8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): June 7, 2018

Karyopharm Therapeutics Inc.

(Exact Name of Registrant as Specified in Charter)

Delaware	001-36167	26-3931704
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
85 Wells Avenue, 2nd Floor Newton, Massachusetts		02459
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s 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 Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☒

Item 7.01.     Regulation FD Disclosure.

A copy of the slide presentation that will be used by representatives of Karyopharm Therapeutics Inc. (the “Company”) in connection with investor meetings and presentations from time to time (the “Corporate Presentation”) is attached to this Current Report on Form 8-K as Exhibit 99.1. The Corporate Presentation is current as of June 7, 2018, and the Company disclaims any obligation to correct or update this material in the future.

The information in this Form 8-K (including Exhibit 99.1) shall not be deemed “filed” for purposes of Section 18 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 deemed incorporated 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.

Item 9.01.     Financial Statements and Exhibits.

(d) Exhibits

The following exhibit relating to Item 7.01 shall be deemed to be furnished and not filed:

Exhibit Number	Description of Exhibit
99.1	Corporate Presentation current as of June 7, 2018

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 by the undersigned hereunto duly authorized.

	KARYOPHARM THERAPEUTICS INC.
Date: June 7, 2018	By:	/s/ Christopher B. Primiano
		Christopher B. Primiano
		Executive Vice President, Chief Business Officer, General Counsel and Secretary

EX-99.1

Exhibit 99.1

Targeting Disease at the Nuclear Pore
Corporate Presentation
June 2018

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, of the reporting of data from such trials, of the submissions to regulatory authorities and of potential commercial launches, the potential availability of accelerated approval pathways, the potential size of the markets for multiple myeloma drugs and multiple myeloma drugs for treatment of patients with relapsed multiple myeloma and Karyopharm’s strategic and financial plans and expectations as well as financial projections for Karyopharm. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Karyopharm’s current expectations. For example, there can be no guarantee that regulators will agree that selinexor qualifies for accelerated approval in the U.S. or conditional approval in the E.U. as a result of the data from the STORM study in patients with penta-refractory myeloma or SADAL study in patients with relapsed/refractory DLBCL or that any of Karyopharm’s drug candidates, including selinexor (KPT-330) and eltanexor (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 FDA and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm’s competitors for diseases for which Karyopharm is currently developing its drug candidates; that the markets for multiple myeloma drugs will grow as predicted; 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, 2018, which is on file with the SEC, and in subsequent filings filed by Karyopharm with the SEC. 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. In addition, data included in this presentation have not been updated and are as of the cutoff date for the applicable medical conference presentation. Unless otherwise noted, all reference to market sizes are based on reports from Global Data or Karyopharm internal estimates.
©2018 Karyopharm Therapeutics Inc. 2

Karyopharm Highlights
Hematologic
Malignancies
Multiple Myeloma
Diffuse Large B-cell Lymphoma
Solid Tumor
Malignancies
Liposarcoma
Gynecologic Cancers
First-in-class, oral SINE compounds
Lead asset with significant commercial potential
Strong leadership team and balance sheet
Multiple near term catalysts from broad, late-stage pipeline
Preparing for potential product launches and revenues
Novel, broadly applicable mechanism of action with single agent activity and works well in combinations; patent life through 2032+
Selinexor demonstrated robust activity in penta-refractory myeloma, is combinable with existing therapies and has the potential to be the next “backbone” therapy in myeloma, a market projected to be $22.6B in 20231
Executive team with past successes in lead indications; with recent offering proceeds, cash expected to fund the company into 3Q 2019
Anticipated data readouts (2018-2019): SADAL (end of 2018),
BOSTON (end of 2019; pending PFS events), SEAL (end of 2019) Regulatory Profile: Fast Track and orphan designations granted in multiple myeloma. Planned requests for accelerated approval in multiple myeloma (2H18), accelerated approval in DLBCL (2019)2, full approval in multiple myeloma (2020)3, full approval in liposarcoma (2020)4
Preparing for potential launch of selinexor in multiple myeloma and DLBCL in 2019, followed by expansion to other potential indications
1 Global Data, 2 Assuming positive outcome from Phase 2b SADAL study, 3 Assuming positive outcome from Phase 3 BOSTON study, 4 Assuming positive outcome from Phase 3 portion of SEAL study
©2018 Karyopharm Therapeutics Inc.
3

All Oral Pipeline
AREA OF THERAPY
HEMATOLOGIC MALIGNANCIES
Multiple Myeloma
Relapsed/refractory | BOSTON    Penta-refractory | STORM    Relapsed/refractory | STOMP
Diffuse Large B-cell Lymphoma | SADAL
SOLID TUMOR MALIGNANCIES
Liposarcoma | SEAL
Endometrial Cancer | SIENDO4
Glioblastoma | KING
ADDITIONAL ONCOLOGY PROGRAMS
MDS, CRC, PrC
Solid Tumors & Lymphoma
OTHER INDICATIONS
Lymphoma in Companion Animals
PRECLINICAL PHASE I PHASE II PHASE III COMMERCIAL RIGHTS
SELINEXOR + VELCADE1 SELINEXOR2 SELINEXOR + BACKBONE THERAPIES3 SELINEXOR
SELINEXOR
SELINEXOR
SELINEXOR
ELTANEXOR (KPT-8602)
KPT-9274
VERDINEXOR (KPT-335)
Japan*
China**
China***
Oral SINE compound and XPO1 inhibitor KPT-350 acquired by Biogen for treatment of certain neurological and neurodegenerative conditions, including ALS, in Jan 2018
1 Oral selinexor, Velcade® (bortezomib) and dexamethasone vs. Velcade and dexamethasone
2 Oral selinexor + dexamethasone
3 Oral selinexor and dexamethasone + Revlimid® (lenalidomide), Pomalyst® (pomalidomide), Velcade, Kyprolis® (carfilzomib) or Darzalex® (daratumumab)
4 Investigator-sponsored randomized Phase III trial
*Territories: Japan, S. Korea, Taiwan, Hong Kong, and ASEAN countries.
** Antengene licensed rights to selinexor and eltanexor in China and Macau.
*** Antengene licensed rights to KPT-9274 and verdinexor in mainland China, Macau, Taiwan, Hong Kong, South Korea, and the ASEAN countries.
**** Anivive holds exclusive worldwide rights to research, develop and commercialize verdinexor only for the treatment of cancer in companion animals
©2018 Karyopharm Therapeutics Inc.
4

Selinexor/SINE Mechanism of Action: Inhibition of XPO1
©2018 Karyopharm Therapeutics Inc.
5

Selinexor: A Growing Body of Safety Data
2,400
Total patients treated to date
~481
Number of clinical trials ongoing and/or completed
>10
Number of cancers explored
• Favorable emerging tolerability profile; multiple ongoing Phase 3 studies
• Dosing regimens utilized in key Phase 2 and 3 trials (e.g., BOSTON, STORM, STOMP, SADAL and SEAL) have shown generally predictable and manageable tolerability, particularly when used once weekly in combination regimens
• Common side effects are generally predictable across multiple tumor types and generally reversible and/or manageable with standard supportive care
• Combination regimens have demonstrated a predictable and manageable tolerability profile, with observed additive or synergistic activity and potential to re-sensitize to prior therapies
• Phase 3 BOSTON selinexor regimen allows for use of 40% less Velcade® and 25% less dexamethasone than standard Velcade® and dexamethasone dosing
• In certain trials, side effects reported from treatment arms evaluating selinexor and dexamethasone in combination with other anti-myeloma agents are similar to, or reduced, compared to selinexor and dexamethasone alone
1 Per ClinicalTrials.gov (as of Apr 26, 2018); 5 of 46 are company-sponsored and currently enrolling
©2018 Karyopharm Therapeutics Inc.
6

Selinexor: Regulatory Strategy in United States and Europe
Multiple Myeloma
DLBCL
Liposarcoma
• FDA granted Fast Track status to selinexor in multiple myeloma and Orphan
Drug Designation has been awarded to selinexor in multiple myeloma and
DLBCL by FDA and EMA and in liposarcoma by FDA
• Fast Track allows more frequent interaction with FDA, rolling New Drug Application
(NDA) submission and ability to request priority review and accelerated approval
• Orphan Drug Designation in the US and EU can provide regulatory development
support, tax credits (US), reduced or waived marketing applications fees and
marketing exclusivity periods
• Planning to utilize Fast Track benefits in submitting first NDA during the second
half of 2018 based on data from the STORM study of penta-refractory myeloma
• EMA submission expected to follow in early 2019 with a request for conditional
approval in penta-refractory myeloma
• Marketing approval opportunities in multiple indications: multiple myeloma
(STORM and BOSTON), DLBCL (SADAL) and liposarcoma (SEAL)
©2018 Karyopharm Therapeutics Inc.
7

Selinexor in Hematologic Malignancies
Multiple Myeloma

Multiple Myeloma
Multiple myeloma is a cancer of plasma cells. Normal plasma cells are found in the bone marrow and make antibodies that help the body attack and kill germs1
Myeloma is characterized by low blood counts (e.g., anemia), bone and calcium problems, infections, kidney problems and light chain amyloidosis1
Myeloma is treatable, but >12,000 deaths still occur each year in the U.S.1
An 30,000 estimated people in the US are diagnosed annually1
An 86,000 estimated people worldwide are diagnosed annually2
Approximately 120,000
Americans are currently living with MM3
50%
of patients survive 5 years3
1 American Cancer Society 2 Becker, N. Recent Results Cancer Res. 2011;183:25-35. doi: 10.1007/978-3-540-85772-3_2 3 National Cancer Institute
©2018 Karyopharm Therapeutics Inc.
9

Planned Selinexor Development Strategy in Multiple Myeloma
Phase 2b STORM study1 addressing patients with penta-refractory2 myeloma
• Disease refractory to PIs, IMiDs and Darzalex®
• Highest unmet medical need in multiple myeloma
Pivotal Phase 3 BOSTON study addressing patients with relapsed or refractory disease following 1-3 prior lines of therapy
• Selinexor combined with once-weekly Velcade®
Phase 1b/2 STOMP as a potential backbone therapy in combination with standard approved therapies
• Selinexor and low-dose dexamethasone combined with Revlimid®, Pomalyst®, Velcade®, Kyprolis® or Darzalex®
• Future Phase 2/3 studies in combination for labeling
1 Evaluating selinexor with low-dose dexamethasone. 2 Patients who have previously received two PIs, Velcade® (bortezomib) and Kyprolis® (carfilzomib), and two IMiDs, Revlimid® (lenalidomide) and Pomalyst® (pomalidomide), and their disease is refractory to at least one PI, at least one IMiD, and their disease is also refractory to the anti-CD38 monoclonal antibody Darzalex® (daratumumab), and has progressed following their most recent therapy.
©2018 Karyopharm Therapeutics Inc.
10

STORM1: A Phase 2b Study In Myeloma
Ongoing single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in patients2 with penta-refractory3 myeloma
Selinexor received Fast Track designation from the FDA for this indication, acknowledging the unmet need
1 Selinexor Treatment of Refractory Myeloma 2 Median 7 prior regimens 3 Patients who have previously received two PIs, Velcade® (bortezomib) and Kyprolis® (carfilzomib), and two IMiDs, Revlimid® (lenalidomide) and Pomalyst® (pomalidomide), and their disease is refractory to at least one PI, at least one IMiD, and their disease is also refractory to the anti-CD38 monoclonal antibody Darzalex® (daratumumab), and has progressed following their most recent therapy
©2018 Karyopharm Therapeutics Inc.
11

STORM: A Phase 2b Study In Myeloma
OVERALL RESPONSE RATE1
INCLUDING:
2 CRs
29 VGPRs or PRs
Penta-refractory (n=122):
25.4%
DURATION OF RESPONSE1
4.4 MONTHS
We believe selinexor is the furthest advanced agent being investigated in penta-refractory myeloma
Next steps:
• Plan to submit NDA to FDA during second half of 2018, requesting accelerated approval
• Potential for rolling NDA
• Plan to submit MAA to EMA in early 2019
• Detailed efficacy and safety results to be submitted for presentation at an upcoming medical oncology meeting
Safety:
• Predictable and manageable tolerability profile; results consistent with those reported previously from Part 1 of STORM and from other selinexor studies.
• As anticipated, the most common non-hematologic AEs were nausea, vomiting, fatigue and reduced appetite; primarily low grade and manageable with standard supportive care and/or dose modification.    
• The most common hematologic AEs were Grade ³3 cytopenias and were generally not associated with clinical sequelae.
• No new safety signals.
1 As confirmed by an Independent Review Committee.
©2018 Karyopharm Therapeutics Inc.
12

BOSTON1: A Phase 3 Study In Myeloma
Top-line data expected end of 20193
Ongoing randomized, open-label clinical trial evaluating once weekly selinexor and Velcade
(bortezomib) plus low-dose dex versus standard twice-weekly Velcade® plus low-dose dex in patients with relapsed or refractory MM, who have had 1-3 prior lines of therapy
1 Bortezomib, Selinexor and dexamethasone 2 Pts must have achieved ³PR, and completed proteasome inhibitor therapy at least 60 days prior. 3 Pending PFS events.
©2018 Karyopharm Therapeutics Inc.
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STOMP: A Phase 1b/2 Study In Myeloma
Selinexor + Revlimid® + dex (SRd)1 (n=16)
ORR ORR
92% 81%
(Revlimid-Naïve) (All)
Selinexor + Pomalyst®
+ dex (SPd)2 (n=27)
ORR ORR
63% 56%
Revlimid-Relapsed (Pomalyst-Naïve and or - (All)
Refractory )
Selinexor + Velcade® + dex (SVd)3 (n=40)
ORR ORR
83% 4 63%
(Non-Refractory to PIs) (All)
Selinexor + Darzalex® + dex (SDd)5 (n=8)
ORR ORR
83% 63%
(Darzalex-Naïve) (All)
Next steps:
• Efficacy and safety observed in SVd arm informing ongoing Phase 3 BOSTON study
• Plan to report updated data from ongoing arms at future medical meetings
• Plan to initiate arm evaluating selinexor, Revlimid® and dexamethasone in patients with newly diagnosed multiple myeloma
Safety:
• SRd (n=19): Most common Grade 1/2 AEs were nausea, anorexia, fatigue, weight loss, constipation and vomiting; most common Grade ³3 adverse events were thrombocytopenia and neutropenia
• SPd (n=31): Most common Grade 1/2 AEs were nausea, anorexia, fatigue and diarrhea; most common Grade ³3 AEs were neutropenia, thrombocytopenia and anemia
• SVd (n=42): All Grade AEs were consistent with those reported previously from SVd arm; Low rate of peripheral neuropathy (14%; n=6, all Grade 1/2)
• SDd (n=9): Most common Grade 1/2 AEs were fatigue, nausea and neutropenia; most common Grade 3/4 AEs were thrombocytopenia, leukopenia, anemia and neutropenia
1 White D, et al. ASH 2017. Abstract 1861. 2 Chen C, et al. ASH 2016. Abstract 3330. 3 Bahlis NJ, et al. ASH 2016. Abstract 977. 4 Patient population eligible for Phase 3 BOSTON study. 5 Gasparetto C, et al. ASH 2017. Abstract 3100.
©2018 Karyopharm Therapeutics Inc. 14

Integration of Selinexor into the MM Landscape in 2019 and Beyond
FRONTLINE
FOLLOW ON
2nd LINE
FOLLOW ON
3rd/4th LINE
~65%
Transplant Ineligible
VRd, Vd or Rd
KRd (high risk)
VMP (DVMP) (EU mainly), (DRd)
Continuous treatment until progression
(may move to doublet)
DVd, DRd, KRd, NRd, V or N + Cd, ERd, High Kd
~35%
Transplant Eligible Induction
VRd, KRd, DRd, Others
Low Risk: Intermediate Autologous or High Risk:
Rd                
SCT Vd or Kd Maintenance Maintenance
Autologous
SCT if prior KRd, DRd, Clinical SCT had DVd, ERd Trial PFS of >18 months
KPd, VPd, DPd Antibody and triplets, FVd
Clinical study / Other Triplets or Quadruplets No Standard of Care
• The worldwide market for multiple myeloma drugs is expected to grow from annual sales of $19.7 billion in 2018 to $22.6 billion in 2023.1
• The worldwide market for multiple myeloma drugs for treatment of patients with relapsed multiple myeloma is approximately two-thirds of the total market.2
Phase 3 BOSTON Study
Phase 2b STORM Study
V=Velcade® (bortezomib), R=Revlimid® (lenalidomide), d=dexamethasone, K=Kyprolis® (carfilzomib), D=Darzalex® (daratumumab), SCT=Stem cell transplantation, R/R=Relapsed/refractory, P=Pomalyst® (pomalidomide),
DOR=Duration of response, F=Farydak® (panobinostat), M=melphalan, N=Ninlaro® (ixazomib), C=cyclophosphamide, E=Empliciti™ (elotuzumab). 1 Global Data. 2 Internal estimate.
©2018 Karyopharm Therapeutics Inc. 15

Selinexor in Hematologic Malignancies
Diffuse Large B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma
DLBCL is an aggressive lymphoma that can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain1
DLBCL is characterized by painless, rapid swelling in the neck, underarms, or groin that is caused by enlarged lymph nodes1
An 25,000 estimated people in the U.S. are diagnosed annually2,3
In the U.S., Japan and EU5, an estimated
58,000
people will be diagnosed with DLBCL in 20184
Overall, ~60% of patients are cured, but the remainder have limited treatment options and eventually succumb to their disease5
1 Lymphoma Research Foundation 2 ACS Cancer Facts and Figures 2015 3 Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer (IARC); 2008
4 Global Data 5 Kantar Health
©2018 Karyopharm Therapeutics Inc. 17

SADAL1: A Phase 2b Study In DLBCL
Top-line data expected
by end 2018
Ongoing open-label clinical trial evaluating selinexor in patients with relapsed or refractory (³3rd line) DLBCL; at least 50% of patients with GCB-DLBCL
1 Selinexor Against Diffuse Aggressive Lymphoma
©2018 Karyopharm Therapeutics Inc. 18

SADAL: A Phase 2b Study In DLBCL1,2
ORR in patients with
ORR across ORR ‘Double- or Triple-Hit” mDOR all patients (n=63) across genetic subsets DLBCL (n=14)
(CRs 14%; PRs 19%) GCB (n=32): non-GCB (n=31):
33% 35% >7MONTHS 28% 38%
Most responses at first scan (~2 months)
Next steps:
• Top-line data from expanded 60mg cohort expected by end of 2018
• If data are positive, potential NDA submission in 2019 requesting accelerated approval
Safety (n=90):
• Most common AEs were fatigue, nausea, thrombocytopenia, anorexia, vomiting and anemia; primarily Grade 1/2 and were managed with dose modifications and/or standard supportive care
• Most common Grade 3/4 AEs were thrombocytopenia, neutropenia, anemia, and fatigue and were also manageable with dose modifications and/or standard supportive care
1 Per Lugano Classification (Cheson, 2014); as adjudicated by an Independent Central Radiological Review Committee 2 Maerevoet M, et al. EHA 2017. Abstract S469.
©2018 Karyopharm Therapeutics Inc. 19

US DLBCL Treatment Landscape in 2020+
Initial Therapy
2nd line Therapy for
Relapsed/Refractory
Consolidation
3rd Line Therapy for
Relapsed/Refractory
Chemoimmunotherapy
• R-CHOP • EPOCH • RGCVP • Other
60% Possible Cure CR/Pet Neg
Relapse 10% (usually >2 years)
Partial    Response
30%    PET Positive
ASCT or Clinical Trial
Unfit Patients
Non-Intensive Therapy
• R-Bendamustine
• R-GemOx, R-GDP
• Revlimid + R (R2)
• Brentuximab vendotin
• Clinical Trial
CR or PR
No Response PD
Continue Non-Intensive Chemo until Relapse
CAR-T Clinical Trial
Different Second Line Option
Clinical Trial
Different Second Line Option
Two approved CAR-T treatments; applicable in a select number of patients
Selinexor has the potential to be the new 3rd line standard of care
Planned Phase 3 study in second-line (selinexor + R-
Chemo vs. R-Chemo)
The SADAL Study
Source: Adapted from NCCN guidelines
©2018 Karyopharm Therapeutics Inc.
20

Other Programs and Assets
• Selinexor in Solid Tumor Malignancies
• Eltanexor
• KPT-9274

Selinexor in Solid Tumor Malignancies
Selinexor
in Liposarcoma
Selinexor
in Endometrial Cancer
• Ongoing Phase 3 SEAL study; randomized, double-blind trial evaluating single-agent
selinexor versus placebo in patients with advanced unresectable dedifferentiated
liposarcoma after at least two systemic therapies
• Primary endpoint: PFS (crossover from placebo to selinexor is allowed)
• Top-line data expected by the end of 2019
• Achieved superior PFS over placebo in Phase 2 (n=56), HR=0.67 (RECIST v1.1)1
• Ongoing Phase 3 SIENDO study; investigator-sponsored trial evaluating
once weekly selinexor as a maintenance therapy versus placebo in
patients with endometrial cancer after first- or second-line chemotherapy
• Top-line data expected in 2020
• Achieved 45% DCR, 3 months mPFS and 8 months mOS in Phase 2
SIGN study (n=20)2
1 Gounder, M, et al. ASCO 2018. Abstract 11512. 2 Vergote, I, et al. ESMO 2016. Abstract 8540.
©2018 Karyopharm Therapeutics Inc. 22

Other Pipeline Programs
Eltanexor
(KPT-8602)
• Oral, 2nd generation SINE compound
• Preclinical results show substantially less brain penetration versus selinexor
• In Phase 1/2 clinical testing; reported updated data from Phase 1 portion at ASH 2017
• Good tolerability shown to date in >50 patients
• Expanding development to include myelodysplastic syndrome (MDS),
colorectal cancer (CRC) and castrate-resistant prostate cancer (crPC)
KPT-9274
• Oral dual Inhibitor of PAK4 and NAMPT
• In Phase 1 clinical testing in advanced solid tumors
• Generally well tolerated (n=21) with early signals of anti-tumor activity
• Additional supportive preclinical research presented at ASH 2017
©2018 Karyopharm Therapeutics Inc. 23

Building Commercial Capabilities
Preparing for potential U.S. launch of selinexor
1Q 2018
Hired VPs of Marketing, Sales, and Market Access
Remainder of 2018
Building out commercial infrastructure
Early 2019
Plan to hire sales force of ~70 oncology specialists
1H 2019
Potential launch in penta-refractory myeloma
Developing commercial partnerships in parallel to serve global markets
Ono Pharmaceutical Co. Ltd.
Licensing transaction for selinexor and eltanexor in all oncology indications in Japan and other Asian countries1
Antengene Corporation
Licensing transaction for selinexor, eltanexor, verdinexor and KPT-9274 in China and other Asian countries2
Europe and Other Key Markets
Seeking collaboration arrangements with commercial partners
Karyopharm is committed to working across the globe to bring novel therapies to patients
1 Transaction includes Japan, South Korea, Taiwan, Hong Kong and ASEAN countries.
2 Transaction includes China and Macau for selinexor and eltanexor and China, Macau, Taiwan, Hong Kong, South Korea and the ASEAN countries for verdinexor and KPT-9274.
©2018 Karyopharm Therapeutics Inc.
24

Significant Regulatory and Commercial Experience
Michael Kauffman Sharon Shacham Chris Primiano Mike Falvey Jatin Shah
Chief Executive Officer President and Chief Business Officer Chief Financial Officer SVP, Clinical Development
Chief Scientific Officer
Bill Hatfield Joan Wood Ran Frankel Kevin Malobisky Brian Austad Ronit Milstein
SVP, Product Strategy Chief Human Chief Development SVP, Regulatory Affairs, SVP, Pharmaceutical VP Operations
& Market Development Resources Officer Operations Officer Quality, & Pharmacovigilance Sciences
©2018 Karyopharm Therapeutics Inc.
25

Financial Highlights
$142M
Cash, cash equivalents and investments – March 2018
$146M1
Net proceeds raised in May 2018
BALANCE SHEET
Into
3Q 2019
Expected 2018 operating cash burn - $175-185M2,3
EXPECTED RUNWAY WITH CASH ON HAND AND NET OFFERING PROCEEDS
60M
69M fully diluted
SHARES OUTSTANDING 8-May-2018
1 Net proceeds after deducting the underwriting discounts and commissions and other estimated offering expenses. 2 Including research and development and general and administrative expenses. 3 Guidance issued 10-May-18.
©2018 Karyopharm Therapeutics Inc. 26

Expected Milestones: Looking Ahead to an Event-Driven 2018-20
SELINEXOR SELINEXOR
Solid Tumor Malignancies Hematologic Malignancies
Multiple Myeloma
(Penta-refractory1)
 Top-line Phase 2b STORM data
• NDA submission2 – 2H 2018
• MAA submission3 – early 2019
• Launch in the U.S.4 – 1H 2019
Liposarcoma
(Relapsed/refractory)
Multiple Myeloma
(Relapsed/refractory; 1-3 prior lines of therapy)
• Provide updates for Phase 1b/2 STOMP study at future medical meetings
• Top-line Phase 3 BOSTON data – end of 20195
• NDA submission6 – 2020
Endometrial Cancer
(Maintenance after first- or second-line therapy)
DLBCL
(Relapsed/refractory)
Top-line Phase 2b SADAL data – end of 2018 NDA submission2,7 – 2019 Launch in the U.S.4 – end of 2019
Other Programs
Eltanexor: Report Phase 2 solid tumor
data – 1H 2019
KPT-9274: Report updated Phase 1/2
safety and tolerability data – 2Q 2019
1 Patients who have previously received two PIs, Velcade® (bortezomib) and Kyprolis® (carfilzomib), and two IMiDs, Revlimid® (lenalidomide) and Pomalyst® (pomalidomide), and their disease is refractory to at least one PI, at least one IMiD, and their disease is also refractory to the anti-CD38 monoclonal antibody Darzalex® (daratumumab), and has progressed following their most recent therapy. 2 With request for accelerated approval. 3 With request for full approval. 4 Assuming priority review and FDA approval. 5 Pending PFS events. 6 Assuming positive outcome from Phase 3 BOSTON study. 7 Assuming positive outcome from Phase 2b SADAL study. 8 Assuming positive outcome from Phase 3 portion of SEAL study. 9 Investigator-sponsored trial.
©2018 Karyopharm Therapeutics Inc.
27

Karyopharm Highlights
Hematologic
Malignancies
Multiple Myeloma
Diffuse Large B-cell Lymphoma
Solid Tumor
Malignancies
Liposarcoma
Gynecologic Cancers
First-in-class, oral SINE compounds
Lead asset with significant commercial potential
Strong leadership team and balance sheet
Multiple near term catalysts from broad, late-stage pipeline
Preparing for potential product launches and revenues
Novel, broadly applicable mechanism of action with single agent activity and works well in combinations; patent life through 2032+
Selinexor demonstrated robust activity in penta-refractory myeloma, is combinable with existing therapies and has the potential to be the next “backbone” therapy in myeloma, a market projected to be $22.6B in 20231
Executive team with past successes in lead indications; with recent offering proceeds, cash expected to fund the company into 3Q 2019
Anticipated data readouts (2018-2019): SADAL (end of 2018),
BOSTON (end of 2019; pending PFS events), SEAL (end of 2019) Regulatory Profile: Fast Track and orphan designations granted in multiple myeloma. Planned requests for accelerated approval in multiple myeloma (2H18), accelerated approval in DLBCL (2019)2, full approval in multiple myeloma (2020)3, full approval in liposarcoma (2020)4
Preparing for potential launch of selinexor in multiple myeloma and DLBCL in 2019, followed by expansion to other potential indications
1 Global Data. 2 Assuming positive outcome from Phase 2b SADAL study. 3 Assuming positive outcome from Phase 3 BOSTON study. 4 Assuming positive outcome from Phase 3 portion of SEAL study.
©2018 Karyopharm Therapeutics Inc. 28

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