Targeting Disease at the Nuclear Pore Karyopharm Reports Fourth Quarter and Full Year 2016 Financial Results and Provides Selinexor Clinical Update Overall Response Rate of 28.4% Observed in Phase 2b SADAL Study in Relap

Karyopharm Reports Fourth Quarter and Full Year 2016 Financial Results and Provides Selinexor Clinical

Overall Response Rate of 28.4% Observed in Phase 2b SADAL Study in Relapsed/Refractory DLBCL; Additional Top-line

Data to be Presented as a Late-Breaker at AACR 2017 Annual Meeting

Company Announces FDA-Affirmed Development Path

for Selinexor in DLBCL with Potential for Accelerated Approval

Conference Call Scheduled for Today at 8:30 a.m. ET

NEWTON, Mass. March 16, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company,

today reported financial results for the fourth quarter and full year 2016 and provided a clinical update for selinexor (KPT-330), its lead, novel, oral Selective Inhibitor of Nuclear Export (SINE ) compound. The Company also provided an

overview of select accomplishments related to its other pipeline assets, including KPT-8602, its second-generation oral SINE compound, KPT-9274, its oral, dual inhibitor of p21-activated kinase 4 (PAK4) and nicotinamide

phosphoribosyltransferase (NAMPT), and KPT-350, an oral SINE compound with potential applications in neurological and autoimmune indications.

2016 marked a year of several key achievements for Karyopharm, including the rapid advancement of oral selinexor in relapsed or refractory multiple

myeloma (MM), a disease for which we believe we have a path to regulatory approval, said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. To date, 2017 has brought several significant developments. Today we announced

the planned development path for selinexor in diffuse large B-cell lymphoma (DLBCL), our second lead indication after MM. Following the observation of a 28.4% overall response rate (ORR) in the Phase 2b SADAL study, we consulted with the U.S. Food

and Drug Administration (FDA) and obtained their agreement to our amendment of the SADAL study to focus solely on the 60mg twice weekly treatment cohort, in which we plan to enroll up to 90 more patients. Assuming we continue to see the response

rate we have observed to date, we intend to use the data from the SADAL study to support an accelerated approval in DLBCL. We look forward to presenting additional top-line data from the Phase 2b SADAL study in a late-breaking poster at the upcoming

American Association for Cancer Research (AACR) 2017 annual meeting in early April.

As previously announced on March 10, 2017,

Karyopharm s selinexor clinical trials have been placed on a partial clinical hold by the FDA due to incomplete information in the existing version of the investigator s brochure (IB), including an incomplete list of serious adverse events

(SAEs) associated with selinexor. The partial clinical hold is not the result of any patient death or any new information regarding the safety profile of selinexor. While the partial clinical hold remains in effect, patients with stable disease or

better may remain on selinexor therapy, but no new patients may be enrolled until the partial clinical hold is lifted. The Company has provided all requested materials to the FDA believed to be required to lift the partial clinical hold. Karyopharm

is working diligently with the FDA to seek the release of the partial clinical hold and resume enrollment in its selinexor clinical trials as expeditiously as possible. The Company believes that its previously disclosed enrollment rates and

timelines for its ongoing trials will remain materially unchanged.

Clinical Update for Selinexor in DLBCL:

Today Karyopharm reported a 28.4% overall response rate (ORR) in the ongoing Phase 2b SADAL study evaluating 60mg and 100mg of selinexor dosed twice weekly in

patients with relapsed or refractory DLBCL. In a recent analysis of the first 63 patients between both arms, the ORR, as determined by independent Central Radiological Review, was 28.4%, with consistent response rates across both arms, but greater

durability and tolerability observed in the 60mg arm. As a result of these findings, and in consultation with the FDA, the Company has decided to amend the SADAL study protocol to become a single-arm study focusing solely on single-agent selinexor

dosed at 60mg twice weekly, eliminating the 100mg arm. The Company will also make certain other protocol amendments, including reducing the 14-week washout period to 8 weeks for patients who achieved at least a partial response on their most recent

therapy. The FDA agreed that the changes to the single-arm study were reasonable and that the proposed trial design and indication appear appropriate for accelerated approval, though eligibility for accelerated approval will depend on the complete

trial results and available therapies at the time of regulatory action. The Company plans to enroll up to an additional 90 patients to the new 60mg single-arm cohort, and expects to report top-line results from the completed SADAL study in mid-2018.

Dr. Kauffman continued, Looking ahead to the remainder of 2017, we are focusing on initiation of the pivotal Phase 3 BOSTON trial where we

will evaluate selinexor in combination with Velcade (bortezomib) and dexamethasone in patients with MM previously treated with one to three regimens, moving selinexor into much earlier lines

of treatment. After the presentation of the SADAL data at the AACR 2017 annual meeting, we anticipate multiple other important data readouts during the year, including top-line data from the Phase 2 portion of our randomized Phase 2/3 SEAL study in

patients with liposarcoma, our most advanced solid tumor indication in mid-2017. We also plan to present top-line Phase 1 safety and tolerability data for KPT-9274 in the second half of the year.

Our other key objectives include continued execution of the expanded STORM and STOMP studies in relapsed or refractory MM. For STORM, the expansion arm

evaluating oral selinexor in patients with penta-refractory MM is expected to read out in early 2018. Assuming a positive outcome, we intend to use the STORM study data to support accelerated approval for selinexor in MM. For STOMP, we recently

completed enrollment in the selinexor, Velcade (bortezomib) and dexamethasone arm and expect to soon initiate a new expansion arm evaluating oral selinexor in combination with the anti-CD38

monoclonal antibody Darzalex , Dr. Kauffman concluded.

Fourth Quarter 2016 and

Recent Events, Highlights and Milestones:

Selinexor in Multiple Myeloma (MM)

Selinexor in Diffuse Large B-Cell Lymphoma

Selinexor in Other Hematologic Malignancies

Selinexor in Solid Tumors

Selinexor Early Scientific Research

Fourth Quarter and Year Ended December 31, 2016 Full Year Financial Results

Cash, cash equivalents and investments as of December 31, 2016, including restricted cash, totaled $175.5 million, compared to $210.0 million as of

For the year ended December 31, 2016, research and development expense was $86.9 million compared to $97.7 million for the

year ended December 31, 2015. For the year ended December 31, 2016, general and administrative expense was $23.9 million compared to $21.6 million for the year ended December 31, 2015.

Karyopharm reported a net loss of $109.6 million, or $2.92 per share, for the year ended December 31, 2016, compared to a net loss of $118.2 million, or

$3.32 per share, for the year ended December 31, 2015. Net loss includes stock-based compensation expense of $22.3 million and $17.1 million for the years ended December 31, 2016 and December 31, 2015, respectively.

For the quarter ended December 31, 2016, research and development expense was $20.7 million compared to $24.1 million for the quarter ended

December 31, 2015. The decrease in research and development expenses resulted primarily from the timing of clinical expenses related to the development of selinexor. For the quarter ended December 31, 2016, general and administrative

expense was $6.5 million compared to $5.3 million for the quarter ended December 31, 2015. Karyopharm reported a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016, compared to a net loss of $29.0

million, or $0.81 per share, for the quarter ended December 31, 2015. Net loss includes stock-based compensation expense of $5.1 million and $5.4 million for the quarters ended December 31, 2016 and December 31, 2015, respectively.

Karyopharm expects its operating

cash burn, including research and development and general and administrative expenses, for the year ending December 31, 2017 to be in the range of $85 to 90 million. Based on current operating plans, Karyopharm expects that its existing cash

and cash equivalents will fund its research and development programs and operations until the end of 2018, including through the data readout for the expanded STORM cohort, completion of enrollment for the BOSTON study and the advancement of other

ongoing selinexor clinical studies to their next data inflection points.

Conference Call Information:

Karyopharm will host a conference call today, Thursday, March 16, 2017, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full-year 2016

financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 (US) or (484) 756-4292 (international) at least five minutes prior to the start time

and refer to conference ID: 79794446. An audio recording of the call will be available under Events & Presentations in the Investor section of Karyopharm s website, http://www.karyopharm.com,

approximately two hours after the event.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clinical-stage pharmaceutical company focused on the discovery and development of novel first-in-class drugs

directed against nuclear transport and related targets for the treatment of cancer and other major diseases. Karyopharm s SINE compounds function by binding with and inhibiting the nuclear export protein XPO1 (or CRM1). The Company s

initial focus is on seeking regulatory approval and commercialization of its lead drug candidate, oral selinexor (KPT-330). To date, over 1,900 patients have been treated with selinexor and it is currently being evaluated in several mid- and

later-phase clinical trials across multiple cancer indications, including multiple myeloma in combination with low-dose dexamethasone (STORM) and backbone therapies (STOMP), diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL), among

others. Karyopharm plans to initiate a pivotal randomized Phase 3 study of selinexor in combination with bortezomib (Velcade ) and low-dose dexamethasone (BOSTON) in patients with multiple

myeloma in early 2017. In addition to single-agent and combination activity against a variety of human cancers, SINE compounds have also shown biological activity in models of neurodegeneration, inflammation, autoimmune disease, certain

viruses and wound-healing. Karyopharm, which was founded by Dr. Sharon Shacham, currently has five investigational programs in clinical or preclinical development. For more information, please visit www.karyopharm.com.

Forward-Looking Statements

This press release contains

forward-looking statements within the meaning 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 for

Karyopharm s drug candidates, including the timing of initiation of certain trials and of the reporting of data from such trials, the anticipated impact of the partial clinical hold, timing of FDA review of Karyopharm s response and

Karyopharm s plans for obtaining the release of the partial clinical hold. 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), KPT-8602, Karyopharm s next generation SINE compound, or KPT-9274, Karyopharm s

first-in-class oral dual inhibitor of PAK4 and NAMPT, or any other drug candidate that 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 FDA will release the partial clinical hold 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. Management s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, 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 in 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 are described under the caption Risk Factors in Karyopharm s Annual Report on Form 10-K for the year ended December 31 2016, which was filed

with the Securities and Exchange Commission (SEC) on March 16, 2017, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and

Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

Velcade is a registered trademark of Takeda

Pharmaceutical Company Limited

Darzalex is a registered trademark of Janssen Biotech, Inc.

Karyopharm Therapeutics Inc.

Consolidated Balance Sheets

(in thousands, except share and per share amounts)

Karyopharm Therapeutics Inc.

CONSOLIDATED STATEMENTS OF OPERATIONS

(in thousands, except share and per share amounts)