Targeting Disease at the Nuclear Pore Karyopharm Reports Third Quarter 2018 Financial Results and Highlights Recent Company Progress U.S. Food and Drug Administration Accepts Karyopharm s New Drug Application for Selinex

Karyopharm Reports Third Quarter 2018 Financial Results and Highlights Recent Company Progress

U.S. Food and Drug Administration Accepts Karyopharm s New Drug Application for Selinexor and Grants Priority Review; Assigns

PDUFA Action Date of April 6, 2019

Fast Track Designation Received for Selinexor in Relapsed or Refractory

DLBCL; Top-Line Phase 2b SADAL Data in DLBCL Selected for Presentation at ASH 2018

Successfully Completed $172.5M Convertible Senior Note Offering;

Cash-on-Hand Expected to Fund the Company Into 2Q 2020

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

NEWTON, Mass. November 8, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, today reported

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

We continued to make tremendous progress towards bringing selinexor, our lead drug candidate, to patients with highly refractory multiple myeloma. Most

notably, the U.S. FDA has now accepted our New Drug Application (NDA), granting it a Priority Review with an action date of April 6, 2019, under the Prescription Drug User-Fee Act (PDUFA), said

Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. In this NDA, we are requesting accelerated approval for selinexor as a new treatment for patients with penta-refractory multiple myeloma. If selinexor is approved, we believe

that its novel mechanism of action and oral administration, along with its compelling clinical profile, will make it a meaningful treatment option for patients with highly refractory myeloma. Additionally, we continue to believe selinexor holds

broad utility beyond highly refractory myeloma. We recently received Fast Track Designation for selinexor in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and were also very pleased to learn

that the top-line results from the Phase 2b SADAL study in patients with relapsed or refractory DLBCL have been selected for presentation at the American Society of Hematology (ASH) Annual Meeting on

December 1, 2018. Finally, by the end of 2018, we remain on track to complete enrollment in the pivotal Phase 3 BOSTON study evaluating selinexor in combination with once weekly Velcade

and low-dose dexamethasone versus standard twice weekly Velcade dexamethasone in patients with multiple myeloma who have had one to three prior lines of therapy.

As we await the upcoming FDA review decision for selinexor, we are building our U.S. commercial capabilities, which will include hiring our U.S. sales

force in early 2019. In order to strengthen our financial position, we recently increased our cash position through a private offering of convertible senior notes resulting in net proceeds of approximately $166.9 million which helps extend our

estimated cash runway into the second quarter of 2020. Additionally, our future capital needs could potentially be partially offset with cash generated from sales of selinexor following commercialization, which could come as early as the second

quarter of 2019, pending FDA approval. concluded Dr. Kauffman.

Third Quarter 2018 and Recent Events

Selinexor in Multiple Myeloma

Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)

Selinexor in Solid Tumors

Other ASH 2018 Highlights

Third Quarter Ended September 30, 2018 Financial Results

Cash, cash equivalents and investments as of September 30, 2018, including restricted cash, totaled $212.3 million, compared to $176.4 million

as of December 31, 2017.

On October 26, 2018, Karyopharm completed a private offering securing a $172.5 million aggregate principal amount

of 3.00% convertible senior notes due in 2025, including the full exercise of the initial purchasers option to purchase additional notes. After deducting the initial purchasers discounts and commissions and other offering expenses the

net proceeds are estimated to be $166.9 million.

For the quarter ended September 30, 2018, research and development expense was

$36.4 million compared to $25.2 million for the quarter ended September 30, 2017. For the quarter ended September 30, 2018, general and administrative expense was $13.0 million compared to $5.8 million for the quarter

ended September 30, 2017.

Karyopharm reported a net loss of $48.1 million, or $0.79 per share, for the quarter ended

September 30, 2018, compared to a net loss of $30.6 million, or $0.65 per share, for the quarter ended September 30, 2017. Net loss includes stock-based compensation expense of $4.8 million and $4.9 million for the quarters

ended September 30, 2018 and September 30, 2017, respectively.

Karyopharm 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. Following Karyopharm s private placement of convertible senior notes during October 2018, and based on its current operating plans, Karyopharm expects that its existing cash, cash

equivalents and investments will be sufficient to fund its operations into the second quarter of 2020. This estimate does not account for any cash generated from product sales that the Company expects to generate from the commercial launch of

selinexor, which could come as early as the second quarter 2019, if selinexor is approved by the FDA s assigned PDUFA date. Karyopharm s future capital needs could potentially be partially offset by cash generated from these sales of

Karyopharm s current operating plans include the continued clinical development of selinexor in the Company s lead indications and

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.

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 data reported in April and September 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, Thursday, November 8, 2018, at 8:30 a.m. Eastern Time, to discuss the third 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 7946498. 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 2,800 patients have been treated with selinexor. In April and September 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in

the STORM study. Karyopharm s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible 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. 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 our expectations relating to submissions and to the review and potential approval of

selinexor by regulatory authorities, including the anticipated timing of such submissions and actions, and the potential availability of accelerated approval pathways, the therapeutic potential of and potential clinical development plans for

Karyopharm s drug candidates, especially selinexor, and the plans for commercialization. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm s control, 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 the SADAL study in patients with relapsed or refractory DLBCL or that any of Karyopharm s drug candidates, including selinexor, will successfully

complete necessary 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 U.S. Food and Drug Administration 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 June 30, 2018, which was filed with the Securities and Exchange Commission (SEC) on August 7, 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

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.

CONDENSED CONSOLIDATED BALANCE SHEETS

thousands, except share and per share amounts)