Corporate Presentation. May 2016

Transcription

1 Corporate Presentation May 2016

2 Karyopharm: At the Nucleus of Cancer Care

3 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 Such forward-looking statements include those regarding the therapeutic potential of and potential clinical development plans and commercialization for Karyopharm s drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials, and assumptions of management regarding strategic and financial expectations and projections. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the company s current expectations. For example, there can be no guarantee that any of Karyopharm s SINE compounds, including selinexor (KPT-330) and KPT-8602, Karyopharm s second generation SINE compound, or KPT-9274, Karyopharm s first-in-class oral dual inhibitor of PAK4 and NAMPT, or any other drug candidate Karyopharm is developing, will successfully complete necessary preclinical and clinical development phases or that development of any of Karyopharm s drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharm s drug candidate portfolio will result in stock price appreciation. In addition, even if Karyopharm receives marketing approval for selinexor or another drug candidate, there can be no assurance that Karyopharm will be able to successfully commercialize that drug candidate. Management s expectations and, therefore, any forward-looking statements in this presentation could also be affected by risks and uncertainties relating to a number of other factors, many of which are beyond Karyopharm s control, including the following: Karyopharm s 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 boards at clinical trial sites and publication review bodies; Karyopharm s ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm s competitors for diseases for which Karyopharm is currently developing its drug candidates; and Karyopharm s ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. These and other risks, including those which may impact management s expectations, are described in greater detail under the heading "Risk Factors" in Karyopharm s Quarterly Report on Form 10-Q for the quarter ended March 31, 2016, which is on file with the Securities and Exchange Commission, and in subsequent filings filed by Karyopharm with the Securities and Exchange Commission. Any forward-looking statements contained in this presentation are for informational purposes only and speak only as of the date hereof. Other than as is 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 s website is Karyopharm regularly uses its website to post information regarding its business, drug development programs and governance. Karyopharm 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 into this presentation by reference. Unless otherwise noted, this presentation contains data that are interim and unaudited based on site reports Karyopharm Therapeutics Inc. 3

4 Karyopharm Highlights The first company to enter clinical development with oral XPO1 inhibitors for the treatment of cancer and other major diseases Lead drug candidates are first-in-class, oral Selective Inhibitor of Nuclear Export, or SINE compounds a novel, unique and broadly applicable mechanism of action SINE TM compounds are fully owned by Karyopharm; composition of matter patents granted for selinexor with protection to at least 2032 Based on its novel mechanism of action, oral bioavailability, safety profile and singleagent activity, selinexor could serve as a backbone therapy with a diverse array of anticancer agents Data expected for multiple later-stage selinexor trials within six to 12 months (SOPRA, STORM, SADAL, SEAL) Management with track record of success in oncology drug development, regulatory approval and commercialization Well capitalized with cash runway through mid-2018, beyond advancing the four laterstage clinical studies to their next data inflection points Karyopharm Therapeutics Inc. 4

5 Selinexor Oncology Pipeline AREA OF THERAPY PHASE 1B or PHASE 2 RANDOMIZED PHASE 2 or PHASE 3 Hematological Malignancies STORM: Selinexor and Dexamethasone Multiple Myeloma STOMP: Selinexor and Dexamethasone + Lenalidomide, Pomalidomide or Bortezomib SCORE: Selinexor, Carfilzomib and Dexamethasone vs. Placebo, Carfilzomib and Dexamethasone * Acute Myeloid Leukemia SOPRA: Selinexor vs. Physician s Choice Diffuse Large B-cell Lymphoma SADAL: Selinexor (high dose vs. low dose) Solid Tumors Liposarcoma SEAL: Selinexor vs. Placebo Gynecologic Malignancies SIGN: Selinexor Glioblastoma KING: Selinexor *not yet initiated 2016 Karyopharm Therapeutics Inc. 5

6 Additional Pipeline Assets AREA OF THERAPY PRECLINICAL PHASE 1 Oncology KPT-8602 Oral 2nd Generation SINE TM Compound Multiple Myeloma KPT-9274 Oral Dual PAK4/NAMPT Inhibitor Lymphoma & Solid Tumors* Other Indications Verdinexor (KPT-335) Oral SINE TM Compound Influenza KPT-350 Oral SINE TM Compound ALS, TBI, MS, RA, SLE *not yet initiated Also subject to an ongoing New Animal Drug Application being submitted to FDA s Center for Veterinary Medicine for the treatment of canine lymphoma; Effectiveness and Safety sections have been accepted Karyopharm Therapeutics Inc. 6

7 Selinexor: Novel Oral Anti-Cancer Agent Restores Tumor Suppressors & Reduces Oncoproteins Karyopharm Therapeutics Inc. 7

8 Initial Focus for Single-Agent Approval of Selinexor in: Multiple Myeloma Acute Myeloid Leukemia DLBCL

9 Selinexor s Broad and Durable Oral Single-Agent Anti-Tumor Activity Up to 80% Up to 50% Patients treated to Disease control Disease control date with single agent or across hematologic rates in patients with in combination malignancies advanced solid tumors >6 month Durability some patients on >1 year (longest 2+ years) Karyopharm Therapeutics Inc. 9

10 STORM: Selinexor in Quadruple Exposed, Dual Refractory Myeloma

11 Multiple Myeloma: Still Unmet Need Multiple Myeloma represents a significant opportunity for selinexor Second most commonly diagnosed blood cancer, after NHL In the US, ~12,000 deaths expected in 2016 Initial focus on patients with recurrent disease following multiple lines of therapy Unmet need for patients with refractory MM after proteasome inhibitors, immunomodulatory drugs (IMIDs) and monoclonal antibodies Despite many new approvals in MM, the majority succumb to their disease Karyopharm Therapeutics Inc. 11

12 STORM: Phase 2b Trial in Quadruple Exposed, Dual Refractory in Multiple Myeloma STORM: Selinexor Treatment of Refractory Myeloma Initiated May 2015, ~80 patients Quadruple exposed: REVLIMID, POMALYST, KYPROLIS and VELCADE ~ 25% of patients also exposed to DARZALEX (daratumamab) or any other anti-cd38 Ab Single-arm, open label trial, selinexor (80 mg, twice weekly) + dexamethasone (20 mg) Primary endpoint: overall response rate Data on first 80 patients anticipated mid-2016; study may be expanded to >150 patients for potential accelerated approval Phase 1/2 Clinical Results to Date 10 patients w/ RR-MM on selinexor + low dose dexamethasone High ORR and durable responses Preparation for Additional Studies Phase 3: selinexor-pi-dex vs. PI-dex and/or selinexor-imid-dex vs. IMID-dex Additional Phase 1/2s to begin in Karyopharm Therapeutics Inc. 12

13 Multiple Myeloma: Phase 1 Data Selinexor + Dexamethasone (N= 10) selinexor (45 mg/m 2 ) + low dose dexamethasone (20 mg) Heavily pretreated (median 7 prior therapies) 6/10 responses (60%): (1 CR, 5 PR, 2 MR, 1 PD, 1 not evaluable) Median DOR ~ 7 months Patient ID MM Type Group A Patients with Rel/Ref MM Treated with Twice Weekly Oral Combination: Selinexor 45 mg/m 2 + Dexamethasone 20 mg (As of 10-May-2015) Maximal Response #Prior TX 76 IgG-k 71% PR 7 77 FLC-l -- NE 8 Prior Therapies Dox-Vinc-Dex, Thal-Dex, Carfil-Dex, VRD, Cyclo-Pred-BCNU, Sel, Doxil-Carfil-Dex Len-Dex, Cyclo-Etop-Cis-Mel-Dex-ASCT, VRD, Carfil-Cyclo-Dex, Carfil-Cyclo-Dex-Len, Carm-Thal-Cis-Etop-Cyta-Vel-Mel, Cyclo-Carfil-Pom-Dex, Vor-Len-Dex 79 FLC-k 53% PR 3 Thal-Pred-Dex-ASCT, Cyclo-Vel-Dex, Len-Dex FLC-k 99% scr 6 VAD-ASCT, Cyclo-Pred-ASCT, Rev-Dex, Cyclo-BorD (x2), Pom-Carfil-Dex IgG-k 84% PR 9 Vel-Dex, ASCT, Len-Dex, Vel-Dex, Vel, Carfil, Pom-Dex, Carfil, DT-PACE-Thal 170 Study Days IgG-k 41% PD 5 Cyclo-Vel-Len-Dex (x2), Carfil-Mel-ASCT, Cyclo-Vel-Dex, Pom-Carfil-Dex IgA-k 55% PR 9 93 IgG-l 41% MR 9 98 IgG-l 48% MR 16 Vel-Dex, VRD, ASCT, Len-Dex, Reolysin, TG02, Carfil-Dex, Carfil-Cyclo-Dex, Carfil-Pom-Dex VAD, VTD+ASCT, Vel-Len-Dex, Experim, Carfil-Panob, Len-Elotu-Dex, Experim, Pom-Dex, Benda-Pom-Dex Len-Dex, ASCT (x2), Vel-Len-Dex, Vid-Len, Benda-Vel-Dex, VAD, Ritux, Vel-Thal, Carfil-Dex, Carfil-Dex-Cis-Adria, Len-Ritux-Inter, Carfil-Pom, Vel-Thal-Dex-Adria-Cis-ATRA-Arsenic Trioxide, Len-Dex, TG02-Carfil IgA-k 82% PR 6 Sal, Thal-Dex, Len-Dex, Vel-Dex, ASCT, Ibrut-Dex Karyopharm Therapeutics Inc. 13

14 SCORE: Selinexor, Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma

15 SCORE: Phase 2/3 Trial in Refractory Multiple Myeloma SCORE: Selinexor, Carfilzomib, and Dexamethasone versus Placebo, Carfilzomib, and Dexamethasone in Refractory Multiple Myeloma Randomized, double-blind, placebo-controlled Phase 2/3 study Expected to be initiated in mid-2016, ~84 patients Relapsed/refractory MM previously treated with a proteosome inhibitor and an immunomodulatory drug Phase 2 primary endpoint: overall response rate; Data from Phase 2 anticipated mid-2017 Phase 3 primary endpoint: progression free survival Study may be expanded to ~200 patients for potential approval Clinical Results to Date Phase 1 selinexor + carfilzomib + dexamethasone combination study Early signs of promising efficacy: 67% ORR: 2 VGPR and 4 PR out of 9 patients Preparation for Additional Studies Phase 3: selinexor-pi-dex vs. PI-dex and/or selinexor-imid-dex vs. IMID-dex Karyopharm Therapeutics Inc. 15

16 Sel-Car-Dex Has High Level Activity in Carfil Refractory MM Carfil Refractory Selinexor + Carfilzomib + Dexamethasone Combination: Patient Prior Therapies Age Response # Prior TX Prior Therapies Time on Study (months) 59 VGPR 4 Len-Dex-Transplant, Bortez-Dex, Len-Dex, Carfil-Panob 4 73 PR 2 Bortez-Len-Dex-Transplant+Len Maint., Pom-Carfil-Dex 4 64 PR 5 Vinc-Dox-Dex, Bortez-Dex, Thal-Dex-Transplant, Len-Dex, Pom-Carfil-Dex PD 5 Ixaz-Len-Dex-Transplant, Carfil-Cyclo-Dex, Carfil-Dox-Cyclo-Etop-Dex, Pom-Carfil-Dex, Carfil-Dox-Cyclo-Etop-Dex-Radiation 1 63 VGPR 5 Melp-Bortez-Pred, Cyclo-Bortez-Dex, Len-Dex, Carfil, Pom-Dex PR 2 Cyclo-Bortez-Pom-Dex-Transplant, Pom-Carfil-Dex 2 68 MR 5 Len-Bortez-Dex-Len Maint., Len-Bortez-Dex-Transplant+Bortez Maint., Carfil-Bortez-Dex-Radiation, Carfil-Dex, ACY-1215-Pom-Dex 3 55 PR 2 Len-Bortez-Dex-Bortez-Carfil-Dex-HdC-ASCT-Transplant, Pom-Carfil-Dex PD 3 Carfil-Len-Dex, VDT-PACE w/asct then Cyclo-Bortez-Dex consolidation and Bortez-Dex Maint., Investigational-Carfil-Pom-Dex 1 Best Responses in Evaluable (N=9) Patients (as of 30-Sept-2015) Selinexor + Carfilzomib + Dexamathasone Combination N CBR ORR VGPR PR MR PD 9 7 (78%) 6 (67%) 2 (22%) 4 (44%) 1 (11%) 2 (22%) CBR=Clinical Benefit Response (VGPR+PR+MR), ORR=Overall Response Rate (VGPR=PR), VGPR=Very Good Partial Response, PR=Partial Response, MR=Minor Response, PD=Progressive Disease. Response as of 30-Sep-2015 based on interim unaudited data. Responses were adjudicated according to the International Myeloma Working Group criteria Karyopharm Therapeutics Inc. 16

17 Potential Selinexor MM Development H2 H1 H1 H2 H1 H2 H1 H2 H1 Ph 1 Sel + Dex STORM: Ph 2b Sel + Low Dose Dex (80 patients mid-2016; potential upsize) Prep/Submit NDA/EMA Ph 1/2 Sel + Carfil + Dex SCORE: Ph 2/3 Sel + Carfil + Dex vs. Carfil + Dex (84 patients mid-2017; potential upsize) Prep/Submit NDA/EMA STOMP: Ph 1/2 Sel + Pom + Dex; Sel + Bortez + Dex; Sel + Len + Dex Ph 3: Sel + x + Dex vs. x + Dex Ph 1/2 Sel + PLD Ph 1/2: Pre-Transplant Sel + Bortez + Dex Slide Key Bortez bortezomib (Velcade ) Carfil carfilzomib (Kyprolis ) Dex dexamethasone Len lenalidomide (Revlimid ) PI proteasome inhibitor PLD pegylated liposomal doxorubicin Pom pomalidomide (Pomalyst ) Sel selinexor Phase 1 Phase 2 Phase 3 Investigator Sponsored Karyopharm Therapeutics Inc. 17

18 SOPRA: Selinexor in Older Patients with Relapsed/Refractory AML

19 Acute Myeloid Leukemia: High Unmet Need Significant opportunity exists for selinexor in AML as few treatment options exist ~18,860 new diagnoses of AML and approximately 7,330 deaths per year in the US >50% of patients not candidates for intensive chemotherapy Only two approved treatment options for AML since 1995 Median survival of patients >60 years old unfit for chemotherapy is ~9 months Approval Plans SOPRA: Older unfit patients with AML after one line of therapy; survival data expected at end of 2016 Combination studies ongoing to inform use in first line therapy for older patients Additional opportunities for AML patients fit for chemotherapy Greatest unmet need for patients with high risk AML (~20%) All patients with relapse after initial chemotherapy Pediatric patients with relapsed disease (>50% of pediatric AML) Karyopharm Therapeutics Inc. 19

20 SOPRA: Randomized Phase 2 Trial in 2 nd Line AML SOPRA: Selinexor in Older Patients With Relapsed AML AML patients >60 years old after first relapse Hypomethylating agents or low dose cytarabine or supportive care only Randomized 2:1, open label, single-agent selinexor (60 mg fixed dose, twice weekly) vs. Physician s Choice Primary endpoint: overall survival Dose adjusted in July 2015; ~170 additional patients Interim analysis in late 2016; topline data readout anticipated mid-2017 Updated Phase 1 Clinical Results Based on 95 total patients, 78 evaluable for response (median 3+ prior therapies) Overall complete response rate: 10% [8/78 with CR/CR(i/p)] 45 patients with stable disease (58%) 68% (53 of 78) disease control rate (CR/CR(i/p) & stable disease) Karyopharm Therapeutics Inc. 20

21 SAIL: Phase 2 Selinexor + Ara-C / Idarubicin in AML SAIL: Selinexor, Ara-C and Idarubicin in AML Prognosis of relapsed/refractory AML patients is remarkably poor (expected response rate = 10-20%) Patients had a median of 3.5 (range 1-6) prior chemotherapeutic regimens; 35% had prior SCT / DLI Single-arm, open label, selinexor (40 mg/m 2, twice weekly) + ARA-C (100 mg/m 2 ) + idarubicin (10 mg/m 2 ), ~ 40 patients enrolled Primary endpoint: complete remission (CR) rate or morphologic complete remission with incomplete blood count recovery (CRi) after Initial Investigator Sponsored Trial Phase 2 Results Selinexor combines with Ara-C and idarubicin without unexpected toxicities Overall response rate was 60% (12/20): 45% CR, 5% CRi, 10% PR 60% of patients went on to receive stem cell transplantation or donor lymphocyte infusion Karyopharm Therapeutics Inc. 21

22 Potential Selinexor AML Development H1 H2 H1 H2 H1 H2 H1 H2 Ph 1 Sel in R/R AML Sel + Decitabine (OSU) SOPRA: Ph 2b Sel vs. Physician s Choice (2:1) 170 pts; OS Endpoint Phase 3: Randomized Studies with Sel in Combination Prep/Submit NDA/EMA Slide Key AraC CLAG Dauno Ida LDAC MEC Sel arabinoside cytosine clofarabine + arac + G-CSF daunorubicin idarubicin low dose arac mitoxantrone + etoposide + arac selinexor Phase 1 Phase 2 Phase 3 Investigator Sponsored SAIL: Ph 2 Induction: Sel + Ida/AraC Induction: Sel + Dauno/AraC Pediatric Acute Leukemia: AraC + Flu Relapse: Sel + MEC Relapse: Sel + CLAG Front Line Induction High Risk AML: Sel + Dauno/AraC Front Line (Older): Sel + LDAC Pick the Winner (L1 Study); Interim Data Karyopharm Therapeutics Inc. 22

23 SADAL: Selinexor Against Diffuse Aggressive Lymphoma

24 Diffuse Large B-Cell Lymphoma: High Unmet Need Aggressive form of Non-Hodgkin s Lymphoma (NHL) Incidence: 25,000 new cases annually in the US ~40% of patients will succumb to their disease ~10,000 deaths per year in USA (~22,500 worldwide) Greatest unmet need currently in GCB and double-hit subtypes of DLBCL Selinexor has shown durable single-agent activity across all subtypes of DLBCL Karyopharm Therapeutics Inc. 24

25 SADAL: Randomized Phase 2b Trial in DLBCL SADAL: Selinexor Against Diffuse Aggressive Lymphoma Ongoing Randomized Trial for Accelerated Approval Initiated December 2014, targeting ~ 200 patients Relapsed / refractory 3rd line; At least 50% of patients with GCB-DLBCL Randomized 1:1, open label, single-agent selinexor 60 mg vs. 100 mg, twice weekly Primary endpoint: overall response rate Data readout anticipated in early 2017 Preparations for Phase 3 Study Selinexor+Rituximab+Chemotherapy vs. Rituximab+Chemotherapy alone Combinations for 3rd, 2nd and 1st Line Phase 1/2 Studies to Initiate 2016 Phase 3 studies planned for Karyopharm Therapeutics Inc. 25

26 NHL: Updated Phase 1 Data Recently Highlighted at ASH Meeting NHL RESPONSE RATES Type N DCR (%) ORR (%) CR (%) PR (%) SD (%) PD (%) DLBCL (50%) 12 (30%) 4 (10%) 8 (20%) 8 (20%) 20 (50%) Richter s 5 4 (80%) 2 (40%) - 2 (40%) 2 (40%) 1 (20%) Other NHL (73%) 6 (32%) 1 (5%) 5 (26%) 8 (42%) 5 (26%) Responses were adjudicated according to the International Working Group Response Criteria for Non-Hodgkin s Lymphoma (NHL) 2007 based on interim unaudited data. DCR=Disease Control Rate (CR+PR+SD) ORR=Objective Response Rate (CR+PR), CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive Disease. RESPONSES IN IDENTIFIED SUBTYPES* Type N DCR (%) ORR (%) CR (%) PR (%) SD (%) PD (%) GCB (79%) 6 (43%) 3 (21%) 3 (21%) 5 (36%) 3 (21%) Non GCB 4 4 (100%) 1 (25%) 1 (25%) -- 3 (75%) -- *GCB/non-GCB subtypes were not defined for all patients. GCB=Germinal Center B Cell. Patient ID PATIENTS WITH OBJECTIVE RESPONSES IN DOUBLE OR SINGLE HIT DLBCL Translocation(s) Best Response % Reduction in Lymph Nodes Days on Study Prior Therapies 046 MYC/BCL2 CR -73% a 589 R-CHOP, RICE 072 MYC/BCL2 PR -63% 214 R-CHOP, Benda, RICE 432 MYC/BCL2 PR -50% b 91 (transplant) R-CHOP, RICE, Ofa-Etop-Ifo 050 BCL2 CR -100% a 737+ R-CHOP, Etop-Cyclo, R-GDP, Panob 003 BCL2 PR -93% 729 R-CHOP, R-DHAP, BEAM, GDP 402 BCL2 PR -52% 119 R-CHOP, R-GDP 72 total patients, heavily pretreated (median 4 prior therapies), with disease progression 64 evaluable patients Anti-tumor activity across all NHL types Overall response rate ( PR): 31% (8% CR, 23% PR) Disease control rate ( SD): 59% Data as of December 6, 2015 a PET-negative; b estimated, (+) patient still on therapy Karyopharm Therapeutics Inc. 26

27 Potential Selinexor NHL Development H1 H2 H1 H2 H1 H2 H1 H2 SADAL: Ph 2b Sel in DLBCL (high vs. low Sel dose) Prep/Submit NDA/EMA Ph 2 Sel in Richter s transformation (single arm) Ph 1 Sel + Ritux in NHL Ph 1/2 (2 nd /3 rd Line) Sel + Ritux + X in NHL Slide Key Dex Ibrut Ritux R-CHOP R-ICE Sel dexamethasone Imbruvica (ibrutinib) Rituxan (rituximab) Rituxan, cyclophosphamide, doxorubicin hydrochloride (Hydroxydaunomycin), vincristine sulfate (Oncovin ), prednisone, Rituxan, ifosfamide, carboplatin, etoposide selinexor Phase 1 Phase 2 Phase 3 Investigator Sponsored Ph 1/2 Sel + Ibrut in NHL + CLL Ph 1/2 (2 nd Line) Sel + R-ICE in DLBCL Ph 1/2 (1 st /2 nd Line) Sel + R-CHOP in NHL Karyopharm Therapeutics Inc. 27

28 Selinexor in Solid Tumors

29 SEAL: Phase 2/3 Trial in Liposarcoma SEAL: Selinexor in Advanced Liposarcoma Initiated January 2016; Phase 2 portion target = ~50 patients Evaluating patients with advanced unresectable dedifferentiated liposarcoma Randomized 1:1, double blind, single-agent selinexor (60mg fixed dose, twice weekly) vs. placebo Primary endpoint: progression-free survival Trial design and endpoints agreed with FDA Topline data readout from Phase 2 portion anticipated in mid-2017; study may be expanded to Phase 3 following an interim analysis Karyopharm Therapeutics Inc. 29

30 SEAL Rationale Selinexor in Phase 1 Sarcoma Single-agent selinexor demonstrated durable stable disease in liposarcoma, leiomyosarcoma and other sarcomas In patients with previously treated liposarcoma, PFS on selinexor was longer than the patient s most recent anti-cancer regimen Best Responses in Evaluable* Phase 1 Patients by Subtype as of 10-May-2015 Sarcoma Type N SD-Total (%) SD 4 Months PD(%) Liposarcoma (78%) 6 (43%) 4 (22%) Leiomyosarcoma 8 5 (63%) 3 (60%) 3 (37%) Other Sarcoma 19 8 (42%) 4 (50%) 11 (58%) Total (60%) 13 (48%) 18 (40%) *Responses were adjudicated according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) based on interim unaudited data SD-Total = Stable Disease All Patients, SD 4 Months = Patients with SD for at least 4 months Progression Free Survival (%) 100 Selinexor (19.4 wks) Last prior regimen (7.7 wks) 80 p<0.02, HR = N= Time (weeks) Karyopharm Therapeutics Inc. 30

31 KING: Phase 2 Trial in Glioblastoma Multiforme (GBM) Single-agent 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 activity Days on study T T T PR On study PD WC PR SD PD pending T Best Responses N PR SD PD DCR 16 2 (13%) 4 (25%) 10 (62%) 6 (38%) Karyopharm Therapeutics Inc. 31

32 SIGN: Phase 2 Trial in Gynecological Malignancies Single-agent selinexor showed broad anti-tumor activity across all three heavily pretreated gynecological cancer populations: Selinexor induced meaningful single-agent anti-cancer activity in patients with ovarian and endometrial cancers with disease control rates (PR+ 12 week SD) of 55% and 62% respectively, and several patients remaining on study for 6 to >11 months Cancer type Ovarian Endometrial Cervical Dose N DCR PR All mg/m 2 BIW 50 mg/m 2 QW 35 mg/m 2 BIW 50 mg/m 2 BIW 50 mg/m 2 BIW (55%) 12 (50%) 3 (60%) 3 (75%) 8 (67%) 7 (39%) 4 (12%) 3 (13%) 1 (20%) -- 2 (17%) 1 (6%) SD 12 Weeks 14 (42%) 9 (37%) 2 (40%) 3 (75%) 6 (50%) 6 (33%) PD 15 (46%) 12 (50%) 2 (40%) 1 (25%) 4 (33%) 11 (61%) Days on study Û Û Û Ovarian Endometrial Cervical ÛÚ Û Ú Ú Û Û Ú Ú Ú Ú Ú Û Ú Û Ú Ú PR On study WC PD Deceased ÚÚ Karyopharm Therapeutics Inc. 32

33 Expanding the Pipeline

34 KPT-8602: Second Generation SINE TM Compound Karyopharm is committed to maintaining its leadership position in the discovery and development of SINE TM compounds KPT-8602 is a novel chemical series with pharmacological properties distinct from selinexor More reversible binding to XPO1 at Cys528 versus selinexor Similar potency in cell-based assays (IC 50 ~20nM) Substantially reduced brain penetration KPT-8602 can be dosed daily over five days per week in animals with tolerability at least equivalent to twice weekly dosing with selinexor Apparent reduction in fatigue in animals Increased and/or more frequent dosing with continued XPO1 inhibition and potential to overcome selinexor resistance Promising efficacy including cures in difficult animal models of AML and CLL Phase 1/2 open label, dose escalation trial; 116 patients with relapsed/refractory multiple myeloma Topline safety and tolerability data readout from Phase I portion (initiated January 2016) anticipated in late Karyopharm Therapeutics Inc. 34

35 KPT-9274: First-in-Class Oral PAK4/NAMPT Inhibitor Non-competitive dual modulator of: PAK4: p21-activated kinase 4 NAMPT: Nicotinamide phosphoribosyltransferase (PBEF/Visfatin) Co-inhibition of these targets leads to synergistic anti-tumor effects through energy depletion, inhibition of DNA repair, cell cycle arrest, inhibition of proliferation, and ultimately apoptosis Oral activity in solid tumor and lymphoma xenografts with good tolerability Preparations for Phase 1 Study PANAMA: PAK4 and NAMPT in Patients with Solid MAlignancies or NHL FIH anticipated in mid-2016; 175 patients Advanced solid tumors or NHL Open label, dose escalation Primary endpoint: overall response rate at 8 weeks Karyopharm Therapeutics Inc. 35

36 Finance Update, Upcoming Milestones & Newsflow

37 Financial Overview Cash, Cash Equivalents & Investments ~$187 MM at March 31, 2016 Expected to fund the Company into mid-2018 Shares Outstanding at March 31, 2016 Basic: ~35.9 MM Fully diluted: ~41.8 MM Karyopharm Therapeutics Inc. 37

38 Anticipated Timelines STORM: Phase 2b topline data (ORR) from first 80 patients Mid-2016 Multiple Myeloma STOMP: Phase 1b topline data (recommended Phase 2 Dose) Late 2016 KPT-8602: Phase 1/2 topline data (safety and tolerability) Late 2016 SCORE: Phase 2 topline data (ORR) Mid-2017 AML DLBCL SOPRA: Phase 2 interim analysis Late 2016 Phase 2 topline data (OS) Mid-2017 SADAL: Phase 2b topline data (ORR) Early 2017 Solid Tumors SEAL: Phase 2 topline data (PFS) SIGN: Phase 2 updated data KING: Phase 2 updated data Mid-2017 Mid-2016 Mid Karyopharm Therapeutics Inc. 38

39 Karyopharm Highlights The first company to enter clinical development with oral XPO1 inhibitors for the treatment of cancer and other major diseases Lead drug candidates are first-in-class, oral Selective Inhibitor of Nuclear Export, or SINE compounds a novel, unique and broadly applicable mechanism of action SINE TM compounds are fully owned by Karyopharm; composition of matter patents granted for selinexor with protection to at least 2032 Based on its novel mechanism of action, oral bioavailability, safety profile and singleagent activity, selinexor could serve as a backbone therapy with a diverse array of anticancer agents Data expected for multiple later-stage selinexor trials within six to 12 months (SOPRA, STORM, SADAL, SEAL) Management with track record of success in oncology drug development, regulatory approval and commercialization Well capitalized with cash runway through mid-2018, beyond advancing the four laterstage clinical studies to their next data inflection points Karyopharm Therapeutics Inc. 39

40 Karyopharm Therapeutics, Inc. May 2016