Targeting Disease at the Nuclear Pore Karyopharm Reports Second Quarter 2018 Financial Results and Highlights Recent Progress Completed Rolling Submission of a New Drug Application to FDA Seeking Accelerated Approval for

Karyopharm Reports Second Quarter 2018 Financial Results and Highlights Recent Progress

Completed Rolling Submission of a New Drug Application to FDA Seeking Accelerated Approval for Selinexor As a New Treatment for

Patients with Penta-Refractory Multiple Myeloma

On Track to Report Top-Line

Phase 2b SADAL Data in DLBCL and Complete Enrollment in the Pivotal Phase 3 BOSTON Study in Multiple Myeloma by the End of 2018

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

NEWTON, Mass. August 7, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today reported

financial results for the second quarter 2018 and provided an overview of recent accomplishments and clinical development plans for selinexor, its lead, novel, oral SINE compound and its other pipeline programs.

We have made tremendous progress toward advancing our lead drug candidate, selinexor, as we strive to improve the lives of patients with myeloma and

other forms of cancer. Most notably, we have now completed the submission of our first New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for selinexor as a potential new treatment for patients with penta-refractory

myeloma, said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. The positive results from the Phase 2b STORM study announced during the quarter demonstrated that treatment with selinexor may result in an important

clinical benefit in this patient population and we look forward to working with the FDA during their review of the application. We are making excellent progress in advancing commercial preparation for the potential launch of selinexor in the U.S.,

as well as preparing a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA), which we expect to submit in early 2019, with a request for conditional approval, also in penta-refractory myeloma. Finally, while completing

our first-ever NDA submission is clearly a landmark event for Karyopharm, we remain committed to fulfilling the full potential of selinexor as we advance our clinical strategy in earlier lines of treatment in myeloma and in additional tumor

Second Quarter 2018 and Recent Events

Selinexor in Multiple Myeloma

Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Selinexor in Solid Tumors

Second Quarter Ended June 30, 2018 Financial Results

Cash, cash equivalents and investments as of June 30, 2018, including restricted cash, totaled $250.5 million, compared to $176.4 million as of

On May 7, 2018, Karyopharm completed an underwritten public offering of 10,525,424 shares of its common stock at a price to

the public of $14.75 per share, resulting in net proceeds of approximately $145.7 million after deducting the underwriting discounts and commissions and other offering expenses.

For the quarter ended June 30, 2018, Karyopharm recognized $19.9 million in revenue, compared to a small amount of grant revenue for the three

months ended June 30, 2017. The increase in revenue was primarily the result of recognizing $19.7 million of revenue related to fulfilling an obligation under our license agreement with Ono Pharmaceutical Co., LTD. The cash related to this

revenue was received as part of the upfront payment received from Ono in October 2017.

For the quarter ended June 30, 2018, research and development

expense was $44.7 million compared to $23.1 million for the quarter ended June 30, 2017. For the quarter ended June 30, 2018, general and administrative expense was $9.5 million compared to $6.6 million for the quarter

ended June 30, 2017.

Karyopharm reported a net loss of $33.7 million, or $0.60 per share, for the quarter ended June 30, 2018, compared to

a net loss of $29.4 million, or $0.64 per share, for the quarter ended June 30, 2017. Net loss includes stock-based compensation expense of $4.4 million and $5.1 million for the quarters ended June 30, 2018 and June 30,

expects its operating cash burn, including research and development and general and administrative expenses, for the year ending December 31, 2018 to be in the range of $175 to 185 million. Based on current operating plans, Karyopharm

expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations for at least the next twelve months. These plans include the continued clinical development of selinexor in the Company s lead

indications with a focus on preparing the commercial infrastructure and hiring a sales force for the potential launch of selinexor in the U.S. Additional key activities expected in 2018 include preparing for a potential MAA submission to the EMA

requesting conditional approval for selinexor in multiple myeloma, topline data from the SADAL study and completion of enrollment in the Phase 3 BOSTON study.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need

based on a surrogate endpoint or an intermediate clinical endpoint

thought to predict clinical benefit, like overall response rate (ORR). Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at

the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as multiple myeloma,

accelerated approval carries a high regulatory threshold. Consistent with its general guidance, the FDA has noted to the Company its preference for randomized studies geared toward full approval, which the Company has undertaken with the ongoing

pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all available approved therapies. FDA s Fast Track designation is available to therapeutics treating an unmet medical need

in a serious condition; the Company has received Fast Track designation from the FDA specifically for the population treated in the STORM trial. In light of this recognition that the STORM patient population represents an unmet medical need and the

positive top-line data reported in April 2018, the Company believes that the STORM study should support its request to the FDA for accelerated approval.

Conference Call Information

Karyopharm will host a

conference call today, Tuesday, August 7, 2018, at 8:30 a.m. Eastern Time, to discuss the second quarter 2018 financial results, recent accomplishments, clinical developments and business plans. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference ID 3084449. A live audio webcast of the call will be

available under Events & Presentations in the Investor section of the Company s website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company s website

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 2,600 patients have been treated with selinexor. In April 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study

evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. For the STORM study s primary objective, oral selinexor achieved a 25.4% overall

response rate, which included two stringent complete responses, both of which were negative for minimal residual disease, and 29 partial or very good partial responses. The median duration of response, a key secondary objective, was 4.4 months, and

patients with any response had a significantly prolonged overall survival as compared with patients who did not respond. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population

evaluated in the STORM study. Karyopharm has completed a rolling submission for a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA), with a request for accelerated approval for oral selinexor as a new treatment for patients

with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in

several other 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), as a potential backbone therapy in combination with approved therapies (STOMP), in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned,

including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm 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 timing of submissions to regulatory authorities, the potential availability of

accelerated approval pathways, therapeutic potential of and potential clinical development plans for Karyopharm s drug candidates, including the timing of enrollment of certain trials, the plans for commercialization, the reporting of data from

such trials and the impact on potential regulatory filings, the potential to receive milestone and royalty payments under third party arrangements 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 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 that any of Karyopharm s drug candidates, 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 its third party collaborators or successors in interest to fully perform their respective obligations under collaboration or license agreements and the potential future implications of

such agreements; 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, 2018, which was filed with the Securities and Exchange Commission (SEC) on May 10, 2018, 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

Pomalyst are registered trademarks of Celgene Corporation

Kyprolis is a registered trademark of Onyx Pharmaceuticals, Inc.

Darzalex is a registered trademark of Janssen Biotech, Inc.

1 American Cancer Society.

Karyopharm Therapeutics Inc.

Vice President, Investor and Public Relations

857-297-2241 | ikarp@karyopharm.com

212-600-1902 | david.rosen@argotpartners.com

Karyopharm Therapeutics Inc.

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