Karyopharm Therapeutics : Corporate Presentation August 2022

• Commercial-StagePharmaceutical Company Pioneering Novel Cancer Therapies

August 2022

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 financial guidance for full year 2022; Karyopharm's expected cash runway; the ability of selinexor or eltanexor to treat patients with multiple myeloma, diffuse large B-cell lymphoma, solid tumors and other diseases; and expectations related to future clinical development and potential regulatory submissions of 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 June 30, 2022, which was filed with the Securities and Exchange Commission (SEC) on August 4, 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, 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.

• ©202 2 KARYOPHARM THER APEUTICS INC .

Leveraging the

inhibition of

nuclear export as a mechanism to treat cancer

Passionately driven in its

mission to positively impact

lives and defeat cancer

Expanding	Focused mid- and late-	Strong executive	Well-capitalized
on multiple myeloma	stage clinical pipeline	leadership
foundation	Multiple catalysts expected
Continued expansion of	near and mid-term, including	Strengthened leadership	Cash runway into early
XPOVIO by driving	pursuing approvals	team with key appointments	2024
commercial excellence,	in endometrial cancer,	in 2022
moving into earlier lines and	myelofibrosis and
global approvals	myelodysplastic syndromes

• ©202 2 KARYOPHARM THER APEUTICS INC .

Second Quarter 2022 and Recent Highlights

Strong Financials	2Q22 Total Revenue
with Increasing	$39.7M; 76% YoY growth
Revenues and Cost	• Expanding global approvals driving growing levels of license and other revenue
Savings in 2022
• Cost management to match a focused pipeline

Expanding on Multiple Myeloma Foundation Globally

Continue to Advance Clinical Pipeline in Core Indications

2Q22 Net Product Revenue

$29.0M; 44% YoY growth

• Full EU approval for NEXPOVIO expanding indication to 2L+	Approved in 39 countries
• Launches in mainland China by Antengene and Canada by Forus

Selinexor in Myelofibrosis

• Orphan drug designation by FDA
• Completing enrollment in Phase 1/2 frontline study in myelofibrosis for interim analysis in 2H22; encouraging initial data from selinexor + ruxolitinib combo presented at ASCO 2022

Eltanexor in MDS

• FDA Fast Track designation1 and EU orphan drug designation
• Completed enrollment for interim analysis in relapsed refractory MDS Phase 2 study

4	©202 2 KARYOPHARM THER APEUTICS INC .	1. For the development of eltanexor as a monotherapy for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk MDS per IPSS-R

Prioritized and Targeted Core Programs Focused on Driving Improved Patient Outcomes in Areas of High Unmet Need

MULTIPLE		ENDOMETRIAL		MYELOFIBROSIS		MYELODYSPLASTIC
MYELOMA		CANCER				SYNDROMES
Enabling a 'Class		Potential to be the		Potential to improve		Potential to improve
Switch' in Earlier		First Maintenance-		patient outcomes		patient outcomes in
Lines of Therapy to		Only Treatment		in frontline and		frontline and
continue improving		Option for patients		relapsed/refractory		relapsed/refractory
patient outcomes		whose tumors are		MF		MDS
		p53 wild-type

Opportunity to expand into additional lines of therapy in all four core indications

• ©202 2 KARYOPHARM THER APEUTICS INC .