Randomized Trial for Accelerated Approval • Relapsed/ Refractory>3rd line • Twice-weeklyrandomizedsingle-agentselinexor1:1: selinexor60 mg vs.selinexor100 mg • >50%of patientswith GCB-DLBCL • Target

  14. Slide 14: Potential Selinexor NHL Development

    Potential Selinexor NHL Development 2014 2015 2016 2017 H1 H2 H1 H2 H1 H2 H1 H2 Ph1 Ph2 Sel+ Rituxin NHL Selinexorin PTCL and CTCL Phase 3 Studies: Randomized SADAL: Ph 2 Selinexor in DLBCL Studies with (high vs. low Sel dose) Selinexor- Rituximab in Combination Ph2 Selinexorin Richter’s transformat

  15. Slide 15: Multiple Myeloma: The Opportunity

    Multiple Myeloma: The Opportunity Multiple Myeloma represents a significant patient population for selinexor Second most commonly diagnosed blood cancer, after NHL • 114,000new casesworldwideeachyear • In the US,a prevalenceof approximately83,000,with 24,050new casesand 11,090deathsin 2014 • Initial

  16. Slide 16: STORM & STOMP

    STORM & STOMP STORM: Selinexor Treatment of Refractory Myeloma • PlannedSingleArm Trialfor Relapsed/Refractoryafter > 4 approvedagents • Quadrupledrug exposed,dual-classrefractory: REVLIMID®, POMALYST®, KYPROLIS® and VELCADE® • Initiated May 2015,~80patients • PrimaryEndpoint:OverallResponseRate • I

  17. Slide 17: Multiple Myeloma: Phase 1/2 Data, Selinexor + Dexamethasone

    Multiple Myeloma: Phase 1 Data Selinexor + Dexamethasone • Phase1/2 combinationstudywith ten evaluablepatientstreatedwith selinexor(45mg/m2 ) + low dose dexamethasone(20 mg) • Heavily pretreated with a median of 7 prior therapies • In ten patients: 6 responses (5 PR, 1 CR), 2 MR, 1 PD, 1 not evaluab

  18. Slide 18: Promising Potential in Patients with Carfilzomib-Refractory MM

    Promising Potential in Patients with Carfilzomib-Refractory MM SELINEXOR + CARFILZOMIB IN PATIENTS WITH CARFILZOMIB-REFRACTORY MM (Selinexor30 mg/m 2 + Carfilzomib(20/27 mg/m 2) Days Patient Age Best Response # Prior Tx on Tx 59 113+ VGPR 4 73 85+ PR 2 64 71+ PR 5 Additional patient responses to be

  19. Slide 19: Potential Selinexor MM Development

    Potential Selinexor MM Development 2014 2015 2016 2017 2018 H2 H1 H2 H1 H2 H1 H2 H1 Ph1 STORM: Ph 2 Selinexor+ Low Dose Dex Prep/Submit Selinexor+ Dex (80 patients initially; potential upsize) NDA/EMA LAUNCH * Ph1/2 Selinexor+ Carfil+ Dex STOMP: Ph 1/2 Ph3: Selinexor + PI (Carfil / Bortez/ Len) + De

  20. Slide 20: Acute Myeloid Leukemia: The Opportunity

    Acute Myeloid Leukemia: The Opportunity Significant opportunity exists for selinexor in AML as few treatment options exist for patients • Approximately18,860newdiagnosesof AMLandapproximately7,330deathsperyearin the US • Theaverageageof a patient with AMLis 66 Older patients with relapsed AML have l

  21. Slide 21: SOPRA: Randomized Phase 2 Trial in 2nd Line AML

    SOPRA: Randomized Phase 2 Trial in 2nd Line AML SOPRA: Selinexor in Older Patients with Relapsed/Refractory AML OngoingRandomizedStudyin AMLin pts > 60 yearsold – after at leastone therapy • PrimaryEndpoint:OverallSurvival • Randomized2:1 – single-agentselinexor(60mgfixeddose)vs.“Physician’sChoice”(

  22. Slide 22: Selinexor AML Phase 1 Study: Activity in Relapsed/Refractory AML

    Selinexor AML Phase 1 Study: Activity in Relapsed/Refractory AML Best Responses in Patients with AML as 10-June-2014 N DCR ORR CR CR(i) PR MLFS SD PD NE 65 32 10 5 2 1 2 22 16 17 % 49% 15% 8% 3% 2% 3% 34% 25% 26% Selinexor Phase 1 AML Patients: Prolonged SD Patient Dose Doses/Prior Cyogenic t Days o

  23. Slide 23: Selinexor Phase 1 AML Patients with Responses

    Selinexor Phase 1 AML Patients with Responses Patient Dose Doses/ Prior Cyogenic t Prior Dayson Age 2 Flt3 NPM Response ID (mg/m) Cycle MDS Risk Therpies a Study DAU, CYT, 138 39 40 8 N N N Favorable CR 178 MITO, 111 70 23 10 Y N N Intermedate i DEC, CYT CR 157 505 82 40 8 N N N Adverse CYT CR 142 5

  24. Slide 24: Potential Selinexor AML Development

    Potential Selinexor AML Development 2014 2015 2016 2017 H1 H2 H1 H2 H1 H2 H1 H2 Ph1 Selin R/R AML SOPRA: Ph 2 Selinexor vs. Physician’s Choice (2:1) Prep/Submit NDA/EMA 170 pts; OS Endpoint Front Line (Older): Selinexor + LDAC * Pick the Winner (L1 Study); Interim 2015-6 Data Launch Phase 3 : Random

  25. Slide 25: Selinexor in Solid Tumors & Combination Studies

    Selinexor in Solid Tumors & Combination Studies 25 ©2015 –Karyopharm Therapeutics Inc.

  26. Slide 26: ASCO Summary & Conclusions – KING, SIGN, & Sarcoma

    ASCO Summary & Conclusions – KING, SIGN, & Sarcoma Selinexor shows anti-tumor activity with 13% ORR and 38% DCR in patients with GBM that progressed after temozolomide and radiation Selinexor levels in brain tumor tissue 2 hours after dosing were at or higher than those with known anti-cancer activi

  27. Slide 27: Progression Free Survival (PFS) by Sarcoma Type

    Progression Free Survival (PFS) by Sarcoma Type A All Sarcomas B Liposarcoma 100 Liposarcoma (19.4 wks, N=19) 100 Selinexor (19.4 wks) Leiomyosarcoma (16.4 wks, N=10) Last prior regimen (7.7 wks) Other sarcoma (8.3 wks, N=22) 80 80 p<0.02, HR = 0.53 p<0.03, HR = 0.55 for liposarcoma vs other 60 60 4

  28. Slide 28: ISTs Using Selinexor: Planned or Ongoing in Combination With Other Therapies

    ISTs Using Selinexor: Planned or Ongoing in Combination With Other Therapies Hematological Malignancies • Selinexor+ Carfilzomib+ Dexamethasone in patients with R/R MM • Selinexor+ Fludarabine+ Cytarabinein pediatric patients with relapsed or refractory leukemia or myelodysplastic syndrome • Selinex

  29. Slide 29: Financial and Commercial Overview

    Financial and Commercial Overview 29 ©2015 –Karyopharm Therapeutics Inc.

  30. Slide 30: Financial Overview

    Financial Overview Cash, Cash Equivalents & Investments: • ~$230.2 MM at September 30, 2015 • Expected to fund the Company into 2018 Shares Outstanding at September 30, 2015 • Basic: ~35.7 MM as of September 30, 2015 • Fully diluted: ~40.2 MM as of September 30, 2015 30 ©2015 – Karyopharm Therapeuti

  31. Slide 31: Karyopharm: At the Nucleus of Cancer Care

    Karyopharm: At the Nucleus of Cancer Care Selinexor is a novel, oral selective inhibitor of XPO1-mediated nuclear export with broad single-agent anti-cancer activity Karyopharm wholly owns the worldwide rights to selinexor with patent protection through at least 2032 Three ongoing later phase studie

  32. Slide 32: Karyopharm Therapeutics Inc.

    Karyopharm Therapeutics Inc. NASDAQ: KPTI

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