Karyopharm Therapeutics : Corporate Presentation Sept 2021

1. Commercial-StagePharmaceutical Company Pioneering Novel Cancer Therapies

September 2021

1 ©2021 KARYOPHARM THERAPEUTICS INC .

Forward-looking Statements and Other Important Information

This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Karyopharm's guidance on its expected cash runway; expectations and plans relating to XPOVIO for the treatment of adult patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma and other hematologic malignancies and solid tumors; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the Company's regulatory strategy, the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor. 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 Karyopharm will successfully commercialize XPOVIO; that regulators will grant confirmatory approval in the European Union based on the BOSTON study in adult patients with multiple myeloma; or that any of Karyopharm's drug candidates, including selinexor and eltanexor, 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 the development or commercialization of 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: the risk that the COVID-19 pandemic could disrupt Karyopharm's business more severely than it currently anticipates, including by negatively impacting sales of XPOVIO, interrupting or delaying research and development efforts, impacting the ability to procure sufficient supply for the development and commercialization of selinexor or other product candidates, delaying ongoing or planned clinical trials, impeding the execution of business plans, planned regulatory milestones and timelines, or inconveniencing patients; the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; 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; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. 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, 2021, which was filed with the Securities and Exchange Commission (SEC) on August 5, 2021, 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. Karyopharm regularly uses its website to post information regarding its business, drug development programs and governance. Karyopharm encourages investors to use www.karyopharm.com, particularly the information in the section entitled "Investors," as a source of information about Karyopharm. References to www.karyopharm.com in this presentation are not intended to, nor shall they be deemed to, incorporate information on www.karyopharm.com into this presentation by reference. Other than the currently approved indications of XPOVIO, selinexor, eltanexor, KPT-9274 and verdinexor are investigational drugs that have not been approved by the FDA or any other regulatory agency, and the safety and efficacy of these drugs has not been established by any agency.

XPOVIO® and NEXPOVIO ® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this presentation are the property of their respective owners. All rights reserved.

2 ©2021 KARYOPHARM THERAPEUTICS INC .

Leveraging the

inhibition of

nuclear export as

a mechanism to

treat cancer

APPROVED IN THE US FOR 3 INDICATIONS1

• Multiple myeloma as early as first relapse2
• Relapsed/refractory diffuse large B-cell lymphoma3,4

Building on	Expanding	Key phase 3	Focused	Well-capitalized
myeloma	global footprint	solid tumor data	clinical	Cash runway into
foundation		remains on track	pipeline
Expect CHMP	mid-2023
Driving depth and	review of MAA in	SIENDO top-line	Targeting high
breadth of	2L+ to be completed	results in endometrial	unmet need
leadership presence	in 1H22	cancer expected by	hematological and
in myeloma		year end 2021	solid tumor cancers

		1 Approved only in combination with Velcade® and dexamethasone for patients who have received at least one prior therapy. Full Prescribing Information available
3	©2021 KARYOPHARM THERAPEUTICS INC .	at XPOVIO.com 2 XPOVIO is approved in the US and Europe for the treatment of penta-refractory multiple myeloma, and in the US for second-line and
higher multiple myeloma. 3 Diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at

least 2 lines of systemic therapy. 4 This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Novel XPOVIO® (selinexor) Mechanism: Only Approved, First in Class SINE that is Broadly Applicable and Foundational to Cancer Biology1-4

XPO1 OVEREXPRESSION

• Enables cancer cells to escape tumor suppressor proteins (TSPs), mediated cell cycle arrest, and induction of apoptosis
• Correlates with poor prognosis and drug resistance

INHIBITION OF XPO1 IMPACTS TUMOR

CELLS VIA 3 CORE MECHANISMS

1. Increases nuclear levels and activation of TSPs
2. Traps oncoprotein mRNA in the nucleus leading to reduced oncoprotein levels
3. Retains activated glucocorticoid receptor in the nucleus

4		1 Gupta A, et al. J Thorac Oncol. 2017. 2 Sun Q, et al. Signal Transduct Target Ther. 2016.
©2021 KARYOPHARM THERAPEUTICS INC .	3 Gandhi UH, et al. Clin Lymphoma Myeloma Leuk. 2018. 4 Gravina GL, et al. J Hematol Oncol. 2014

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Progression Free Survival (PFS) Significantly Longer with XVd Compared to Vd

ONCE-WEEKLY, ORAL XPOVIO + VD DELIVERED AN EARLY AND SUSTAINED PFS ADVANTAGE VERSUS TWICE-WEEKLY Vd1

30% reduction in risk of progression or death1

Hazard ratio: 0.70

(96% CI 0.5-0.93),p=0.0075

Hazard ratio (HR) is based on stratified Cox's proportional hazard regression modeling, p-value based on stratified log-rank test.

*According to the International Myeloma Working Group (IMG Uniform Response Criteria for Multiple Myeloma, as assessed by

an Independent Review Committee (IRC). XVd=XPOVIO® (selinexor) with Velcade® (bortezomib) and dexamethasone; Vd=Velcade and dexamethasone.

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©2021 KARYOPHARM THERAPEUTICS INC .

1 XPOVIO (selinexor) package insert

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