Karyopharm Therapeutics : Corporate Presentation January 2023

A Commercial-Stage

Pharmaceutical

Company Pioneering

Novel Cancer Therapies

JP MORGAN 2023 HEALTHCARE CONFERENCE

January 11, 2023

Richard Paulson

Chief Executive Officer

OVERVIEW

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 preliminary fourth quarter and full year 2022 financial results; Karyopharm's expected cash runway; the ability of selinexor or eltanexor to treat patients with multiple myeloma, endometrial cancer, myelofibrosis, myelodysplastic neoplasms, diffuse large B-cell lymphoma, and other diseases; expectations related to future clinical development and potential regulatory submissions of selinexor or eltanexor; expectations with respect to commercialization efforts; submissions to, and the review and potential approval of selinexor, eltanexor or any of its other product candidates 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 product candidates, especially selinexor and eltanexor. 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 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 September 30, 2022, which was filed with the Securities and Exchange Commission (SEC) on November 3, 2022, 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 and eltanexor 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® (selinexor) and NEXPOVIO® (selinexor) 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.

3 © 2 0 2 3 K A R Y O P H A R M T H E R A P E U T I C S I N C .

Innovation and Patient Focused

Founded in 2008, building on over a decade of research into selective inhibition of nuclear export (SINE) as a novel mechanism of action

Positioned for Next

Stage of Growth

XPOVIO / NEXPOVIO

Approved in Multiple Myeloma (MM) and DLBCL1

• Expanded global footprint with regulatory approvals in 40 countries
• Expect total revenues to be ~$157.7m in 2022
• Moving into earlier lines of therapy in MM

Passionately driven in its mission

to positively impact lives and

defeat cancer

4 © 2 0 2 3 K A R Y O P H A R M T H E R A P E U T I C S I N C .

Focused Clinical Pipeline with One Planned and Two Ongoing Pivotal Studies; Optimizing Dose for Efficacy and Tolerability

• Phase 3 selinexor+ruxolitinib in treatment naïve MF (planned)2
• Phase 3 SPd3 in R/R MM post anti-CD38
• Phase 3 selinexor as maintenance in TP53 wildtype EC4

Strong Financial Position

• Cash position of ~$279m at end of 2022*
• Cash runway until late 2025
  1. * Based on preliminary unaudited estimate

1. 1. DLBCL approved in the U.S. under accelerated approval pathway 2. MF: myelofibrosis; pending regulatory feedback 3. selinexcor + pomalidomide + dexamethasone 4. Endometrial cancer

Key Program Accomplishments in 2022

Multiple Myeloma		Endometrial Cancer		Myelofibrosis

Myelodysplastic

Neoplasms

Grew U.S. XPOVIO net sales by 22% to $120.4m*

• Received full marketing authorization in the EU for NEXPOVIO; Approved in 40 countries
• Commercial launches by partners ex-US
• Initiated pivotal Phase 3 study evaluating lower dose selinexor, SPd1, an all oral regimen in R/R
  MM

Initiated pivotal Phase 3 study of selinexor as a maintenance therapy in TP53 wild-type EC

• Partnership with Foundation Medicine to develop TP53 companion diagnostic
• Presented top-line and subgroup analysis data from SIENDO in EC

Initial results from Phase 1 evaluating selinexor+ruxolitinib in treatment naïve MF

• Encouraging preliminary results across the three relevant endpoints of SVR35, TSS50 and hemoglobin stabilization

Completed recruitment for interim analysis of Phase 2 study evaluating eltanexor in high-risk relapsed/refractory MDS

• Evaluating eltanexor, second SINE compound, in patients of high unmet need

		1. * Based on preliminary unaudited estimate;
5	© 2 0 2 3 K A R Y O P H A R M T H E R A P E U T I C S I N C .	1. 1. Selinexor + pomalidomide + dexamethasone