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

Corporate Presentation April 2017

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 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, that development of any of Karyopharm's drug

candidates will continue, or that the partial clinical hold imposed by the U.S. Food and Drug Administration on selinexor clinical trials will be released in a timely manner or at all. 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 FDA 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 Annual Report on Form 10-K for the year ended December 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 http://www.karyopharm.com. Karyopharm regularly uses its

website to post information regarding its business, drug development programs and governance. Karyopharm encourages investors to use www.karyopharm.com, particularly the information in the section entitled "Investors," as a source of

information about Karyopharm. References to www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on www.karyopharm.com into this presentation by reference. Unless otherwise noted, this

presentation contains data that are interim and unaudited based on site reports. 2017 Karyopharm Therapeutics Inc.

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 owned; COM patent for selinexor with protection to at least 2032 Strong Leadership Experienced management team CEO integral in accelerated approvals of Velcade and Kyprolis Track record of success in

oncology drug development, regulatory approval and commercialization Near Term Catalysts Several data readouts expected over the next 18 months SADAL SEAL STOMP KPT-8602 STORM BOSTON Well Capitalized Cash runway until the end of 2018 Beyond expected

key data inflection points including expanded STORM data and BOSTON enrollment Selinexor Oral, take-at-home, broad single-agent activity. Combinable with favorable safety profile Potential to serve as a backbone therapy with diverse array of

anti-cancer agents 2017 Karyopharm Therapeutics Inc.

Selinexor: Novel Oral Anti-Cancer Agent

Restores Tumor Suppressors & Reduces Oncoproteins 2017 Karyopharm Therapeutics Inc.

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 Hematological Malignancies - Oral Selinexor Solid Tumors - Oral Selinexor SEAL: Selinexor vs. Placebo SIGN: Selinexor KING: Selinexor SADAL: Selinexor Additional Oncology Programs Other Indications PHASE I PHASE II

KPT-8602 Oral 2nd Generation SINETM Compound KPT-9274 Oral Dual PAK4/NAMPT Inhibitor Verdinexor (KPT-335) Oral SINE Compound KPT-350 Oral SINE Compound MM, MDS, CRC, PrC Lymphoma & Solid Tumors Influenza & Other Viruses

ALS, MS, DMD, TBI & Other Indications * 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. STORM: Selinexor and Dexamethasone BOSTON*: Selinexor, Bortezomib and Dexamethasone vs. Bortezomib and Dexamethasone 2017 Karyopharm Therapeutics Inc. STOMP:

Selinexor in Myeloma: First Oral Agent

with Novel Mechanism and Single Agent Activity Since the IMiDs

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 Combination regimens appear to be well tolerated Side effects reported in the SVd arm of STOMP are similar to, or reduced, compared with Sd Phase 3 SVd regimen uses 40% less Velcade and 25% less Dex than standard Vd dosing Planned

additional combination regimens (plus Darzalex, plus Ninlaro) Worldwide MM market estimated ~$11 billion in 2015, increasing to > $22 billion by 2023 Individual MM drugs may generate peak sales in excess of $1-2B Selinexor could be the next

anti-MM agent with potential as a "backbone" therapy 2017 Karyopharm Therapeutics Inc.

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) + Dex 2013 Prior Vel + Rev, combo w/ Dex 29.2% (7.4% alone) Pd, KPd Darzalex (D, Daratumumab) 2015 >3 priors or dual refractory 29.4% (21% Quad) DVd, DRd, DPd Revlimid (R, Lenalidomide) + Dex 2006 Full Approval for >1 Prior

Therapy N/A Rd, R maint, RMP-R, VRd, KRd, DRd, IRd 2017 Karyopharm Therapeutics Inc.

STORM: Selinexor in Refractory Myeloma:

Quad and Penta Populations

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 (83%) : 8 (17%) 11 (35%) : 20 (65%) Median Years from Diagnosis (range) 4 years (1 - 16) 4 years (<1 - 35) Median Prior Regimens (range) 7 (3 - 16) 7 (5 - 17) Prior

Therapies Alkylating Agents Anthracyclines Glucocorticoid Stem Cell Transplant 47 (98%) 20 (42%) 48 (100%) 37 (77%) 30 (97%) 12 (39%) 31 (100%) 24 (77%) 2017 Karyopharm Therapeutics Inc. * one patient did not have measurable disease at

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) Penta (n = 30) 6 Doses per mo (n = 51) 8 Doses per mo (n = 27) VGPR PR MR SD PD NE Pts (%) ORR: 21% CBR: 29% ORR: 20% CBR: 40% ORR: 20% CBR: 29% ORR: 22% CBR: 41%

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

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% Vomiting 30% 10% 4% -- 44% Diarrhea 34% 4% 5% -- 43% Dehydration 1% 8% 3% -- 11% Dysgeusia 6 5% -- -- 11% Constitutional Fatigue 15% 33% 15% -- 63% Weight Loss 19% 13% 1% -- 33% Blood Thrombocytopenia 6% 8% 25% 34% 73%

Anemia 3% 19% 27% 1% 49% Leukopenia 4% 14% 13% 1% 32% Neutropenia 3% 4% 11% 6% 24% Lymphopenia -- 4% 9% 1% 14% CPK Increase 3% 5% 3% -- 10% Other Hyponatremia 20% -- 22% -- 42% Dizziness 9% 1% -- -- 10% Fever 6% 3% 1% -- 10% 2017 Karyopharm

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. FDA Division of Hematology Products Target topline data from the expanded cohort in early 2018 Potential NDA Submission in Mid-2018 Engage regulatory agencies on potential expedited review opportunities Assuming positive

data from STORM expansion, plan to seek accelerated approval (FDA) and conditional approval (EMA) 2017 Karyopharm Therapeutics Inc.

STOMP: Selinexor and Backbone

Treatments for Relapsed/Refractory Multiple Myeloma

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

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% Hematologic Thrombocytopenia -- -- 6% 12% 18% Other Abdominal Pain 6% - 6% - 12% Escalation Patients - Treatment Related AEs at Recommended Dose One case of Grade 1 peripheral neuropathy across all SVd cohorts Minimal Grade 3/4

toxicities. Considering prolonged tolerability and efficacy across all cohorts, the recommended combination dose is: 100 mg oral selinexor QW 1.3 mg/m2 Velcade SC QW 40 mg oral dexamethasone QW 2017 Karyopharm Therapeutics Inc.

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 last therapy Best response MR PR VGPR n=19 n=19 n=12 100 80 60 40 20 0 Response, %

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 (VGPR+PR+MR). Responses as of November 28, 2016 based on interim unaudited site data. Selinexor + Pomalyst (Pomalidomide) + Dexamethasone (SPd) Efficacy - Phase 1 Best Responses in Evaluable SPd

Patients as of November 28, 2016 Category N ORR(%) CBR(%) VGPR(%) PR (%) MR(%) SD(%) PD(%) All Patients 15 9 (60%) 11 (73%) 3 (20%) 6 (40%) 2 (13%) 3 (20%) 1 (7%) 2017 Karyopharm Therapeutics Inc.

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, na ve to proteasome inhibitors (PIs), or if patient had prior PI, then must have had PR and at least 6 months since last PI SVd Arm: Weekly Velcade sc dosing 4 / 5 weeks with weekly selinexor and

dexamethasone Vd Arm: Standard Velcade sc BIW 2/3 weeks x 8 cycles then QW 4 / 5 weeks for cycles 9+ 1:1 randomization Interim PFS analysis after 75% of the PFS events for potential sample size adjustment For Vd arm, cross-over to SVd at objective

progression permitted Planned in US, Canada, Europe, and Asia Primary Endpoint (EP) PFS Key Secondary EPs ORR, DOR, PFS 1 + PFS 2, OS, QOL Statistical Assumptions Vd (9.4 mo., based on ENDEAVOR), 65% ORR SVd (13.5 mo.; HR ~ 0.67), 85% ORR ~360 pts

(180/arm) 2017 Karyopharm Therapeutics Inc.

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 Repeat Therapy if DOR > 6mos Clinical Trial KPd KRd DRd DVd DVd ICd ECd Repeat Therapy if DOR > 6mos DRd IRd ICd ERd 3rd Line Therapy for Relapsed/Refractory Pom based Dara based regimens Kyprolis based regimens

Panobinostat Alkylator based regimens Clinical Trial Initial Therapy Transplant Eligible VRD KRD Other Triplet Transplant Ineligible VRD Other Triplet Vd or Rd US Treatment Landscape for Multiple Myeloma 2017 Karyopharm Therapeutics Inc.

Adapted from NCCN and SMART Guidelines Other Selinexor Combinations STORM Trial BOSTON Trial

SADAL Study 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 months Planned protocol amendment following consultation with FDA Discontinue 100mg arm Targeting an additional 90 patients at 60mg in single arm Primary endpoint: overall response rate Recent FDA correspondence confirms

potential for accelerated approval pending data and treatment landscape Top-line expanded 60mg data readout anticipated in mid-2018 2017 Karyopharm Therapeutics Inc.

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 (37.5%) 4 (12.5%) 5 (15.6%) 3 (9.4%) 17 (53.1%) 3 (9.4%) 100 mg 31 9 (29.0%) 15 (48.4%) 3 (9.7%) 6 (19.4%) 6 (19.4%) 12 (38.7%) 4 (12.9%) GCB - Subtype 32 8 (25.0%) 14 (43.8%) 3 (9.4%) 5 (15.6%) 6 (18.8%) 13

(40.6%) 5 (15.6%) Non-GCB - Subtype 31 10 (32.3%) 13 (41.9%) 4 (12.9%) 6 (19.4%) 3 (9.7%) 16 (51.6%) 2 (6.5%) Overall response rate as determined by an independent central radiological review Responses were adjudicated according to the

Lugano Classification (Cheson, 2014) by an independent central radiological review committee. ORR=Overall Response Rate (CR+PR), DCR=Disease Control Rate (CR+PR+SD), CR=Complete Response, PR=Partial Response, SD=Stable Disease, PD=Progressive

Disease, NE=Non-evaluable. Responses are based on interim unaudited data as of March 1, 2017 for the first 63 patients (of 72 total patients). 2017 Karyopharm Therapeutics Inc. * Presented at AACR 2017