Targeting Disease at the Nuclear Pore Karyopharm Reports Fourth Quarter and Full Year 2017 Financial Results and Highlights Recent Progress - Phase 2b STORM Study Evaluating Selinexor in Patients with Penta-Refractory My

Karyopharm Reports Fourth Quarter and Full Year 2017 Financial Results and Highlights Recent Progress

- Phase 2b STORM Study Evaluating Selinexor in Patients with Penta-Refractory Myeloma Remains on Track; Top-Line Data Expected end of April 2018

- Company Executes Two High-Value Strategic

Transactions Providing Substantial Validation for Its Lead Assets and XPO1 Inhibition

- Conference Call Scheduled for Today

NEWTON, Mass. March 15, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical

company, today reported financial results for the fourth quarter and full year 2017 and provided an overview of recent accomplishments and clinical development plans for selinexor, its lead, novel, oral SINE compound, and eltanexor, its

second-generation oral SINE compound.

2017 was a year of significant achievement for Karyopharm where we reported positive clinical data from our

lead selinexor programs, including the Phase 1b/2 STOMP study in multiple myeloma (MM), the Phase 2b SADAL study in diffuse large B-cell lymphoma (DLBCL), and the Phase 2/3 SEAL study in liposarcoma, and the

subsequent advancement of each study, said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. We are looking forward to an event-driven 2018 beginning at the end of April with

top-line results from the Phase 2b STORM study, followed by top-line data from the Phase 2b SADAL study by the year end. Assuming positive outcomes, we plan to use the

data from both of these studies to support requests for accelerated approval from the U.S. Food and Drug Administration (FDA) and conditional approval from the European Medicines Agency (EMA) in these indications. On the corporate front, we continue

to build out our commercial team in anticipation of a potential selinexor launch in the U.S. in 2019.

Fourth Quarter 2017 and Recent Events

New Strategic Relationships

Selinexor in Multiple Myeloma

Selinexor in Diffuse Large B-Cell Lymphoma

Selinexor in Solid Tumors

Fourth Quarter and Year Ended December 31, 2017 Financial Results

Cash, cash equivalents and investments as of December 31, 2017, including restricted cash, totaled $176.4 million, compared to $175.5 million as

of December 31, 2016.

For the year ended December 31, 2017, research and development expense was $107.3 million compared to

$86.9 million for the year ended December 31, 2016. For the year ended December 31, 2017, general and administrative expense was $24.9 million compared to $23.9 million for the year ended December 31, 2016.

Karyopharm reported a net loss of $129.0 million, or $2.81 per share, for the year ended December 31, 2017, compared to a net loss of

$109.6 million, or $2.92 per share, for the year ended December 31, 2016. Net loss includes stock-based compensation expense of $20.4 million and $22.3 million for the years ended December 31, 2017 and December 31,

For the quarter ended December 31, 2017, research and development expense was $34.8 million compared to $20.7 million

for the quarter ended December 31, 2016. The increase in research and development expenses resulted primarily from increased expenses on our late stage clinical trials for selinexor and from payments of a portion of the upfront fees we received

under our license agreement with Ono. For the quarter ended December 31, 2017, general and administrative expense was $6.2 million compared to $6.5 million for the quarter ended December 31, 2016. Karyopharm reported a net loss

of $39.0 million, or $0.80 per share for the quarter ended December 31, 2017, compared to a net loss of $26.9 million, or $0.65 per share, for the quarter ended December 31, 2016. Net loss includes stock-based compensation

expense of $4.5 million and $5.1 million for the quarters ended December 31, 2017 and December 31, 2016, respectively.

Based on current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations through

at least the first quarter of 2019. These plans include the continued clinical development of selinexor in the Company s lead indications with a focus on filing an NDA with the FDA requesting accelerated approval in MM during 2018, assuming

positive data from the STORM study, and preparing the commercial infrastructure for the potential launch of selinexor in the United States. Additional key milestones expected in 2018 include a potential MAA filing to the EMA requesting conditional

approval for selinexor in MM, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Conference Call Information

Karyopharm will host a conference call today, Thursday, March 15, 2018, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year

2017 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 or (484)

756-4292 (international) at least five minutes prior to the start time and refer to conference ID: 1181109. 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.

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 2,200 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 in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose

dexamethasone (BOSTON), in combination with low-dose dexamethasone (STORM) and standard therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL) and liposarcoma

(SEAL), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform the Company s

clinical development priorities for selinexor. 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 four 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 enrollment of certain trials, the reporting of data from such trials and potential regulatory filings, the potential to receive milestone and royalty payments under the arrangements with Ono

and Biogen and Karyopharm s financial outlook

and 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 any of Karyopharm s SINE compounds, including selinexor (KPT-330), eltanexor

(KPT-8602), Karyopharm s second-generation oral 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 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. 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, including with respect to the need for additional clinical studies; Karyopharm s ability to obtain and maintain requisite regulatory approvals and to enroll

patients in its clinical trials; the ability of Karyopharm or Ono to fully perform their respective obligations under the license agreement and the potential future implications of such agreement; the impact of volatility in currency exchange rates;

the ability of Karyopharm or Biogen to fully perform their respective obligations under their agreement and the potential future implications of such agreement; 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2017, which was filed with

the Securities and Exchange Commission (SEC) on November 2, 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,

except as 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.

Velcade is a registered trademark of Takeda Pharmaceutical Company Limited

Revlimid and Pomalyst are registered

trademarks of Celgene Corporation

Kyprolis is a registered trademark of Onyx Pharmaceuticals,

Darzalex is a registered trademark of Janssen Biotech, Inc.

Karyopharm Therapeutics Inc.

Consolidated Balance Sheets

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Karyopharm Therapeutics Inc.

Consolidated Statements of Operations

(in thousands, except share and per share amounts)