Targeting Disease at the Nuclear Pore Karyopharm Reports Second Quarter 2017 Financial Results and Highlights Recent Progress Pivotal Phase 3 BOSTON Study Underway Updated Phase 1b/2 STOMP Data Expected by Year End 2017;

Karyopharm Reports Second Quarter 2017 Financial Results and Highlights Recent Progress

Pivotal Phase 3 BOSTON Study Underway

Updated Phase 1b/2 STOMP Data Expected by Year End 2017; Top-line Phase 2b STORM Data

Expected by April 2018

Phase 2 SEAL Hazard Ratio Expected in September/October 2017, Along with Other Pipeline

Program Updates During the Second Half of 2017

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

NEWTON, Mass. August 8, 2017 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today

reported financial results for the second quarter 2017 and commented on recent accomplishments and clinical development plans for its lead, novel, oral Selective Inhibitor of Nuclear Export (SINE ) compound selinexor (KPT-330), and other pipeline assets verdinexor (KPT-335), and KPT-9274, its oral, dual inhibitor of

p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT).

achievements marked significant progress across several of our development programs, and especially for selinexor, said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. At the 2017 European Hematology Association

(EHA) Annual Meeting, we reported updated data from the Phase 2b SADAL study investigating selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The overall response rate

(ORR) increased to 33.3% for the overall trial population with similar response rates in patients with double- or triple-hit DLBCL, indicating clear activity in this population which usually has a particularly

poor prognosis. As we move to the second half of the year, our focus remains on execution of key later-stage trials in our lead indications of multiple myeloma (MM), DLBCL and liposarcoma. In myeloma, the pivotal Phase 3 BOSTON study is now

underway. The Phase 2b STORM study, for possible accelerated approval, continues to enroll well with top-line data expected by April 2018. In liposarcoma, the Phase 2 portion of the blinded, randomized Phase

2/3 SEAL study recently completed enrollment and we look forward to reporting the hazard ratio for progression-free survival (PFS) and providing an update regarding the planned development path in this indication during September or October

Second Quarter 2017 and Recent Events, Highlights and Milestones:

Selinexor in Multiple Myeloma

Selinexor in Diffuse Large B-Cell Lymphoma

In consultation with the U.S. Food and Drug Administration (FDA), Karyopharm amended the

SADAL study, removing the 100mg arm and continuing enrollment only in the 60mg twice weekly arm. The FDA has agreed that the single-arm trial design appears appropriate for accelerated approval in DLBCL,

though eligibility for accelerated approval will depend on the complete trial results and available therapies at the time of regulatory action. The SADAL study is expected to enroll up to a total of 130 patients in the 60mg single-arm cohort and Karyopharm plans to report top-line results in the second half of 2018.

Selinexor in Other Hematologic Malignancies

Phase 1 Data Demonstrating Selinexor s Activity in Patients with Relapsed/Refractory Non-Hodgkin s Lymphoma (NHL) in the Journal Blood. A paper describing results from the

first in human Phase 1 clinical study assessing safety and preliminary activity of selinexor in patients with relapsed or refractory NHL was recently published in the journal Blood. In the paper, authored by John Kuruvilla, et al., titled

Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin s lymphoma, Karyopharm collaborators reported that selinexor was generally well tolerated. Of the 70

evaluable patients, 22 (31%) achieved an objective response (OR), including 4 CRs and 18 PRs, which were observed across a spectrum of NHL subtypes, including DLBCL, Richter s transformation, mantle cell lymphoma, follicular lymphoma and

chronic lymphocytic leukemia. All four CRs were in patients with DLBCL, and two of the four patients are believed to have remained relapse-free as of the publication date, greater than 3 years since initiation of single agent selinexor therapy.

Tumor biopsies showed decreases in cell signaling pathways, reduced proliferation, nuclear localization of XPO1 cargos and increased apoptosis after treatment. The most common grade 3-4 drug-related AEs were

thrombocytopenia (47%), neutropenia (32%), anemia (27%), leukopenia (16%), fatigue (11%) and hyponatremia (10%). A maximum tolerated dose was not defined, but the highest allowable dose was ~120 mg twice weekly. Based on both tolerability and

antitumor activity, the recommended Phase 2 dose of selinexor in NHL is 35 mg/m2 (~60 mg) twice weekly.

Selinexor in Solid Tumors

Other Corporate and Clinical

Second Quarter 2017 Financial Results

Cash, cash equivalents and investments as of June 30, 2017, including restricted cash, totaled $181.2 million, compared to $175.5 million as of

On April 28, 2017, Karyopharm completed an underwritten public offering of 3,902,439 shares of its common stock at a price

to the public of $10.25 per share. The net proceeds to Karyopharm from the offering, after deducting the underwriting discounts and commissions and offering expenses, were approximately $37.9 million. In addition, during April 2017, the Company

sold approximately 1.3 million shares under its ATM offering facility for net proceeds of approximately $14.4 million.

For the quarter ended

June 30, 2017, research and development expense was $23.1 million compared to $24.6 million for the quarter ended June 30, 2016. For the quarter ended June 30, 2017, general and administrative expense was $6.6 million

compared to $6.0 million for the quarter ended June 30, 2016.

Karyopharm reported a net loss of $29.4 million, or $0.64 per share, for the

quarter ended June 30, 2017, compared to a net loss of $30.2 million, or $0.84 per share, for the quarter ended June 30, 2016. Net loss includes stock-based compensation expense of $5.1 million and $6.4 million for the

quarters ended June 30, 2017 and June 30, 2016, 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 $90-95 million. Based on current operating plans, Karyopharm expects that its existing cash and cash equivalents will be sufficient to fund its research and development programs

and operations into 2019, including the continued clinical development of selinexor in the Company s lead indications with a focus on filing for accelerated approvals for both MM and DLBCL during 2018, and preparing a commercial infrastructure

for the potential launch of selinexor in North America and Western Europe.

Conference Call Information:

Karyopharm will host a conference call today, Tuesday, August 8, 2017, at 8:30 a.m. Eastern Time, to discuss the second quarter 2017 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: 53128722. 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 2,100 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 backbone 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 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 and enrollment of certain trials and of the reporting of data from such trials, 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) 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; 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 March 31, 2017, which was filed with the Securities and Exchange Commission (SEC) on May 4, 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

Darzalex is a registered trademark of Janssen Biotech, Inc.

EvaluatePharma World Preview 2017, Outlook to 2022 is copyrighted by Evaluate Ltd.

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