What changed in this filing

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Item 1A. Risk Factors

2026-05-14 compared with 2025-11-03 · 277 added, 338 removed, 1195 unchanged (34% of the section changed)

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We have incurred significant operating losses since our inception.

As of September 30, 2025, we had approximately $45.9 million in cash, cash equivalents, and investments.

In October 2025, we completed a series of financing transactions that resulted in the receipt of approximately $36.0 million of gross proceeds.

We expect our existing cash resources, as well as cash flow from net product revenue and license and other revenue, to fund our existing operations into the second quarter of 2026.

We will require additional capital to complete the ongoing clinical development of selinexor, including the Phase 3 SENTRY trial beyond top-line results and the Phase 3 XPORT-EC-042 trial.

As of March 31, 2026, we had approximately $90.9 million in cash and cash equivalents.

We believe that our existing liquidity, including cash and cash equivalents, as well as cash flow from net product revenue and license and other revenue, will enable us to fund our current operating plans to late in the third quarter of 2026.

We will require additional capital to fund the ongoing clinical development of selinexor and other product candidates and to pursue potential regulatory approvals.

We have based this assessment on assumptions that may prove to be wrong, and we could exhaust our capital resources sooner than we expect.

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If we are unable to raise sufficient capital or to enter into strategic alternatives on acceptable terms to meet our needs, we may be forced to delay, reduce or eliminate our research and development programs and/or commercialization efforts ,” below.

Based on our current business plan and current capital resources, given the uncertainty regarding the availability of additional funding or other strategic alternatives and considering our debt service obligations, including requirements under our Amended Credit Agreement, as defined below, and the indentures governing our 9.00% convertible senior notes due 2028 (the “2028 Notes”) and 9.00% convertible senior notes due 2029 (the “New 2029 Notes”, and together with the 2028 Notes, the “Convertible Notes”) to maintain cash, cash equivalents and investments of at least $10.0 million, subject to increase in the event we issue indebtedness for borrowed money or issue capital stock, through October 10, 2026, after which we will be required to maintain liquidity of at least $25.0 million, we have concluded that there is substantial doubt regarding our ability to continue as a going concern within one year after the date the accompanying consolidated financial statements are issued.

Based on our current business plan and current capital resources, combined with the uncertainty regarding the availability of additional funding or other strategic alternatives and considering our debt service obligations, including requirements under the Amended Credit Agreement, as defined below, and the indentures governing our 9.00% convertible senior notes due 2028 (the “2028 Notes”) and 9.00% convertible senior notes due 2029 (the “New 2029 Notes”, and together with the 2028 Notes, the “Convertible Notes”) to maintain cash, cash equivalents and investments through October 10, 2026 of at least the lesser of (i) $10.0 million plus 50% of the net cash proceeds received from certain debt and equity issuances and (ii) $25.0 million, and $25.0 million thereafter, we have concluded that there is substantial doubt regarding our ability to continue as a going concern within one year after the date the accompanying consolidated financial statements are issued.

We plan to address the conditions that raise substantial doubt regarding our ability to continue as a going concern by, among other things, obtaining additional funding through equity offerings, debt financings and refinancings, collaborations, strategic alliances and/or licensing arrangements.

In addition, we expect to evaluate opportunities to raise additional funds from time to time, including though the issuance and sale of shares of our common stock under our 2023 Open Market Sale Agreement with Jefferies and in connection with the reporting of data from our ongoing Phase 3 clinical trials.

However, there is no assurance that such additional financing or strategic alternatives will be available on terms acceptable to us, or at all.

In addition, we expect to evaluate opportunities to raise additional funds from time to time, including through the issuance and sale of shares of our common stock under our Open Market Sale Agreement with Jefferies LLC and in connection with the reporting of data from our ongoing Phase 3 clinical trials.

However, there is no assurance that additional financing or strategic alternatives will be available on terms acceptable to us, or at all, or that such additional financing or strategic alternatives, if consummated, will be sufficient to address doubt regarding our ability to continue as a going concern.

If we utilize our capital resources more quickly than anticipated or are unable to obtain additional funding or engage in strategic alternatives, we may have to significantly curtail, delay, reduce or eliminate one or more of our research and development programs or any current or future commercialization efforts for one or more of our products or product candidates, which could materially adversely affect our business, financial condition, and results of operations.

We may determine to take additional actions to reduce our spending in the near term.

As we announced on July 11, 2025, we reduced our workforce by approximately 20% as part of our ongoing careful management of operating expenses.

We have and may in the future determine to take actions to reduce our spending in the near term, including reductions to our workforce.

If we are unable to continue as a going concern, we may have to liquidate assets and may receive less than the value at which those assets are carried on our financial statements.

We may also determine to cease operations or file for bankruptcy protection.

In any of these circumstances, it is likely that investors will lose all or part of their

In any of these circumstances, it is likely that investors will lose all or part of their investment.

If there remains substantial doubt about our ability to continue as a going concern, investors or other financing sources may be unwilling to provide funding to us on commercially reasonable terms, if at all.

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Since inception, we have incurred significant operating losses.

Our net loss was $93.8 million for the nine months ended September 30, 2025.

As of September 30, 2025, we had an accumulated deficit of $1.7 billion.

Our loss from operations was $26.8 million for the quarter ended March 31, 2026.

As of March 31, 2026, we had an accumulated deficit of $1.8 billion.

As described above in “ Our financial condition raises substantial doubt as to our ability to continue as a going concern ,” our financial condition raises substantial doubt about our ability to continue as a going concern.

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The net losses we incur may fluctuate significantly from quarter to quarter.

While we began to generate revenue from the sales of XPOVIO in July 2019 and have received revenue from our license arrangements, such as the partnership we have with Antengene Therapeutics Limited (“Antengene”) for our programs across most of the Asia-Pacific region, and with Berlin-Chemie AG, an affiliate of the Menarini Group (“Menarini”) for our programs in Europe, Latin America, certain Middle East and Africa regions and other key countries, there can be no assurance as to the amount or timing of future product or license and other revenues, and we may not achieve profitability for several years, if at all.

Our ability to become and remain profitable depends significantly on our success in many areas, including:

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• the impact of current or future competing products on product sales of XPOVIO or any of our future products;

• obtaining sufficient pricing, coverage and reimbursement, including government pricing and reimbursement policies or a change in the mix of our business effecting rebates related to 340B Programs, Medicare and Medicaid, for XPOVIO and any of our other approved products from private and government payers and the impact of any pricing changes, any of which can impact our gross-to-net provisions related to product sales;

• initiating and successfully completing clinical trials required to file for, obtain and maintain marketing approval for our product candidates;

• obtaining sufficient pricing, coverage and reimbursement, including government pricing and reimbursement policies or a change in the mix of our business affecting discounts and/or rebates related to 340B Programs, Medicare and Medicaid, for XPOVIO and any of our other approved products from private and government payers and the impact of any pricing changes, any of which can impact our gross-to-net provisions related to product sales;

• initiating and successfully completing clinical trials required to file for, obtain and maintain marketing approval for our product candidates, including reporting a positive benefit-risk profile from our ongoing Phase 3 clinical trial in endometrial cancer, with topline data anticipated in mid-2026;

• obtaining and maintaining regulatory approvals, either by us or our collaborators, and the timing of such approvals;

• placement of selinexor in the treatment recommendations adopted by the National Comprehensive Cancer Network and similar guidelines;

• manufacturing at commercial scale;

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• the willingness of patients to pay out-of-pocket in the absence of third-party coverage or as co-pay amounts under third-party coverage;

for example, multiple myeloma foundation closures during 2023 resulted in significantly increased use of our PAP, which adversely impacted our 2023 revenues;

• navigating the negative impacts to healthcare systems, the ability of our clinical trial sites to conduct current or future trials and the regulatory review process as the result of pandemics or other public health emergencies.

We anticipate that our operating expenses will continue to be significant and increase as we continue to:

for example, multiple myeloma foundation closures during 2023 resulted in significantly increased use of our Patient Assistance Program, which adversely impacted our 2023 revenues;

• navigating the negative impacts to healthcare systems, the ability of our clinical trial sites to conduct current or future trials and the regulatory review process.

We anticipate that our operating expenses will continue to be significant and could increase as we continue to:

• commercialize XPOVIO in the U.S., including maintaining our commercial infrastructure, and engage in activities to prepare for the potential approval and commercialization of additional indications for selinexor;

• obtain and/or maintain regulatory approval for XPOVIO and our product candidates, including completing any required post-marketing requirements to the satisfaction of the FDA or other regulatory agencies;

• expand our research and development programs, identify additional product candidates and initiate and conduct clinical trials, including clinical trials required by the FDA or other regulatory agencies in addition to those that have been or are currently expected to be conducted;

• invest in our research and development programs, identify additional product candidates and initiate and conduct clinical trials, including clinical trials required by the FDA or other regulatory agencies in addition to those that have been or are currently expected to be conducted;

• maintain, expand and protect our intellectual property portfolio;

• manufacture XPOVIO and our product candidates;

• acquire or in-license other products, product candidates or technologies.

• evaluate strategic opportunities, such as the acquisition or in-license of other products, product candidates, technologies or companies.

Because of the numerous risks and uncertainties associated with pharmaceutical product development and commercialization, we are unable to accurately predict the timing or amount of our revenue and expenses or when, or if, we will be able to achieve profitability.

We cannot be certain that our revenue from sales of XPOVIO alone, in the currently approved indications, will be sufficient for us to become profitable for several years, if at all.

We cannot be certain that our revenue from sales of XPOVIO alone, in the currently approved indications, will be sufficient for us to become profitable in the near-term, if at all.

We may never generate revenues that are significant or large enough to achieve profitability.

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Discovering, developing and commercializing products involve time-consuming, expensive and uncertain processes that take years to complete.

We have used substantial funds to develop XPOVIO and expect our operating expenses to continue to increase as we continue to commercialize XPOVIO or any future approved product, conduct further research and development of our product candidates, seek marketing approval and prepare for commercialization of selinexor in additional indications or for our other product candidates, if approved, to the extent that such functions are not the responsibility of a collaborator.

We have used substantial funds to develop XPOVIO and our operating expenses could continue to increase as we continue to commercialize XPOVIO or any future approved product, conduct further research and development of our product candidates, seek marketing approval and prepare for commercialization of selinexor in additional indications or for our other product candidates, if approved, to the extent that such functions are not the responsibility of a collaborator.

Furthermore, we will continue to incur additional costs associated with operating as a public company, hiring or retaining personnel and expanding our geographical reach.

Although currently XPOVIO is commercially available in three indications, we do not anticipate that our revenue from product sales of XPOVIO or any funds we may receive from our collaborators will be sufficient for us to become profitable for several years, if at all.

We do not anticipate that our revenue from product sales of XPOVIO or any funds we may receive from our collaborators will be sufficient for us to become profitable in the near-term, if at all.

Accordingly, we will need to continue to rely on additional financing, or strategic alternatives, to achieve our business objectives.

We believe that our existing cash, cash equivalents and investments, as well as cash flow from net product revenue and license and other revenue, will enable us to fund our current operating plans into the second quarter of 2026.

The amount and timing of our future capital requirements will depend on many factors, including, but not limited to:

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• our ability to establish and maintain collaboration, partnership, licensing, marketing, distribution or other arrangements on favorable terms and the level and timing of success of these arrangements, and our ability to use proceeds of those arrangements in our business as opposed to being required to pay those proceeds to the lenders of our $112.5 million senior secured term loan facility, as amended in October 2025 (the “Amended Term Loan”) and/or holders of the Convertible Notes;

• the extent to which we acquire or in-license other products, product candidates and technologies, and our ability to enter into such acquisitions and in-licenses pursuant to the restrictions under the Amended Term Loan and the Convertible Notes;

• the extent to which we acquire or in-license other products, product candidates, technologies or other companies, and our ability to enter into such acquisitions and in-licenses pursuant to the restrictions under the Amended Term Loan and the Convertible Notes;

• the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims;

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In addition, the terms of any financing may adversely affect the holdings or the rights of our stockholders.

If we raise additional funds by issuing equity securities, dilution to our existing stockholders will result.

If we raise additional funds by issuing equity or equity-linked securities, dilution to our existing stockholders will result.

In addition, as a condition to providing additional funding to us, future investors may demand, and may be granted, rights superior to those of existing stockholders.

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Our ability to satisfy and meet our current and any future debt service obligations will depend upon our future performance, which will be subject to financial, business and other factors affecting our operations, many of which are beyond our control.

Even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital due to favorable market conditions or strategic considerations.

Any future fundraising efforts could divert management’s attention away from their day-to-day activities.

Further, adequate additional financing has not been, and may continue to not be, available to us on acceptable terms, or at all.

In addition, raising funds in the current economic environment may present additional challenges.

For example, any sustained disruption in the capital markets from adverse macroeconomic conditions, such as the disruption and uncertainty caused by tariffs and other trade restrictions, inflation, sustained high interest rates and slower economic growth or recession, could negatively impact our ability to raise capital and we cannot predict the extent or duration of such macro-economic disruptions.

Moreover, there has been turmoil in the global banking system, which could result in loss of our access to our deposits, and an inability to obtain financing from other sources.

If adequate funds are not available to us on a timely basis or on attractive terms, we may be required to delay, reduce or eliminate our research and development programs or any current or future commercialization efforts for one or more of our products or product candidates, any of which could have a material adverse effect on our business, operating results and prospects.

We are continuing to evaluate strategic alternatives, which may include a potential merger or sale of the Company;

in or out of court restructurings;

repurchases, redemptions, exchanges or other refinancings of the Company’s existing debt;

potential financing transactions;

among other potential alternatives.

The potential impact and success of our exploration of any strategic alternatives, if available at all, are uncertain and may not be successful.

On October 8, 2025, we announced that we are continuing to evaluate potential financing transactions along with strategic alternatives to maximize near and long-term stockholder value, which may include, but is not limited to, a merger or sale of the Company, in or out of court restructurings, repurchases, redemptions, exchanges or other refinancings of our existing debt, and financing transactions, among other potential alternatives.

Our ability to successfully raise additional funds or execute on a financing transaction or a strategic alternative is dependent on a number of factors.

If we are not able to successfully consummate a financing transaction or strategic alternative, our Board may explore a sale of assets or the initiation of bankruptcy proceedings under Chapter 11 of the U.S.

Bankruptcy Code.

Further, our indebtedness, as discussed under the risk factor titled “ Our indebtedness could limit cash flow available for our operations, expose us to risks that could adversely affect our business, financial condition and results of operations and impair our ability to satisfy our obligations under the Amended Term Loan, the Convertible Notes or the Amended Revenue Interest Agreement ,” may be unattractive to potential sources of funding and strategic partners and may decrease our ability to consummate a financing transaction or enter into a strategic alternative.

Additionally, the negotiation and consummation of a financing transaction or strategic alternative may be costly and time-consuming.

Even if we are able to consummate a financing transaction or a strategic alternative, it may not maximize or even enhance stockholder value, could result in total costs and expenses that are greater than expected, could make it more difficult to attract and retain qualified personnel and may disrupt our operations, each of which could have a material adverse effect on our business.

The market price of our common stock may reflect a market assumption that a strategic alternative will occur, and a failure to complete a strategic alternative on favorable terms, in an advantageous timeframe, or at all could result in negative investor perceptions and could cause a decline in the market price of our common stock, which could adversely affect our ability to access the equity and financial markets, as well as our ability to explore and enter into future strategic alternatives.

In addition, potential strategic alternatives, if available, that require stockholder approval may not be approved by our stockholders.

Even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital due to favorable market conditions or strategic considerations, and any such efforts could divert management’s attention away from their day-to-day activities.

However, adequate additional financing has not been, and may continue to not be, available to us on acceptable terms, or at all.

Raising additional capital may be particularly challenging in the current economic environment, as adverse or uncertain financial market conditions, including inflationary pressures, sustained high interest rates, volatility in the capital markets and slower economic growth or recession, could negatively impact investor demand for biotechnology equity or debt offerings.

We cannot predict the extent or duration of such conditions or their impact on our ability to access the capital markets on acceptable terms.

In addition, changes in government policies, priorities and administration could create increased uncertainty and volatility that adversely affect our business, our ability to raise capital, and our ability to enter into strategic alternatives.

For example, evolving healthcare, pricing and reimbursement policies, including potential drug pricing reforms such as “most-favored-nation” or similar pricing frameworks, as well as shifts in regulatory or enforcement priorities at federal agencies, including the FDA and other governmental bodies, could negatively affect investor sentiment, the perceived commercial viability of our product and our access to financing.

Further, instability or disruption in the global or domestic banking system could impair our access to cash deposits or limit the availability of financing from financial institutions.

If adequate funds are not available to us on a timely basis or on attractive terms, we may be required to delay, reduce or eliminate our research and development programs or any current or future commercialization efforts for one or more of our products or product candidates, which could have a material adverse effect on our business, operating results and prospects.

Our Amended Revenue Interest Agreement with KKR contains various covenants and other provisions, which, if violated, could, subject to the Amended and Restated Intercreditor Agreement, result in the acceleration of payments due under such agreement or the foreclosure on the pledged collateral, including all of our present and future assets relating to selinexor.

In September 2019, we entered into the Revenue Interest Financing Agreement with certain entities managed by HealthCare Royalty Management, LLC (“HCRx”), which was amended on June 23, 2021, August 1, 2023, May 8, 2024, August 14, 2025, August 27, 2025 and October 7, 2025 and which was assigned by HCRx to KKR & Co.

(“KKR”) in July 2025 in connection with its acquisition of a majority ownership stake in HCRx (the “Amended Revenue Interest Agreement”).

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Our Credit Agreement and the indentures governing the Convertible Notes contain various covenants and other provisions, which will limit the manner in which we may operate, and, if violated, could, subject to the Amended and Restated Intercreditor Agreement, result in the acceleration of payments due under such agreements or the foreclosure on the pledged collateral, including all of our present and future assets.

The October 2025 First Amendment and Waiver to Credit and Guaranty Agreement, with the lenders party thereto and Wilmington Savings Fund Society, FSB, as administrative agent for the lenders and collateral agent (as amended, the “Amended Credit Agreement”) which amended the May 2024 credit and guaranty agreement and the indentures governing the Convertible Notes contain, and any future indebtedness that we incur may contain, various negative covenants that restrict, among other things, our indebtedness, liens, fundamental changes, asset sales, investments and other matters.

In addition, the Amended Credit Agreement and the indentures governing the Convertible Notes each have a financial covenant requiring us to maintain liquidity of at least $10.0 million, subject to increase in the event we issue indebtedness for borrowed money or issue capital stock, through October 10, 2026, after which we will be required to maintain liquidity of at least $25.0 million.

The October 2025 First Amendment and Waiver to Credit and Guaranty Agreement and February 2026 Second Amendment to Credit and Guaranty Agreement, with the lenders party thereto and Wilmington Savings Fund Society, FSB, as administrative agent for the lenders and collateral agent which amended the May 2024 credit and guaranty agreement and the indentures governing the Convertible Notes (as amended, the “Amended Credit Agreement”) contain, and any future indebtedness that we incur may contain, various negative covenants that restrict, among other things, our indebtedness, liens, fundamental changes, asset sales, investments and other matters.

In addition, the Amended Credit Agreement and the indentures governing the Convertible Notes each have a financial covenant requiring us to maintain liquidity through October 10, 2026 of at least the lesser of (i) $10.0 million plus 50% of the net cash proceeds received from certain debt and equity issuances and (ii) $25.0 million, after which we will be required to maintain liquidity of at least $25.0 million.

As a result, we are limited in the manner in which we conduct our business and we may be unable to engage in favorable business activities.

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Our indebtedness could limit cash flow available for our operations, expose us to risks that could adversely affect our business, financial condition and results of operations and impair our ability to satisfy our obligations under the Amended Term Loan, the Convertible Notes or the Amended Revenue Interest Agreement.

On October 7, 2025, we entered into a series of transactions with our term loan lenders, holders of our outstanding convertible notes and other investors to provide financial flexibility, additional working capital and equitize maturing notes (collectively, the “Financing Transactions”).

Following consummation of the Financing Transactions, we have (i) $112.5 million of aggregate principal amount under the Amended Term Loan;

In October 2025, we entered into a series of transactions with our term loan lenders, holders of our outstanding convertible notes and other investors to provide financial flexibility, additional working capital and equitize maturing notes (collectively, the “Financing Transactions”).

Following consummation of the Financing Transactions, we had (i) $112.5 million of aggregate principal amount under the Amended Term Loan;

(ii) $15.0 million aggregate principal amount of the 2028 Notes;

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We may also incur additional indebtedness to meet future financing needs, to the extent such indebtedness is available and permitted under the agreements governing our existing indebtedness.

Our indebtedness could have

significant negative consequences for our security holders and our business, results of operations and financial condition by, among other things:

Our indebtedness could have significant negative consequences for our security holders and our business, results of operations and financial condition by, among other things:

• increasing our vulnerability to adverse economic and industry conditions;

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• limiting our flexibility to plan for, or react to, changes in our business;

• diluting the interests of our existing stockholders as a result of issuing shares of our common stock upon conversion of the Convertible Notes;

• diluting the interests of our existing stockholders as a result of issuing shares of our common stock upon conversion of the Convertible Notes and/or the exercise of outstanding warrants;

• placing us at a possible competitive disadvantage with competitors that are less leveraged than we are or have better access to capital.

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Note holders may require us to repurchase their Convertible Notes following a fundamental change at a cash repurchase price generally equal to the principal amount of the Convertible Notes to be repurchased, plus accrued and unpaid interest.

The 2028 Notes will be convertible by holders of the 2028 Notes into shares of common stock at an initial conversion rate of 150.6024 shares per $1,000 principal amount of 2028 Notes (equivalent to an initial conversion price of $6.64 per share of common stock).

The conversion rate will be subject to adjustment upon the occurrence of certain events as provided in the 2028 Notes Indenture.

The 2028 Notes are convertible by holders of the 2028 Notes into shares of common stock at an initial conversion rate of 150.6024 shares per $1,000 principal amount of 2028 Notes (equivalent to an initial conversion price of $6.64 per share of common stock).

The conversion rate is subject to adjustment upon the occurrence of certain events as provided in the 2028 Notes Indenture.

Holders of the 2028 Notes may convert their 2028 Notes at their option at any time prior to the close of business on the scheduled trading day immediately preceding the maturity date of the 2028 Notes.

The 2029 Notes will be convertible by holders of the 2029 Notes into shares of common stock at an initial conversion rate of 44.444 shares per $1,000 principal amount of 2029 Notes (equivalent to an initial conversion price of $22.50 per share of common stock).

The conversion rate will be subject to adjustment upon the occurrence of certain events as provided in the 2029 Notes Indenture.

The 2029 Notes are convertible by holders of the 2029 Notes into shares of common stock at an initial conversion rate of 44.444 shares per $1,000 principal amount of 2029 Notes (equivalent to an initial conversion price of $22.50 per share of common stock).

The conversion rate is subject to adjustment upon the occurrence of certain events as provided in the 2029 Notes Indenture.

Holders of the 2029 Notes may convert their 2029 Notes at their option at any time prior to the close of business on the scheduled trading day immediately preceding the maturity date of the 2029 Notes.

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Moreover, the occurrence of a fundamental change under the indentures governing the Convertible Notes could constitute an event of default under any such agreements.

If the repayment of the related indebtedness were to be accelerated after any applicable

notice or grace periods, we may not have sufficient funds to repay the indebtedness and repurchase the Convertible Notes or to pay cash upon conversion or at maturity of the Convertible Notes.

If the repayment of the related indebtedness were to be accelerated after any applicable notice or grace periods, we may not have sufficient funds to repay the indebtedness and repurchase the Convertible Notes or to pay cash upon conversion or at maturity of the Convertible Notes.

The accounting method for convertible debt securities such as the Convertible Notes could have a material effect on our reported financial results.

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Raising additional capital and other equity issuances by us may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our product candidates.

Until such time, if ever, as we can generate substantial revenues from the sale of our products, we expect to finance our cash needs through a combination of equity offerings, debt financings and refinancings, collaborations, strategic alliances and/or licensing arrangements.

We do not have any committed external source of funds.

To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interests of stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of common stockholders.

In addition, our ability to raise additional capital through the sale of equity or convertible debt securities may be limited by the extent of our then remaining authorized and available shares of common stock.

Debt financing, if available and permitted, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

For example, during the terms of the Amended Revenue Interest Agreement, the Amended Credit Agreement and the indentures governing the Convertible Notes, we cannot make any voluntary or optional cash payment or prepayment on our existing convertible debt and cannot enter into any new debt without the consent of KKR, the required lenders or the required holders, respectively, subject to the exceptions and other provisions under the applicable governing document.

Debt financing, if available and permitted, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such

as incurring additional debt, making capital expenditures or declaring dividends.

For example, during the terms of the Amended Revenue Interest Agreement, the Amended Credit Agreement and the indentures governing the Convertible Notes, we cannot make any voluntary or optional cash payment or prepayment on our existing convertible debt and, other than certain permitted refinancings, cannot enter into any new debt without the consent of KKR, the required lenders or the required holders, respectively, subject to the exceptions and other provisions under the applicable governing document.

Further, any future renegotiation of these agreements will require extensive, multi-party discussions that will require significant time and resources and could result in additional debt, higher rates of interest, the issuance of additional warrants or equity securities, and dilution to our current stockholders.

If we raise additional funds through further collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.

If we are unable to raise sufficient additional funds through equity or debt financings, we may be required to delay, limit, reduce or terminate our research and drug development or current or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

We may also issue additional equity securities in other types of transactions that result in additional significant dilution to you, for example, in connection with other strategic or financing transactions, in exchange transactions similar to the exchange transactions we completed in October 2025 and May 2024 or in other future exchange transactions with our lenders and convertible noteholders, to satisfy obligations to our lenders and our convertible noteholders or other creditors, as equity compensation, or for other reasons.

We may also issue additional equity securities in other types of transactions that result in additional significant dilution to our stockholders, for example, in connection with other strategic or financing transactions, in exchange transactions similar to the exchange transactions we completed in October 2025 and May 2024 or in other future exchange transactions with our lenders and convertible noteholders, to satisfy obligations to our lenders and our convertible noteholders or other creditors, as equity compensation, or for other reasons.

Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price.

Global credit and financial markets have experienced extreme disruptions over the past several years.

Such disruptions have resulted, and could in the future result, in diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability.

Our general business strategy may be compromised by economic downturns, a volatile business environment and unpredictable and unstable market conditions, such as the current global situation resulting, in part, from tariffs and other trade restrictions, the ongoing conflicts in Ukraine and the Middle East, inflation, failures and instability in U.S.

and international banking systems, sustained high interest rates and slower economic growth or recession.

Further, developments in the banking industry could adversely affect our business.

If the financial institutions with which we do business enter receivership or become insolvent in the future, there is no guarantee that the Department of the Treasury, the Federal Reserve and the FDIC will intercede to provide us and other depositors with access to balances in excess of the $250,000 FDIC insurance limit, that we would be able to access our existing cash, cash equivalents and investments, that we would be able to maintain any required letters of credit or other credit support arrangements, or that we would be able to adequately fund our business for a prolonged period of time or at all, any of which could have a material adverse effect on our business, financial condition and results of operations.

We cannot predict the impact that the high market volatility and instability of the banking sector more broadly could have on economic activity and our business in particular.

In addition, there is a risk that one or more of our current service providers, manufacturers or other third parties with which we conduct business may not survive difficult economic times,

including the current global situation resulting, in part, from tariffs and other trade restrictions, the ongoing conflicts in Ukraine and the Middle East, the instability of the banking sector, and the uncertainty associated with current worldwide economic conditions, which could directly affect our ability to attain our operating goals on schedule and on budget.

Unstable market and economic conditions may have serious adverse consequences on our business, financial condition and stock price.

Global credit and financial markets have experienced periods of extreme disruption in recent years, which have contributed to diminished liquidity and credit availability, declines in consumer and investor confidence and slower economic growth.

As a result, financial institutions and markets face a range of risks that could adversely affect our operations and access to capital, including the potential for future banking failures, changes in regulatory frameworks, governing banks and deposit insurance, tightened credit conditions that reduce liquidity availability, volatility in interest rates and evolving cyber threats and disruptions to financial systems and payment networks.

If the financial institutions with which we do business were to enter receivership, become insolvent or suffer a significant cyber incident or operational disruption, there is no guarantee that we would have access to our existing cash and cash equivalents, or that we would be able to finance or fund our business on acceptable terms or at all, and any of these outcomes could materially and adversely affect our business, financial condition and results of operations.

In addition to financial market risks, broader geopolitical and economic volatility could adversely affect our business.

Uncertainty associated with governmental policies, shifts in regulatory priorities, and geopolitical tensions, such as conflicts involving multiple regions and nations including Ukraine, Russia, China, the Middle East and other areas of international concern, could negatively influence investor perceptions and economic conditions.

While the direct effects of tariffs and trade restrictions to date have been limited, such measures, along with other macroeconomic pressures such as inflation and slower economic growth or recession, may contribute to instability in global markets.

There is also a risk that one or more of our service providers, manufacturers or other third parties with which we conduct business may face financial difficulties, geopolitical disruption or operational challenges, which could hinder our ability to meet developmental and commercial objectives on schedule and on budget.

If these risks materialize in a manner that disrupts normal economic activity or financial markets, our business, results of operations and financial condition could be materially and adversely affected.

Risks Related to Commercialization and Product Development

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XPOVIO is currently approved and marketed in the U.S.

in multiple hematologic malignancy indications, including in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy;

in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody;

and under accelerated approval as a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (“DLBCL”), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

in multiple hematologic malignancy indications, including (i) in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy;

and (ii) in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two

immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Efforts to drive adoption within the medical community and third-party payors based on the benefits of our products and product candidates require significant resources and may not be successful.

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• our ability to achieve broad adoption of XPOVIO in earlier lines of therapy or to successfully launch and achieve broad adoption of any future XPOVIO indications or any product candidates for which we obtain marketing approval;

• the outcome of discussions with the FDA regarding the regulatory pathway for a potential supplemental New Drug Application (“sNDA”) for selinexor in combination with ruxolitinib in myelofibrosis following our announcement that the SENTRY trial met one, but not both, of its two co-primary endpoints, including whether the FDA agrees that the data from the SENTRY trial support filing an sNDA and the possibility that the FDA may require additional clinical data, longer follow-up, an additional clinical trial, or impose other requirements in advance of an sNDA submission;

• reporting a positive benefit-risk profile from our ongoing Phase 3 clinical trials in endometrial cancer and multiple myeloma, with topline data anticipated in mid-2026 and the second half of 2026, respectively;

• the competitive landscape for our products, including the timing of new competing products entering the market and the level and speed at which these products achieve market acceptance;

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• the effectiveness of our sales, marketing, manufacturing and distribution strategies and operations;

• the consistency of any new data we collect and analyses we conduct with prior results, whether they support a favorable benefit-risk profile of XPOVIO and any potential impact on our U.S.

Food and Drug Administration (“FDA”) approvals and/or FDA package insert for XPOVIO and comparable foreign regulatory approvals and package inserts;

• the consistency of any new data we collect and analyses we conduct with prior results, whether they support a favorable benefit-risk profile of XPOVIO and any potential impact on our FDA approvals and/or FDA package insert for XPOVIO and comparable foreign regulatory approvals and package inserts;

• our ability to comply with the FDA’s and comparable foreign regulatory authorities’ post-marketing requirements and commitments, including through successfully conducting, on a timely basis, additional studies that confirm clinical efficacy, effectiveness and safety of XPOVIO and acceptance of the same by the FDA or similar foreign regulatory bodies;

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• the willingness of patients to pay out-of-pocket in the absence of third-party coverage or as co-pay amounts under third-party coverage;

for example, multiple myeloma foundation closures during 2023 resulted in significantly increased use of our Patient Assistance Program (“PAP”), which adversely impacted our 2023 revenues;

• our ability to enforce intellectual property rights in and to our products to prohibit a third-party from marketing a competing product and our ability to avoid third-party patent interference or intellectual property infringement claims;

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• any significant misestimations of the size of the market and market potential for any of our products or product candidates;

• establishing and maintaining commercial manufacturing capabilities or making arrangements with third-party manufacturers;

• establishing and maintaining commercial manufacturing capabilities or entering into, maintaining and managing supply and manufacturing agreements with qualified third-party manufacturers;

• the willingness of the target patient population to try new therapies or new treatment paradigms such as bridging therapies and of physicians to prescribe these therapies, based, in part, on their perception of our clinical trial data and/or the actual or perceived safety, tolerability and effectiveness profile;

• the ability for patients to continue on therapies once prescribed, which may be driven by factors such as progression of disease, line of therapy, tolerability and the availability of other competitor therapies;

• maintaining an acceptable safety and tolerability profile of our approved products, including the prevalence and severity of any side effects;

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If we do not achieve one or more of these factors in a timely manner, or at all, either on our own or with our collaborators, we could experience significant delays or an inability to successfully commercialize XPOVIO or our product candidates, if approved, which would materially harm our business.

We face substantial competition, which may result in others discovering, developing or commercializing drugs before or more successfully than we do.

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

The discovery, development and commercialization of new drugs is highly competitive, particularly in the cancer field.

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Several new novel therapeutics have recently entered, and are expected to continue to enter, the multiple myeloma treatment landscape.

For example, TECVAYLI (teclistamab-cqyv), the first bispecific T-Cell engager, was approved by the FDA in October 2022, followed by approvals of two more bispecifics, ELREXFIO (elranatamab-bcmm) and TALVEY (talquetamab-tgvs) in August 2023.

For example, TECVAYLI ® (teclistamab-cqyv), the first bispecific T-Cell engager, was initially approved by the FDA in October 2022, followed by approvals of two more bispecifics, ELREXFIO ® (elranatamab-bcmm) and TALVEY ® (talquetamab-tgvs) in August 2023.

Other T-cell engaging therapies, bispecifics with different targets, and immunomodulators are in clinical development and may be introduced into the multiple myeloma market in 2026 and beyond.

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In October 2025, BLENREP (belantamab mafodotin), a BCMA-targeted bispecific antibody, in combination with bortezomib and dexamethasone was approved.

In addition, new competitors and label expansions into earlier lines of existing therapies could also be approved in the future, which could negatively impact our product revenues.

In addition, new competitors and label expansions into earlier lines of existing therapies, such as the March 2026 approval of TECVAYLI ® in combination with daratumumab for adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, could also be approved in the future, which could negatively impact our product revenues.

The approval of these anti-cancer agents, or any others which may receive regulatory approval, have had a significant impact and may continue to have a significant impact on the therapeutic landscape and our product revenues.

See Item 1 under the heading Business - Competition in our Annual Report on Form 10-K for the year ended December 31, 2024 as filed with the Securities and Exchange Commission (the “SEC”) on February 19, 2025 for more information on competition.

See Item 1 under the heading Business - Competition included in our Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the SEC on February 13, 2026 (“Annual Report”) for more information on competition.

We are currently focused on developing and commercializing our products and product candidates for the treatment of cancer and there are a variety of available therapies marketed for cancer.

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Further, our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize drugs that are or are perceived to be more effective, safer, more tolerable, more convenient and/or less costly than any of our currently approved products or product candidates or that would render our products obsolete or non-competitive.

Our competitors may also obtain

marketing approval from the FDA or other regulatory authorities for their products more rapidly than we, or our collaborators, may obtain approval for ours, which could result in our competitors establishing a stronger market position before we, or our collaborators, are able to enter the market or preventing us, or our collaborators, from entering into a particular indication at all.

Our competitors may also obtain marketing approval from the FDA or other regulatory authorities for their products more rapidly than we, or our collaborators, may obtain approval for ours, which could result in our competitors establishing a stronger market position before we, or our collaborators, are able to enter the market or preventing us, or our collaborators, from entering into a particular indication at all.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.

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Clinical testing is expensive, time consuming, difficult to design, implement and enroll, inherently uncertain as to outcome, and can fail at any stage of testing.

For example, in March 2026 we announced that our SENTRY Trial for myelofibrosis met one, but not both, of its two co-primary endpoints.

Furthermore, the failure of any product candidates to demonstrate safety and effectiveness in any clinical trial could negatively impact the perception of selinexor or our other product candidates and/or cause the FDA or other regulatory authorities to require additional testing before any of our product candidates are approved and/or adversely impact the inclusion of current or future indications of selinexor or other products or product candidates on pharmaceutical/drug compendia and/or negatively impact treating physicians’ confidence in the benefit observed in earlier phase clinical trials.

For example, if the benefit-risk profile from our global Phase 3 trial sponsored by the European Myeloma Network evaluating an all-oral combination of selinexor 40 mg in combination with pomalidomide and dexamethasone versus elotuzumab, pomalidomide, and dexamethasone in patients with previously treated multiple myeloma who received an anti-CD38 in their immediate prior line of therapy is not positive, the commercialization and listed compendia for our currently approved indications of selinexor could be adversely impacted, as well as their perception of the benefit of selinexor in combination with pomalidomide and dexamethasone.

Numerous unforeseen events during, or as a result of, clinical trials could delay or prevent our or our collaborators’ ability to complete such clinical trials or receive marketing approval of our product candidates, including, but not limited to, the following:

• delays or failure to reach agreement with regulatory authorities on a trial design or the receipt of feedback requiring us to modify the design of our clinical trials, perform additional or unanticipated clinical trials to obtain approval or alter our regulatory strategy, as is the case in connection with the feedback we received from the FDA in February 2022 on our SIENDO trial and the feedback from the FDA that we announced in December 2024 regarding the appropriateness of our global, Phase 3 trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “EC-042 Trial”) given the evolving treatment landscape for patients with advanced or recurrent endometrial cancer;

• delays or failure to reach agreement with regulatory authorities on a trial design or the receipt of feedback requiring us to modify the design of our clinical trials, perform additional or unanticipated clinical trials to obtain approval or alter our regulatory strategy, as is the case in connection with the feedback from the FDA that we announced in December 2024 regarding the appropriateness of our global, Phase 3 trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “XPORT-EC-042 Trial”) given the evolving treatment landscape for patients with advanced or recurrent endometrial cancer, further in March 2026 the FDA requested and we agreed to voluntarily withdraw the accelerated approval of the DLBCL indication in light of the infeasibility of completing the confirmatory trial, especially considering the evolving treatment landscape, including the availability of new therapeutic options;

• clinical trials of our product candidates may produce negative or inconclusive results or other patient safety concerns, including undesirable side effects or other unexpected characteristics, and we may decide, or regulatory authorities may require us, to conduct additional clinical trials, suspend ongoing clinical trials or abandon drug development programs, including as a result of a finding that the participants are being exposed to unacceptable health risks;

• enrollment in our clinical trials may be slower than we anticipate, including as a result of competition with other ongoing clinical trials or recently approved agents, which could decrease the overall supply of patients, or decreasing interest from selected clinical trial sites, delays in site activation, higher than expected screen failure rates, newly approved competitive products for the same indications as our product candidates or new or amended regulations;

for example, in August 2024, we announced expected delays in our top-line data readout for our EC-042 Trial due primarily to higher than expected screen failure rates, which has required us to screen a larger number of patients than originally planned;

for example, in August 2024, we announced expected delays in our topline data readout for our XPORT-EC-042 Trial due primarily to higher than expected screen failure rates, which has required us to screen a larger number of patients than originally planned;

• changes in the treatment landscape on which a clinical development plan was based, such as the approval of new therapies during the course of a clinical trial, can change the potential approvability of a drug even if the results of a pivotal, Phase 3 clinical trial are considered clinically meaningful and the primary endpoints achieve statistical significance since global regulatory agencies, including the FDA, often consider approvability in light of the current treatment landscape at the time of approval, and not at the time when a clinical trial is first designed;

for example, in recent years three new novel agents (dostarlimab-gxly, pembrolizumab and durvalumab) have been approved for treatment in patients with endometrial cancer, which has evolved the treatment landscape;

for example, in recent years three new novel agents

(dostarlimab-gxly, pembrolizumab and durvalumab) have been approved for treatment in patients with endometrial cancer, which has evolved the treatment landscape;

• modifications of clinical trial protocols impacting the patient population under study, including any modifications to the eligibility criteria or the total number of patients targeted for enrollment;

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The applicability of statutory obligations to submit DAPs and the FDA’s current thinking on best practices for clinical development remain unclear.

Similarly, the regulatory landscape related to clinical trials in the EU recently evolved.

Similarly, the regulatory landscape related to clinical trials in the EU evolved in 2022.

The Clinical Trials Regulation (“CTR”), which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.

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In addition, these side effects may not be appropriately recognized or managed by the treating medical staff.

Inadequate training or education of healthcare professionals to recognize or manage the potential side effects of XPOVIO or our product candidates, if approved, could result in increased treatment-related side effects and cause patients to discontinue treatment.

Inadequate training or education of healthcare professionals to recognize or manage the potential side effects of

XPOVIO or our product candidates, if approved, could result in increased treatment-related side effects and cause patients to discontinue treatment.

Any of these occurrences may harm our business, financial condition and prospects significantly.

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The FDA or foreign regulatory authorities may require more information related to the safety of our products or product candidates, including additional preclinical or clinical data to support approval, which may cause us to incur additional expenses, delay or prevent the approval of one of our product candidates, and/or delay or cause us to change our commercialization plans, or we may decide to abandon the development of the product candidate altogether.

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.

The results of previous clinical trials may not be predictive of future trial results, and interim or topline 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.

Clinical failure can occur at any stage of the clinical development process and, therefore, the outcome of preclinical studies and early-stage clinical trials may not be predictive of the success of later stage clinical trials.

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Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies have suffered significant setbacks in late-stage clinical trials after achieving positive results in earlier development, and we could face similar setbacks.

We may publicly disclose preliminary, interim or top-line data from our clinical trials.

These interim updates are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change as further patient data become available and following a more comprehensive review of the data related to the particular study or trial.

For any trial for which we report preliminary, interim or top-line data, we make assumptions, estimations, calculations and conclusions as part of our analyses of data.

We may publicly disclose preliminary or interim data from our clinical trials.

These data may be based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change as further patient data become available and following a more comprehensive review of the data related to the particular study or trial.

For any trial for which we report preliminary, interim or topline data, we make assumptions, estimations, calculations and conclusions as part of our analyses of data.

We may not have received or had the opportunity to fully and carefully evaluate all data or perform all analyses or our conclusions may differ from those of the FDA or other regulatory authorities.

Consequently, the interpretation of preliminary, interim or top-line data results that we report may differ from future interpretations of the same studies once additional data have been received and fully evaluated or based on differing views from regulatory agencies.

Preliminary, interim or top-line data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.

Consequently, the interpretation of preliminary or interim data results that we report may differ from future interpretations of the same studies once additional data have been received and fully evaluated or based on differing views from regulatory agencies.

Preliminary or interim data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published.

As a result, these early data points should be viewed with caution until the final data are available.

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Furthermore, we may report interim analyses of only certain endpoints rather than all endpoints.

Investors may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or our business.

If the interim or top-line data that we report differ from future or more comprehensive data, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for and commercialize our product candidates, our business, operating results, prospects, or financial condition may be harmed.

Investors may not agree with what we determine is the material or otherwise appropriate information to include in our

disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular product, product candidate or our business.

If the preliminary or interim data that we report differ from future or more comprehensive data, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for and commercialize our product candidates, our business, operating results, prospects, or financial condition may be harmed.

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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Further, we may underestimate the size of the sales force required for a successful product launch and we may need to expand our sales force earlier and at a higher cost than we anticipated.

If the commercial launch of any of our product candidates is delayed or does not occur for any reason, including if we do not receive marketing approval in the timeframe we expect, we may have prematurely or unnecessarily incurred commercialization expenses.

If the commercial launch of any of our product candidates is delayed or does not occur for any reason, including if we do

not receive marketing approval in the timeframe we expect, we may have prematurely or unnecessarily incurred commercialization expenses.

This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

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As a result, we or our collaborators might obtain marketing approval for a drug in a particular country, but then be subject to price regulations that delay the commercial launch of the product, possibly for lengthy time periods, and negatively impact the revenues we, or our collaborators, are able to generate from product sales in that country.

In the U.S., approval and reimbursement decisions are not linked directly, but there is increasing scrutiny from the Congress, regulatory authorities, payers, patients and pathway organizations of the pricing of pharmaceutical products.

In the U.S., approval and reimbursement decisions are not linked directly, but there is increasing scrutiny from Congress, regulatory authorities, payers, patients and pathway organizations of the pricing of pharmaceutical products.

Adverse pricing limitations may also hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.

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There may be significant delays in obtaining reimbursement for newly-approved drugs, and coverage may be more limited than the indications for which the drug is approved by the FDA or comparable foreign regulatory authorities.

Moreover, eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution.

Interim reimbursement levels for new drugs, if applicable, may also not be sufficient

to cover our costs and may not be made permanent.

Moreover, eligibility for

reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution.

Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent.

Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs and may be incorporated into existing payments for other services.

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In order to market and sell our products in the EU and many other jurisdictions, we and our collaborators must obtain separate marketing approvals and comply with numerous and varying regulatory requirements.

The FDA and comparable foreign regulatory authorities, whose laws and regulations may differ from country to country, impose substantial requirements on the development of product candidates to become eligible for marketing approval and have substantial discretion in the process and may refuse to accept any application or may decide that the data are insufficient for approval and require additional preclinical studies, clinical trials or other studies and testing.

The time required to obtain approval outside of the U.S.

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(ii) the dose used in a clinical trial has not been optimized and require us to conduct additional dose optimization studies;

or (iii) the comparator arm and/or endpoint in a trial is no longer the appropriate comparator or endpoint due to the evolution of the

competitive landscape or subsequent data of the comparator product, even if the FDA or other regulatory authority had previously approved the trial design, and we may be required to amend the trial or we may not receive approval of the indication.

or (iii) the comparator arm and/or endpoint in a trial is no longer the appropriate comparator or endpoint due to the evolution of the competitive landscape or subsequent data of the comparator product, even if the FDA or other regulatory authority had previously approved the trial design, and we may be required to amend the trial or we may not receive approval of the indication.

For example, in December 2024, we announced that we were engaged in discussions with the FDA regarding the evolving treatment landscape in advanced or recurrent endometrial cancer, particularly the approval of checkpoint inhibitors (e.g., pembrolizumab, dostarlimab-gxly and durvalumab).

We have submitted to the FDA and other relevant global regulatory authorities an amendment to the EC-042 Trial protocol incorporating modifications, which we believe are responsive to certain of the FDA’s concerns.

However, the FDA may not agree that some or all of our proposed modifications to the EC-042 Trial adequately address their concerns, which may ultimately impact approvability.

However, the FDA may not agree that some or all of our proposed modifications to the XPORT-EC-042 Trial adequately address their concerns, which may ultimately impact approvability.

In addition, the FDA’s Oncology Center of Excellence has a number of projects to advance the development and regulation of medical products for patients with cancer, such as Project Optimus to reform the dose optimization and dose selection paradigm in oncology drug development to emphasize selection of an optimal dose.

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This could result in a delay in approval, or rejection, of our marketing applications by the FDA or comparable foreign regulatory authority, as the case may be, and may ultimately lead to the denial of marketing approval of one or more of our product candidates.

Further, under the Pediatric Research Equity Act (“PREA”), an New Drug Application (“NDA”) or supplement to an NDA for certain drugs must contain data to assess the safety and effectiveness of the drug in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless the sponsor receives a deferral or waiver from the FDA.

Further, under the Pediatric Research Equity Act (“PREA”), a New Drug Application (“NDA or sNDA for certain drugs must contain data to assess the safety and effectiveness of the drug in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective, unless the sponsor receives a deferral or waiver from the FDA.

A deferral may be granted for several reasons, including a finding that the product or therapeutic candidate is ready for approval for use in adults before pediatric trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric trials begin.

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and the EU and thus the attendant risks and uncertainties.

Our ability to develop and market new drug products may also be impacted by litigation challenging the FDA’s approval of another company’s drug product.

In April 2023, the U.S.

District Court for the Northern District of Texas invalidated the approval by the FDA of mifepristone, a drug product which was originally approved in 2000 and whose distribution is governed by various measures adopted under a Risk Evaluation and Mitigation Strategy (“REMS”).

The Court of Appeals for the Fifth Circuit declined to order the removal of mifepristone from the market but did hold that plaintiffs were likely to prevail in their claim that changes allowing for expanded access of mifepristone, which the FDA authorized in 2016 and 2021, were arbitrary and capricious.

In June 2024, the Supreme Court reversed that decision after unanimously finding that the plaintiffs (anti-abortion doctors and organizations) did not have standing to bring this legal action against the FDA.

On October 11, 2024, the Attorneys General of three states (Missouri, Idaho and Kansas) filed an amended complaint in the district court in Texas challenging FDA’s actions.

On January 16, 2025, the District Court agreed to allow these states to file an amended complaint and continue to pursue this challenge.

Depending on the outcome of this litigation, our ability to develop new drug product candidates and to maintain approval of existing drug products could be delayed, undermined or subject to protracted litigation.

The approval of our and our collaborators’ current or future product candidates for commercial sale could be delayed, limited or denied or we or they may be required to conduct additional studies for a number of reasons, including, but not limited to, the following:

reported during clinical trials or the FDA determines that the patient population enrolled is either (i) not consistent with the demographics of the patient population in the U.S.

• regulatory authorities may determine that our or our collaborators’ product candidates do not demonstrate safety and effectiveness in accordance with regulatory agency standards based on a number of considerations, including AEs that are reported during clinical trials or the FDA determines that the patient population enrolled is either (i) not consistent with the demographics of the patient population in the U.S.

or (ii) does not reflect the U.S.

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• regulatory authorities could analyze and/or interpret data from clinical trials and preclinical testing in different ways than we, or our collaborators, interpret them and determine that our data is insufficient for approval;

• regulatory authorities may require more information, including additional preclinical or clinical data or trials, to support approval, as in the case of our initiation of the EC-042 Study for patients with TP53 wild-type advanced or recurrent endometrial cancer following discussions with the FDA in early 2022 on our SIENDO trial;

• regulatory authorities may require more information, including additional preclinical or clinical data or trials, to support approval, as in the case of our initiation of the EC-042 Trial for patients with TP53 wild-type advanced or recurrent endometrial cancer following discussions with the FDA in early 2022 on our SIENDO trial;

• regulatory authorities could determine that our manufacturing processes are not properly designed, are not conducted in accordance with federal or other laws or otherwise not properly managed, and we may be unable to obtain regulatory approval for a commercially viable manufacturing process for our product candidates in a timely manner, or at all;

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The RRs notably include EMA and regulators in the EU/European Economic Area (“EEA”) member states for approvals in the EU centralized procedure and mutual recognition procedure as well as the FDA (for product approvals granted in the U.S.).

However, the concrete functioning of the IRP is currently unclear.

Any delay in obtaining, or an inability to obtain, any marketing approvals, may force us or our collaborators to restrict or delay efforts to seek regulatory approval in the UK for our product candidates, which could significantly and materially harm our business.

Should we or our collaborators seek to rely on the IRP to obtain regulatory approval in the U.K., any delay in obtaining, or an inability to obtain, any marketing approvals from RRs may force us or our collaborators to restrict or delay efforts to seek regulatory approval in the UK for our product candidates, which could significantly and materially harm our business.

We, or our collaborators, may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our or their products in any market.

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If we, or our collaborators, are not able to use such pathways, we, or they, may be required to conduct additional clinical trials beyond those that are contemplated, which would increase the expense of obtaining, and delay the receipt of, necessary marketing approvals, if we, or they, receive them at all.

In addition, even if an

accelerated approval pathway is available to us, or our collaborators, it may not lead to expedited approval of our product candidates, or approval at all.

In addition, even if an accelerated approval pathway is available to us, or our collaborators, it may not lead to expedited approval of our product candidates, or approval at all.

Under the Federal Food, Drug and Cosmetic Act (“FDCA”) and implementing regulations, the FDA may grant accelerated approval to a product candidate to treat a serious or life-threatening condition that provides meaningful therapeutic benefit over available therapies, upon a determination that the product has an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit.

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The accelerated approval pathway may be used in cases in which the advantage of a new drug over available therapy may not be a direct therapeutic advantage, but is a clinically important improvement from a patient and public health perspective.

Similar risks to those described above are also applicable to any application that we, or our collaborators, have submitted or may submit in other jurisdictions outside of the U.S.

Similar risks to those described above are also applicable to any application that we, or our collaborators, have submitted

or may submit in other jurisdictions outside of the U.S.

Prior to seeking such accelerated approval, we, or our collaborators, will continue to seek feedback from the FDA or comparable foreign regulatory agencies and otherwise evaluate our, or their, ability to seek and receive such accelerated approval.

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Accordingly, a failure to obtain and maintain accelerated approval or any other form of expedited development, review or approval for our product candidates, or withdrawal of a product candidate, would result in a longer time period until commercialization of such product candidate, could increase the cost of development of such product candidate and could harm our competitive position in the marketplace.

Additionally, the U.S.

federal government has been shut down since October 1, 2025.

During the shutdown, the FDA has operated on a reduced basis with many non-essential functions suspended.

While reviews tied to already paid user fees are continuing, companies may experience slower communications and selective deferrals.

If this shutdown continues, it may prevent the FDA from conducting their regular inspections, reviews or other regulatory activities, and could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse impact on our business.

For example, during the shutdown, the FDA does not currently have legal authority to accept user fees assessed for fiscal year 2026 until a fiscal year 2026 appropriation or continuing resolution for the FDA is enacted, which means that the FDA will not be able to accept any regulatory submissions for fiscal year 2026 that require a fee payment and that are submitted during the shutdown.

Further, in our operations as a U.S.

public company, future government shutdowns or delays could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

XPOVIO and any of our product candidates for which we, or our collaborators, obtain marketing approval in the future are subject to post-marketing regulatory requirements, including following accelerated or conditional approvals of our product candidates, and could be subject to post-marketing restrictions or withdrawal from the market, and we, and our collaborators, may be subject to substantial penalties if we, or they, fail to comply with regulatory requirements or if we, or they, experience unanticipated problems with our products following approval.

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These requirements include submissions of safety and other post-marketing information and reports, registration and listing requirements, requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, and requirements regarding the distribution of samples to physicians and record keeping.

For example, as a condition of the XPOVIO accelerated approvals by the FDA for the multiple myeloma and DLBCL indications, we are required to complete certain post-marketing commitments.

There is no assurance that we will be able to timely complete such obligations.

Failure to comply with such requirements may have an adverse impact on the accelerated approval status of selinexor in DLBCL.

Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the drug may be marketed or to the conditions of approval, including the requirement to implement a REMS, which could include requirements for a restricted distribution system.

The FDA also imposes requirements for costly post-marketing studies or clinical trials to maintain approval of any products that received accelerated or conditional approval.

Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses

for which the drug may be marketed or to the conditions of approval, including the requirement to implement a REMS, which could include requirements for a restricted distribution system.

The FDA also imposes requirements for costly post-marketing studies or clinical trials to maintain approval of any products that received accelerated approval.

For drugs approved under the FDA’s Accelerated Approval Program, the FDA typically requires post-marketing confirmatory trials to evaluate the anticipated effect on irreversible morbidity or mortality or other clinical benefit.

These confirmatory trials must be completed with due diligence.

For example, in June 2020, the FDA approved XPOVIO to treat DLBCL under the FDA’s accelerated approval regulations and as a condition of the accelerated approval for this indication we are required to comply with a number of post-approval requirements.

In March 2026 the FDA requested and we agreed to voluntarily withdraw the accelerated approval of the DLBCL indication in light of the infeasibility of completing the confirmatory trial, especially considering the evolving treatment landscape, including the availability of new therapeutic options.

Although we do not actively promote XPOVIO in DLBCL and generate insignificant revenue from this indication, withdrawal of the accelerated approval may require certain of our ex-U.S.

partners to take action to maintain their current approvals in DLBCL to the extent such approvals reference the U.S.

We may not be able to successfully and timely complete these post-approval requirements, obtain an extension, if needed, or complete any other post-marketing confirmatory study as required to maintain approval or achieve full approval of our products.

If required post-approval studies fail to verify the clinical benefits of our products or confirm that the surrogate marker used for accelerated approval of our products showed an adequate correlation with clinical outcomes, if a sufficient number of participants cannot be enrolled, or if we fail to perform the required post-approval studies with due diligence or on a timely basis, the FDA has the authority to withdraw approval of the drug following a hearing conducted under the FDA’s regulations, which could have a material adverse impact on our business.

We cannot be certain of the results of the confirmatory clinical studies for the DLBCL indication or any other future conditional approval we receive or what action the FDA may take if the results of those studies are not as expected based on clinical data that FDA has already reviewed.

We cannot be certain of the results of the confirmatory clinical studies for or any future conditional approval we receive or what action the FDA may take if the results of those studies are not as expected based on clinical data that FDA has already reviewed.

Similar risks to those described above are also applicable to any application that we, or our collaborators, have submitted or may submit in other jurisdictions outside of the U.S., including applications submitted to the EMA to support approval of selinexor to treat patients with multiple myeloma or any other cancer indication.

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Once a conditional marketing authorization has been granted, the marketing authorization holder must fulfill specific obligations within defined timelines.

These obligations could include completing ongoing or new studies or collecting additional data to confirm

the medicine’s benefit-risk balance remains positive.

These obligations could include completing ongoing or new studies or collecting additional data to confirm the medicine’s benefit-risk balance remains positive.

For example, the July 2022 marketing authorization from the European Commission (“EC”) for NEXPOVIO to treat adult patients with multiple myeloma after at least one prior therapy satisfied the conditional approval obligation for NEXPOVIO for patients with multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

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The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use, and if we, or our collaborators communicate about any of our product candidates for which we, or they, receive marketing approval in a way that regulators assert goes beyond their approved indications, we, or they, may be subject to warnings or enforcement action for off-label marketing.

Alleged violations of the FDCA or other statutes, including the False Claims Act (the “FCA”), relating to the promotion and advertising of prescription drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.

Alleged violations of the FDCA or other statutes, including the False Claims Act (the “FCA”), relating to the promotion and advertising of prescription

drugs may lead to investigations or allegations of violations of federal and state health care fraud and abuse laws and state consumer protection laws.

We will need to carefully monitor and navigate the FDA’s various regulations, guidance and policies, along with recently enacted legislation, to ensure compliance with restrictions governing promotion of our products.

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It involves a rigorous pre-market review during which the sponsor must prepare and provide the FDA with reasonable assurance of the device’s safety and effectiveness and information about the device and its components regarding, among other things, device design, manufacturing, and labeling.

After a device is placed on the market, it remains subject to significant regulatory requirements, including requirements, such as the Quality Management System Regulation as part of 21 CFR 820, which governs development, testing, manufacturing, distribution, marketing, promotion, labeling, import, export, record-keeping, and adverse event reporting.

Similar risks to those described above are also applicable to any companion diagnostic that we, or our collaborators, utilize in our clinical trials in connection with approval of a product candidate outside of the U.S.

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Companion diagnostics will have to undergo a conformity assessment by a notified body.

Before it can issue an EU certificate, the notified body must seek a scientific opinion from the EMA on the suitability of the companion diagnostic to the medicinal product concerned if the medicinal product falls exclusively within the scope of the centralized procedure for the authorization of medicines, or the medicinal product is already authorized through the centralized procedure, or a marketing authorization application for the medicinal product has been submitted through the centralized procedure.

As part of the process to obtain a CE-mark for the FMI FoundationOne ® CDx for the purpose of determining TP53 wild-type status for use of selinexor in the maintenance treatment of TP53 wild-type endometrial cancer patients, a performance study is required which leverages our EC-042 Trial (e.g., using the unapproved FoundationOne ® CDx IVD to screen for TP53 wild-type patients in the EC-042 Trial and using the data generated to validate the CDx itself).

authorization application for the medicinal product has been submitted through the centralized procedure.

As part of the process to obtain a CE-mark for the FMI FoundationOne ® CDx for the purpose of determining TP53 wild-type status for use of selinexor in the maintenance treatment of TP53 wild-type endometrial cancer patients, a performance study is required which leverages our XPORT-EC-042 Trial (e.g., using the unapproved FoundationOne ® CDx IVD to screen for TP53 wild-type patients in the XPORT-EC-042 Trial and using the data generated to validate the CDx itself).

As the regulations are relatively new, the industry is gaining experience in the compilation of these submissions while the national Competent Authorities and the respective Ethics Committees are also gaining expertise in assessing these applications.

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For example, in 2023, site activation for our Phase 3 clinical trial in endometrial cancer was delayed in the EU due to the new IVDR regulations.

Consequently, the ability to use the FoundationOne ® CDx in vitro diagnostic medical devices to screen patients for TP53 status in the EC-042 Trial has been delayed in various countries in the EU.

Consequently, the ability to use the FoundationOne ® CDx in vitro diagnostic medical devices to screen patients for TP53 status in the XPORT-EC-042 Trial has been delayed in various countries in the EU.

We may rely on third parties for the design, development and manufacture of companion diagnostic tests for our product candidates, such as in the case of our ongoing Phase 3 trial evaluating selinexor in patients with TP53 wild-type advanced or recurrent endometrial cancer.

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We may also seek a Priority Review designation for one or more of our product candidates.

If the FDA determines that a product candidate would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review.

If the FDA determines that a product candidate would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate

for priority review.

A Priority Review designation means that the goal for the FDA to review an application is six months, rather than the standard review period of ten months.

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and ten years in the EU.

The exclusivity period in the EU can be reduced to six years if a

product no longer meets the criteria for Orphan Drug Designation, in particular if the product is sufficiently profitable so that market exclusivity is no longer justified.

The exclusivity period in the EU can be reduced to six years if a product no longer meets the criteria for Orphan Drug Designation, in particular if the product is sufficiently profitable so that market exclusivity is no longer justified.

In order for the FDA to grant orphan drug exclusivity to one of our products, the agency must find that the product is indicated for the treatment of a condition or disease with a patient population of fewer than 200,000 individuals annually in the U.S.

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Orphan drug exclusivity may also be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients with the rare disease or condition.

In 2017, the Congress passed the FDA Reauthorization Act of 2017 (the “FDARA”).

In 2017, Congress passed the FDA Reauthorization Act of 2017 (the “FDARA”).

The FDARA, among other things, codified the FDA’s pre-existing regulatory interpretation, to require that a drug sponsor demonstrate the clinical superiority of an orphan drug that is otherwise the same as a previously approved drug for the same rare disease in order to receive orphan drug exclusivity.

Under omnibus legislation signed by former President Trump in December 2020, the requirement for a product to show clinical superiority applies to drugs and biologics that received Orphan Drug Designation before the enactment of the FDARA in 2017, but have not yet been approved or licensed by the FDA.

The FDA and Congress may further reevaluate the Orphan Drug Act and its regulations and policies.

This may be particularly true in light of a decision from the Court of Appeals for the 11th Circuit in September 2021.

In Catalyst Pharms, Inc.

Becerra (“Catalyst”), the court held that, for the purpose of determining the scope of orphan drug exclusivity, the term “same disease or condition” in the statute means the designated “rare disease or condition” and could not be interpreted by the FDA to mean the “indication or use.” Thus, the court concluded, orphan drug exclusivity applies to the entire designated disease or condition rather than the approved “indication or use.” Although there have been legislative proposals to overrule this decision, they have not been enacted into law.

On January 23, 2023, the FDA announced that, in matters beyond the scope of the Catalyst court order, the FDA will continue to apply its existing regulations tying orphan-drug exclusivity to the uses or indications for which the orphan drug is approved.

More recently however, on February 14, 2025, a federal district court in Washington, D.C.

fully embraced the reasoning of the Catalyst decision in another decision challenging the scope of orphan drug exclusivity.

On April 17, 2025, the FDA appealed this decision to the U.S.

Court of Appeals for the D.C.

The implications of this decision, and its impact on the FDA’s implementation of the Orphan Drug Act, are unclear at this point.

Under omnibus legislation signed by President Trump in December 2020, the requirement for a product to show clinical superiority applies to drugs and biologics that received Orphan Drug Designation before the enactment of the FDARA in 2017, but have not yet been approved or licensed by the FDA.

It is also possible that current or future litigation or action by Congress could change the scope of available orphan exclusivity.

Any changes to the orphan drug provisions could change our opportunities for, or likelihood of success in obtaining, orphan drug exclusivity and could materially adversely affect our business, financial condition, results of operations, cash flows and prospects.

We do not know if, when, or how the FDA may change the orphan drug regulations and policies in the future or whether Congress will take legislative action, and it is uncertain how any changes might affect our business.

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In March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Affordability Reconciliation Act (collectively the “PPACA”).

The PPACA has been subject to litigation challenging its provisions, and such litigation is likely to continue with uncertain results.

In addition, other legislative changes have been proposed and adopted since the PPACA was enacted.

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A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031.

The American Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Further, with the passage of

the Inflation Reduction Act (the “IRA”) in August 2022, Congress extended the expansion of PPACA premium tax credits through 2025.

These and other laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our products or product candidates for which we may obtain regulatory approval or the frequency with which any such product is prescribed or used.

Since enactment of the PPACA, there have been, and continue to be, numerous legal challenges and Congressional actions to repeal and replace provisions of the law.

For example, with the enactment of the Tax Cuts and Jobs Act of 2017 (the “TCJA”), Congress repealed the “individual mandate” provision.

The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.

Further, in December 2018, a U.S.

District Court judge in the Northern District of Texas ruled that the individual mandate portion of the PPACA is an essential and inseverable feature of the PPACA, and therefore because the mandate was repealed as part of the TCJA, the remaining provisions of the PPACA are invalid as well.

In June 2021, the U.S.

Supreme Court dismissed this action after finding that the plaintiffs did not have standing to challenge the constitutionality of the PPACA.

Litigation and legislation over the PPACA are likely to continue, with unpredictable and uncertain results.

These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through fiscal year 2032 unless additional congressional action is taken.

Additionally, the Inflation Reduction Act of 2022 (the “IRA”) also capped Medicare out-of-pocket drug costs at an estimated $2,000 a year (to be adjusted annually for inflation) beginning in 2025.

In the EU, on December 13, 2021, Regulation No 2021/2282 on Health Technology Assessment (“HTA”), amending Directive 2011/24/EU, was adopted.

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Individual EU member states will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement.

We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria and new payment methodologies that govern XPOVIO or any other approved product and/or the level of reimbursement physicians receive for administering XPOVIO or any other approved product we, or our collaborators, might bring to market.

We expect that these laws and other healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding and otherwise affect the reimbursement we may obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any such product is prescribed or used.

These healthcare reforms may result in more rigorous coverage criteria and new payment methodologies that govern XPOVIO or any other approved product and/or the level of reimbursement physicians receive for administering XPOVIO or any other approved product we, or our collaborators, might bring to market.

Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered.

Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors.

Any reduction in reimbursement from Medicare or other federal healthcare programs may result in a similar reduction in reimbursement from private payors.

Accordingly, such reforms, if enacted, could have an adverse effect on anticipated revenue from XPOVIO or from product candidates for which we may obtain marketing approval and may affect our overall financial condition and ability to develop or commercialize product candidates.

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congressional inquiries, as well as proposed and enacted state and federal legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and Medicaid.

In 2020, former President Trump issued several executive orders intended to lower the costs of prescription products and certain provisions in these orders have been incorporated into regulations.

These regulations include an interim final rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021.

That rule, however, has been subject to a nationwide preliminary injunction and, on December 29, 2021, Centers for Medicare & Medicaid Services (“CMS”) issued a final rule to rescind it.

With issuance of this rule, CMS stated that it will explore all options to incorporate value into payments for Medicare Part B pharmaceuticals and improve beneficiaries’ access to evidence-based care.

For example, in August 2022, the IRA was signed into law by former President Biden.

The legislation requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation;

and replaces the Part D coverage gap discount program with a new discounting program.

The IRA permits the Secretary of the HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

Specifically, with respect to price negotiations, Congress authorized Medicare to negotiate lower prices for certain costly single-source drug and biologic products that do not have competing generics or biosimilars and are reimbursed under Medicare Part B and Part D.

Ten high-cost drugs paid for by Medicare Part D are subject to negotiated prices starting in 2026 to be followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond.

This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years.

When originally enacted, the IRA explicitly excluded from price negotiation orphan drugs designated for only one rare disease or condition and for which the only active approved indication is for such disease or condition.

However, the One Big Beautiful Bill Act signed into law on July 4, 2025 amended the applicable statute to broaden the orphan drug exclusion to include products with more than one orphan designation and more than one approved indication.

Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law.

CMS has and continues to take steps to implement the IRA, including negotiating and publishing “maximum fair prices” for drugs selected under the IRA’s price negotiation framework and releasing quarterly lists of Medicare Part B products and annual lists of Medicare Part D products that are subject to adjusted coinsurance rates based on the inflationary rebate provisions of the IRA.

While it remains to be seen how the drug pricing provisions imposed by the IRA will affect the broader pharmaceutical industry, several pharmaceutical manufacturers and other industry stakeholders have challenged the law, including through lawsuits brought against the HHS, the Secretary of the HHS, CMS, and the CMS Administrator challenging the constitutionality and administrative implementation of the IRA’s drug price negotiation provisions.

This litigation is ongoing and its results, and potential impacts on our business, are uncertain.

In addition, in October 2020, HHS and the FDA published a final rule allowing states and other entities to develop a Section 804 Importation Program to import certain prescription drugs from Canada into the U.S.

That regulation was challenged in a lawsuit by the Pharmaceutical Research and Manufacturers of America (“PhRMA”) but the case was dismissed by a federal district court in February 2023 after the court found that PhRMA did not have standing to sue HHS.

Seven states (Colorado, Florida, Maine, New Hampshire, New Mexico, Texas and Vermont) have passed laws allowing for the importation of drugs from Canada.

Dakota and Virginia have passed legislation establishing workgroups to examine the impact of a state importation program.

As of October 2024, five states (Colorado, Florida, Maine, New Hampshire and New Mexico) had submitted Section 804 Importation Program proposals to the FDA.

Vermont has submitted a concept letter to HHS.

On January 5, 2024, the FDA approved Florida’s plan for Canadian drug importation.

That state now has authority to import certain drugs from Canada for a period of two years once certain conditions are met.

Florida will first need to submit a pre-import request for each drug selected for importation, which must be approved by the FDA.

The state will also need to relabel the drugs and perform quality testing of the products to meet FDA standards.

Further, in November 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers.

The final rule would also eliminate the current safe harbor for Medicare drug rebates and create new safe harbors for beneficiary point-of-sale discounts and pharmacy benefit manager service fees.

It originally was set to go into effect on January 1, 2022, but with passage of the IRA has been delayed by Congress to January 1, 2032.

On August 16, 2022, the IRA was signed into law by former President Biden.

The new legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation.

The new law also caps Medicare out-of-pocket drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year.

CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond.

This provision applies to drug products that have been approved for at least nine years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition.

The first cycle of negotiations for the Medicare Drug Price Negotiation Program commenced in the summer of 2023.

On August 15, 2024, HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis.

The prices of these ten drugs will become effective January 1, 2026.

On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations.

Thereafter, following the change in administrations, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.

The second cycle of negotiations with participating drug companies will occur during 2025, and any negotiated prices for this second set of drugs will be effective starting January 1, 2027.

On June 6, 2023, Merck & Co.

filed a lawsuit against HHS and CMS asserting that, among other things, the IRA’s Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution.

Subsequently, a number of other parties, including the U.S.

Chamber of Commerce, Bristol Myers Squibb Company, the PhRMA, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca, Boehringer Ingelheim, and Teva also filed lawsuits in various courts with constitutional and Administrative Procedure Act claims against HHS and CMS.

There have been various decisions by the courts considering these cases since they were filed.

HHS has generally won the substantive disputes in these cases or succeeded in getting claims dismissed for lack of standing.

Most of these cases are now on appeal.

On October 30, 2024, the U.S.

Court of Appeals for the Third Circuit heard oral argument in three of these cases.

In April 2025, the U.S.

Court of Appeals for the Second Circuit and the U.S.

Court of Appeals for the Third Circuit heard argument in an additional three cases.

On May 8, 2025, the Third Circuit rejected AstraZeneca’s challenge to the Medicare price negotiation program, finding that the program did not violate the company’s due process rights under the Constitution since there is no protected property interest in selling goods to Medicare beneficiaries at a price higher than what the government is willing to pay in reimbursement.

Accordingly, while it is currently unclear how the IRA will be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition.

More recently, on April 15, 2025, President Trump issued an Executive Order which directs HHS to take steps to reduce the prices of pharmaceutical products.

The new Order repeats many of the proposals advanced during the first Trump Administration, including directing the FDA to streamline and improve its existing drug importation program so as to make it easier for states to obtain approval without sacrificing the safety or quality of drug products.

Other provisions of the Executive Order relate to the 340B program.

Specifically, one provision calls on the Secretary of HHS to determine the hospital acquisition cost for covered outpatient drugs at hospital outpatient departments and to consider and propose any appropriate adjustments for Medicare payment.

The other provision directs HHS to condition grant funding to certain health centers on those centers passing through the 340B discounts they receive on insulin and injectable epinephrine products to patients who meet certain requirements.

Several states have passed laws allowing for the importation of drugs from Canada.

On April 15, 2025, President Trump issued an executive order that directs HHS to take steps to reduce the prices of pharmaceutical products.

The executive order repeats many of the proposals advanced during the first Trump Administration, including directing the FDA to streamline and improve its existing drug importation program so as to make it easier for states to obtain approval without sacrificing the safety or quality of drug products.

With respect to the IRA’s Medicare drug pricing program, the executive order, among other things, calls for alignment in “the treatment of small molecule prescription drugs with that of biological products, ending the distortion that undermines relative investment in small molecule prescription drugs, coupled with other reforms to prevent any increase in overall costs to Medicare and its beneficiaries.”

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Subsequently, on May 12, 2025, President Trump issued an additional executive order (the Additional Order) calling on pharmaceutical manufacturers to voluntarily reduce the prices of medicines in the U.S.

The Additional Order directs the Secretary of HHS to communicate “most-favored-nation” price targets to pharmaceutical manufacturers to bring prices in line with comparably developed nations.

Since the Additional Order, the Trump administration has continued to exert pressure on drug manufacturers to implement “most-favored-nation” pricing.

For example, in November 2025, CMS announced a new voluntary payment initiative called the GENEROUS Model (GENErating cost Reductions for U.S.

Medicaid Model) where drug manufacturers may voluntarily offer supplemental rebates to participating state Medicaid programs that are intended to provide such Medicaid programs with a “most-favored-nation” price for participating manufacturers’ products.

Additionally, on December 21, 2025, CMS issued two proposed rules that, if implemented, would introduce two mandatory payment models, the Global Benchmark for Efficient Drug Pricing (GLOBE) and Guarding U.S.

Medicare Against Rising Drug Costs (GUARD) models, where manufacturers of certain

Medicare Part B and Medicare Part D drugs would be assessed rebates if the prices for such products exceed those paid in economically comparable countries.

Most recently, on April 2, 2026, President Trump issued an executive order establishing a tariff framework for imported patented pharmaceuticals and related inputs, with more favorable rates and / or exceptions tied to most-favored-nation pricing and domestic manufacturing commitments.

It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.

state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Another emerging trend at the state level is the establishment of prescription drug affordability boards, some of which will prospectively permit certain states to establish upper payment limits for drugs that the state has determined to be “high-cost.” Prescription drug affordability boards in several states have begun identifying products for affordability reviews and issuing information request to manufacturers to determine whether upper payment limits may be justified.

In addition, regional healthcare organizations and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs.

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Our relationships with healthcare providers, physicians and third-party payers will be subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

Healthcare professionals, including but not limited to physicians, nurses, medical directors, hospitals, pharmacies, pharmacy benefit managers, group purchasing organizations, wholesalers, insurers, and all individuals employed by such entities (collectively, “HCPs”), may influence the recommendation and prescription of our approved products.

Our arrangements with HCPs and others who have the ability to influence the recommendation and prescription of our products may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell and distribute our medicines for which we obtain marketing approval.

Restrictions under applicable federal and state healthcare laws and regulations include the following:

• the federal healthcare anti-kickback statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order, or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid;

• the FCA imposes criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting or causing to be presented, to the federal government, claims for payment or approval from Medicare, Medicaid or other government payers that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties;

• the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as further amended by the Health Information Technology for Economic and Clinical Health Act, which imposes certain requirements, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, healthcare clearinghouses and healthcare providers;

Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and prescription of any products for which we are able to obtain marketing approval.

Our arrangements with healthcare providers, third-party payors, and customers and others who have the ability to influence the recommendation and prescription of our products will subject us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we conduct clinical research, market, sell and distribute any products for which we obtain marketing approval.

These include, but are not limited to, the following:

• the federal healthcare Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving, or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order, or recommendation of, any good or service, for which payment may be made under federal and state healthcare programs such as Medicare and Medicaid;

• the federal false claims and civil monetary penalties laws, including the federal civil FCA, which impose criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting or causing to be presented, to the federal government, claims for payment by federal healthcare program payers that are false or fraudulent or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties;

contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information without appropriate authorization by entities subject to the rule, such as health plans, healthcare clearinghouses and healthcare providers;

• the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items or services;

• the federal transparency requirements under the federal Physician Payment Sunshine Act, which requires manufacturers of drugs, devices, biologics and medical supplies to report to HHS, information related to payments and other transfers of value to physicians, other healthcare providers and teaching hospitals and ownership and investment interests held by physicians and their immediate family members and applicable group purchasing organizations;

• analogous state laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers, including private insurers, and certain state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws.

If our operations are found to be in violation of any of the laws described above or any other government regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines, exclusion from participation in government healthcare programs, such as Medicare and Medicaid, imprisonment and the curtailment or restructuring of our operations, any of which could adversely affect our business, financial condition, results of operations and prospects.

• the federal transparency requirements under the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to CMS, information related to payments and other transfers of value to U.S.-licensed physicians and certain other U.S.-licensed healthcare providers, and U.S.

teaching hospitals, as well as information regarding ownership and investment interests held by physicians and their immediate family members;

• analogous state and foreign fraud and abuse laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payers, including private insurers, and certain state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.

It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.

If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations.

If any of the physicians or other providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines, exclusion from federal healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations.

Liabilities they incur pursuant to these laws could result in significant costs or an interruption in operations, which could have a material adverse effect on our business, financial condition, results of operations and prospects.

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Any failure to comply with those obligations could subject us to penalties and sanctions.

As a condition of reimbursement by various federal and state health insurance programs, we are required to calculate and report certain pricing information to federal and state agencies.

We participate in the Medicaid Drug Rebate Program, as administered by CMS, the 340B Drug Pricing Program (the “340B Program”), as administered by the Health Resources and Services Administration (“HRSA”), and other federal and state government drug pricing programs in the U.S., and we may participate in additional government pricing programs in the future.

These programs generally require us to pay rebates or otherwise provide discounts to government payors and/or required covered entities in connection with drugs that are dispensed to beneficiaries/recipients of these programs.

In some cases, such as with the Medicaid Drug Rebate Program, the rebates are based on pricing metrics that we report on a monthly and quarterly basis to the government agencies that administer the programs.

The regulations governing the calculations, price reporting and payment obligations are complex and subject to interpretation by various government and regulatory agencies, as well as the courts.

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Such revisions could affect our liability to federal and state payers and also adversely impact our reported financial results of operations in the period of such restatement.

Further, a number of states have either implemented or are considering implementation of drug price transparency legislation that may prevent or limit our ability to take price increases at certain rates or frequencies.

Requirements under such laws include advance notice of planned price increases, reporting price increase amounts and factors considered in taking such increases, wholesale acquisition cost information disclosure to prescribers, purchasers, and state agencies, and new product notice and reporting.

Such legislation could limit the price or payment for certain drugs, and a number of states are authorized to impose civil monetary penalties or pursue other enforcement mechanisms against manufacturers for the untimely, inaccurate, or incomplete reporting of drug pricing information or for otherwise failing to comply with drug price transparency requirements.

If we are found to have violated state law requirements, we may become subject to significant penalties or other enforcement mechanisms, which could have a material adverse effect on our business.

Uncertainty exists as new laws, regulations, judicial decisions, or new interpretations of existing laws, or regulations related to our calculations, price reporting or payments obligations increases the chances of a legal challenge, restatement or investigation.

If we become subject to investigations, restatements, or other inquiries concerning our compliance with price reporting laws and regulations, we could be required to pay or be subject to additional reimbursements, penalties, sanctions or fines, which could have a material adverse effect on our business, financial condition and results of operations.

In addition, it is possible that future healthcare reform measures could be adopted, which could result in increased pressure on pricing and reimbursement of our products and thus have an adverse impact on our financial position or business operations.

Additionally, HHS, the HHS Office of Inspector General and other governmental enforcement and administrative bodies have increased their focus, including through recent enforcement actions against manufacturers, on pricing requirements for products, including, but not limited to the methodologies used by manufacturers to calculate average manufacturer price and best price for compliance with reporting requirements under the Medicaid Drug Rebate Program.

In addition to retroactive rebates, if we are found to have knowingly submitted any false price information related to the Medicaid Drug Rebate Program to CMS, we may be liable for civil monetary penalties and potential liability under the federal False Claims Act.

Such failure could also be grounds for CMS to terminate our Medicaid drug rebate agreement, pursuant to which we participate in the Medicaid program.

If CMS were to terminate our rebate agreement, federal payments may not be available under federal healthcare programs, including Medicaid or Medicare Part B, for our covered outpatient drugs.

Further, state Medicaid programs may be slow to invoice pharmaceutical companies for calculated rebates, resulting in a lag between the time a sale is recorded and the time the rebate is paid.

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If actual claims are higher than current estimates, our financial position and results of operations could be adversely affected.

In addition to retroactive rebates and the potential for 340B Program refunds, if we are found to have knowingly submitted any false price information related to the Medicaid Drug Rebate Program to CMS, we may be liable for civil monetary penalties.

Such failure could also be grounds for CMS to terminate our Medicaid drug rebate agreement, pursuant to which we participate in the Medicaid program.

In the event that CMS terminates our rebate agreement, federal payments may not be available under government programs, including Medicaid or Medicare Part B, for our covered outpatient drugs.

We may also be affected by developments relating to the 340B Drug Program.

Multiple states have recently enacted or are currently considering laws that require manufacturers to ship 340B drugs to certain contract pharmacies and impose various civil and criminal penalties on manufacturers that do not comply.

These laws have been challenged in federal court and many of the cases are pending.

In March 2024, the US Court of Appeals for the Eight Circuit upheld the Arkansas law prohibiting drug makers for restricting 340B drug discounts for providers using contract pharmacies.

DHHS also issued a final rule on procedures for the 340B Program’s administrative dispute resolution process in April 2024.

Additionally, under the Trump administration, several changes to the 340B program have been considered, including a proposal in the President’s 2026 budget to shift oversight of the 340B program from the HRSA to CMS.

Additionally, on July 31, 2025, the HRSA announced that it will implement a 340B Rebate Model Pilot Program that will be open to a selected group of drugs and manufacturers.

However, the HRSA withdrew this proposal in January 2026 following litigation that resulted in a federal court granting a temporary restraining order to block the program and has since requested information from stakeholders as to alternative rebate models.

It is unclear how the other pending litigation, proposed legislation, or future administrative action relating to the 340B Program will impact our business

Additionally, if we overcharge the government in connection with the Federal Supply Schedule pricing program or Tricare Retail Pharmacy Program, whether due to a misstated Federal Ceiling Price or otherwise, we are required to refund the difference to the government.

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Unexpected refunds to the government, and responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have a material adverse effect on our business, financial condition, results of operations and growth prospects.

If we are found to have violated state law requirements, we may become subject to significant penalties or other enforcement mechanisms, which could have a material adverse effect on our business.

Uncertainty exists as new laws, regulations, judicial decisions, or new interpretations of existing laws, or regulations related to our calculations, price reporting or payment obligations, which increases the chances of a legal challenge, restatement or investigation.

Our collaborators are also subject to similar requirements outside of the U.S.

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federal and state laws and regulations related to the privacy and security of personal information.

In particular, regulations promulgated pursuant to HIPAA establish privacy and security standards that limit the use and disclosure of individually identifiable health information, or protected health information, and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information and ensure the confidentiality, integrity and availability of electronic protected health information.

and availability of electronic protected health information.

Determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations can be complex and may be subject to changing interpretation.

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We cannot be sure how these regulations will be interpreted, enforced or applied to our operations.

In addition to the risks associated with enforcement activities and potential contractual liabilities, our ongoing efforts to comply with evolving laws and regulations at the federal and state level may be costly

and require ongoing modifications to our policies, procedures and systems.

Additionally, OCR is looking to amend the HIPAA Security Rule, which (if and when finalized) could create additional compliance obligations and risk for our business.

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The provisions in the CPRA may apply to some of our business activities.

In addition to California, at least eighteen other states have passed comprehensive privacy laws similar to the CCPA and CPRA.

In addition to California, several other states have passed comprehensive privacy laws similar to the CCPA and CPRA.

These laws are either in effect or will go into effect over the next few years.

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Some of the provisions of these laws may apply to our business activities.

There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2024 legislative sessions that will go into effect in 2025 and beyond, including New Hampshire and New Jersey.

Other states will be considering these laws in the future, and Congress has also been debating passing a federal privacy law.

There are also states that are specifically regulating health information that may affect our business.

For example, Washington state passed a health privacy law in 2023 that regulates the collection and sharing of health information, and the law also has a private right of action, which further increases the relevant compliance risk.

Connecticut and Nevada have also passed similar laws regulating consumer health data, and more states are considering such legislation in 2025.

These laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products.

Plaintiffs’ lawyers are also increasingly using privacy-related statutes at both the state and federal level to bring lawsuits against companies for their data-related practices.

In particular, there have been a significant number of cases filed against companies for their use of pixels and other web trackers.

In particular, there have been a significant number of cases filed against companies for their

use of pixels and other web trackers.

These cases often allege violations of the California Invasion of Privacy Act and other state laws regulating wiretapping, as well as the federal Video Privacy Protection Act.

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Similar to the laws in the U.S., there are significant privacy and data security laws that apply in Europe and other countries.

The collection, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are

located in the European Economic Area (“EEA”), and the processing of personal data that takes place in the EEA, is regulated by the GDPR, which went into effect in May 2018 and which imposes obligations on companies that operate in our industry with respect to the processing of personal data and the cross-border transfer of such data.

The collection, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are located in the European Economic Area (“EEA”), and the processing of personal data that takes place in the EEA, is regulated by the GDPR, which went into effect in May 2018 and which imposes obligations on companies that operate in our industry with respect to the processing of personal data and the cross-border transfer of such data.

The GDPR imposes onerous accountability obligations requiring data controllers and processors to maintain a record of their data processing and policies.

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With the passage of the CREATES Act, we are exposed to possible litigation and damages by competitors who may claim that we are not providing sufficient quantities of our approved products on commercially reasonable, market-based terms for testing in support of their ANDAs and 505(b)(2) applications.

In December 2019, former President Trump signed legislation intended to facilitate the development of generic and biosimilar products.

In December 2019, President Trump signed legislation intended to facilitate the development of generic and biosimilar products.

The bill, previously known as the CREATES Act, authorizes sponsors of Abbreviated New Drug Applications (“ANDAs”) and 505(b)(2) applications to file lawsuits against companies holding NDAs that decline to provide sufficient quantities of an approved reference drug on commercially reasonable, market-based terms.

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These third parties may voluntarily require compliance or supply chain requirements that go above and beyond potential legislation to address perceived risk of “pass through,” which would make it difficult for us to operate our business.

In addition, in September 2024 during the 118th Congress, the U.S.

House of Representatives passed the BIOSECURE Act (H.R.

This bill names the following as biotechnology companies of concern:

“BGI, MGI, Complete Genomics, WuXi AppTec, and WuXi Biologics.

The Senate advanced a substantially similar bill (S.

3558) but it did not pass.

The Senate bill named the following as biotechnology companies of concern:

“BGI, MGI, Complete Genomics, WuXi AppTec, and any subsidiary, parent affiliate, or successor of such entities.

If this legislation had been enacted into law, and while both bills had certain grandfather provision, the legislation would have potentially restricted the ability of U.S.

biotechnology companies like ours to purchase services or products from, or otherwise collaborate with, specifically named Chinese biotechnology companies, including WuXi, and it would have authorized the U.S.

government to impose such restrictions on entities' transactions with additional Chinese biotechnology

companies as a condition of U.S.

government contract, grant and loan funding.

We anticipate these bills will be reintroduced during the 119th Congress but, as of September 30, 2025, they have not been introduced in either chamber.

If these bills become law, or similar laws are passed, they would have the potential to severely restrict the ability of companies like ours to contract with certain Chinese biotechnology companies of concern without losing the ability to contract with, or otherwise received funding from, the U.S.

Such disruptions could have adverse effects on the development of our product candidates and our business operations.

In December 2025, Congress enacted a law that, subject to certain grandfather provisions, will prohibit U.S.

federal agencies from procuring or obtaining “biotechnology equipment or services” from certain Chinese companies designated as “biotechnology companies of concern.” It will also prohibit U.S.

federal agencies from entering into, extending or renewing contracts with any entity that either uses biotechnology equipment or services provided by a designated biotechnology company of concern in performance of the contract or enters into any contract with a third party that requires either party to use biotechnology equipment or services produced or provided by a biotechnology company of concern.

It also prohibits an executive agency from obligating or expending a loan or grant to procure biotechnology equipment or services produced or provided by a designated biotechnology company of concern.

Regulatory or legislative action taken by the U.S.

government to impose restrictions on transactions with China, like the

restrictions described above, could have the potential to severely restrict the ability of companies like ours to contract with Chinese biotechnology companies of concern, which could have adverse effects on the development of our product candidates and our business operations.

Any unfavorable government policies on international trade, such as export controls, capital controls or tariffs, may increase the cost of manufacturing our product candidates and platform materials, affect the demand for our drug products (if and once approved), the competitive position of our product candidates, and the import or export of raw materials and finished product candidate used in our and our collaborators’ preclinical studies and clinical trials, particularly with respect to any product candidates and materials that we import from China, including pursuant to our manufacturing service arrangements with a Chinese-based supplier of raw materials used to manufacture our API.

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The biopharmaceutical industry is 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.

On June 28, 2024, the U.S.

Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by the FDA, HHS, CMS and other agencies with significant oversight of the biopharmaceutical industry.

The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.

In June 2024, the U.S.

Supreme Court issued an opinion in Loper Bright Enterprises v.

Raimondo holding that courts reviewing agency action pursuant to the Administrative Procedure Act “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision has impacted and will impact how lower courts evaluate challenges to agency interpretations of law, including those by the FDA, HHS, CMS and other agencies with significant oversight of the biopharmaceutical industry.

This framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.

As a result, significant regulatory policies will be subject to increased litigation and judicial scrutiny.

In addition, federal agency priorities, leadership, policies, rulemaking, communications, spending and staffing may be significantly impacted by election cycles.

In addition, federal agency activities, priorities, leadership, policies, rulemaking, communications, spending and staffing may be significantly impacted by election cycles and legislative developments.

For example, the current presidential administration aims to significantly reduce government spending through cuts to federal healthcare programs and reductions in the workforces of key government agencies, such as the FDA, HHS, and CMS.

Efforts by the current administration to limit federal agency budgets or personnel may result in reductions to agency budgets, employees and operations, which may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.

Efforts by the current administration to limit federal agency budgets or personnel may result in reductions to agency budgets, employees and operations.

The administration and agencies have also made abrupt announcements about new or changed regulatory policies, such as policies related to use of artificial intelligence to review product applications.

Additionally, any federal government shutdowns may prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews or other regulatory activities, and may significantly impact the ability of the FDA to timely review and process our regulatory submissions.

These developments may lead to slower response times and longer review periods, potentially affecting our ability to progress development of our product candidates or obtain regulatory approval for our product candidates.

Any resulting changes in regulation may result in unexpected delays, increased costs, or other negative impacts on our business that are difficult to predict.

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In addition, we intend to seek one or more collaborators to aid in the further development, marketing and/or commercialization of selinexor and our other compounds for indications both within and outside of oncology.

All of the risks relating to product development, regulatory approval and commercialization described in this Quarterly Report on Form 10-Q also apply to the activities, including activities in any country or territory outside of the U.S.

All of the risks relating to product development, regulatory approval and commercialization described in our Annual Report also apply to the activities, including activities in any country or territory outside of the U.S.

and EU, as applicable, of our collaborators.

Potential collaborators include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies and we face significant competition in seeking appropriate collaborators, including as a result of a significant number of recent business combinations among large pharmaceutical companies that have reduced the number of potential collaborators.

Whether we reach a definitive agreement for a collaboration will depend, among other things, upon the assessment of the potential collaborator’s expertise, its current and expected resources and competing priorities, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.

Those factors may include the design or

results of clinical trials, the likelihood of approval by the FDA or foreign regulatory authorities, the potential market for the product or product candidate, the costs and complexities of manufacturing and delivering such product or product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of intellectual property, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally.

proposed collaboration and the proposed collaborator’s evaluation of a number of factors.

Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or foreign regulatory authorities, the potential market for the product or product candidate, the costs and complexities of manufacturing and delivering such product or product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of intellectual property, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally.

A potential collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us.

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• a collaborator with marketing and distribution rights to one or more products or product candidates may not commit sufficient resources to the marketing and distribution of our products or product candidates;

• disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development or commercialization, might cause delays or termination of the research, development or commercialization of products or product candidates, might lead to additional responsibilities for us with respect to our products or product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

products or product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive;

• collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;

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For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial.

Moreover, the FDA requires us to comply with GCP

standards when conducting, recording and reporting the results of clinical trials to ensure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected.

Moreover, the FDA requires us to comply with GCP standards when conducting, recording and reporting the results of clinical trials to ensure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected.

The EMA also requires us to comply with comparable standards.

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Consequently, we may not be able to reach agreement with third-party manufacturers on satisfactory terms, which could negatively impact our XPOVIO revenues or delay commercialization of any product candidates that are subsequently approved.

If, because of the factors discussed above, we are unable to have our products manufactured on a timely or sufficient basis, we may not be able to meet clinical development needs or commercial demand for our products or product candidates or we may not be able to manufacture our products in a cost-effective manner.

able to manufacture our products in a cost-effective manner.

As a result, we may lose sales, fail to generate projected revenues or suffer development or regulatory setbacks, any of which could have an adverse impact on our profitability and future business prospects.

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We seek to protect our proprietary position by filing patent applications related to our novel products and product candidates and other discoveries that are important to our business.

As of October 30, 2025, 192 patents were in force that relate to exportin 1 inhibitors, including composition of matter patents for selinexor, verdinexor and eltanexor in the U.S., and their use in targeted therapeutics.

As of May 7, 2026, 200 patents were in force that relate to exportin 1 inhibitors, including composition of matter patents for selinexor, verdinexor and eltanexor in the U.S., and their use in targeted therapeutics.

In addition, 34 patents were in force that relate to our PAK4/NAMPT inhibitors, including four composition of matter patents for KPT-9274 in the U.S.

and its use in targeted therapeutics.

With respect to our KPT-1200 program, as of October 30, 2025, 13 patents were in force that relate to IL-12 compositions and uses of IL-12 in targeted therapeutics.

With respect to our KPT-1200 program, as of May 7, 2026, 13 patents were in force that relate to IL-12 compositions and uses of IL-12 in targeted therapeutics.

We cannot be certain that any other patents will issue with claims that cover any of our key products, product candidates or other discoveries.

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Such challenges may result in loss of exclusivity or in patent claims being narrowed, invalidated or held unenforceable, which could limit our ability to stop others from using or commercializing similar or identical discoveries and drugs, or limit the duration of the patent protection of our products, product candidates and discoveries.

Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized.

Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting

such candidates might expire before or shortly after such candidates are commercialized.

As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing drugs similar or identical to ours.

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Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities.

We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings.

We may not have sufficient financial or other resources to adequately

conduct such litigation or proceedings.

Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources.

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The Hatch-Waxman Amendments permit a patent term extension of up to five years for one patent covering an approved product as compensation for effective patent term lost during product development and the FDA regulatory review process.

However, we may

not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements.

However, we may not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements.

Moreover, the length of the extension could be less than we request.

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Failure to secure those registrations could adversely affect our business.

As of October 30, 2025, we have trademark registrations in the U.S.

As of May 7, 2026, we have trademark registrations in the U.S.

for KARYOPHARM, KARYOPHARM THERAPEUTICS, our color logo, our logo in grayscale, KARYOPHARM THERAPEUTICS with the color logo, XPOVIO, PORE for our online research portal, and KARYFORWARD and our KARYFORWARD logo for our financial aid and charitable services.

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NEXPOVIO is registered or pending in 45 jurisdictions outside the U.S.

and pending in Cyrillic characters in Russia.

and pending in Cyrillic characters in Russia and Kazakhstan.

We also have registrations or applications for seven additional possible drug names in one or more foreign jurisdictions.

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The FDA typically conducts a review of proposed drug names, including an evaluation of potential for confusion with other drug names.

If the FDA objects to any of our proposed proprietary drug names for any of our product candidates, if approved, we may be required to expend significant additional resources in an effort to identify a suitable proprietary drug name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA.

If the FDA objects to any of our proposed proprietary drug names for any of our product candidates, if approved, we may be required to expend significant additional resources

in an effort to identify a suitable proprietary drug name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA.

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.

We use and integrate artificial intelligence (“AI”) into our business processes, such as generative AI tools, primarily to support internal productivity activities, including drafting documents, job postings, and other non-clinical, non-operational materials.

We do not use our AI systems to make autonomous decisions related to clinical development, patient care, biometrics, pricing, credit, employment decisions, or other regulated or sensitive activities, and outputs generated using AI are subject to human review and approval prior to any external use or publication.

Notwithstanding these controls, the use of AI presents evolving risks, including potential inaccuracies, unintended disclosure of confidential information, including personal information, intellectual property concerns, including compromises to proprietary intellectual property and intellectual property infringement, and cybersecurity risks.

Failure to effectively manage these risks could adversely affect our operations, reputation, or compliance posture and therefore, our business.

Moreover, our use of AI is governed by internal policies that are informed by emerging regulatory frameworks, and is designed to restrict use of prohibited or high-risk AI use cases.

We expect to see increased regulation related to AI use and ethics, which may also significantly increase the burden and cost of compliance in this area.

For example, the EU’s Artificial Intelligence Act (“EU AI Act”), the world’s first comprehensive AI law, entered into force in 2024 and, with some exceptions, will become effective in 2026.

This legislation imposes significant obligations on providers and deployers of high risk AI systems, and encourages providers and deployers of AI systems to account for EU ethical principles in their development and use of these systems.

In the future, our development or use of AI systems that are governed by the EU AI Act and/or uncertainty arising from rapidly developing laws and regulations governing AI may necessitate higher standards of data quality, transparency, and human oversight, as well as adhering to specific and potentially burdensome and costly ethical, accountability, and administrative requirements.

Further, bad actors around the world use increasingly sophisticated methods, including the use of AI, to engage in illegal activities involving the theft and misuse of personal information, confidential information, and intellectual property.

Any of these effects could damage our reputation, result in the loss of valuable property and information, cause us to breach applicable laws and regulations, and adversely impact our business.

Risks Related to Our Operations and Employee Matters

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Recruiting and retaining qualified scientific, clinical, manufacturing and sales and marketing personnel is critical to our success.

We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel.

Due to our limited resources, we may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel.

Recent operational and financial challenges as well as constraints on our ability to make equity grants to employees have made it more difficult to effectively recruit, retain and incentivize talent.

The inability to offer competitive compensation, including equity compensation, could place us at significant disadvantage relative to the companies with whom we compete for specialized talent and increase the risk of attrition of key employees critical to achieving our near-term clinical regulatory objectives.

We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions.

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Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us.

On August 2, 2023, we announced that we had reduced our workforce by approximately 20%, in August 2024, we reduced our workforce by approximately 7% and on July 11, 2025, we announced that we had further reduced our workforce by approximately 20% as part of the Company’s ongoing careful management of operating expenses.

In each of August 2023, August 2024 and July 2025 we announced reductions to our workforce.

Reductions in force may decrease employee morale and productivity and lead to increased turnover, and they may have a negative effect on our ability to attract and retain qualified personnel.

In addition, concerns about our ability to continue as a going concern or raise sufficient capital

to fund our ongoing trials could result in the departure of personnel that are critical to our operations.

Departures may be disruptive to our operations and ability to retain employees and increase our dependency on other employees who are not contractually obligated to remain employed with us, and those employees may leave at any time.

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Our business and operations may be materially adversely affected in the event of information technology system failures or security breaches, and the costs and consequences of implementing data protection measures could be significant.

Despite the implementation of security measures, our internal computer systems, and those of our CROs and other third parties on which we rely, are vulnerable to damage or other impacts from cyber-attacks, computer viruses, unauthorized access, sabotage, natural disasters, fire, terrorism, war and telecommunication and electrical failures.

Despite the implementation of security measures, our internal computer systems, and those of our CROs and other third parties on which we rely, are vulnerable to damage or other impacts from cyber-attacks, computer viruses, unauthorized access, unverified AI-generated material, sabotage, natural disasters, fire, terrorism, war and telecommunication and electrical failures.

Such systems are also vulnerable to service interruptions or to security breaches from inadvertent or intentional actions by our employees, third-party vendors and/or business partners, or from cyber incidents initiated by malicious third parties.

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To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability, our reputation or competitive position could be damaged, and the further development and commercialization of our products or product candidates could be delayed or halted.

We may not have adequate

insurance coverage to provide compensation for any losses associated with such events.

We may not have adequate insurance coverage to provide compensation for any losses associated with such events.

In addition, we may in certain instances be required to provide notification to individuals or others in connection with the loss of their personal or commercial information.

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In the past, we have received written notification from the Nasdaq Stock Market (“Nasdaq”) informing us that we were not in compliance with certain continued listing requirements of the Nasdaq Global Select Market.

As previously disclosed, on September 16, 2024, we received a deficiency letter from the Listing Qualifications Department (the “Staff”) of Nasdaq notifying us that, for the prior 32 consecutive business days, the bid price of our common stock had closed below the minimum $1.00 per share requirement for continued inclusion on the Nasdaq Global Select Market pursuant to Nasdaq Listing Rule 5450(a)(1) (the “Bid Price Rule”).

On February 25, 2025, we effected a 1-for-15 reverse stock split of our issued and outstanding shares of common stock (the “Reverse Stock Split”).

On March 13, 2025 we received a letter from the Staff notifying us that we regained compliance with the Bid Price Rule for continued inclusion on the Nasdaq Global Select Market.

For example, in September 2024, we received a deficiency letter from the Listing Qualifications Department (the “Staff”) of Nasdaq notifying us that, for the prior 32 consecutive business days, the bid price of our common stock had closed below the minimum $1.00 per share requirement for continued inclusion on the Nasdaq Global Select Market pursuant to Nasdaq Listing Rule 5450(a)(1) (the “Bid Price Rule”).

In March 2025, following a 1 for 15 reverse stock split of our issued and outstanding shares of common stock, we received a letter from the Staff notifying us that we regained compliance with the Bid Price Rule for continued inclusion on the Nasdaq Global Select Market.

There can be no assurances that we will continue to maintain compliance with the requirements for listing our common stock on Nasdaq.

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The exercise of our outstanding warrants will dilute existing stockholders and could adversely affect the trading price of our common stock.

Following the consummation of the Financing Transactions, we have outstanding warrants to purchase, without regard to any beneficial ownership limitations, and excluding pre-funded warrants to purchase common stock up to 9,622,478 shares of common stock at a weighted average exercise price of $12.50 share.

As of March 31, 2026, we had outstanding warrants to purchase, without regard to any beneficial ownership limitations, and excluding pre-funded warrants to purchase common stock, up to 14,043,996 shares of common stock at a weighted average exercise price of $11.71 per share.

The exercise of our outstanding warrants could result in significant dilution to existing stockholders, cause the trading price of our common stock to decline and impair our ability to raise capital through the sale of additional equity securities.

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In connection with any capital raising transactions that we may consummate, we may determine to issue additional warrants, which could result in further dilution to our stockholders.

The liquidity of our common stock may be adversely affected by our Reverse Stock Split.

On February 25, 2025, we effected the Reverse Stock Split.

The liquidity of our common stock may be adversely affected by the Reverse Stock Split given the reduced number of shares that are outstanding following the Reverse Stock Split, which may lead to reduced trading and a smaller number of market makers for our common stock.

In addition, the Reverse Stock Split may have increased the number of stockholders who own “odd lots” of less than 100 shares of our common stock.

Odd lot shares may be more difficult to sell, and brokerage commissions and other costs of transactions in odd lots may be higher than the costs of transactions in “round lots” of even multiples of 100 shares.

Despite the Reverse Stock Split, the resulting per-share trading price of our common stock may nevertheless fail to attract institutional investors and may not satisfy the investing guidelines of such investors and, consequently, the trading liquidity of our common stock may be adversely affected.

Accordingly, the Reverse Stock Split may not achieve the desired results of increasing marketability of our common stock.

Provisions in our corporate charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

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Our stock price has been, and may continue to be, volatile and your investment in our stock could decline or fluctuate significantly.

Our common stock price has ranged from $3.54 to $14.85 in the 52-week period ended October 30, 2025.

On October 30, 2025, the closing sale price of our common stock on the Nasdaq Global Select Market was $5.96 per share.

Our common stock price has ranged from $3.77 to $10.09 in the 52-week period ended May 7, 2026.

On May 7, 2026, the closing sale price of our common stock on the Nasdaq Global Select Market was $8.85 per share.

The stock market in general and the market for pharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies, such as the response to world-wide economic disruptions related to tariffs and other trade restrictions, uncertainty associated with governmental policies, shifts in regulatory priorities, and geopolitical tensions, such as conflicts involving multiple regions and nations including Ukraine, Russia, China, the Middle East and other areas of international concern, reduced investor confidence in the capital markets, inflation and sustained high interest rates.

The market price for our common stock may be influenced by many factors, including:

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• market conditions in the pharmaceutical and biotechnology sectors, including as the result of uncertainties due to or impacts from pandemics or other public health emergencies;

• general economic, industry and market conditions, such as those caused by tariffs and other trade restrictions, the conflicts in Ukraine and the Middle East, inflation and fluctuations in interest rates;

• general economic, industry and market conditions, such as those caused by tariffs and other trade restrictions, the conflicts involving multiple regions and nations, including Ukraine, Russia, China, the Middle East and other areas of international concern, inflation and fluctuations in interest rates;

• sales of large blocks of our common stock, including by our executive officers, directors and significant stockholders, or substantial changes in short interest in our common stock;

• the other risks and uncertainties described in this “ Risk Factors ” section.

The COVID-19 pandemic caused significant disruptions in the financial markets and also impacted the volatility of our stock price and trading in our stock.

In addition, U.S.

and global markets are experiencing volatility and disruption following the escalation of geopolitical tensions and the ongoing conflicts in Ukraine and the Middle East, inflation and sustained high interest rates.

A continuation or worsening of the levels of market disruption and volatility could have an adverse effect on the market price of our common stock.

Furthermore, the trading market for our common stock relies, in part, on the research and reports that industry or financial analysts publish about us or our business.

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Securities class action litigation is often brought against a company following a decline or periods of volatility in the market price of its securities.

This risk is especially relevant for us because pharmaceutical companies have experienced significant stock price volatility in recent years, including as a result of the COVID-19 pandemic, and we are therefore a target of this type of litigation.

This risk is especially relevant for us because pharmaceutical companies have experienced significant stock price volatility in recent years and we are therefore a target of this type of litigation.

For example, we were subject to a class action lawsuit and a shareholder derivative lawsuit alleging federal securities laws violations, both of which have been dismissed.

We may face additional securities class action litigation or other litigation in the future, including

if we fail to successfully commercialize XPOVIO, or if we cannot obtain regulatory approvals for, or if we otherwise fail to successfully commercialize and launch, our product candidates.

We may face additional securities class action litigation or other litigation in the future, including if we fail to successfully commercialize XPOVIO, or if we cannot obtain regulatory approvals for, or if we otherwise fail to successfully commercialize and launch, our product candidates.

The outcome of litigation is necessarily uncertain, and we could be forced to expend significant resources in the defense of such suits, and we may not prevail.

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A decision adverse to our interests on one or more legal matters or litigation could result in the payment of substantial damages, or possibly fines, and could have a material adverse effect on our reputation, financial condition and results of operations.

We have broad discretion in the use of our cash, cash equivalents and investments and may not use them effectively.

Our management has broad discretion to use our cash, cash equivalents and investments to fund our operations and could spend these funds in ways that do not improve our results of operations or enhance the value of our common stock.

We have broad discretion in the use of our cash and cash equivalents and may not use them effectively.

Our management has broad discretion to use our cash and cash equivalents to fund our operations and could spend these funds in ways that do not improve our results of operations or enhance the value of our common stock.

The failure by our management to apply these funds effectively could result in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and delay the development of our product candidates.

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Any system of internal controls, however well designed and operated, is based in part on certain assumptions and can provide only reasonable, not absolute, assurances that the objectives of the system are met.

If we, or our independent registered public accounting firm, determine that our internal control over our financial reporting is not effective, or we discover areas that need improvement in

the future, or we experience high turnover of our personnel in our financial reporting functions, these shortcomings could have an adverse effect on our business and financial results, and the price of our common stock could be negatively affected.

If we, or our independent registered public accounting firm, determine that our internal control over our financial reporting is not effective, or we discover areas that need improvement in the future, or we experience high turnover of our personnel in our financial reporting functions, these shortcomings could have an adverse effect on our business and financial results, and the price of our common stock could be negatively affected.

If we cannot conclude that we have effective internal control over our financial reporting, or if our independent registered public accounting firm is unable to provide an unqualified opinion regarding the effectiveness of our internal control over financial reporting, investors could lose confidence in the reliability of our financial statements, which could lead to a decline in our stock price.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 1A. Risk Factors