form 8-k - sec.gov | home 8-k current report . pursuant to section 13 or 15(d) of the securities...

0001193125-15-285046.txt : 201508100001193125-15-285046.hdr.sgml : 2015081020150810170137ACCESSION NUMBER:0001193125-15-285046CONFORMED SUBMISSION TYPE:8-KPUBLIC DOCUMENT COUNT:31CONFORMED PERIOD OF REPORT:20150810ITEM INFORMATION:Regulation FD DisclosureITEM INFORMATION:Financial Statements and ExhibitsFILED AS OF DATE:20150810DATE AS OF CHANGE:20150810

FILER:

COMPANY DATA:COMPANY CONFORMED NAME:Karyopharm Therapeutics Inc.CENTRAL INDEX KEY:0001503802STANDARD INDUSTRIAL CLASSIFICATION:PHARMACEUTICAL PREPARATIONS [2834]IRS NUMBER:263931704STATE OF INCORPORATION:DEFISCAL YEAR END:1231

FILING VALUES:FORM TYPE:8-KSEC ACT:1934 ActSEC FILE NUMBER:001-36167FILM NUMBER:151041544

BUSINESS ADDRESS:STREET 1:85 WELLS AVENUESTREET 2:SECOND FLOORCITY:NEWTONSTATE:MAZIP:02459BUSINESS PHONE:617-658-0600

MAIL ADDRESS:STREET 1:85 WELLS AVENUESTREET 2:SECOND FLOORCITY:NEWTONSTATE:MAZIP:02459

8-K1d69642d8k.htmFORM 8-K

Form 8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM8-K

CURRENT REPORT

Pursuantto Section13 or 15(d)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported):August10, 2015

Karyopharm Therapeutics Inc.

(Exact Name of Registrant as Specified in Charter)

Delaware001-3616726-3931704

(State or Other Jurisdiction

of Incorporation)

(Commission

File Number)

(IRS Employer

Identification No.)

85 Wells Avenue, 2nd Floor

Newton, MA

02459

(Address of Principal Executive Offices)(Zip Code)

Registrants telephone number, including area code: (617)658-0600

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form8-K filing is intended to simultaneously satisfy the filing obligation of the registrantunder any of the following provisions:

Written communications pursuant to Rule425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule14d-2(b)under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule13e-4(c)under the Exchange Act (17 CFR 240.13e-4(c))

Item7.01.Regulation FD Disclosure.

A copy of the slide presentation that will be used by representatives ofKaryopharm Therapeutics Inc. (the Company) in connection with investor meetings or presentations from time to time is attached to this Current Report on Form 8-K as Exhibit 99.1. The slide presentation is current as of August10,2015, and the Company disclaims any obligation to correct or update this material in the future.

The information in this Form 8-K (including Exhibit99.1) shall not be deemed filed for purposes of Section18 of the Securities Exchange Act of 1934, as amended (the Exchange Act), or otherwise subject to the liabilities of that section, nor shall it be deemedincorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item9.01Financial Statements and Exhibits.

(d)Exhibits

The following exhibit relating to Item7.01 shall be deemed to be furnished, andnot filed:

99.1Investor Presentation current as of August10, 2015

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf bythe undersigned hereunto duly authorized.

KARYOPHARM THERAPEUTICS INC.

Date: August10, 2015

By:

/s/ Christopher B. Primiano

Christopher B. Primiano

Vice President, Corporate Development, General Counsel and Secretary

EXHIBIT INDEX

Exhibit
NumberDescription of Exhibit

99.1Investor Presentation current as of August 10, 2015

EX-99.12d69642dex991.htmEX-99.1

EX-99.1

Exhibit 99.1

NASDAQ:KPTI

Corporate Presentation

August 2015

Targeting Disease at the Nuclear Pore

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 Karyopharms lead drugcandidate, 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 resultsto differ materially from the companys 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 developmentphases or that development of any of Karyopharms drug candidates will continue. Further, there can be no guarantee that any positive developments in Karyopharms drug candidate portfolio will result in stock price appreciation. Inaddition, 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. Managements 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 Karyopharms control, including the following: Karyopharmsresults 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 otherregulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Karyopharms ability to obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplannedcash requirements and expenditures; development of drug candidates by Karyopharms competitors for diseases for which Karyopharm is currently developing its drug candidates; and Karyopharms ability to obtain, maintain and enforce patentand other intellectual property protection for any drug candidates it is developing.

These and other risks,including those which may impact managements expectations, are described in greater detail under the heading Risk

Factors in Karyopharms Annual Report on Form 10-Q for the quarter ended June30, 2015, which is on file with the Securities and Exchange Commission, and in subsequentfilings filed by Karyopharm with the Securities and Exchange Commission.

Any forward-looking statementscontained 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 ofnew information, future events or otherwise.

Karyopharms 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 entitledInvestors, 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 byreference.

Unless otherwise noted, this presentation contains data that are interim and unaudited based onsite reports.

2

Karyopharm: At the Nucleus of Cancer Care

Karyopharms 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 andcommit suicide

Novel mechanism First in class Oral, small molecule Fully Owned

Tumor Suppressor Protein (TSP) activation and oncoprotein reduction

Potentially relevant to any type of cancer

4

ongoing later stage Heme trials

3

ongoing Ph 2 Solid Tumor trials

>40 combination studies ongoing or planned

Prepare to commercialize selinexor in NA and Western EU

Seek collaborators for other geographies

Selinexor

New Drug Class in Oncology

Clinical DevelopmentStrategy

Commercial Strategy

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 diseasesin areas of unmet medical need

3

Selinexor:SINE Compound with Broad Clinical Development Strategy

DRUG CANDIDATE AREA OF THERAPY PRECLINICAL PHASE1 & PHASE 2 PHASE 2 or 3

Oral Selinexor (KPT-330)

Hematological Malignancies

Solid Tumors

AML (SOPRA)

Richters (SIRRT)

DLBCL (SADAL)

Multiple Myeloma (STORM)

Multiple Myeloma (STOMP)

Sel+Pom+Dex; Sel+Bort+Dex; Sel+Len+Dex

DLBCL

Sel+Rituximab + backbone therapies

Various Hematological Malignancies

CombinationRegimens

Gynecologic Malignancies (SIGN) Glioblastoma (KING) Prostate (SHIP)

Liposarcoma

Ovarian or Endometrial

Selinexor + Paclitaxel +Carboplatin

Various Solid Tumors

Standard Chemotherapy Regimens

= Initiated

Company Sponsored

Investigator Sponsored

4

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

Cell Membrane

Tumor Suppressors

CYTOPLASM

Nuclear Envelope

Nuclear Pore Complex

XPO-1

Tumor Suppressors

p53

Par-4

PP2A pRB

p21

IkB

BRCA1

p27

elF4E

(myc,bcl2)

Tumor Suppressors

5

SelinexorBlocks XPO1 Forcing Nuclear Localization of Tumor Suppressor Proteins

6

InitialFocus for Single-Agent Approval of Selinexor in:

DLBCL

Acute Myeloid Leukemia

Multiple Myeloma

Richters Transformation

7 2015 Karyopharm Therapeutics Inc.

Selinexors Broad and Durable Oral Single-Agent Anti-Tumor Activity

Selinexor 1,000+ up to 80% >6 month up to 50%

Broad and durable single-agent anti-tumor activity in a pill Patients treated to date with single agent or in combination Disease control across hematologic malignancies Durability some patients on >1 year (longest 2+ years)

Disease control rates in patients with advanced solid tumors

8

Selinexor:First Potential Approvals

Key Milestones for First Potential Approvals:

AML DLBCL

Richters

MM

Top Line Data Q4 2016

NDA Filing H1 2017

Top Line Data Mid-2017

NDA Filing H1 2018

US Patient Populations by Indication:

AML 19,000DLBCL 25,000

Richters 1,200

MM 24,000

Citations: ACS and Leukemia andLymphoma Society, Pasqualucci et al, 2013;

ACS, Tsimberidou et al, MDACC; Globocan 2012, IARC; ACS 9

DiffuseLarge B-Cell Lymphoma: The Opportunity

Aggressive form of Non-Hodgkins Lymphoma (NHL)

Incidence: 25,000 new cases annually in the US

~40% of incident 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, 2013

10

NHL: Phase1 Data Recently Highlighted at ASH Meeting

Fifty-two patients, heavily pretreated (median 4 therapies) withdisease progression

Anti-tumor activity across all NHL types

Durable cancer control and median DOR ~7 months (some pts on >1 year)

Overall response rate (PR): 37% (10% CR, 27% PR)

Disease control rate (SD): 73%

NHL RESPONSE RATES

Type N DCR (%)ORR (%)CR (%)PR (%)SD (%)PD (%)

DLBCL 32 21 (66%)11 (34%)4 (13%)7 (22%)10 (31%)11 (34%)Richters 4 4 (100%)2 (50%)2 (50%)2 (50%)Other NHL 16 13(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 57 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 December1, 2014

Presented at ASH 2014

11

SADAL:Randomized Phase 2b trial in DLBCL

SADAL: Selinexor Against Diffuse Aggressive Lymphoma

Ongoing Randomized Trial for Accelerated Approval

Relapsed / Refractory 3rd line

Twice-weekly randomized single-agent selinexor 1:1: selinexor 60 mg vs. selinexor 100 mg

50% of patients with GCB-DLBCL

Targeting ~200 patients

Primary Endpoint: OverallResponse Rate

Data read out anticipated in Q4 2016

Preparations for Phase 3 Study

Selinexor-Rituximab + Chemo vs. Rituximab + Chemo Alone

Combinations for 3rd, 2nd and 1st Line Phase 1/2 Studies to Initiate 2015

Phase 3s planned for 2016

12

PotentialSelinexor NHL Development

2014 2015 2016 2017 H1 H2 H1 H2 H1 H2 H1 H2

Ph 1 Ph 2

Sel + Ritux in NHL Selinexor in PTCL and CTCL

SADAL: Ph 2b Selinexor in DLBCL

(high vs. low Sel dose)

Ph 2 Selinexor inRichters transformation (single arm)

Ph 1/2 (2nd/3rd Line) Sel + Ritux + X in NHL

Ph 1/2

*

Sel + Ibrut in NHL + CLL

Phase 3 Studies: Randomized Studies with Selinexor-Rituximab in Combination

Slide Key

*


CHOP-R Cyclophosphamide, Doxorubicin Hydrochloride (Hydroxydaunomycin), Vincristine Sulfate (Oncovin), Predisone, RituxanDex dexamethasone Ibrut IMBRUVICA (ibrutinib) Ritux Rituxan(rituximab) R-ICE Rituxan, fosfamide, carboplatin, etoposide

Ph 1/2 (2nd Line) Sel + R-ICE in DLBCL

Ph 1/2(1st/2nd Line)

*

Sel + CHOP-R in NHL

13

MultipleMyeloma: 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 for patients after proteasome inhibitors and immunomodulatory drugs (IMIDs)

Citations: ACS Facts and Figures 2014; GLOBOCAN 2012, IARC, http:///seer.cancer.gov/

14

STORM:Phase 2 Clinical Trial in R/R x 4 MM

STORM: Selinexor Treatment of Refractory Myeloma

Planned Single Arm Trial for Relapsed/Refractory after 4 approved agents

Quadruple refractory: REVLIMID, POMALYST, KYPROLIS and VELCADE

Initiated May 2015, ~80 patients

Primary Endpoint: Overall Response Rate

Interimdata anticipated mid-2016; Study may be expanded to >200 patients for potential accelerated approval

Clinical Results to date

Phase 1/2 combination study: 10 patients w/ RR-MM on selinexor + low dose dexamethasone (dex)

- High ORR and durable responses

Phase 1Selinexor + 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 2015

15

MultipleMyeloma: Phase 1 Data

Selinexor + Dexamethasone

Phase 1/2 combination study with ten evaluable patients treated with selinexor (45 mg/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 evaluable, Median DOR ~ 7 months

Group A Patients with ReI/Ref MM Treated with Twice Weekly

(As of 1D-M ay-2015) 2

Oral CombinationSelinexor 45 mg/m + Dexamethasone 20 mg

Patient MM Maximal Response # Prior Prior Therapies Study ID Type 0. Tx Days

76 IgG-K -71% PR 7 Dox-Vine-Dex, Thal-Dex, Carfil-Dex, VRD, Cyclo-Pred-BCNU, Sel, Doxil-Carfil-Dex 391 FLC-A len-Dex, Cyclo-Etop-Cis-Mel-Dex-ASCT, VRD, CartH-Cycio-Dex,Carfil-Cyclo-Dex-len,

77 NE 8 Carm-Thal-Cis-Etop-Cyta-Vel-Mel, Cyclo-CartiMultiple Myeloma: Phase 1Datal-Pom-Dex, Vor-len-Dex 15

79 FLC-K -53% PR 3 Thal-Pred-Dex-ASCT, Cyclo-Vel-Dex, len-Dex 52

81 FLC-K -99% sCR 6 VAD-ASCT, Cyclo-Pred-ASCT, Rev-Dex, Cycio-BorD (xz), Pom-Carfil-Dex 280

84 IgG-K -84% PR 9 Vel-Dex, ASCT, len-Dex, Vel-Dex, Vel, Carfil , Pom-Dex, Carfil, DT-PACE-Thal 170

90 IgG-K 41% PD 5 Cyclo-Vel-len-Dex (x2), Carfil-Mel-ASCT, Cyclo-Vel-Dex, Pom-Carfil-Dex 31

92 IgA-K -55% PR 9 Vel-Dex, VRD, ASCT, len-Dex, Reolysin, TG02, Cart il-Dex, Carfil-Cyclo-Dex, Carfil-Pom-Dex 121

93 IgG-K -41% MR 9 VAD, VTD+ASCT, Vel-len-Dex, Experim, Carfil-Panob, len-Elotu-Dex, Experim, Pom-Dex,Benda-Pom-Dex 114 IgG-A len-Dex, ASCT (x2), Vel-len-Dex, Vid-len, Benda-Vel-Dex, VAD, Ritux , Vel-Thai, Carfil-Dex, Carfil-Dex-Cis-

98 -48% MR 16 Adria, len-Ritux-Inter, Carfil-Pom, Vel-Thal-Dex-Adria-Cis-ATRA-Arsenie Trioxide, len-Dex, TG02-Carfil 79

99 IgA-K -82% PR 6 Sal, Thal-Dex, len-Dex, Vel-Dex, ASCT, Ibrut-Dex 285

16

PromisingPotential in Patients with Carfilzomib-Refractory MM

SELINEXOR + CARFILZOMIB

IN PATIENTS WITH CARFILZOMIB-REFRACTORY MM

(Selinexor 30 mg/m2 + Carfilzomib (20/27 mg/m2)

Days

Patient Age Best Response # Prior Tx on Tx

59113+ VGPR 4

73 85+ PR 2

64 71+ PR 5

Data as of November1, 2014Presented at ASH 2014

17

PotentialSelinexor MM Development

2014 2015 2016 2017 2018 H2 H1 H2 H1 H2 H1 H2 H1

Ph 1 STORM: Ph 2 Selinexor + Low Dose Dex Prep/Submit Selinexor + Dex (80 patients initially; potential upsize) NDA/EMA

*

Ph 1/2 Selinexor + Carfil + Dex

Ph 1/2 Selinexor+ Pom + Dex Selinexor + Bortez + Dex Selinexor + Len + Dex

Ph 1/2

*

Selinexor + PLD

*

Ph 1/2: Pre-Transplant Selinexor + Bortez + Dex

Ph 3: Selinexor + PI (Carfil / Bortez / Len) + Dex vs. PI + Dex

AND/OR

Ph 3: Selinexor + Pom + Dex vs. Pom + Dex

SlideKey

*


Bortez

bortezomib (Velcade)

Carfil

carfilzomib (Kyprolis)

Dex

dexamethasone

PI

proteasome inhibitor

PLD

pegylated liposomal doxorubicin

Pom

pomalidomide

Rev

Revlimid(lenalidomide)

18

AcuteMyeloid Leukemia: The Opportunity

Significant opportunity exists for selinexor in AML as few treatment optionsexist 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 with poorer outcomes than younger patients due tocomorbidities and increased resistance to chemotherapy

Median Survival of older patients unfit forchemotherapy is ~9 months

Approval Plans

SOPRA: Older patients with AML after 1 line of therapy; topline survival data end of 2016

Combination studies ongoing to inform use in first line therapy for older patients

Additional opportunities for younger patients with high risk AML in front line

About 20% of patients at first diagnosis

All patients with relapse after initial chemotherapy

Pediatric patients with relapsed disease (>50% of pediatric AML)

Citations: ACS Facts and Figures 2014

19

SOPRA:Randomized Phase 2 Trial in 2nd Line AML

SOPRA: Selinexor in Older Patients with Relapsed/Refractory AML

Ongoing Randomized Study in AML in pts > 60 years old after first relapse

Primary Endpoint: Overall Survival

Randomized 2:1 single-agent selinexor (60mg fixed dose) vs. Physicians Choice (hypomethylating agents or LDAC or Supportive Care only)

Dose adjusted in July 2015; ~170 patients

Interim analysis in mid-2016; Full top-line data read out anticipated Q4 2016

Phase 1 Clinical Results:

Based on 63 totalpatients, 47 evaluable for response at 4 weeks (median 3+ prior therapies)

Seven CR/CR(i/p) (11%)

One PR and two Morphological Leukemia Free (MF) (5%)

Overall response rate: 16% (10/63)

21 stable disease patients (33%)

49% (31 of 63)disease control rate (CR/CR(i/p), PR, MF& SD)

20

PotentialSelinexor AML Development

2014 2015 2016 2017 H1 H2 H1 H2 H1 H2 H1 H2

Ph 1 Sel in R/R AML

SOPRA: Ph 2b Selinexor vs. Physicians Choice (2:1)Prep/Submit 170 pts; OS Endpoint NDA/EMA

Front Line (Older): Selinexor + LDAC Launch

*

Pick the Winner (L1 Study); Interim 2015-6 Data

*

Phase 3 : Randomized Studies with Selinexor + Decitabine (OSU) Selinexor in Combination

*

Induction: Dauno/AraC + Sel

*

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

21

Selinexorin Solid Tumors& Combination Studies


ASCOSummary& Conclusions KING& SIGN& Sarcoma

Selinexor shows anti-tumoractivity 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

Selinexor showed broad anti-tumor activity across all three heavily pretreated gynecological cancerpopulations:

Selinexor induced meaningful single-agent anti-cancer activity in patients with ovarian andendometrial 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.

Single agent oral selinexor demonstrated durable stable disease in liposarcoma, leiomyosarcoma and other sarcomas

In patients with previously treated liposarcoma, PFS on selinexor was longer than the patients most recent anti-cancer regimen

Post-treatment biopsies demonstrated pharmacological activity based upon decreased tumor cell number, proliferative rateand increased stromal tissue

23

2015 Karyopharm Therapeutics, Inc.

ISTs UsingSelinexor: Planned or Ongoing in Combination With Other Therapies


Selinexor + Carfilzomib + Dexamethasone in patients with R/R MM

Selinexor + Fludarabine + Cytarabine in pediatric patients with relapsed or refractory leukemia or myelodysplasticsyndrome

Selinexor + Bortezomib + Dexamethasone in patients with progressive of refractory MM

Selinexor + Ibrutinib in patients with R/R CLL and NHL

Selinexor + Decitabine in patients with AML

Solid Tumors

Selinexor + Paclitaxel + Carboplatinin patients with advanced ovarian or endometrial malignancies

Selinexor + Gemcitabine + Abraxane in patientswith 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

24

Financialand Commercial Overview


FinancialOverview

Cash, Cash Equivalents& Investments:

~$255.9 MM at June30, 2015

Expected to fund the Company into 2018

SharesOutstanding at June30, 2015

Basic: ~35.7 MM as of June30, 2015

Fully diluted: ~40.0 MM as of June30, 2015

26

Selinexor:SINE Compound with Broad Clinical Development Strategy

DRUG CANDIDATE AREA OF THERAPY PRECLINICAL PHASE1 & PHASE 2 PHASE 2 or 3

Oral Selinexor (KPT-330)


Solid Tumors

AML (SOPRA)

Richters (SIRRT)

DLBCL (SADAL)

Multiple Myeloma (STORM)

Multiple Myeloma (STOMP)

Sel+Pom+Dex; Sel+Bort+Dex; Sel+Len+Dex

DLBCL

Sel+Rituximab + backbone therapies

Various Hematological Malignancies

CombinationRegimens

Gynecologic Malignancies (SIGN) Glioblastoma (KING) Prostate (SHIP)

Liposarcoma

Ovarian or Endometrial

Selinexor + Paclitaxel +Carboplatin

Various Solid Tumors

Standard Chemotherapy Regimens

= Initiated

Company Sponsored


27

Karyopharms Broad Therapeutic Pipeline

SINE

COMPOUNDS

DRUG CANDIDATES AREA OF THERAPY PRECLINICAL PHASE 1 & PHASE 2 REGISTRATION DIRECTED*

Topical Selinexor (KPT-330) Wound Healing Diabetic Foot Ulcers

Hematological Malignancies Canine Lymphoma NADA Submission in Progress (MUMS designation received)

Oral Verdinexor (KPT-335)

Antiviral Influenza

Inflammation&Autoimmune / TBI

Oral KPT-350 = Initiated

Autoimmune

PAK4 Inhibitors Oncology Various

*Designed toserve as the basis for an application seeking regulatory approval for the applicable drug candidate in the specified indication

28

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 studies (SOPRA, SADAL and SIRRT) are expected to have topline data by the end of 2016

Two ongoing later phase studies (SOPRA and STORM) are expected to have interim analyses in mid-2016

Multiple combination studies are ongoing or planned to incorporate selinexor into treatment regimens acrossmany cancer types

29

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