Karyopharm Therapeutics Inc.

Forward-Looking Information

This Annual Report on Form 10-K contains forward-looking statements regarding the expectations of Karyopharm Therapeutics Inc., herein referred to as “Karyopharm,” the “Company,” “we,” or “our,” with respect to the possible achievement of discovery and development milestones, our future discovery and development efforts, including regulatory submissions and approvals, our commercialization efforts, our partnerships and collaborations with third parties, our future operating results and financial position, our ability to continue as a going concern, our business strategy, and other objectives for future operations. We often use words such as “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” and other words and terms of similar meaning to help identify forward-looking statements, although not all forward-looking statements contain these identifying words. You also can identify these forward-looking statements by the fact that they do not relate strictly to historical or current facts. There are a number of important risks and uncertainties that could cause actual results or events to differ materially from those indicated by forward-looking statements. These risks and uncertainties include, but are not limited to, those described in “Part I—Item 1A. Risk Factors” of this Annual Report on Form 10-K and under the heading “Summary of Risk Factors” below. As a result of these and other factors, we may not actually achieve the plans, intentions, expectations or results disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, joint ventures or investments we may make. We do not assume any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

References to XPOVIO® (selinexor) also refer to NEXPOVIO® (selinexor) when discussing its approval and commercialization in certain countries or territories outside of the U.S.

Summary of Risk Factors

Below is a summary of the principal factors that make an investment in our common stock speculative or risky. This summary does not address all of the risks that we face. Additional discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the heading “Risk Factors” and should be carefully considered, together with other information in this Annual Report on Form 10-K and our other filings with the SEC, before making an investment decision regarding our common stock.

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We may not be able to continue as a going concern. We believe that our existing liquidity, including cash, cash equivalents and investments, as well as cash flow from net product revenue and license and other revenue, will only enable us to fund our current operating plans into the second quarter of 2026.

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We may never achieve or maintain profitability and will need additional funding or to enter into strategic alternatives to achieve our business objectives.

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We may not be able to satisfy our indebtedness or comply with various covenants and other provisions under our credit agreement and the indentures under outstanding convertible notes, on a timely basis or at all.

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Our business, financial condition and stock price may be impacted by unstable market and economic conditions.

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If we or our collaborators are unable to successfully commercialize current and future indications of XPOVIO or other products or product candidates on a timely basis, our business, financial condition and future profitability will be materially harmed.

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We face substantial competition for XPOVIO in multiple myeloma and will face competition for selinexor in any additional indications for which it may be approved.

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We or our collaborators may be unable to successfully enroll patients in our ongoing and planned clinical trials in a reasonable timeframe, or at all. If our clinical trials fail to demonstrate safety and effectiveness to the satisfaction of regulatory authorities or do not otherwise produce positive results, we or our collaborators may incur additional costs, experience delays or be unable to complete the development of such product candidates.

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Serious adverse or unacceptable side effects related to XPOVIO, our product candidates or future products may delay or prevent their regulatory approval, cause us or our collaborators to suspend or discontinue clinical trials, or limit the commercial value of our approved indications or result in significant negative financial consequences following any marketing approval.

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The results of previous clinical trials may not be predictive of future trial results and interim or top-line data may be subject to change or qualification based on the complete analyses of data and, therefore, may not be predictive of the final results of a trial.

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We may not be successful in our efforts to identify or discover additional potential product candidates, or our decisions to prioritize the development of certain product candidates over others may later prove wrong.

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We may not be able to maintain or expand our sales, marketing and distribution capabilities in order to successfully commercialize XPOVIO or any of our products or product candidates, if approved.

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Any business that we or our collaborators conduct outside of the U.S. may be adversely affected by international risks and uncertainties.

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We or our collaborators may not receive regulatory approvals for the commercialization of some or all of our or their product candidates, including necessary companion diagnostic devices, in a timely manner, or at all.

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We or our collaborators may not be able to utilize accelerated development pathways to obtain regulatory approval, orphan drug exclusivity or certain other designations for our or their product candidates, which may result in delays receiving necessary marketing approvals.

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Our or our collaborators’ ability to commercialize our or their products may be limited by the terms of their respective regulatory approvals and ongoing regulation of our products.

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Our failure to comply with post-approval development and regulatory requirements, pricing regulations, reporting and payment obligations under governmental drug pricing programs, applicable healthcare, privacy and data security laws and environmental, health and safety laws and regulations may have a material adverse effect on our business, financial condition or results of operations.

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Changes in U.S. and international trade policy could have a material adverse impact on our business, financial condition and results of operations.

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We are subject to extensive regulatory obligations and policies that may be subject to change, including due to judicial challenges, election cycles, and resulting regulatory updates and changes in policy priorities.

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Our dependence on third parties for certain aspects of our business, such as clinical development, manufacturing, marketing, distribution and/or commercialization of XPOVIO and/or our product candidates, could negatively impact our development and commercialization plans.

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If we are unable to obtain and maintain patent protection for our products and product candidates and other discoveries, or the scope of the patent protection obtained is not sufficiently broad, our ability to successfully commercialize our products or product candidates may be adversely affected.

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We may become involved in lawsuits to protect or enforce our intellectual property rights, or third parties may initiate legal proceedings against us alleging our infringement of their intellectual property rights.

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If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

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Information technology system failures or security breaches may materially adversely affect our business and operations.

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We use artificial intelligence in our business processes, which could adversely impact our business and operations, including by posing security and other risks to our confidential or proprietary information, including personal information, and, as a result, we may be exposed to reputational harm and liability.

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Our stockholders may be significantly diluted in connection with additional capital raises or equity issuances, or exercises of a substantial number of outstanding warrants to purchase our common stock.

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The price of our common stock has been and may continue to be volatile and if we fail to maintain compliance with Nasdaq our common stock could be delisted.

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Securities or other litigation could result in substantial costs and may divert management’s time and attention from our business.