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Item 1A. Risk Factors

2025-08-11 compared with 2025-05-12 · 298 added, 312 removed, 1243 unchanged (33% of the section changed)

7 unchanged sentences

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

Risks Related to Our Financial Position and Capital Requirements

Our financial condition raises substantial doubt as to our ability to continue as a going concern.

We will require substantial funds to maintain our research and development programs, including as we continue to develop and seek regulatory approval of selinexor for multiple cancer indications, and to support our continued operations.

We have incurred significant operating losses since our inception.

As of June 30, 2025, we had approximately $51.7 million in cash, cash equivalents, and investments.

We expect these cash resources, as well as cash flow from net product revenue and license and other revenue, to fund our existing operations into October 2025 given the $24.5 million aggregate principal amount of the 2025 Notes and $25.0 million minimum liquidity covenant.

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

We anticipate that we will continue to incur significant operating losses as we continue our research and development programs, including as we continue to develop and seek regulatory approval of selinexor for multiple cancer indications, and to support our continued operations.

As a result, our continued operations are dependent on our ability to raise additional funding and/or enter into strategic alternatives, as described in the risk factor entitled “ We will need additional funding or to enter into strategic alternatives to achieve our business objectives.

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 the October 15, 2025 maturity date of our 3.00% convertible senior notes due 2025 (the “2025 Notes”) with an aggregate principal amount of $24.5 million and a requirement under our Credit Agreement, as defined below, and the indenture governing our 6.00% convertible senior notes due 2029 (the “2029 Notes”) to maintain cash, cash equivalents and investments of at least $25.0 million at all times, 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, as we announced on July 11, 2025, our Board is evaluating potential financing transactions, along with 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 our existing debt;

among other potential alternatives.

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

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.

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 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.

We have incurred significant losses since inception, expect to continue to incur significant losses, and may never achieve or maintain profitability.

Since inception, we have incurred significant operating losses.

Our net loss was $37.3 million for the three months ended June 30, 2025.

As of June 30, 2025, we had an accumulated deficit of $1.6 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.

Although we received our first FDA-approval for XPOVIO in July 2019, we may never attain profitability or positive cash flows from operations.

We have historically financed our operations primarily through a combination of proceeds from (i) product revenue sales, (ii) public and private placements of equity securities, (iii) the issuance of convertible debt, (iv) a term loan, (v) our deferred royalty obligation, (vi) at the market offerings and (vii) business development activities.

Substantially all of our operating losses have resulted from costs incurred in connection with our research and development programs, the pursuit of regulatory approvals within and outside of the U.S., and the commercialization of XPOVIO.

We expect to continue to incur significant expenses and operating losses as we continue to commercialize XPOVIO in the U.S.

and engage in activities to prepare for the potential approval and commercialization of additional indications for selinexor as well as any other product candidates we develop or acquire.

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:

• effectively commercializing XPOVIO or any future products either on our own or with a collaborator, including by maintaining a full commercial organization required to market, sell and distribute our products, and achieving an adequate level of market acceptance;

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

• manufacturing at commercial scale;

• establishing and managing any collaborations for the development, marketing and/or commercialization of our products and product candidates, including the level of success of our collaborators’ efforts and the timing and amount of any milestone or royalty payments we may receive;

• obtaining, maintaining and protecting our intellectual property rights;

• 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:

• 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;

• maintain, expand and protect our intellectual property portfolio;

• manufacture XPOVIO and our product candidates;

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

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

Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.

Our failure to become and remain profitable would decrease the value of our company and could impair our ability to raise capital, maintain our research and development and commercialization efforts, expand our business and/or continue our operations.

A decline in the value of our company could also cause our stockholders to lose all or part of their investment.

We will need additional funding or to enter into strategic alternatives to achieve our business objectives.

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.

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.

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

As of June 30, 2025, 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 and debt obligation requirements into October 2025 given the $24.5 million aggregate principal amount of the 2025 Notes and $25.0 million minimum liquidity covenant.

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

• the timing and success of our efforts to enter into strategic alternatives, if available;

• our ability to extend our cash runway through additional financing activities;

• the scope, progress, results, timing and costs of our current and planned development efforts and regulatory review of our product candidates;

• the amount and timing of revenues from sales of XPOVIO, or any product candidate that we develop or acquire;

• the cost of, and our ability to expand and maintain, the commercial infrastructure required to support the commercialization of XPOVIO and any other product for which we receive marketing approval, including medical affairs, manufacturing, marketing and distribution functions;

• 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 $100.0 million senior secured term loan facility (the “Term Loan”) and/or holders of the 2025 Notes and the 2029 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 Term Loan and the 2029 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;

• our ability to continue as a going concern.

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.

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.

Moreover, in addition to the restrictions on our operations under the Term Loan and the 2029 Notes, the restrictions contained in the Amended Revenue Interest Agreement (defined below) and the repayment requirements in respect of obligations from proceeds of the transactions under each of the foregoing agreements, any future debt financing, if available and permitted, may involve further restrictive covenants that could limit our flexibility in conducting future business activities and using transaction proceeds in our business and, in the event of insolvency, the Term Loan, the 2029 Notes, the 2025 Notes, the Amended Revenue Interest Agreement obligations, and any further indebtedness, if available and permitted, would be paid before holders of equity securities received any distribution of corporate assets.

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 evaluating 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 July 11, 2025, we announced that our Board is considering potential financing transactions along with strategic alternatives to maximize near and long-term stockholder value, including, but 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 execute on a strategic alternative is dependent on a number of factors and we may not be able to execute upon a transaction or other strategic alternative having favorable terms within an advantageous timeframe and/or recognize significant value for our assets, if at all.

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 Term Loan, the 2029 Notes, the 2025 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.

If we are not able to successfully consummate a successful financing transaction or strategic alternative, our Board may decide to pursue a dissolution and liquidation of our company.

In such an event, we would be required under Delaware corporate law to pay our outstanding obligations, as well as to make reasonable provision for contingent and unknown obligations, prior to making any distributions in liquidation to our stockholders.

As a result of this requirement, a portion of our assets may need to be reserved pending the resolution of such obligations.

In addition, we may be subject to litigation or other claims related to a dissolution and liquidation of our company.

If our Board determined to pursue a dissolution and liquidation, our Board, in consultation with its advisors, would need to evaluate these matters and make a determination about a reasonable amount to reserve.

Depending on these factors, the amount available for distribution to our common stockholders in such an event could be as low as zero and result in a total loss of investment to our stockholders.

Our Amended Revenue Interest Agreement with KKR contains various covenants and other provisions, which, if violated, could, subject to the 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 in June 2021, August 2023 and May 2024, and which was subsequently assigned by HCRx to KKR & Co.

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

Pursuant to the Amended Revenue Interest Agreement, we are required to comply with various covenants relating to the conduct of our business and the commercialization of XPOVIO, including obligations to use commercially reasonable efforts to commercialize our products.

In addition, the Amended Revenue Interest Agreement limits our ability to incur or prepay indebtedness, create or incur liens, pay dividends on or repurchase outstanding shares of our capital stock or dispose of assets.

The Amended Revenue Interest Agreement also includes customary events of default upon the occurrence of enumerated events, including non-payment of revenue interests, failure to perform certain covenants and the occurrence of insolvency proceedings, specified judgments, specified cross-defaults and specified revocations, withdrawals, suspensions or cancellations of regulatory approval for XPOVIO.

Upon the occurrence of an event of default and in the event of a change of control, KKR may accelerate payments due under the Amended Revenue Interest Agreement up to $128.3 million, less the aggregate amount of all of the payments paid to HCRx and KKR after the date of the May 2024 amendment.

Our obligations to KKR are secured by a second-priority security interest in certain assets of ours related to selinexor, which shares such second priority with the 2029 Notes and which is subordinated to the first-priority security interest securing the Term Loan.

Subject to an intercreditor agreement with KKR, the Term Loan lenders and the holders of the 2029 Notes (the “Intercreditor Agreement”), in the event that an uncured default by us under the Amended Revenue Interest Agreement results in an acceleration of obligations by KKR which we are unable to pay, KKR will have the right to foreclose on the collateral that was pledged to KKR.

Any such foreclosure remedy would significantly and adversely affect us and could result in us losing our interest in such assets, which would have a material adverse impact on our business.

Our Credit Agreement and indenture governing the 2029 Notes contain various covenants and other provisions, which will limit the manner in which we may operate, and, if violated, could, subject to the 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 May 2024 credit and guaranty agreement (the “Credit Agreement”) and the indenture governing the 2029 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 Credit Agreement and the indenture governing the 2029 Notes each have a financial covenant requiring us to maintain liquidity of at least $25.0 million at all times.

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.

The Credit Agreement and the indenture governing the 2029 Notes also contain certain events of default, after which the Term Loan or the 2029 Notes may be due and payable immediately, including, without limitation, withdrawal of approval for selinexor with respect to its current approved indication for use with bortezomib and dexamethasone, payment defaults, material inaccuracy of representations and warranties, covenant defaults, bankruptcy and insolvency proceedings, cross-defaults to certain other agreements, judgments against us and our subsidiaries, change in control and lien priority.

Our obligations under the Credit Agreement and the indenture governing the 2029 Notes are secured by substantially all of our assets.

Subject to the Intercreditor Agreement, in the event that an uncured default by us under the Credit Agreement or the indenture governing the 2029 Notes results in an acceleration of obligations thereunder, the Term Loan lenders and the holders of the 2029 Notes will have the right to foreclose on the collateral that was pledged to each such party.

Any such foreclosure remedy would significantly and adversely affect us and could result in us losing our interest in such assets, which would have a material adverse impact on our business.

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 Term Loan, the 2029 Notes, the 2025 Notes or the Amended Revenue Interest Agreement.

As of June 30, 2025, we have indebtedness of $356.7 million in aggregate principal amount.

We have incurred (i) $172.5 million of indebtedness as a result of the sale of the 2025 Notes, of which approximately $24.5 million remained outstanding following completion of the May 2024 exchange of certain of our 2025 Notes for 2029 Notes (the “Exchange Transactions”);

(ii) $263.3 million of indebtedness under the Amended Revenue Interest Agreement, of which $147.1 million was repaid after giving effect to the May 2024 amendment to the Amended Revenue Interest Agreement, resulting in a remaining maximum aggregate repayment amount to KKR (as successor in interest to HCRx) of $116.2 million, (iii) $100.0 million of indebtedness under the Term Loan, and (iv) approximately $116.0 million of indebtedness as a result of the issuance of the 2029 Notes pursuant to the Exchange Transactions.

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

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;

• limiting our ability to obtain additional financing;

• requiring the dedication of a substantial portion of our cash flow from operations to service our indebtedness, which would reduce the amount of cash available for other purposes;

• 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 2025 Notes, which are scheduled to mature on October 15, 2025, or the 2029 Notes;

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

Our ability to pay the principal of or interest or other obligations on our present and any future indebtedness, including our remaining obligations to KKR and under the Credit Agreement, the 2029 Notes and the 2025 Notes, or to make cash payments in connection with any conversion of the 2029 Notes or the 2025 Notes, depends on our future performance and ability to raise additional funds, which is subject, in part, to economic, financial, competitive and other factors beyond our control.

Our business may not generate cash flow from operations in the future sufficient to service the Term Loan, the Amended Revenue Interest Agreement, the 2029 Notes, the 2025 Notes or any other future indebtedness and make necessary capital expenditures.

We may not have the ability to raise the funds necessary to settle any conversions of or other obligations in respect of the 2029 Notes or the 2025 Notes required to be settled in cash, to repay the 2029 Notes or the 2025 Notes at maturity, to repurchase the 2029 Notes or the 2025 Notes for cash upon a fundamental change, to pay the redemption price for any 2029 Notes or 2025 Notes we redeem or to refinance the 2029 Notes or the 2025 Notes, and any future debt we incur may contain limitations on our ability to pay cash upon conversion or repurchase of the 2029 Notes or the 2025 Notes.

If we do not have enough available cash at the time we are required to repurchase the 2029 Notes or the 2025 Notes, pay cash amounts due upon conversion or redemption of, at maturity or otherwise required to be paid in respect of the 2029 Notes or the 2025 Notes or refinance the 2029 Notes or the 2025 Notes, we may be required to adopt one or more alternatives, such as selling assets, restructuring indebtedness or obtaining additional debt financing or equity capital on terms that may be onerous or highly dilutive.

Our ability to refinance the 2029 Notes or the 2025 Notes or other future indebtedness will depend on the capital markets, our financial condition at such time and our obligations under any other existing indebtedness in effect at such time.

We may not be able to engage in any of these activities on desirable terms, or at all, which could result in a default on our debt obligations, including the 2029 Notes and the 2025 Notes.

In addition, our ability to repurchase the 2029 Notes or the 2025 Notes, to pay cash upon conversion or redemption or at maturity of the 2029 Notes or the 2025 Notes or to refinance the 2029 Notes or the 2025 Notes may be limited by law, regulatory authority or agreements governing any future indebtedness that we may incur.

Our failure to repurchase the 2029 Notes or the 2025 Notes at a time when the repurchase is required by the applicable indenture governing such notes or to pay cash upon conversion or at maturity of or in respect of other obligations under the 2029 Notes or the 2025 Notes as required by the applicable indenture governing such notes would constitute a default under such indenture.

Note holders may require us to repurchase their 2029 Notes or 2025 Notes following a fundamental change at a cash repurchase price generally equal to the principal amount of the 2029 Notes or the 2025 Notes to be repurchased, plus accrued and unpaid interest.

As discussed under the risk factor entitled “ If we fail to maintain compliance with the continued listing requirements of Nasdaq, our common stock could be delisted from trading, which would adversely affect the liquidity of our common stock and our ability to raise additional capital.

”, the transfer of the listing of our common stock to the Nasdaq Capital Market would constitute a fundamental change under the indenture governing the 2025 Notes, which could negatively impact our financial condition if the note holders required us to repurchase their notes upon such fundamental change.

The 2025 Notes are scheduled to mature on October 15, 2025.

The current conversion price of the 2025 Notes is approximately $237.82 per share of common stock, which is significantly above the current trading price of our common stock, and as a result, we do not expect that any holders will convert their notes at or prior to maturity.

Unless the 2025 Notes are repurchased or we are able to complete a transaction that retires or refinances these notes or extends their maturity, we will be required to pay the outstanding principal amount of these notes in cash at maturity, which as of June 30, 2025 was $24.5 million.

We cannot assure you that we will have the necessary cash on hand or access to other sources of funds that will allow us to repay or refinance the 2025 Notes at maturity;

unless we obtain additional funding or are able to consummate a transaction to refinance or pay off our indebtedness, we will not be able to remain compliant with the terms of such indebtedness.

A default under the indenture governing the 2029 Notes or the 2025 Notes or the fundamental change itself could also lead to a default under the Credit Agreement, the Amended Revenue Interest Agreement or agreements governing our future indebtedness, if any.

Moreover, the occurrence of a fundamental change under the indenture governing the 2029 Notes or the 2025 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 2029 Notes or the 2025 Notes or to pay cash upon conversion or at maturity of the 2029 Notes or the 2025 Notes.

The accounting method for convertible debt securities such as the 2025 Notes and the 2029 Notes could have a material effect on our reported financial results.

Conversions of the 2025 Notes may be settled in cash or shares, or a combination of cash and shares.

Conversions of the 2029 Notes may only be settled in shares (subject to, and in accordance with, the settlement provisions of the indenture governing the 2029 Notes), plus cash in lieu of any fractional shares.

Under the if-converted method, the maximum potential dilutive impact of the conversion of the 2025 Notes or the 2029 Notes is assumed when calculating diluted earnings per share during periods of net income.

This could result in a material impact to diluted earnings per share.

Diluted earnings per share is not impacted by the 2025 Notes or the 2029 Notes during periods of net loss.

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 Credit Agreement and the indenture governing the 2029 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.

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 transaction we completed in 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.

Risks Related to Commercialization and Product Development

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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 2 lines of systemic therapy.

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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In addition, new competitors and label expansions into earlier lines of existing therapies could also be approved in the future (e.g.

belantamab mafodotin and linvoseltamab), which could negatively impact our product revenues.

belantamab mafodotin), 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.

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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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• 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;

• strategic revisions to clinical trial designs, including a change in primary endpoints or the total number of patients targeted for enrollment, which could negatively impact our ability to submit and/or receive regulatory approval for the indication sought;

for example, in 2024 we decreased the number of total patients to be enrolled in the ongoing Phase 3 trial evaluating selinexor in combination with pomalidomide and dexamethasone versus elotuzumab, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma;

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• the number of patients required for clinical trials of our product candidates may be larger than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate, which can increase the cost of our trials, extend clinical trial timelines and provide competitors with additional time to seek regulatory approval for their products prior to the finalization of our trials;

• our third-party contractors, including manufacturers or CROs, may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all;

• we or our investigators might be found to be non-compliant with regulatory requirements;

• we, our investigators, or our third-party contractors, including manufacturers or CROs, may fail to comply with regulatory requirements, which include requirements related to the implementation of clinical trials, such as requirements for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial, perform effectively, or meet their contractual obligations to us in a timely manner, or at all;

• the cost of clinical trials of our product candidates may be greater than we anticipate;

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In addition, if we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted.

For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act (“FDORA”), Congress required sponsors to develop and submit a Diversity Action Plan (“DAP”) for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

For example, in December 2022, with the

passage of Food and Drug Omnibus Reform Act (“FDORA”), Congress required sponsors to develop and submit a Diversity Action Plan (“DAP”) for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

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Serious AEs generally refer to AEs that result in death, are life threatening, require hospitalization or prolonging of hospitalization, or cause a significant and permanent disruption of normal life functions, congenital anomalies or birth defects, or require intervention to prevent such an outcome.

The occurrence of AEs in either our clinical trials or following regulatory approval could result in a more restrictive label for any product candidates approved for marketing or could result in the delay or denial of approval to market any product candidates by the FDA or comparable foreign regulatory authorities, which could prevent us from generating sufficient revenue from product sales

or ultimately achieving profitability.

Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial, result in potential product liability claims or cause patients and/or healthcare providers to elect alternative courses of treatment.

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In such an event, our trials could be suspended or terminated by us or the FDA or comparable foreign regulatory authorities could order us or our collaborators to cease further development of or deny approval of our product candidates for any or all targeted indications.

Many compounds that initially showed promise in early-stage trials for treating cancer or other diseases have later been found to cause side effects that prevented further development of the compound.

Many compounds that initially showed promise in early-stage trials for treating cancer or other diseases have later been found to cause side effects that prevented

further development of the compound.

If such an event occurs after any of our or our collaborators’ product candidates are approved and/or commercialized, a number of potentially significant negative consequences may result, including:

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We are working with existing and potential partners to establish the commercial infrastructure to support the sale of selinexor outside of the U.S.

For example, we entered into a license agreement with the Menarini Group (“Menarini”) in December 2021, and as amended in March 2023, to, among other things, develop and commercialize NEXPOVIO ® for all human oncology indications in Europe (including the United Kingdom (“UK”)), Latin America, certain Middle East and Africa regions and other key countries.

For example, we entered into a license agreement with Menarini in December 2021, and as amended in March 2023, to, among other things, develop and commercialize NEXPOVIO ® for all human oncology indications in Europe (including the United Kingdom (“UK”)), Latin America, certain Middle East and Africa regions and other key countries.

For additional risks associated with commercializing our products outside of the U.S., please see the risk factor entitled “ We depend on collaborations with third parties for certain aspects of the development, marketing and/or commercialization of XPOVIO and/or our product candidates.

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Accordingly, we cannot be sure that reimbursement will be or will continue to be available for XPOVIO and any product that we, or our collaborators, commercialize and, if reimbursement is available, we cannot be sure as to the level of reimbursement and whether it will be adequate.

reimbursement may impact the demand for or the price of XPOVIO or any product candidate for which we, or our collaborators, obtain marketing approval.

Coverage and reimbursement may impact the demand for or the price of XPOVIO or any product candidate for which we, or our collaborators, obtain marketing approval.

If reimbursement is not available or is available only at limited levels, we, or our collaborators, may not be able to successfully commercialize XPOVIO or any other approved products.

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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.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S.

Net prices for drugs may be reduced by mandatory discounts or rebates required by government

healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the U.S.

Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies.

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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).

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 intend to submit to 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.

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and the EU and thus the attendant risks and uncertainties.

In addition, we could be adversely affected by several significant administrative law cases decided by the U.S.

Supreme Court in 2024.

In Loper Bright Enterprises v.

Raimondo, for example, the court overruled Chevron U.S.A., Inc.

Natural Resources Defense Council, Inc., which for 40 years required federal courts to defer to permissible agency interpretations of statutes that are silent or ambiguous on a particular topic.

Supreme Court stripped federal agencies of this presumptive deference and held that courts must exercise their independent judgment when deciding whether an agency such as the FDA acted within its statutory authority under the Administrative Procedure Act (the “APA”).

Additionally, in Corner Post, Inc.

Board of Governors of the Federal Reserve System, the court held that actions to challenge a federal regulation under the APA can be initiated within six years of the date of injury to the plaintiff, rather than the date the rule is finalized.

The decision appears to give prospective plaintiffs a personal statute of limitations to challenge longstanding agency regulations.

Another decision, Securities and Exchange Commission v.

Jarkesy, overturned regulatory agencies’ ability to impose civil penalties in administrative proceedings.

These decisions could introduce additional uncertainty into the regulatory process and may result in additional legal challenges to actions taken by federal regulatory agencies, including the FDA and the Centers for Medicare & Medicaid Services (“CMS”), that we rely on.

In addition to potential changes to regulations as a result of legal challenges, these decisions may result in increased regulatory uncertainty and delays and other impacts, any of which could adversely impact our business and operations.

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.

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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:

• 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.

standard of care;

• 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;

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• regulatory authorities may change their approval policies or adopt new regulations;

• regulatory authorities may not be able to undertake reviews, applicable inspections or approval processes in a timely manner including as the result of the implementation of policies by the current Trump administration that may affect the

FDA review process, such as efforts to downsize the U.S.

federal workforce, remove job elimination protections for U.S.

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• the results of our earlier clinical trials may not be representative of our future, larger trials;

• regulatory authorities may not agree with our or our collaborators’ regulatory approval strategies or components of our or their regulatory filings, such as the design or implementation of the relevant clinical trials;

compared to U.S.

patients or the demographics of the population;

for example, the FDA identified multiple risks related to our decision to decrease the total number of patients to be enrolled in our ongoing Phase 3 multiple myeloma trial, including the ability to adequately assess benefit-risk with a limited number of patients;

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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.

reasonably likely to predict clinical benefit.

The FDA considers a clinical benefit to be a positive therapeutic effect that is clinically meaningful in the context of a given disease, such as irreversible morbidity or mortality.

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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.

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.

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

In September 2021, the FDA published final regulations which describe the types of evidence that the agency will consider in determining the intended use of a drug or biologic.

Moreover, with passage of the Pre-Approval Information Exchange Act in December 2022, sponsors of products that have not been approved may proactively communicate to payors certain information about products in development to help expedite patient access upon product approval.

In addition, in January 2025, the FDA published final guidance outlining the agency’s non-binding policies governing the distribution of scientific information on unapproved uses to healthcare providers.

This final guidance calls for such communications to be truthful, non-misleading, factual, and unbiased and include all information necessary for healthcare providers to interpret the strengths and weaknesses and validity and utility of the information about the unapproved use.

If a company engages in such communications consistent with the guidance’s recommendations, the FDA indicated that it will not treat such communications as evidence of unlawful promotion of a new intended use for the approved product.

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.

Promotion of prescription products is currently an area of government scrutiny, and the applicable statutes, regulations and guidance and policies are complex, subject to changing interpretation, and subject to amendment.

For example, new FDA regulations and guidance have been issued in recent years, current Department of Health and Human Services (“HHS”) and FDA officials have expressed interest in new restrictions on direct-to-consumer (“DTC”) advertising, and bills have been introduced in Congress related to disclosure of price information in DTC advertisements, restrictions on DTC advertising, promotion by social media influencers and telehealth companies, and tax deductions available for DTC promotion expenses.

In addition, manufacturers of approved products and those manufacturers’ facilities are required to comply with extensive requirements by the FDA and comparable foreign regulatory authorities, including ensuring that quality control and manufacturing procedures conform to current Good Manufacturing Practice (“cGMP”), which include requirements relating to quality control and quality assurance as well as the corresponding maintenance of records and documentation and reporting requirements.

contract manufacturers, our collaborators and their contract manufacturers could be subject to periodic unannounced inspections by the FDA or foreign regulatory authorities to monitor and ensure compliance with cGMPs or other regulations.

We, our contract manufacturers, our collaborators and their contract manufacturers could be subject to periodic unannounced inspections by the FDA or foreign regulatory authorities to monitor and ensure compliance with cGMPs or other regulations.

Post-approval discovery of previously unknown problems with our products, including AEs of unanticipated severity or frequency, or relating to our manufacturing processes, data integrity issues with regulatory filings, or failure to comply with regulatory requirements, may yield various results, including:

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Accordingly, in connection with our currently approved products and assuming we, or our collaborators, receive marketing approval for one or more of our product candidates, we, and our collaborators, and our and their contract manufacturers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.

If we, and our collaborators, are not able to comply with post-approval regulatory requirements, our or our

collaborators’ ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability.

If we, and our collaborators, are not able to comply with post-approval regulatory requirements, our or our collaborators’ ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability.

Further, the cost of compliance with post-approval regulations may have a negative effect on our operating results and financial condition.

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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.

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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If we enter into such collaborative agreements, we will be dependent on the sustained cooperation and effort of our future collaborators in developing and obtaining clearance or approval for these companion diagnostics.

It may be necessary to

resolve issues such as selectivity/specificity, analytical validation, reproducibility, or clinical validation of companion diagnostics during the development and regulatory clearance or approval processes.

It may be necessary to resolve issues such as selectivity/specificity, analytical validation, reproducibility, or clinical validation of companion diagnostics during the development and regulatory clearance or approval processes.

Moreover, even if data from preclinical studies and early clinical trials appear to support development of a companion diagnostic for a product candidate, data generated in later clinical trials may fail to support the analytical and clinical validation of the companion diagnostic.

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The program focuses on medicines that target conditions for which there exists no satisfactory method of treatment in the EU or even if such a method exists, it may offer a major therapeutic advantage over existing treatments.

PRIME is limited to

medicines under development and not authorized in the EU and the sponsor intends to apply for an initial MAA through the centralized procedure.

PRIME is limited to medicines under development and not authorized in the EU and the sponsor intends to apply for an initial MAA through the centralized procedure.

To be accepted for PRIME, a product candidate must meet the eligibility criteria with respect to its major public health interest and therapeutic innovation based on information that is capable of substantiating the claims.

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In addition, even after an orphan drug is approved, the FDA and comparable foreign regulatory authorities, such as the EMA, can subsequently approve the same product for the same condition if the FDA or such other authorities conclude that the later product is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.

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.

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”).

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Depending on what changes the FDA or Congress may make to orphan drug regulations and policies, our business could be adversely impacted.

Disruptions at the FDA and other government agencies from funding cuts, personnel losses, regulatory reform, government shutdowns and other developments could hinder our ability to obtain guidance from the FDA regarding our clinical development program and develop and secure approval of our product candidates in a timely manner, which would negatively impact our business.

The FDA and comparable regulatory agencies in foreign jurisdictions, such as the EMA and CHMP, play an important role in the development of our product candidates by providing guidance on our clinical development programs and reviewing our regulatory submissions, including Investigational New Drug applications (“INDs”), requests for special designations and marketing applications.

If these oversight and review activities are disrupted, then correspondingly our ability to develop and secure timely approval of our product candidates could be impacted in a negative manner.

For example, the recent loss of FDA leadership and personnel could lead to disruptions and delays in FDA guidance, review and approval of our product candidates.

Pursuant to President Trump's E.O.

14210, “Implementing the President’s ‘Department of Government Efficiency’ Workforce Optimization Initiative,” the Secretary of the Department of Health and Human Services (“HHS”) announced on March 27, 2025, a reorganization and Reduction in Force (“RIF”), across HHS of approximately 20,000 employees (82,000 to 62,000), with the FDA’s workforce to decrease by 3,500 full-time employees.

Shortly thereafter, thousands of employees at the FDA were fired on April 1, 2025.

Subsequently, there have been reports from the preliminary budget memorandum for HHS that the administration will propose an additional 30% cut in the overall budget for HHS, with a reduction of $700 million in funding at the FDA ($7.2 billion to $6.5 billion) for the 2026 federal fiscal year.

Further, while the FDA’s review of marketing applications and other activities for new drugs and biologics is largely funded through the user fee program established under the Prescription Drug User Fee Act (“PDUFA”), it remains unclear how the administration’s RIF and budget cuts will impact this program and the ability of the FDA to provide guidance and review our product candidates in a timely manner.

For example, while the FDA RIF did not reportedly specifically target FDA reviewers, many operations, administrative and policy staff that help support such reviews were affected and those losses could lead to delays in PDUFA reviews and related activities.

In addition, while currently unclear, there is a risk that the RIF and budget cutbacks could threaten the integrity of the PDUFA program itself.

That is because, for the FDA to obligate user fees collected under PDUFA in the first place, a certain amount of non-user fee appropriations must be spent on the process for the review of applications plus certain other costs during the same fiscal year.

There is also substantial uncertainty as to how regulatory reform measures being implemented by the Trump Administration across the government will impact the FDA and other federal agencies with jurisdiction over our activities.

For example, since taking office, the President has issued a number of executive orders that could have a significant impact on the manner in which the FDA conducts its operations and engages in regulatory and oversight activities.

These include E.O.

14192, “Unleashing Prosperity Through Deregulation,” January 31, 2025;

14212, “Establishing the President’s Make America Healthy Again Commission,” February 13, 2025;

14219, Ensuring Lawful Governance and Implementing the President’s ‘Department of Government Efficiency” Deregulatory Initiative,” February 21, 2025.

If these or other orders or executive actions impose constraints on the FDA’s ability to engage in oversight and implementation activities in the normal course, our business may be negatively impacted.

Similarly, actions by the U.S.

government have significantly disrupted the operations of U.S.

government agencies such as the National Institutes of Health, National Science Foundation, Centers for Disease Control and Prevention, and FDA, which have traditionally provided funding for basic research, research and development, and clinical testing.

government actions have included, among other things, suspending, terminating and withholding of disbursements of funds owed under ongoing contracts, grants, and other financial assistance agreements;

declining to continue multi-year research projects for additional annual budget periods;

canceling or delaying solicitations for new contracts, grants and other financial assistance awards;

canceling or delaying proposal evaluation processes and issuance of such new awards;

substantially reducing federal agency staff responsible for managing contract and financial assistance programs;

eliminating agency information and resources for facilitating research activity;

delaying or terminating federal agency procedures for authorizing international transactions;

initiating aggressive enforcement actions that may disrupt the operations of major research universities that are significant contributors to life sciences research in the U.S., and threatening access to federal agency contracts and other funding awards based on companies’ otherwise lawful corporate policies and choice of counsel.

government actions could, directly or indirectly, significantly disrupt, delay, prevent, or increase the costs of our research and product commercialization programs, including our ability to develop new product candidates, conduct clinical trials, implement research collaborations with other companies or institutions, and obtain approvals to market and sell new products.

In addition, government funding of the SEC and other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable.

For example, over the last several years, the U.S.

government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical activities.

If a prolonged

government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions and could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

At the same time, disruptions at the FDA and other government agencies may result from public health events similar to the COVID-19 pandemic.

For example, during the pandemic, a number of companies announced receipt of complete response letters due to the FDA’s inability to complete required inspections for their applications.

In the event of a similar public health emergency in the future, the FDA may not be able to continue its current pace and review timelines could be extended.

Regulatory authorities outside the U.S.

facing similar circumstances may adopt similar restrictions or other policy measures in response to a similar public health emergency and may also experience delays in their regulatory activities.

Accordingly, if any of the foregoing developments and others impact the ability of the FDA to provide us with guidance regarding our clinical development programs or delay the agency’s review and processing of our regulatory submissions, including INDs and NDAs and biologics license applications, our business would be negatively impacted.

Further, any future government shutdown could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations.

Current and future legislation may increase the difficulty and cost for us, or any collaborators, to obtain marketing approval and commercialize our or their product candidates, if approved, and affect the prices we, or they, may obtain.

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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.

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.

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The Regulation intends to boost cooperation among EU member states in assessing health technologies, including new medicinal products as well as certain high-risk medical devices, and provide the basis for cooperation at the EU level for joint clinical assessments in these areas.

It will permit EU member

states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

It will permit EU member states to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the highest potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

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.

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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, CMS issued a final rule to rescind it.

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.

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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 or for taking price increases that exceed inflation.

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

increases exceed inflation.

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.

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This may be increasingly true with respect to products approved pursuant to the accelerated approval pathway.

State Medicaid programs and other payers are developing

strategies and implementing significant coverage barriers, or refusing to cover these products outright, arguing that accelerated approval drugs have insufficient or limited evidence despite meeting the FDA’s standards for accelerated approval.

State Medicaid programs and other payers are developing strategies and implementing significant coverage barriers, or refusing to cover these products outright, arguing that accelerated approval drugs have insufficient or limited evidence despite meeting the FDA’s standards for accelerated approval.

Finally, outside of the U.S., in some nations, including those of the EU, the pricing of prescription pharmaceuticals is subject to governmental control and access.

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• 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;

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.

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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.

This results in us having to carry a liability on our consolidated balance sheets for the estimate of rebate claims expected for Medicaid patients.

This results in us having to carry a liability on our consolidated

balance sheets for the estimate of rebate claims expected for Medicaid patients.

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

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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.

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.

Failure to make necessary disclosures and/or to identify contract overcharges can result in allegations against us under the FCA and other laws and regulations.

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We will need to account for the FTC’s evolving rules and guidance for proper privacy and data security practices in order to mitigate risk for a potential enforcement action, which may be costly.

Finally, both the FTC and HHS’s enforcement priorities (as well as those of other federal regulators) may be impacted by the change in administration and new leadership.

Finally, both the FTC and HHS’s enforcement priorities (as well as those of

other federal regulators) may be impacted by the change in administration and new leadership.

These shifts in enforcement priorities may also impact our business.

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companies who self-certify to the EU-U.S.

Data Privacy Framework to rely on it as a valid data transfer

mechanism for data transfers from the EU to the U.S.

Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S.

However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S.

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We are also exposed to risks in connection with any insider trading violations by employees or others affiliated with us.

It is not always possible to identify and deter employee or third-party misconduct, and the precautions we take to detect and prevent these activities may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from significant penalties, governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards, regulations, guidance or codes of conduct.

It is not always possible to identify and

deter employee or third-party misconduct, and the precautions we take to detect and prevent these activities may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from significant penalties, governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws, standards, regulations, guidance or codes of conduct.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions.

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We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes.

Our operations involve the use of

hazardous and flammable materials, including chemicals and biological and radioactive materials.

Our operations involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials.

Our operations and the operations of our third-party vendors also produce hazardous waste products.

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For the purposes of the statute, the term “commercially reasonable, market-based terms” is defined as (1) the nondiscriminatory price at or below the most recent wholesale acquisition cost for the product, (2) a delivery schedule that meets the statutorily defined timetable, and (3) no additional conditions on the sale.

Although we intend to comply fully with the terms of these statutory provisions, we are still exposed to potential 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 ANDAs and 505(b)(2) applications.

In June 2025, we received three requests for drug product under the CREATES Act.

We have responded to such requests and we believe our responses are in compliance with the CREATES Act.

Although we have and intend to comply fully with the terms of these statutory provisions, we are still exposed to potential 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 ANDAs and 505(b)(2) applications.

Such litigation would subject us to additional litigation costs, damages and reputational harm, which could lead to lower revenues.

The CREATES Act may enable generic competition with XPOVIO and any of our product candidates, if approved, which could impact our ability to maximize product revenue.

In September 2022, the FDA issued draft guidance outlining certain of the provisions under this statute.

We are subject to governmental export and import controls that could impair our or our collaborators ’ ability to compete in international markets due to licensing requirements and subject us or them to liability if we or they are not in compliance with applicable laws.

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and, in extreme cases, the incarceration of responsible employees or managers.

In addition, changes in our products or changes in applicable export or import laws and regulations may create delays in the introduction, provision, or sale of our products in international markets, prevent customers from using our products or, in some cases, prevent the export or import of our products to certain countries, governments or persons altogether.

prevent the export or import of our products to certain countries, governments or persons altogether.

Any limitation on our ability to export, provide, or sell our products could adversely affect our business, financial condition and results of operations.

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trading partners effective April 5, 2025, and higher individualized reciprocal tariffs on 57 countries (with certain product exemptions for pharmaceutical-related products, among others).

Previously, the administration had imposed a 25% tariff on Canada and Mexico for goods not covered by the United States-Mexico-Canada Agreement (“USMCA”) and tariffs equaling 20% on China.

The administration has also imposed a 25% tariff on products of Canada and Mexico that are not covered by the United States-Mexico-Canada Agreement (“USMCA”), in addition to an additional 20% tariff on products of China.

In response, several countries threatened retaliatory measures, including Canada and China, which then imposed retaliatory tariffs.

Prior to when the country-specific reciprocal tariffs were scheduled to take effect, the administration delayed the effective date of such tariffs for all countries except China.

baseline reciprocal tariff on all countries remains in effect, in addition to the tariffs on China (which were a minimum of 145% as of May 7, 2025) and Canada and Mexico (which were 25% as of May 7, 2025 for goods that are not covered by the USMCA).

The 10% baseline reciprocal tariff on all countries remains in effect, in addition to the tariffs on China (which, at one point, increased to a minimum of 145% but are at 20% as of August 6, 2025) and Canada and Mexico (which were 25% as of August 6, 2025 for goods that are not covered by the USMCA).

Sustained uncertainty about, or the further escalation of, trade and political tensions between the U.S.

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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.

“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.

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government contract, grant and loan funding.

We anticipate these bills will be reintroduced during the 119th Congress but, as of February 20, 2025, they have not been introduced in either chamber.

We anticipate these bills will be reintroduced during the 119th Congress but, as of June 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.

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 WuXi.

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 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 WuXi.

If any new tariffs, export controls, legislation and/or regulations are implemented, or if existing trade agreements are renegotiated or, in particular, if either the U.S.

or Chinese government takes retaliatory trade actions due to the recent trade tension, such changes could have an adverse effect on our business, financial condition and results of operations.

Risks Related to Our Financial Position and Capital Requirements

Our financial condition raises substantial doubt as to our ability to continue as a going concern.

We have incurred significant operating losses since our inception.

As of March 31, 2025, we had approximately $69.9 million in cash, cash equivalents and investments and an accumulated deficit of $1.6 billion.

We expect these available cash resources to fund our existing operations into early fourth quarter of 2025.

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

We anticipate that we will continue to incur significant operating losses as we maintain our research and development programs, including as we continue to develop and seek regulatory approval of selinexor for multiple cancer indications, and to support our continued operations.

As a result, our continued operations are dependent on our ability to raise additional funding and marketing XPOVIO in its currently approved indications.

Based on our current business plan and current capital resources, combined with the uncertainty regarding the availability of additional funding and considering our debt obligations, including the October 15, 2025 maturity date of our 3.00% convertible senior notes due 2025 (the “2025 Notes”) and a requirement under our other indebtedness to maintain cash, cash equivalents and investments of at least $25.0 million at all times, 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.

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

We may also be required to reduce our current spending requirements where possible.

If we utilize our capital resources more quickly than anticipated or are unable to obtain additional funding, 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.

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 be required 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 investment.

If we seek additional financing to fund our business activities in the future and 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.

We have incurred significant losses since inception, expect to continue to incur significant losses, and may never achieve or maintain profitability.

Since inception, we have incurred significant operating losses.

Our net loss was $23.5 million for the three months ended March 31, 2025.

As of March 31, 2025, we had an accumulated deficit of $1.6 billion.

Although we received our first FDA-approval for XPOVIO in July 2019, we may never attain profitability or positive cash flows from operations.

We expect to continue to incur significant expenses and operating losses as we continue to commercialize XPOVIO in the U.S.

and engage in activities to prepare for the potential approval and commercialization of additional indications for selinexor as well as any other product candidates we develop or acquire.

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

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:

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

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

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

• manufacturing at commercial scale;

• obtaining, maintaining and protecting our intellectual property rights;

• 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;

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

• maintain, expand and protect our intellectual property portfolio;

• manufacture XPOVIO and our product candidates;

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

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

Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.

A decline in the value of our company could also cause our stockholders to lose all or part of their investment.

We will need additional funding to achieve our business objectives.

If we are unable to raise capital when needed or on acceptable terms, we would be forced to delay, reduce or eliminate our research and development programs and/or commercialization efforts.

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

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

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

As of March 31, 2025, we believe that our existing cash, cash equivalents and investments will enable us to fund our current operating plans and debt obligation requirements into early fourth quarter of 2025.

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

• the scope, progress, results, timing and costs of our current and planned development efforts and regulatory review of our product candidates;

• the amount and timing of revenues from sales of XPOVIO, or any product candidate that we develop or acquire;

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

• our ability to continue as a going concern.

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.

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.

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 may not be available to us on acceptable terms, or at all.

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

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.

Our Amended Revenue Interest Agreement with HCRx contains various covenants and other provisions, which, if violated, could, subject to the 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.

Upon the occurrence of an event of default and in the event of a change of control, HCRx may accelerate payments due under the Amended Revenue Interest Agreement up to $128.3 million, less the aggregate amount of all of the payments paid to HCRx after the date of the May 2024 amendment.

Our obligations to HCRx are secured by a second-priority security interest in certain assets of ours related to selinexor, which shares such second priority with the 2029 Notes and which is subordinated to the first-priority security interest securing the Term Loan.

Subject to an intercreditor agreement with HCRx, the Term Loan lenders and the holders of the 2029 Notes (the “Intercreditor Agreement”), in the event that an uncured default by us under the Amended Revenue Interest Agreement results in an acceleration of obligations by HCRx which we are unable to pay, HCRx will have the right to foreclose on the collateral that was pledged to HCRx.

Any such foreclosure remedy would significantly and adversely affect us and could result in us losing our interest in such assets, which would have a material adverse impact on our business.

In addition, the Credit Agreement and the indenture governing the 2029 Notes each have a financial covenant requiring us to maintain liquidity of at least $25.0 million at all times.

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.

Our obligations under the Credit Agreement and the indenture governing the 2029 Notes are secured by substantially all of our assets.

Any such foreclosure remedy would significantly and adversely affect us and could result in us losing our interest in such assets, which would have a material adverse impact on our business.

(ii) $263.3 million of indebtedness under the Amended Revenue Interest Agreement, of which $135.0 million was repaid after giving effect to the May 2024 amendment to the Amended Revenue Interest Agreement, resulting in a remaining maximum aggregate repayment amount to HCRx of $128.3 million, (iii) $100.0 million of indebtedness under the Term Loan, and (iv) approximately $111.0 million of indebtedness as a result of the issuance of the 2029 Notes pursuant to the Exchange Transactions.

We may also incur additional indebtedness to meet future financing needs, to the extent such indebtedness is available

and permitted.

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;

• limiting our ability to obtain additional financing;

• requiring the dedication of a substantial portion of our cash flow from operations to service our indebtedness, which would reduce the amount of cash available for other purposes;

• 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 2029 Notes or the 2025 Notes;

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

Our ability to pay the principal of or interest or other obligations on our present and any future indebtedness, including our remaining obligations to HCRx and under the Credit Agreement, the 2029 Notes and the 2025 Notes, or to make cash payments in connection with any conversion of the 2029 Notes or the 2025 Notes, depends on our future performance, which is subject, in part, to economic, financial, competitive and other factors beyond our control.

Holders may require us to repurchase their 2029 Notes or 2025 Notes following a fundamental change at a cash repurchase price generally equal to the principal amount of the 2029 Notes or the 2025 Notes to be repurchased, plus accrued and unpaid interest.

As discussed in more detail below under the risk factor entitled “ If we fail to maintain compliance with the continued listing requirements of Nasdaq, our common stock could be delisted from trading, which would adversely affect the liquidity of our common stock and our ability to raise additional capital.

In addition, with respect to the 2025 Notes, unless we elect to deliver solely shares of our common stock to settle conversions (other than paying cash in lieu of delivering any fractional share), we must satisfy any conversion in cash.

The 2025 Notes are scheduled to mature on October 15, 2025.

The current conversion price of the 2025 Notes is approximately $237.82 per share of common stock, which is significantly above the current trading price of our common stock.

Unless the 2025 Notes are converted or repurchased or we are able to engage in a transaction that retires or refinances these notes or extends their maturity, we will be required to pay the outstanding principal amount of these notes in cash at maturity.

We cannot assure you that we will have the necessary cash on hand or access to other sources of funds that will allow us to repay or refinance the 2025 Notes if we are required to do so.

We may not be able to engage in any of these activities on desirable terms, or at all, which could result in a default on our debt obligations, including the 2029 Notes and the 2025 Notes.

Moreover, the occurrence of a

fundamental change under the indenture governing the 2029 Notes or the 2025 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 2029 Notes or the 2025 Notes or to pay cash upon conversion or at maturity of the 2029 Notes or the 2025 Notes.

The conditional conversion feature of the 2025 Notes, if triggered, may adversely affect our financial condition and operating results.

In the event the conditional conversion feature of the 2025 Notes is triggered, holders of the 2025 Notes will be entitled to convert the 2025 Notes at any time during specified periods at their option.

If one or more holders elects to convert their 2025 Notes, unless we elect to satisfy our conversion obligation by delivering solely shares of our common stock (other than paying cash in lieu of delivering any fractional share), we would be required to settle a portion or all of our conversion obligation in cash, which could adversely affect our liquidity.

In addition, even if holders do not elect to convert their 2025 Notes, we could be required under applicable accounting rules to reclassify all or a portion of the outstanding principal amount of the 2025 Notes as a current rather than long-term liability, which would result in a material reduction of our net working capital.

The accounting method for convertible debt securities such as the 2025 Notes and the 2029 Notes could have a material effect on our reported financial results.

Conversions of the 2025 Notes may be settled in cash or shares, or a combination of cash and shares.

This could result in a material impact to diluted earnings per share.

Diluted earnings per share is not impacted by the 2025 Notes or the 2029 Notes during periods of net loss.

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.

We do not have any committed external source of funds.

For example, during the terms of the Amended Revenue Interest Agreement, the Credit Agreement and the indenture governing the 2029 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 HCRx, the required lenders or the required holders, respectively, subject to the exceptions and other provisions under the applicable governing document.

If we are unable to raise additional funds through equity or debt financings when needed, 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.

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.

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.

If the equity and credit markets deteriorate, it may make any necessary equity or debt financing more difficult to secure, more costly or more dilutive.

Failure to secure any necessary financing in a timely manner and on favorable terms could harm our growth strategy, financial performance and stock price and could require us to delay or abandon plans with respect to our business, including clinical development plans.

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

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.

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.

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.

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.

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

Risks Related to Our Dependence on Third Parties

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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.

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.

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If we elect to increase our expenditures to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms, or at all.

If we do not have sufficient funds or expertise to undertake the necessary development

and commercialization activities, we may not be able to further develop our product candidates or bring them to market and generate product revenue.

If we do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop our product candidates or bring them to market and generate product revenue.

Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements, and our collaboration agreements may not lead to the development or commercialization of our products or product candidates in the most efficient manner, or at all, and may result in lower product revenues or profitability to us than if we were to market and sell these products ourselves.

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• collaborators may pursue a clinical and/or regulatory strategy for registration outside of the U.S.

that would require our assistance and we may not have the resources to meet their or the regulators’ timelines and/or expectations, which could delay or limit the development, commercialization or approval of our products outside the U.S.;

• collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

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We rely on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, as we conduct our clinical trials.

We currently rely and expect to continue to rely on third parties to conduct some aspects of our research and preclinical studies.

We currently rely and expect to continue to rely on third parties to conduct some aspects of our

research and preclinical studies.

Any of these third parties may terminate their engagements with us at any time.

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Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.

approvals for our product candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our products.

If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and will not be able to, or may be delayed in our efforts to, successfully commercialize our products.

In such an event, our financial results and the commercial prospects for our products or product candidates, if approved, could be harmed, our costs could increase and our ability to generate revenues could be delayed, impaired or foreclosed.

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If these facilities are not approved for commercial manufacture or are not able to maintain approval, we may need to find alternative manufacturing facilities, which could significantly impact our ability to develop, obtain regulatory approval for or market our products or product candidates as alternative qualified manufacturing facilities may not be available on a timely or cost-efficient basis, or at all.

interruptions in supply and criminal prosecutions, any of which could significantly and adversely affect supplies of our products or product candidates and have a material adverse impact on our business, financial condition and results of operations.

Failure by any of our manufacturers to comply with applicable cGMP regulations or other regulatory requirements could result in sanctions being imposed on us or the contract manufacturer, including fines, injunctions, civil penalties, delays, suspensions or withdrawals of approvals, operating restrictions, interruptions in supply and criminal prosecutions, any of which could significantly and adversely affect supplies of our products or product candidates and have a material adverse impact on our business, financial condition and results of operations.

The clinical and commercial supplies of the drug product for XPOVIO are currently manufactured pursuant to a combination of long-term supply agreements and as-needed purchase order agreements with our third-party manufacturers.

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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 May 7, 2025, 186 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, 32 patents were in force that relate to our PAK4/NAMPT inhibitors, including three composition of matter patents for KPT-9274 in the U.S.

As of August 6, 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.

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 May 7, 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 August 6, 2025, 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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In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments and if securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock.

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.

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.

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Because both selinexor and verdinexor are protected by a single family of patents and applications, we may not be able to secure patent term extensions for both of these product candidates in all jurisdictions where these product candidates are approved.

If we are unable to obtain a patent term extension for a product or product candidate or the term of any such extension is less than we request, the period during which we can enforce our patent rights for that product or product candidate, if any, in that

jurisdiction will be shortened and our competitors may obtain approval to market competing products sooner.

As a result, our revenue could be materially reduced.

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Failure to secure those registrations could adversely affect our business.

As of May 7, 2025, we have trademark registrations in the U.S.

As of August 6, 2025, 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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must be approved by the FDA, regardless of whether we have registered it, or applied to register it, as a trademark.

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

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.

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

In addition, we rely on consultants and advisors, including scientific and clinical advisors,

to assist us in formulating our research and development and commercialization strategies.

In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategies.

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.

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.

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.

Our competitors may use these transitions or potential disruptions to gain competitive advantage over us.

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.

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While such events have not directly impacted us, similar events in the future could have a material impact on us.

If a cyber-attack or other security incident were to occur and cause interruptions in our operations, it could result in a material disruption of our development and commercialization programs and our business operations, whether due to a loss of our trade secrets or other proprietary information or other similar disruptions, in addition to possibly requiring substantial expenditures of resources to remedy.

For example, the loss of clinical trial data from completed, ongoing or planned clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.

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For additional risks associated with a fundamental change under the indenture governing the 2025 Notes, please see the risk factor entitled “ We may not have the ability to raise the funds necessary to settle any conversions of or other obligations in respect of the 2029 Notes or the 2025 Notes required to be settled in cash, to repurchase the 2029 Notes or the 2025 Notes for cash upon a fundamental change, to pay the redemption price for any 2029 Notes or 2025 Notes we redeem or to refinance the 2029 Notes or the 2025 Notes, and any future debt we incur may contain limitations on our ability to pay cash upon conversion or repurchase of the 2029 Notes or the 2025 Notes ”.

We have a substantial number of warrants to purchase common stock outstanding and may in the future issue additional warrants.

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

As of June 30, 2025, we had outstanding warrants to purchase, without regard to any beneficial ownership limitations, up to 3,704,122 shares of common stock at a weighted average exercise price of $30.04 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.

Moreover, the expectation of such exercises could encourage the short selling of our common stock, which could place further downward pressure on the trading price of our common stock.

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.

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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 $17.25 in the 52-week period ended May 7, 2025.

On May 7, 2025, the closing sale price of our common stock on the Nasdaq Global Select Market was $6.11 per share.

Our common stock price has ranged from $3.54 to $14.85 in the 52-week period ended August 6, 2025.

On August 6, 2025, the closing sale price of our common stock on the Nasdaq Global Select Market was $4.03 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, the conflicts in Ukraine and the Middle East, inflation and sustained high interest rates.

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• results, delays in, or the halting of our clinical trials or those of our competitors, including reports of AEs related to the use of our products;

• our ability to raise additional capital and/or refinance our debt and the terms on which we can raise capital and/or refinance debt;

• market assumptions regarding the feasibility of a strategic alternative;

• announcements by us or our competitors of new products or data, significant mergers, acquisitions, licenses or joint ventures;

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• developments or disputes concerning patent applications, issued patents or other proprietary rights;

• additions or departures of key personnel;

• additions or departures of key personnel or reductions in force;

• the level of expenses related to the commercialization of XPOVIO and clinical development programs for any of our product candidates;

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• 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;

• our ability to raise additional capital and/or refinance our debt and the terms on which we can raise capital and/or refinance debt;

• 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;

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Our stock price could decline significantly if we fail to meet or exceed analysts’ forecasts and expectations or if one or more of the analysts covering our business downgrade their evaluations of our stock.

Further, if one or more of these analysts cease to cover our stock, we could lose visibility in the market for our stock, which in turn could cause our stock price to decline.

one or more of these analysts cease to cover our stock, we could lose visibility in the market for our stock, which in turn could cause our stock price to decline.

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

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If we fail to meet, or if we are required to change or update any element of, our publicly disclosed financial guidance or other expectations about our business, our stock price could decline.

Further our estimates of the potential market opportunities for XPOVIO and our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which may be based on a

small sample size and fail to accurately reflect market opportunities.

While we believe that our internal assumptions are reasonable, these assumptions involve the exercise of significant judgment on the part of our management, are inherently uncertain and the reasonableness of these assumptions has not been assessed by an independent source.

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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