NASDAQ: KPTI. At the Nucleus of Cancer Care. JP Morgan Conference. January 2015

Transcription

1 NASDAQ: KPTI JP Morgan Conference January 2015 At the Nucleus of Cancer Care

2 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 lead drug candidate, selinexor (KPT-330), including the timing of initiation of certain trials and of the reporting of data from such trials, as well as assumptions of management 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 Selinexor 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 in Exhibit 99.1 to Karyopharm s Current Report on Form 8-K filed with the Securities and Exchange Commission (SEC) on January 5, 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 as of December 1,

3 Karyopharm: At the Nucleus of Cancer Care Karyopharm s 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 First in class Oral Small molecule Selinexor New Drug Class in Oncology Tumor Suppressor Protein (TSP) activation and oncoprotein reduction Potentially relevant to any type of cancer 3 ongoing registrationdirected trials 4 additional Phase 2 trials Additional planned registration and late stage trials Clinical Development Strategy Commercial Strategy Independently commercialize wholly owned selinexor in North America & Western Europe Seek collaborators for other geographies Initial focus on the regulatory approval and commercialization of oral selinexor as a single-agent, while developing SINE compounds as novel approaches to treat a variety of diseases in areas of unmet medical need 3

4 World Renowned Cancer Institutions Leading Selinexor Development 4

5 SINE Compounds Target the Hallmarks of Cancer* Through Unique Dual Pathways Proliferative Signaling Blockers (TKIs: Gleevec, Tarceva, Ibrutinib) Tumor Suppressor Activation (Selinexor, MDM2 Inhibitors) Blocking Anti-apoptosis Proteins (Selinexor, Bcl-2 Inhibitors) Block Angiogenesis (VEGF Inhibitors: Avastin, Sutent) Inhibition of Invasion and Metastasis (Experimental Agents) Killing Replicating Cells (Chemotherapy, Cyclin Inhibitors) *Based on: Hanahan & Weinberg 2012, Cell, volume 144, issue

6 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 Nuclear Envelope Tumor Suppressors SINE IkB p21 BRCA1 p27 elf4e (myc,bcl2) 6

7 Selinexor: Novel Anti-Cancer Agent: Restores Tumor Suppressors & Reduces Oncoproteins Cell Membrane Tumor Suppressors XPO-1 Tumor Suppressors p53 Par-4 PP2A prb Nuclear Pore Complex p21 Nuclear Envelope SINE IkB BRCA1 Tumor Suppressors p27 7

8 Selinexor: Novel Anti-Cancer Agent: Restores Tumor Suppressors & Reduces Oncoproteins Cell Membrane Tumor Suppressors XPO-1 Tumor Suppressors Nuclear Pore Complex Nuclear Envelope SINE Tumor Suppressors elf4e (myc,bcl2) 8

9 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 Nuclear Envelope Tumor Suppressors SINE IkB p21 BRCA1 p27 elf4e (myc,bcl2) 9

10 Initial Focus for Single-Agent Approval of Selinexor in: DLBCL Richter s Transformation Multiple Myeloma Acute Myeloid Leukemia Potential First Launch Targeted for 2H Karyopharm Therapeutics Inc.

11 Broad and Durable Oral Single-Agent Anti-Tumor Activity Data on selinexor has demonstrated promising broad and durable oral single-agent anti-tumor activity 550+ PATIENTS TREATED TO DATE 40-60% response rates and 70-80% disease control across hematologic neoplasms Durability >6 months ~50% disease control rate in patients with advanced solid tumors Generally well tolerated; AEs are typically low grade nausea, vomiting, anorexia and fatigue, etc. 11

12 Selinexor: First Potential Approvals Key Milestones for First Potential Approvals: DLBCL Richter s AML MM Top Line Data 2H 2016 Top Line Data 1H 2017 NDA Filing 1H 2017 NDA Filing 1H 2018 US Patient Populations by Indication: DLBCL 25,000 Richter s 1,200 MM 24,000 AML 19,000 Citations: ACS and Leukemia and Lymphoma Society, Pasqualucci et al, 2013; ACS, Tsimberidou et al, MDACC; Globocan 2012, IARC; ACS 12

13 Diffuse Large B-Cell Lymphoma: The Opportunity Aggressive form of Non-Hodgkin s Lymphoma (NHL) 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 forms of DLBCL Citations: ACS and Leukemia and Lymphoma Society, Pasqualucci et al,

14 SADAL: Registration Directed Trial in DLBCL SADAL: Selinexor Against Diffuse Aggressive Lymphoma Ongoing Randomized Trial for Accelerated Approval Relapsed / Refractory 3rd line Twice-weekly randomized selinexor 1:1: selinexor 60 mg vs. selinexor 100 mg Supportive care dexamethasone (e.g., 4-8 mg) 50% of patients with GCB-DLBCL Initiated December 2014, ~200 patients Primary Endpoint: Overall Response Rate Data read out anticipated, late 2016 Preparations for Phase 3 Study Selinexor-Rituximab + Chemo vs. Chemo Alone Combinations for 3rd, 2nd and 1st Line Phase 1/2 Studies to Initiate 2015 Phase 3s planned for

15 NHL: Phase 1 Data Recently Highlighted at ASH Meeting Fifty-two patients, heavily pretreated (median 4 therapies) with disease progression Anti-tumor activity across all NHL types Durable cancer control and median DOR ~7 months (some pts on >1 year) Overall response rate ( PD): 37% (10% CR, 27% PR) Disease control rate ( SD): 73% NHL RESPONSE RATES Type N DCR (%) ORR (%) CR (%) PR (%) SD (%) PD (%) DLBCL (66%) 11 (34%) 4 (13%) 7 (22%) 10 (31%) 11 (34%) Richter s 4 4 (100%) 2 (50%) - 2 (50%) 2 (50%) - Other NHL (81%) 6 (38%) 1 (6%) 5 (31%) 7 (44%) 3 (19%) RESPONSES IN IDENTIFIED SUBTYPES Type N DCR (%) ORR (%) CR (%) PR (%) SD (%) PD (%) GCB 11 9 (82%) 4 (36%) 1 (9%) 3 (27%) 5 (45%) 2 (18%) Non GCB 5 4 (80%) 2 (40%) 1 (20%) 1 (20%) 2 (40%) 1 (20%) PATIENTS WITH DOUBLE HIT DLBCL Patient ID Best Response % Reduction in Lymph Nodes Days on Study Prior Therapies 046 CR 73% (PET Negative) 429+ CHOP-R, RICE 058 PD CHOP-R, RICE 072 PR -65% 214 R-CHOP, Benda, RICE, DHAP-R, BEAM 086 SD -45% 104 CHOP-R, GDP, Ibrutinib+Lenalidomide Data as of December 1, 2014 Presented at ASH

16 Unique Mechanism in Difficult-to-Treat DLBCL 6.9 x 4.7 cm (32.59cm 2 ) September 2013 Relapsed DLBCL (Feb 2012) Double Hit / GCB Age 73, Stage 4, bulky disease, possible CNS involvement CHOP-R initial therapy + intrathecal MTX and radiation to right arm Relapse in 10 months R-ICE treatment with relapse within 7 months Pain, marked edema, and massive lesion in right arm 4.3 x 2.1 cm (9.12 cm 2 ) October 2013 Initiates selinexor 20 mg/m 2 BIW (Sept 2013) Clinical response within 2 weeks with marked reduction in pain and edema in arm Side effects managed with supportive care; increased dose in Cycle 3 to 30mg/m2 BIW Complete remission (PET negative and biopsy negative for tumor); on study for >420 days as of December 15,

17 Richter s Transformation: The Opportunity Richter s transformation describes the appearance of an aggressive non-hodgkin s lymphoma (NHL) in patients with chronic lymphocytic leukemia (CLL), or less commonly in patients with indolent lymphomas Approx. 1,200 new cases annually in US Approx. 10% of patients with CLL will develop Richter s Transformation over the course of their disease, usually associated with longer treatment duration and certain genetic abnormalities Richter s is genetically distinct from DLBCL and is typically resistant to therapies that are highly active against DLBCL No currently approved drugs for the treatment of Richter s transformation Citations: Tsimberidou et al, MDACC 17

18 SIRRT: Registration Directed Trial in Richter s Transformation SIRRT: Selinexor in Relapsed Richter s Transformation Ongoing Randomized Trial for Accelerated Approval Single arm, open-label study in approx. 50 patients Relapsed after chemotherapy Selinexor (60 mg/m2) Initiated November 2014, ~50 patients Primary Endpoint: Overall Response Rate Data read out anticipated, late 2016 Clinical Results To Date Based on phase 1 data with Disease control in 4 out of 4 evaluable patients with Richter s transformation: 2 PRs and 2 SDs 18

19 Potential Selinexor NHL Development H H2 H H2 H H2 H H2 Ph 1 Sel + Ritux in NHL Ph 2 Selinexor in PTCL and CTCL SADAL: Ph 2b Selinexor + Dex in DLBCL Potential Accelerated Approval (high vs. low Sel dose) Prep/Submit NDA/EMA LAUNCH Ph 2 Selinexor in Richter s transformation Potential Accelerated Approval (single arm) Prepare NDA/EMA LAUNCH Ph ½ (2 nd /3 rd Line) Sel + Ritux + X in NHL Phase 3 Studies: Randomized Studies with Selinexor-Rituximab in Combination Ph 1/2 Sel + Ibrut in NHL + CLL Ph 1/2 (2 nd Line) Sel + R-ICE in DLBCL Slide Key CHOP-R Dex Ibrut Ritux R-ICE Cyclophosphamide, Doxorubicin Hydrochloride (Hydroxydaunomycin), Vincristine Sulfate (Oncovin), Predisone, Rituxan dexamethasone IMBRUVICA (ibrutinib) Rituxan (rituximab) Rituxan, fosfamide, carboplatin, etoposide Ph 1/2 (1 st /2 nd Line) Sel + CHOP-R in NHL 19

20 Multiple Myeloma: The Opportunity Multiple Myeloma represents a significant patient population for selinexor Second most commonly diagnosed blood cancer, after NHL 114,000 new cases worldwide each year In the US, a prevalence of approximately 83,000, with 24,050 new cases and 11,090 deaths in 2014 Initial focus on patients with recurrent disease following multiple lines of therapy Unmet need for patients with recurrent or refractory MM Citations: ACS Facts and Figures 2014; GLOBOCAN 2012, IARC, 20

21 STORM: Potential Registration Directed Trial in R/Rx4 MM STORM: Selinexor Treatment of Refractory Myeloma Planned Single Arm Trial for Potential Accelerated Approval Relapsed/Refractory > 4 line Quadruple refractory: REVLIMID, POMALYST, KYPROLIS and VELCADE for potential accelerated approval To be initiated 1H 2015 Clinical Results to date Phase 1/2 combination study: 9 patients w/ RR-MM on selinexor + low dose dexamethasone (dex) - 89% CBR and 67% ORR Phase 1 Selinexor + Carfilzomib + dex Combination Study - Early signs of promising efficacy: 2PR and 1VGPR Preparation for Phase 3 Studies Selinexor-dex + PI vs. PI-dex and/or Selinexor-IMID-dex vs. IMID-dex Additional Phase 1/2s to begin

22 Durable Responses After Multiple Prior Therapies in Relapsed Refractory MM Patients PATIENTS WITH RR MM (7 median prior Tx) TREATED WITH TWICE WEEKLY ORAL COMBINATION SELINEXOR + DEXAMETHASONE (Selinexor 45 mg/m 2 + Dexamethasone 20 mg) Patient ID Maximal Δ Best Response # Prior Tx Study Days % PR % PR % scr % PR % PD % PR % MR % MR % PR Overall DCR: 88% ORR: 67% Median: 7 DOR: ~7 months Data as of December 1, 2014 Presented at ASH

23 Promising Potential in Carfilzomib Refractory Patients SELINEXOR + CARFILZOMIB IN PATIENTS WITH CARFILZOMIB-REFRACTORY R/R MM (Selinexor 30 mg/m 2 + Carfilzomib (20/27 mg/m 2 ) Patient Age Days on Tx Best Response # Prior Tx VGPR PR PR 5 Data as of November 1, 2014 Presented at ASH

24 Potential Selinexor MM Development 2014 H2 H H2 H H2 H H H1 Ph 1 Selinexor + Dex STORM: Ph 2 Selinexor + Low Dose Dex (80 patients initially; potential upsize) Prep/Submit NDA/EMA LAUNCH * Ph 1/2 Selinexor + Carfil + Dex * Ph 1/2 Selinexor + Pom + Dex Selinexor + Bortez + Dex Ph 1/2 Selinexor + PLD Ph 3: Selinexor + PI (Carfil/Bortez) + Dex vs. PI + Dex AND/OR Ph 3: Selinexor + Pom + Dex vs. Pom + Dex * Ph 1/2: Pre-Transplant Selinexor + Bortez + Dex Slide Key * Investigator Sponsored Bortez bortezomib (Velcade ) Carfil carfilzomib (Kyprolis ) Dex dexamethasone PI proteasome inhibitor PLD pegylated liposomal doxorubicin Pom pomalidomide Rev Revlimid (lenalidomide) * Ph 1/2 Selinexor + Rev + Dex 24

25 Acute Myeloid Leukemia: The Opportunity Significant opportunity exists for selinexor in AML as few treatment options exist for patients Approximately 18,860 new diagnoses of AML and approximately 7,330 deaths per year in the US The average age of a patient with AML is 66 Older patients with relapsed AML have limited treatment options and less favorable outcomes than younger patients due to comorbidities and likelihood of increased resistance to chemotherapy Median Survival of older patients unfit for chemotherapy is ~9 months Citations: ACS Facts and Figures

26 SOPRA: Registration Directed Trial in 2 nd Line AML SOPRA: Selinexor in Older Patients with Relapsed/Refractory AML Ongoing Randomized Study in AML in pts > 60 years old after first relapse Potential for 2nd line approval in AML Randomized 2:1 single-agent selinexor (55 mg/m2) vs. Physician s Choice (hypomethylating agents or LDAC or Supportive Care only) Initiated June 2014, ~150 patients Primary Endpoint: Overall Survival Data read out anticipated, mid-2016 Clinical Results To Date: Based on 47 patients evaluable (n=63, incl. NE pts) Seven CR/CR(i/p) (11%) One PR and two Morphological Leukemia Free (MF) (5%) 21 stable disease patients (33%) 49% disease control rate (CR/CR(i/p), PR, MF & SD) 26

27 Potential Selinexor AML Development H H2 H H2 H H2 H H2 Ph 1 Sel in R/R AML SOPRA: Ph 2b Selinexor vs. Physician s Choice (2:1) 150 pts; OS Endpoint Prep/Submit NDA/EMA LAUNCH Front Line (Older): Selinexor + LDAC Pick the Winner; Interim 2015 Data Prepare NDA/EMA Launch LAUNCH * * Selinexor + Decitabine (OSU) Induction: Dauno/AraC + Sel Phase 3 Studies: Randomized Studies with Selinexor in Combination * Induction: Ida/AraC + Sel * * Relapse: MEC + Sel Relapse: Clag + Sel Slide Key * Investigator Sponsored Ida idarubicin LDAC Low Dose AraC AraC Arabinoside Cytosine Dauno Daunorubicin MEC Mitoxantrone + Etoposide + AraC CLAG Clofarabine + AraC + G-CSF * Pediatric Acute Leukemias * Front Line Induction High Risk AML: Dauno/AraC + Sel 27

28 Selinexor in Solid Tumors Karyopharm Therapeutics Inc.

29 Advanced or Metastatic Solid Tumors: The Opportunity 14.1 M Worldwide Annual Adult Cancer Diagnoses 12.1 M Adults Diagnosed Worldwide with Solid Tumor Cancers Each Year Liquid Cancers 2,000,000 Prostate 1,100,000 Solid Tumor Cancers 12,100, M+ Patients Gynecological 1,087,000 Karyopharm Phase 2 trials targeting area of high unmet need in solid tumors Head & Neck 500,000 Glioblastoma 18,000 Citations: ACS Facts and Figures 2014; GLOBOCAN 2012, IARC; Agrawal et al, Science, 2011; CBTRUS Statistical Report,

30 Selinexor in Solid Tumors: Phase 2s in Multiple Cancers Four Phase 2 clinical trials ongoing Gynecologic Malignancies (SIGN) Glioblastoma (KING) Prostate (SHIP) Head & Neck Squamous Cell Carcinoma (STARRS) Clinical Results To Date Phase 1 studies in over 8 solid tumor indications - Total of 106 evaluable patients relapsed/refractory to available therapies (mean ~4 prior therapies) - PR and SD of 49% (4 PR s and 48 SD) - Phase 1 Results by indication: Ovarian: DCR=60% (1 PR), N=5 Cervical: DCR=80% (1 PR), N=5 Sarcoma: DCR=88%, N=8 Prostate: DCR=88%, N=8 Head & Neck: DCR=64%, N=14 Slide Key DCR = PR+SD 30

31 Combination Trials Karyopharm Therapeutics Inc.

32 ISTs Using Selinexor: Planned or Ongoing in Combination With Other Therapies Hematological Malignancies Selinexor + Fludarabine + Cytarabine in pediatric patients with relapsed or refractory leukemia or myelodysplastic syndrome Selinexor + Bortezomib + Dexamethasone in patients with progressive of refractory MM Selinexor + Ibrutinib in patients with R/R CLL and NHL Selinexor + Carfilzomib + Dexamethasone in patients with R/R MM Selinexor + Decitabine in patients with AML Solid Tumors Selinexor + Paclitaxel + Carboplatin in patients with advanced ovarian or endometrial malignancies Selinexor + Gemcitabine + Abraxane in patients with advanced pancreatic cancer Selinexor + FOLFOX in patients with metastatic colorectal cancer Selinexor + Irinotecan in patients with adenocarcinoma of the stomach and distal esophagus Selinexor + Docetaxel in patients with relapsed squamous cell lung cancer 32

33 Financial and Commercial Overview Karyopharm Therapeutics Inc.

34 Experienced Leadership Team Michael Kauffman, MD, PhD CEO and Director Development and approval of Velcade and Kyprolis as CMO of Onyx Pharmaceuticals and Proteolix CMO of Proteolix Operating Partner at Bessemer Venture Partners President and CEO of Epix Pharmaceuticals VP of Clinical at Millennium Pharmaceuticals Sharon Shacham, PhD, MBA Founder, CSO and President SVP of Drug Development at Epix Pharmaceuticals Director of Algorithm and Software Development at Predix Pharmaceuticals Justin Renz EVP, CFO & Treasurer EVP, CFO & Treasurer of Zalicus (formerly CombinatoRx) Director, Accounting & Financial Operations at Serono, Inc. Sr. Director, Global Accounting & Finance at Coley Pharmaceuticals Ran Frenkel EVP, Worldwide Clinical Development Managing Director, EMEA, Clinipace Worldwide PFC Pharma Focus AG Managing Director, Actelion Pharmaceuticals Chris Primiano VP, Corp Dev, General Counsel & Secretary Counsel, WilmerHale LLP VP, Corporate Development, General Counsel and Secretary at GlassHouse Technologies Gunderson Dettmer LLP 34

35 Financial Overview Cash & Cash Equivalents: ~$214.8 MM at Dec 31, 2014 expect to fund Company into the second half of 2017 Priced an offering of common stock on January 6, 2015 with net primary proceeds of base deal equal to approximately $90.9 MM Shares Outstanding at December 31, 2014 Basic: 32.7 MM as of December 31, 2014 Fully diluted: 35.7 MM as of December 31,

36 Commercial Strategy Seek approval and launch selinexor initially in hematologic indications Initial registration directed studies with topline data 2016 and 2017 Building commercial infrastructure to launch selinexor in initial hematologic indications Initial indications: single-agent selinexor Followed by combinations with selinexor as backbone Independently commercialize wholly-owned selinexor in North America and Western Europe and seek one or more collaborators for other geographies 36

37 Selinexor: 2014 Major Achievements Initiated registration-directed study in AML Reported solid tumor data in Ovarian, Head & Neck, Prostate at ESMO 2014 Initiated registration-directed study in Richter s Transformation (SIRRT) Awarded Orphan Drug designation US & EU for hematologic malignancies currently under study Reported MM (combo w/dex) & NHL Ph 1 data at ASH 2014 Initiated registration-directed study in DLBCL (SADAL) 37

38 Near-term 2015 Value Creating Milestones for Selinexor Timing Event 1H2015 Initiate potential registration-directed single-agent study in MM 1Q2015 Initiate Phase 1b trial of topical selinexor in patients with diabetic foot ulcers Mid-2015 Present solid tumor Phase 2 data at ASCO Mid-2015 Present hematologic tumor updates at EHA 38

39 SINE COMPOUNDS Karyopharm s Broad Therapeutic Pipeline DRUG CANDIDATES AREA OF THERAPY PRECLINICAL PHASE 1 & PHASE 2 REGISTRATION DIRECTED* AML (SOPRA) Hematological Malignancies Richter s (SIRRT) DLBCL (SADAL) Multiple Myeloma Multiple Myeloma (Combo Study: Sel/Bort/Dex vs. Sel/Pom/Dex) Various Oral Selinexor (KPT-330) Gynecologic Malignancies (SIGN) Glioblastoma (KING) = Initiated Solid Tumors Prostate (SHIP) Head & Neck Squamous Cell Carcinoma (STARRS) Various Topical Selinexor (KPT-330) Wound Healing Diabetic Foot Ulcers Oral Verdinexor (KPT-335) Oral KPT-350 Antiviral Inflammation & Autoimmune Influenza Traumatic Brain Injury PAK4 Inhibitors Oncology Various *Designed to serve as the basis for an application seeking regulatory approval for selinexor for the specified indication. 39

40 Karyopharm: At the Nucleus of Cancer Care Karyopharm s novel 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 First in class Oral Small molecule Selinexor New Drug Class in Oncology Tumor Suppressor Protein (TSP) activation of oncoprotein reduction Potentially relevant to any type of cancer 3 ongoing registrationdirected trials 4 additional Phase 2 trials Additional planned registration and late stage trials Clinical Development Strategy Commercial Strategy Independently commercialize wholly owned selinexor in North America & Western Europe Seek collaborators for other geographies Initial focus on the regulatory approval and commercialization of oral selinexor as a single-agent, while developing SINE compounds as novel approaches to treat a variety of diseases in areas of unmet medical need 40

41 Karyopharm Therapeutics Inc. NASDAQ: KPTI