Karyopharm Therapeutics Inc. · NASDAQ:KPTI
Karyopharm Therapeutics — Investor Presentation (April 2017)
35 slides from Karyopharm Therapeutics's investor presentation, Apr 5, 2017
Slide 1: Corporate Presentation April 2017
Corporate Presentation April 2017 Exhibit 99.1
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
Slide 3: Karyopharm Overview
Karyopharm Overview Innovators First to enter clinical development Oral XPO1 inhibitors for the treatment of cancer and other major diseases SINE™ Compounds Novel, unique and broadly applicable MoA Lead candidates are first-in-class, oral Selective Inhibitor of Nuclear Export (SINE™) compounds Fully
Slide 4: Selinexor: Novel Oral Anti-Cancer Agent
Selinexor: Novel Oral Anti-Cancer Agent Restores Tumor Suppressors & Reduces Oncoproteins ©2017 Karyopharm Therapeutics Inc.
Slide 5: Karyopharm's Broad Therapeutic Pipeline
Karyopharm’s Broad Therapeutic Pipeline AREA OF THERAPY Selinexor and Dexamethasone + Bortezomib, Pomalidomide, Lenalidomide, Daratumumab* or Bortezomib & Pomalidomide* PRECLINICAL PHASE III Liposarcoma Gynecologic Malignancies Glioblastoma Diffuse Large B-cell Lymphoma Multiple Myeloma Hematologica
Slide 6: Selinexor in Myeloma: First Oral Agent with Novel Mechanism
Selinexor in Myeloma: First Oral Agent with Novel Mechanism and Single Agent Activity Since the IMiDs
Slide 7: Selinexor Advantages in Multiple Myeloma
Selinexor Advantages in Multiple Myeloma Novel agent with anti-MM activity, including in penta-refractory disease Oral, taken at home Combinable with observed additive or synergistic activity and potential to resensitize to prior therapies PIs: Velcade and Kyprolis IMiDs: Revlimid and Pomalyst Combi
Slide 8: Drugs with Single Agent Activity are Widely Used in MM
Drugs with Single Agent Activity are Widely Used in MM Drug Year Population ORR Key Combinations Velcade (V, Bortezomib) 2003 >2 therapies, refractory to last 27.7% Vd, VRd, VMP, CyBorD Kyprolis (K, Carfilzomib) 2012 Prior Vel + Rev, refractory to last 22.9% Kd, KRd, KPd Pomalyst (P, Pomalidomide) +
Slide 9: STORM: Selinexor in Refractory Myeloma
STORM: Selinexor in Refractory Myeloma: Quad and Penta Populations
Slide 10: STORM – Patient Characteristics
STORM – Patient Characteristics STORM Patient Characteristics Quad Refractory Penta Refractory Patients Enrolled as of November 1, 2016 48 31* Median Age, Years (range) 62 (41 –78) 68 (34 – 78) Males : Females 24 (50%) : 24 (50%) 13 (42%) : 18 (58%) Patients treated with 6 doses : 8 doses / cycle 40
Slide 11: STORM Efficacy (per IRC)
STORM Efficacy (per IRC) ©2017 Karyopharm Therapeutics Inc. ORR: 21% CBR: 33% 5 15 13 35 12 21 4 17 8 44 8 19 7 13 20 20 17 23 6 14 10 41 8 22 4 19 19 22 19 19 Median time to response: 1 mo Median DoR: 5 mos Vogl DT, et al. ASH 2016. Abstract 491. 100 80 60 40 20 0 Overall (n = 78) Quad (n = 48) Pen
Slide 12: STORM: Overall Survival
STORM: Overall Survival (OS) in Patients with ≥MR vs ≤SD Median OS All (N=78) ≥ MR (N=26) ≤ SD (N=52)* 9.3 mos Not Reached 5.7 mos ©2017 Karyopharm Therapeutics Inc. * Includes 16 NE patients
Slide 13: Treatment Related Adverse Events
Treatment Related Adverse Events ≥10% 41 patients (52%) required dose interruptions 29 patients (37%) required dose reductions 14 patients (18%) discontinued treatment due to toxicities AE Term Grade1 Grade 2 Grade 3 Grade 4 Total Gastrointestinal Nausea 41% 25% 8% -- 73% Anorexia 19% 28% 3% -- 49%
Slide 14: Multiple Myeloma Accelerated Approval Strategy
Multiple Myeloma Accelerated Approval Strategy STORM Expansion Underway (N=122 additional patients) Patients with penta-refractory disease are considered an unmet medical need Additional sites being added in the US and EU to support expansion As of March 30 2017, partial clinical hold lifted by U.S.
Slide 15: STOMP: Selinexor and Backbone Treatments
STOMP: Selinexor and Backbone Treatments for Relapsed/Refractory Multiple Myeloma
Slide 16: Selinexor + Velcade + Dexamethasone (SVd) Efficacy – Phase 1
Selinexor + Velcade (Bortezomib) + Dexamethasone (SVd) Efficacy – Phase 1 ORR 67% ORR 77% ORR 100% ORR 100%* ORR 80% ORR 74% ©2017 Karyopharm Therapeutics Inc. * BOSTON study population
Slide 17: SVd Treatment Related AEs at Recommended Dose
100 mg Sel QW + 1.3 mg/m2 Velcade QW + 40 mg Dex RP2D (N=17) AE Term Grade1 Grade 2 Grade 3 Grade 4 Total Gastrointestinal Nausea 24% 35% -- -- 59% Anorexia 35% 6% -- -- 41% Vomiting 29% 6% -- -- 35% Diarrhea 18% -- 6% -- 24% Altered Taste 6% - 6% - 12% Constitutional Fatigue 18% 12% 6% -- 35% Hemat
Slide 18: Selinexor – Kyprolis – Dex Reinforces Sel+PI Synergy
Selinexor – Kyprolis – Dex Reinforces Sel+PI Synergy A Jakubowiak, et al. ASH 2016. Study sponsored by the University of Chicago with support from Karyopharm, Amgen and the MMRF. ©2017 Karyopharm Therapeutics Inc. * 84 47 11 84 63 26 75 67 17 All Pts After 1 cycle All Pts Best response CFZ-ref at la
Slide 19: Selinexor + Pomalyst + Dexamethasone (SPd) Efficacy – Phase 1
†Responses were adjudicated according to the International Myeloma Working Group criteria, ‡ included one unconfirmed PR. ORR=Overall Response Rate (VGPR+PR), VGPR=Very Good Partial Response, PR=Partial Response, MR=Minor Response, SD=Stable Disease, PD=Progressive Disease, CBR=Clinical Benefit Rate
Slide 20: Randomized Phase 3 Global BOSTON Trial
Randomized Phase 3 Global “BOSTON” Trial A Phase 3 Randomized, Open-Label Multicenter Study of Selinexor, Velcade (bortezomib) and Dexamethasone (SVd) vs. Velcade (bortezomib) and Dexamethasone (Vd) in Patients with Relapsed/Refractory Myeloma Key Aspects of Study Design 1-3 prior line of therapy, n
Slide 21: US Treatment Landscape for Multiple Myeloma
Follow On Therapy Auto SCT if prior SCT had DOR of 16-36 mos Follow On Therapy Transplant Ineligible Auto SCT & Rd Maintenance Intermediate or High Risk Auto SCT & Vd or Kd Maintenance Standard Risk Rd Maintenance Intermediate or High Risk Vd Maintenance 2nd line Therapy for Relapsed/Refractory Repe
Slide 22: SADAL Study in DLBCL
e Fy) & SADAL Study in DLBi
Slide 23: SADAL: Randomized Phase 2b Trial in DLBCL
SADAL: Randomized Phase 2b Trial in DLBCL SADAL: Selinexor Against Diffuse Aggressive Lymphoma Ongoing Randomized Trial for Accelerated Approval Relapsed / refractory ≥3rd line; At least 50% of patients with GCB-DLBCL 28.6% ORR in the first 63 patients in Phase 2b DLBCL study with median DOR >7 mont
Slide 24: SADAL Efficacy – Independent Central Radiological Review
SADAL Efficacy – Independent Central Radiological Review (N=63) Best Responses† in the First 63 Patients as of March 1, 2017 * Category N ORR (%) DCR (%) CR (%) PR (%) SD (%) PD (%) NE (%) All Patients 63 18 (28.6%) 27 (42.9%) 7 (11.1%) 11 (17.5%) 9 (14.3%) 29 (46.0%) 7 (11.1%) 60 mg 32 9 (28.1%) 12
Slide 25: SADAL Responders: Duration of Treatment
Among responders in the 60 mg arm the median time on treatment was >9 months (median DOR >7 months) with a follow up of 13 months. Nine responders in total remain on treatment including 6 patients with a CR. The median time to onset of response was ~2 months (i.e., at the first response evaluation).
Slide 26: SADAL Efficacy – Overall Survival
Median overall survival among all patients was 8 months (consistent with published data in this population), un-defined among responders, undefined for patients treated at 60 mg, and 7.5 months for patients treated at 100 mg SADAL Efficacy – Overall Survival * ©2017 Karyopharm Therapeutics Inc. * Pr
Slide 27: US Treatment Landscape for DLBCL
US Treatment Landscape for DLBCL Front line Chemoimmuno- therapy CR PET Negative PR PET Positive No response or PD Initial Therapy 2nd line Therapy for Relapsed/Refractory Consolidation 3rd Line Therapy for Relapsed/Refractory Auto SCT Clinical Trial R-CHOP EPOCH RGCVP Other RICE/ICE DHAP +/- R ESHA
Slide 28: Solid Tumors
e Fy) & Solid Tumors
Slide 29: SEAL: Phase 2/3 Trial in Liposarcoma
SEAL: Phase 2/3 Trial in Liposarcoma SEAL: Selinexor in Advanced Liposarcoma Phase 2 portion fully enrolled = 51 patients Evaluating patients with advanced unresectable dedifferentiated liposarcoma Randomized 1:1, double blind, single-agent selinexor (60mg fixed dose, twice weekly) vs. placebo Prima
Slide 30: SIGN: Phase 2 in Gynecological Malignancies
Cancer Type Dose N DCR (%) PR (%) SD > 12 Weeks (%) Ovarian 35 mg/m2 (BIW) 18 11 (61%) 2 (11%) 50 mg/m2 (BIW) 22 10 (45%) 3 (14%) 50 mg/m2 (QW) 19 8 (42%) 3 (16%) All Doses 59 29 (49%) 8 (14%) 21 (36%) Endometrial 50 mg/m2 (BIW) 20 9 (45%) 3 (15%) 6 (30%) Cervical 50 mg/m2 (BIW) 23 6 (26%) 1 (4%) 5
Slide 31: KPT-8602: Second Generation SINE Compound
KPT-8602: Second Generation SINE™ Compound Karyopharm is committed to maintaining its leadership position in the discovery and development of SINETM compounds KPT-8602 belongs to a novel chemical series with pharmacological properties distinct from selinexor More reversible binding to XPO1 at Cys528
Slide 32: Financial Overview – Unaudited Projections
Financial Overview – Unaudited Projections Cash, Cash Equivalents & Investments ~$175 MM at December 31, 2016 Expected to fund the Company until the end of 2018 Shares Outstanding as of December 31, 2016 Basic: ~41.9 MM common shares Fully diluted: ~47.7 MM common shares ©2017 Karyopharm Therapeutic
Slide 33: Anticipated Corporate Milestones
KPT-8602: Phase 1/2 top-line data Late 2017 KPT-9274: Phase 1/2 top-line data (safety and tolerability) Mid 2017 Anticipated Corporate Milestones STORM: Phase 2b expansion top-line dataEarly 2018 BOSTON: Phase 3 top-line data2019 Multiple Myeloma SEAL: Phase 2 top-line data (PFS)Mid 2017 Solid Tumor
Slide 34: Karyopharm Overview
Karyopharm Overview Innovators First to enter clinical development Oral XPO1 inhibitors for the treatment of cancer and other major diseases SINE™ Compounds Novel, unique and broadly applicable MoA Lead candidates are first-in-class, oral Selective Inhibitor of Nuclear Export (SINE™) compounds Fully
Slide 35: Thank You
Thank You
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