What changed in this filing

/stocks — the workspaceLOADING

Item 1A. Risk Factors

2026-08-13 compared with 2026-05-14 · 223 added, 203 removed, 1269 unchanged (25% of the section changed)

9 unchanged sentences

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 will require substantial funds to maintain our research and development programs, including as we continue to support our operations and develop and seek regulatory approval of selinexor in myelofibrosis or any future products or product candidates.

We have incurred significant operating losses since our inception.

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

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

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

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

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.

As of June 30, 2026, we had approximately $65.1 million in cash, cash equivalents, and investments.

We expect that our existing liquidity, including cash, cash equivalents and investments, as well as cash flow from net product revenue and license and other revenue, will enable us to fund our current operating plans into September 2026.

On September 10, 2026, a $15.8 million principal payment is due under our senior secured term loan facility;

if this payment is made without additional financing or a waiver from our lenders, we expect that (i) our cash, cash equivalents and investments will fall below our $10.0 million minimum liquidity covenant, which would trigger a default on our term loan and (ii) we will not have sufficient resources to fund our operations following such payment.

In addition to the $15.8 million principal payment due on September 10, 2026, we have approximately $10.1 million of aggregate interest payments due on September 30, 2026 under our senior secured term loan, 2028 Notes and 2029 Notes.

We will require additional capital to fund our operations and clinical development of selinexor and to pursue regulatory approval of selinexor in myelofibrosis.

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 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 undertake additional cost reduction measures such as further reducing operating expenses, including through additional workforce reductions, delay, reduce or eliminate our research and development programs and/or commercialization efforts or at any time we may elect to or may be required to cease operations entirely, liquidate all or a portion of our assets, and/or seek protection under the U.S.

Bankruptcy Code, and you may lose all or part of your investment ,” below.

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

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

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

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

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

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

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

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

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

With the assistance of our advisors, including our financial advisor Centerview Partners and other advisors, we are actively evaluating a range of financing opportunities and strategic alternatives with the objective of extending our cash runway, preserving strategic flexibility and maximizing long-term shareholder value as we advance our myelofibrosis program.

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

There is no assurance that these efforts will result in additional funding, executing a strategic alternative transaction, will increase value for stakeholders, or will sufficiently address our ability to continue as a going concern.

Absent additional funding or our ability to successfully complete one or more strategic transactions to extend our cash runway beyond September 10, 2026, we will be unable to continue as a going concern and we may have to consider seeking protection under the bankruptcy laws, liquidating our assets or ceasing our operations.

If we decide to seek protection under the bankruptcy laws, we expect that we would file for bankruptcy protection at a time that is earlier than when we would otherwise exhaust our cash resources.

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.

1 unchanged sentence

Since inception, we have incurred significant operating losses.

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

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

Our loss from operations was $22.5 million for the quarter ended June 30, 2026.

As of June 30, 2026, we had an accumulated deficit of $1.8 billion.

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

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

Although we received our first U.S.

Food and Drug Administration (“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;

7 unchanged sentences

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.

in multiple myeloma and engage in activities to prepare for the potential approval and commercialization of selinexor in myelofibrosis.

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

4 unchanged sentences

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

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

• 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;

14 unchanged sentences

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 in the near-term, if at all.

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

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

2 unchanged sentences

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.

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

Bankruptcy Code, and you may lose all or part of your investment.

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

3 unchanged sentences

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

On September 10, 2026, a $15.8 million principal payment is due under our senior secured term loan facility;

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

4 unchanged sentences

• 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 $112.5 million senior secured term loan facility, as amended in October 2025 (the “Amended Term Loan”) and/or holders of the Convertible Notes;

• 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 senior secured term loan facility, as amended in October 2025 (the “Amended Term Loan”) and/or holders of the Convertible Notes;

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

6 unchanged sentences

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, and any such efforts could divert management’s attention away from their day-to-day activities.

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

Adequate additional financing has not been, and may continue to not be, available to us on acceptable terms.

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

3 unchanged sentences

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

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

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

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

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

If adequate funds are not available to us on a timely basis or on attractive terms, we may be required to take additional actions to address our liquidity needs, including additional cost reduction measures such as further reducing operating expenses, including through additional workforce reductions, or to delay, reduce or eliminate our research and development programs or any current or future commercialization efforts for one or more of our products or product candidates, which could have a material adverse effect on our business, operating results and prospects.

We may be required to or elect to cease operations entirely at any time, liquidate all or a portion of our assets, and/or seek protection under the U.S.

Bankruptcy Code, and you may lose all or part of your investment.

Future sales and issuances of equity securities would result in substantial dilution to our stockholders.

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 our 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 31, 2026, we announced that we are evaluating potential financing transactions along with strategic alternatives in order to maximize near and long-term stakeholder value.

These efforts may include, but are not limited to, a potential merger or sale of the Company, in- or out-of-court restructurings, repurchases, redemptions, exchanges or other refinancings of our existing debt, and

potential financing transactions, among other potential alternatives.

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

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

Bankruptcy Code.

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

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

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

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

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

In the event we file for bankruptcy, we would be subject to the risks and uncertainties associated with such proceedings.

In the event we file for relief under the U.S.

Bankruptcy Code, our operations and our continuation as a going concern will be subject to the risks and uncertainties associated with bankruptcy proceedings.

Any delays in our bankruptcy proceedings would increase the risks of our being unable to reorganize our business and emerge from bankruptcy proceedings and may increase our costs associated with the bankruptcy process or result in prolonged operational disruption for us.

Also, we would need the prior approval of the bankruptcy court for transactions outside the ordinary course of business during the course of any bankruptcy, which may limit our ability to respond timely to certain events or take advantage of certain opportunities.

Because of the risks and uncertainties associated with any bankruptcy proceedings, we cannot accurately predict or quantify the ultimate impact of events that could occur during any such proceedings.

There can be no guarantees that if we file for bankruptcy we will emerge from bankruptcy as a going concern or that holders of our common stock will receive any recovery from any bankruptcy proceedings.

In addition, we would need to have the bankruptcy court confirm any plan of reorganization and for such plan to go effective to emerge from bankruptcy.

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

In September 2019, we entered into the Revenue Interest Financing Agreement with certain entities managed by HealthCare Royalty Management, LLC (“HCRx”), as amended, and which was assigned by HCRx to an affiliate of KKR & Co.

in July 2025 in connection with its acquisition of a majority ownership stake in HCRx (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.

1 unchanged sentence

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 Convertible Notes and which is subordinated to the first-priority security interest securing the Amended Term Loan.

Subject to an intercreditor agreement with KKR, the Amended Term Loan lenders and the holders of the New 2029 Notes (the “Amended and Restated 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.

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 Convertible Notes and which is subordinated to the first-priority security interest securing the Amended Term Loan.

Subject to an intercreditor agreement with HCRx, the Amended Term Loan lenders and the holders of the New 2029 Notes (the “Amended and Restated 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.

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

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

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 Credit and Guaranty Agreement, with the lenders party thereto and Wilmington Savings Fund Society, FSB, as administrative agent for the lenders and collateral agent (as amended, the “Amended Credit Agreement”) contain, and any future indebtedness that we incur may contain, various negative covenants that restrict, among other things, our indebtedness, liens, fundamental changes, asset sales, investments and other matters.

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

See the risk factor captioned “ We need additional funding or to enter into strategic alternatives to achieve our business objectives.

Bankruptcy Code, and you may lose all or part of your investment ” above for a discussion of the risks associated with our need to raise additional capital.

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.

5 unchanged sentences

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

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

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

(iii) $103.5 million aggregate principal amount of the New 2029 Notes;

and (iv) $116.2 million of maximum remaining payments payable under our revenue interest financings agreement.

As of June 30, 2026 we had future obligations of:

(i) $153.6 million related to the Amended Term Loan in addition to the financial covenant to maintain minimum liquidity;

(ii) $19.2 million related to the 2028 Notes;

(iii) $138.3 million related to the New 2029 Notes;

and (iv) $116.2 million of maximum remaining payments payable under our revenue interest financing agreement.

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

6 unchanged sentences

• 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 Amended Credit Agreement, the Convertible Notes, or to make cash payments in connection with any conversion of the Convertible 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 Amended Term Loan, the Amended Revenue Interest Agreement, the Convertible Notes or any other future indebtedness and make necessary capital expenditures.

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 Amended Credit Agreement, the Convertible Notes, or to make cash payments in connection with any conversion of the Convertible 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 Amended Term Loan, the Amended Revenue Interest Agreement, the Convertible 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 Convertible Notes required to be settled in cash, to repay the Convertible Notes at maturity, to repurchase the Convertible Notes for cash upon a fundamental change, to pay the redemption price for any Convertible Notes we redeem or to refinance the Convertible Notes, and any future debt we incur may contain limitations on our ability to pay cash upon conversion or repurchase of the Convertible Notes.

22 unchanged sentences

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.

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

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

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

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.

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

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

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

6 unchanged sentences

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

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

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

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

8 unchanged sentences

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

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

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

immunomodulatory agents, and an anti-CD38 monoclonal antibody.

in multiple hematologic malignancy indications, including (i) in combination

with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy;

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.

The success of XPOVIO and any current or future product candidates, whether alone or in collaboration with third parties, including achieving and maintaining an adequate level of market adoption, depends on several factors, including:

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

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

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

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

• the outcome of discussions with the FDA regarding the regulatory pathway for our anticipated supplemental New Drug Application (“sNDA”) for selinexor in combination with ruxolitinib in myelofibrosis, including the possibility that the FDA may require additional data, longer follow-up, an additional clinical trial, or impose other requirements, and whether an sNDA is ultimately accepted and approved by the FDA;

• any conditions, limitations or restrictions imposed in connection with a potential approval of selinexor in combination with ruxolitinib in myelofibrosis based on accelerated approval, including a narrower-than-anticipated indication or patient population, limitations on the approved labeling or the claims and communications we may use to promote XPOVIO, requirements to submit promotional materials to the FDA prior to dissemination, or requests by the FDA that we revise, delay or refrain from using particular promotional materials or communications;

• reporting a positive benefit-risk profile from our ongoing Phase 3 clinical trial in patients with multiple myeloma, with topline data anticipated in the second half of 2026;

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

38 unchanged sentences

Our products are priced at a significant premium over competitive generic drugs, which may make it difficult for us to achieve our business strategy of using our products in combination with existing therapies or replacing existing therapies with our products.

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.

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.

6 unchanged sentences

In addition, if clinical trials of our product candidates fail to demonstrate safety and effectiveness to the satisfaction of regulatory authorities or do not otherwise produce positive results, we or our collaborators may incur additional costs, fail to secure regulatory approvals, or be unable to commercialize such product candidates.

Our long-term success depends in a large part on our ability to continue to successfully develop new indications of selinexor, our product candidates, or any new product candidates we may develop or acquire.

Our long-term success depends in large part on our ability to continue to successfully develop new indications of selinexor, our product candidates, or any new product candidates we may develop or acquire.

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

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

Following recent engagements with the FDA with respect to the regulatory path forward for the combination of selinexor plus ruxolitinib in myelofibrosis under the accelerated approval pathway utilizing spleen volume reduction ≥ 35% (“SVR35”) as a surrogate endpoint that is reasonably likely to predict clinical benefit, we plan to submit an sNDA in August 2026.

However, there can be no assurance that we will submit the sNDA by this time or that the sNDA, if submitted, will be accepted for review or approved.

In addition, any approval obtained under the accelerated approval pathway would be conditioned on verifying clinical benefit in post-marketing confirmatory trial/data.

Although the SENTRY Trial continues to follow patients for long-term outcomes, there can be no assurance that such data or any other confirmatory trial will verify clinical benefit.

A failure to verify clinical benefit could result in any accelerated approval being withdrawn.

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

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

For example, in July 2026, we announced topline results from our Phase 3 XPORT-EC-042 trial evaluating selinexor as a maintenance-only therapy compared to placebo in adult patients with TP53 wild-type advanced or recurrent endometrial cancer (the “XPORT-EC-042 Trial”).

The trial did not meet the pre-specified threshold for statistical significance for its primary endpoint of progression free survival in the modified intent-to-treat population.

Based on these topline results, we do not expect to pursue U.S.

regulatory approval for selinexor in endometrial cancer and have determined to reduce our planned investment in our endometrial cancer program.

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

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

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

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

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

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

• clinical trials of our product candidates may produce negative or inconclusive results or other patient safety concerns, including undesirable side effects or other unexpected characteristics, and we may decide, or regulatory authorities may require us, to conduct additional clinical trials, suspend ongoing clinical trials, abandon drug development programs or reduced planned investment in such programs, including as a result of a finding that the participants are being exposed to unacceptable health risks or that a trial did not meet its primary endpoint or otherwise did not produce results sufficient to support regulatory approval, as occurred with the XPORT-EC-042 Trial, enrollment in our clinical trials may be slower than we anticipate, including as a result of competition with other ongoing clinical trials or recently approved agents, which could decrease the overall supply of patients, or decreasing interest from selected clinical trial sites, delays in site activation, higher than expected screen failure rates, newly approved competitive products for the same indications as our product candidates or new or amended regulations;

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

for example, in recent years three new novel agents

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

• 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;

8 unchanged sentences

• the supply or quality of our product candidates or other materials necessary to conduct clinical trials may be insufficient or inadequate;

• for any biomarker driven clinical trial, the potential regulatory requirement to develop one or more companion diagnostics;

for example, the required development of companion diagnostics for our ongoing clinical trial evaluating selinexor in patients with TP53 wild-type advanced or recurrent endometrial cancer;

• any partners or collaborators that help us conduct clinical trials may face any of the above issues, and may conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us;

• negative impacts resulting from a pandemic or other public health emergency, including impacts to healthcare systems and our trial sites’ ability to conduct trial.

If we, or our collaborators, are required to conduct additional clinical trials or other testing of our product candidates or a companion diagnostic beyond those that we currently contemplate or are unable to successfully complete clinical trials of our product candidates or other testing, on a timely basis or at all, if changes to the external landscape impact our planned patient population or current clinical trial protocols, and/or if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we, or our collaborators, may:

• negative impacts resulting from a pandemic or other public health emergency, including impacts to healthcare systems and our trial sites’ ability to conduct trials.

If we, or our collaborators, are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate or are unable to successfully complete clinical trials of our product candidates or other testing, on a timely basis or at all, if changes to the external landscape impact our planned patient population or current clinical trial protocols,

and/or if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we, or our collaborators, may:

• need to delay, limit or terminate ongoing or planned clinical trials;

27 unchanged sentences

The most common AEs that are Grade 3 or Grade 4, meaning they are more than mild or moderate in severity, include thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.

To date, the most common AEs in the multiple myeloma patient population have been managed with supportive care and dose modifications.

To date, the most common AEs in the multiple myeloma patient

population have been managed with supportive care and dose modifications.

However, a number of patients had withdrawn from our clinical trials as a result of AEs and some patients across our clinical trials have experienced serious AEs deemed by us and the clinical investigator to be related to selinexor.

3 unchanged sentences

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

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

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

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

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

17 unchanged sentences

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

Although we believe the Phase 3 SENTRY trial generated data supporting the potential use of SVR35 as a surrogate endpoint in myelofibrosis, including data that have been presented at medical meetings and published in a peer-reviewed journal, there can be no assurance that prior, interim, published or presented data from the SENTRY trial or any related clinical or scientific literature will be

predictive of regulatory success.

As discussed above, following recent engagements with the FDA with respect to the regulatory path forward for the combination of selinexor plus ruxolitinib in myelofibrosis under the accelerated approval pathway utilizing SVR35 as a surrogate endpoint that is reasonably likely to predict clinical benefit, we plan to submit an sNDA in August 2026.

There can be no assurance that we will submit the sNDA by this time or that the sNDA, if submitted, will be accepted for review or approved.

The Phase 3 SENTRY trial continues to follow patients for long-term outcomes, and such long-term outcomes may not confirm or support earlier observations, including any overall survival signal, evidence of disease modification or other findings from prior analyses.

Any failure to verify clinical benefit, including in post-marketing confirmatory trials if accelerated approval is granted, could result in an accelerated approval being withdrawn.

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

8 unchanged sentences

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

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

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

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

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

6 unchanged sentences

• potential product candidates may not be effective in treating their targeted diseases.

We are currently advancing multiple clinical development studies of selinexor, which may create a strain on our limited human and financial resources.

As a result, we may not be able to provide sufficient resources to any single product candidate to permit the successful development and commercialization of such product candidate, which could result in material harm to our business.

Further, because we have limited financial and managerial resources, we focus on research programs and product candidates that we identify for specific indications.

Because we have limited financial and managerial resources, we must make significant strategic decisions regarding which product candidates, programs and indications to prioritize and which to delay, reduce, suspend or discontinue.

As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential.

6 unchanged sentences

for XPOVIO, our first commercial product, in hematological malignancies and our company did not previously have any prior experience in the sales, marketing or distribution of pharmaceutical drugs.

If XPOVIO or any of our product candidates is approved for additional indications beyond hematological malignancies, such as solid tumors, we may need to evolve our sales, marketing and distribution capabilities and we may not be able to do so successfully or on a timely basis.

In the future, we may choose to expand our sales, marketing and distribution infrastructure to market or co-promote one or more of our product candidates, if and when they are approved, or enter into additional collaborations with respect to the sale, marketing and distribution of our product candidates.

2 unchanged sentences

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.

If those collaborations are not successful, or if we are not able to maintain our existing collaborations or establish additional collaborations, we may have to alter our development and commercialization plans and may not be able to capitalize on the market potential of XPOVIO or our product candidates ” below.

There are risks involved with establishing and maintaining our own sales, marketing and distribution capabilities.

1 unchanged sentence

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

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

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

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

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

28 unchanged sentences

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

Moreover, eligibility for

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

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

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

65 unchanged sentences

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

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

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

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

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

19 unchanged sentences

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

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

• regulatory authorities may require more information, including additional preclinical or clinical data or trials, to support approval;

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

20 unchanged sentences

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

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

In addition, even if an

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

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

3 unchanged sentences

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

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

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

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

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

There can be no assurance that the FDA or foreign regulatory agencies will agree with our, or our collaborators’, surrogate endpoints or intermediate clinical endpoints in any of our, or their, clinical trials, or that we, or our collaborators, will decide to pursue or submit any additional NDA for accelerated approval or any other form of expedited development, review or approval.

For example, following recent engagements with the FDA with respect to the regulatory path forward for the combination of selinexor plus ruxolitinib in myelofibrosis under the accelerated approval pathway utilizing SVR35 as a surrogate endpoint that is reasonably likely to predict clinical benefit, we plan to submit an sNDA in August 2026.

However, there can be no assurance that the sNDA, if submitted, will be accepted for review or approved.

We also continue to be engaged with the FDA on the final details for the sNDA submission, including data to be used to support the sNDA and convert potential accelerated approval to traditional approval.

In addition, any approval obtained under the accelerated approval pathway would be conditioned on verifying clinical benefit in post-marketing confirmatory trial/data.

Although the SENTRY Trial continues to follow patients for long-term outcomes, there can be no assurance that such data or any other confirmatory trial will verify clinical benefit.

A failure to verify clinical benefit could result in any accelerated approval being withdrawn.

There can be no assurance that the FDA or foreign regulatory agencies will agree with our, or our collaborators’, surrogate endpoints or intermediate clinical endpoints in any of our, or their, clinical trials, or our, or our collaborators’, plans to verify clinical benefit, even after we have obtained feedback from the FDA or foreign regulatory agencies on these topics.

There can also be no assurance that we, or our collaborators, will decide to pursue or submit any additional NDA for accelerated approval or any other form of expedited development, review or approval.

Similarly, there can be no assurance that, after feedback from the FDA or comparable foreign regulatory agencies, we, or our collaborators, will continue to pursue or apply for accelerated approval or any other form of expedited development, review or approval.

11 unchanged sentences

Subsequently, in December 2024 and January 2025, the FDA issued additional draft guidances relating to accelerated approval.

These guidances describe FDA’s latest thinking on what it means to conduct a confirmatory trial with due diligence and how the FDA plans to interpret whether such a study needs to be underway at the time of approval.

These guidances describe FDA’s latest thinking on what it means to

conduct a confirmatory trial with due diligence and how the FDA plans to interpret whether such a study needs to be underway at the time of approval.

While these guidances are currently only in draft form and will ultimately not be legally binding even when finalized, sponsors typically observe the FDA’s guidance closely to ensure that their investigational products qualify for accelerated approval.

5 unchanged sentences

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

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

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

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

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

1 unchanged sentence

These confirmatory trials must be completed with due diligence.

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

For example, we plan to submit an sNDA seeking accelerated approval of selinexor to treat myelofibrosis using overall survival data from long-term follow-up of the ongoing Phase 3 SENTRY trial as the confirmatory trial to verify clinical benefit.

Although the SENTRY Trial continues to follow patients for long-term outcomes, there can be no assurance that such data or any other confirmatory trial will verify clinical benefit.

In addition, in June 2020, the FDA approved XPOVIO to treat DLBCL under the FDA’s accelerated approval regulations and as a condition of the accelerated approval for this indication we are required to comply with a number of post-approval requirements, including timely completion of a confirmatory clinical trial.

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

22 unchanged sentences

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

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

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

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

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

31 unchanged sentences

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

If we, or our collaborators, are required by the FDA, EMA or comparable regulatory authority to obtain clearance or approval of one or more companion diagnostic tests in connection with approval of any of our product candidates or a group of therapeutic products, and we or they do not obtain or there are delays in obtaining clearance or approval of a diagnostic test, we may not be able to commercialize the product candidate and our ability to generate revenue may be materially impaired.

In connection with our ongoing development of selinexor in patients whose endometrial cancer is TP53 wild-type, we are utilizing a companion diagnostic to identify patients whose tumors are TP53 wild-type.

We may be required to develop a second companion diagnostic pending the ultimate patient population included in the potential label for our endometrial indication.

To be successful in developing and commercializing product candidates in combination with companion diagnostics, we or our collaborators will need to address a number of scientific, technical, regulatory and logistical challenges.

According to FDA guidance, if the FDA determines that a companion diagnostic device is essential to ensuring the safety and effectiveness of a novel therapeutic product or new indication, the FDA generally will not approve the therapeutic product or new therapeutic product indication if the companion diagnostic is not also approved or cleared.

In certain circumstances (for example, when a therapeutic product is intended to treat a serious or life-threatening condition for which no satisfactory available therapy exists or when the labelling of an approved product needs to be revised to address a serious safety issue), however, the FDA may approve a therapeutic product without the prior or contemporaneous marketing authorization of a companion diagnostic.

In this case, approval of a companion diagnostic may be a post-marketing requirement or commitment.

If the FDA requires clearance or approval of a companion diagnostic for any of our product candidates, whether before, concurrently with approval, or post-approval of the product candidate, we, and/or our collaborators, may encounter difficulties in developing and obtaining clearance or approval for these companion diagnostics.

The process of obtaining or creating such diagnostic is time consuming and costly.

The FDA previously has required in vitro companion diagnostics intended to select the patients who will respond to a product candidate to obtain pre-market approval (“PMA”), simultaneously with approval of the therapeutic candidate.

The PMA process, including the gathering of clinical data and the submission and review by the FDA, can take several years or longer.

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 AE 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.

For example, in the EU, until May 25, 2022, in vitro diagnostic medical devices were regulated by Directive 98/79/EC (the “IVDD”), which has been repealed and replaced by Regulation (EU) No 2017/746 (the “IVDR”).

The regulation of companion diagnostics is now subject to further requirements set forth in the IVDR.

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

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

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

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

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

As a result, the assessment deadlines of these performance study submissions and amendments are often not met.

These new regulations have and could continue to negatively impact the pace of enrollment in our clinical trials.

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

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

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

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.

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.

We and our future collaborators may encounter difficulties in developing, obtaining regulatory clearance or approval for, manufacturing and commercializing companion diagnostics similar to those we face with respect to our product candidates themselves, including issues with achieving regulatory clearance or approval, production of sufficient quantities at commercial scale and with appropriate quality standards, and in gaining market acceptance.

If we are unable to successfully develop companion diagnostics for our product candidates, or experience delays in doing so, the development of our product candidates may be adversely affected, our product candidates may not obtain marketing approval, and we may not realize the full commercial potential of any of our product candidates that obtain marketing approval.

As a result, our business, results of operations and financial condition could be materially harmed.

In addition, a diagnostic company with whom we contract may decide to discontinue selling or manufacturing the companion diagnostic test that we anticipate using in connection with development and commercialization of product candidates or our relationship with such diagnostic company may otherwise terminate.

We may not be able to enter into arrangements with another diagnostic company to obtain supplies of an alternative diagnostic test for use in connection with the development and commercialization of our product candidates or do so on commercially reasonable terms, which could adversely affect and/or delay the co-development or commercialization of our companion diagnostic and therapeutic product candidates.

We or our collaborators may seek certain designations for our product candidates in or outside of the U.S., including Breakthrough Therapy, Fast Track and Priority Review designations, and PRIME Designation in the EU, but we, or they, might not receive such designations, and even if we, or they, do, such designations may not lead to a faster development or regulatory review or approval process.

6 unchanged sentences

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

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

for priority review.

For example, we intend to request Priority Review at the time of submission of an sNDA for selinexor in combination with ruxolitinib for the treatment of patients with myelofibrosis.

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

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

These designations are within the discretion of the FDA.

Accordingly, even if we believe that one of our product candidates meets the criteria for these designations, the FDA may disagree and instead determine not to make such designation.

Further, even if we receive a designation, such as the receipt of Fast Track designation for selinexor to treat myelofibrosis, the receipt of such designation for a product candidate may not result in a faster development or regulatory review or approval process compared to products considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA.

In addition, even if one or more of our product candidates qualifies for these designations, the FDA may later decide that the product candidates no longer meet the conditions for qualification and rescind the designation or decide that the time period for FDA review or approval will not be shortened.

Accordingly, even if we believe that selinexor in combination with ruxolitinib to treat myelofibrosis meets the criteria for Priority Review or any other designation, or that any of our other product candidates meets the criteria for these designations, the FDA may disagree and instead determine not to make such designation.

Further, even if we receive a designation, the receipt of such designation for a product candidate may not result in a faster development or regulatory review or approval process compared to products considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA.

In addition, even if selinexor in combination with ruxolitinib to treat myelofibrosis qualifies for a Priority Review designation or any other designation, or any of our other product candidates qualifies for these designations, the FDA may later decide that the product candidates no longer meet the conditions for qualification and rescind the designation or decide that the time period for FDA review or approval will not be shortened.

If selinexor in combination with ruxolitinib to treat myelofibrosis is not granted Priority Review, or if any such designation, if granted, is thereafter rescinded, the Prescription Drug User Fee Act target action date would be approximately ten months following the FDA’s receipt of the application.

In the EU, we or our collaborators may seek PRIME designation for some of our product candidates in the future.

17 unchanged sentences

Even if we obtain orphan drug exclusivity for a product, such as the recent receipt of orphan drug exclusivity for selinexor for the treatment of myelofibrosis, that exclusivity may not effectively protect the product from competition because different products can be approved for the same condition.

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.

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.

16 unchanged sentences

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

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

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

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

4 unchanged sentences

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

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

prescribed or used.

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

11 unchanged sentences

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

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

The IRA permits the Secretary of the HHS to implement many of these provisions through guidance, as opposed to regulation until at least 2029.

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

5 unchanged sentences

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

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

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

It remains to be seen how the drug pricing provisions imposed by the IRA will affect the broader pharmaceutical industry.

Although the Supreme Court declined in May 2026 to hear certain manufacturer challenges to the IRA price negotiation program, other litigation remains pending, the outcome of which could affect the scope and operation of the program.

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

4 unchanged sentences

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

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

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

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

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

The Trump administration has also continued to exert pressure on drug manufacturers to implement “most-favored-nation” pricing, with the stated purpose of reducing the price of medicines in the U.S.

as compared to other countries.

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

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

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

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

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

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

Medicare Against Rising Drug Costs (GUARD) models, where manufacturers of certain Medicare Part B and Medicare Part D drugs would be assessed rebates if the prices for such products exceed those paid in economically comparable countries.

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

In May 2026, the Department of Commerce established an application process for the onshoring agreements contemplated by the executive order, and the tariffs are anticipated to take effect on a staggered basis beginning on July 31, 2026 for certain large pharmaceutical companies and September 29, 2026 for others.

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

16 unchanged sentences

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

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

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

program payers that are false or fraudulent or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant per-claim penalties;

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

• 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;

18 unchanged sentences

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

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

Such failure could also be grounds for

CMS to terminate our Medicaid drug rebate agreement, pursuant to which we participate in the Medicaid program.

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

5 unchanged sentences

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

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

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

DHHS also issued a final rule on procedures for the 340B Program’s administrative dispute resolution (“ADR”) process in April 2024 and ADR decisions have been posted on HRSA’s website.

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

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

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

Additionally, after withdrawing a prior program, HRSA is expected to announce a new 340B Rebate Model Pilot Program that will be open to a selected group of drugs and manufacturers as a notice regarding the program is currently under review.

CMS has also proposed new reporting requirements for 340B covered entities that purchase drugs that are also covered under Medicare Part D, among other reporting requirements, and has proposed significant cuts to reimbursement for 340B drugs paid under the Medicare Hospital Outpatient Prospective Payment System.

Congress has also introduced 340B reform legislation.

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

14 unchanged sentences

We are subject to data privacy and protection laws and regulations that apply to the collection, transmission, storage and use of personally-identifying information, which among other things, impose certain requirements relating to the privacy, security and transmission of personal information, including comprehensive regulatory systems in the U.S., EU, UK and other countries in which we may conduct business.

The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions worldwide, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business.

The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions

worldwide, and there has been an increasing focus on privacy and data protection issues with the potential to affect our business.

Failure to comply with any of these laws and regulations could result in enforcement action against us, including fines, imprisonment of company officials and public censure, claims for damages by affected individuals, damage to our reputation and loss of goodwill, any of which could have a material adverse effect on our business, financial condition, results of operations or prospects.

1 unchanged sentence

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

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

and availability of electronic protected health information.

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

18 unchanged sentences

Failure to comply with these rules can lead to a potential FTC enforcement action.

Additionally, the Department of Justice recently finalized a rule implementing Executive Order 14117, which creates similar restrictions related to the transfer of sensitive US data to countries such as China.

Additionally, the Department of Justice finalized a rule implementing Executive Order 14117, which became effective in April 2025 and created similar restrictions related to the transfer of sensitive U.S.

data to countries such as China.

These data transfer restrictions (and others that may pass in the future) may create operational challenges and legal risks for our business.

14 unchanged sentences

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

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

use of pixels and other web trackers.

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

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

35 unchanged sentences

While we continue to address the implications of the recent changes to data privacy regulations, data privacy remains an evolving landscape at both the domestic and international level, with new regulations coming into effect and continued legal challenges, and our efforts to comply with the evolving data protection rules may be unsuccessful.

It is possible that these laws may be interpreted and applied in a manner that is inconsistent with our practices.

It is possible that these laws may be

interpreted and applied in a manner that is inconsistent with our practices.

We must devote significant resources to understanding and complying with this changing landscape.

42 unchanged sentences

Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem.

In addition, the FCPA presents particular challenges in the pharmaceutical industry, because, in many countries, hospitals, clinics, universities and similar institutions are operated by the government, and doctors and other healthcare professionals are considered

foreign officials.

Certain payments to healthcare professionals in connection with clinical trials, regulatory approvals, sales and marketing, and other work have been deemed to be improper payments to government officials and have led to FCPA enforcement actions.

64 unchanged sentences

Regulatory or legislative action taken by the U.S.

government to impose restrictions on transactions with China, like the

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

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

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

4 unchanged sentences

Supreme Court issued an opinion in Loper Bright Enterprises v.

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

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

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

16 unchanged sentences

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

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

All of the risks

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

and EU, as applicable, of our collaborators.

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

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

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

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

18 unchanged sentences

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

• disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development or commercialization, might cause delays or termination of the research, development or commercialization of products or product candidates, might lead to additional responsibilities for us with respect to our

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

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

47 unchanged sentences

Additionally, the FDA or foreign regulatory authorities may disagree with the sufficiency of our right to reference the preclinical, manufacturing or clinical data generated by these investigator-sponsored trials, or our interpretation of preclinical, manufacturing or clinical data from these investigator-sponsored trials.

If so, the FDA or foreign regulatory authorities may require us to obtain and submit additional preclinical, manufacturing, or clinical data before we may initiate our planned trials and/or may not accept such additional data as adequate to initiate our planned trials.

If so, the FDA or foreign regulatory authorities may require us

to obtain and submit additional preclinical, manufacturing, or clinical data before we may initiate our planned trials and/or may not accept such additional data as adequate to initiate our planned trials.

We are completely dependent on third parties for the manufacture of our products and product candidates and any difficulties, disruptions, delays or unexpected costs, or the need to find alternative sources, could adversely affect our results of operations, profitability and future business prospects.

3 unchanged sentences

Similar regulations apply to manufacturers of our product candidates for use or sale in foreign countries.

We do not control the manufacturing processes of, and are completely dependent on, our third-party manufacturers for compliance with the applicable regulatory requirements for the manufacture of our products and product candidates.

We oversee but do not operate the manufacturing processes of, and are completely dependent on, our third-party manufacturers for compliance with the applicable regulatory requirements for the manufacture of our products and product candidates.

Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the U.S.

19 unchanged sentences

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

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

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

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

4 unchanged sentences

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

As of August 6, 2026, 204 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, 2026, 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, 2026, 13 patents were in force that relate to IL-12 compositions and uses of IL-12 in targeted therapeutics.

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

22 unchanged sentences

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

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

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

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

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

30 unchanged sentences

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

We may not have sufficient financial or other resources to adequately

conduct such litigation or proceedings.

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

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

50 unchanged sentences

Failure to secure those registrations could adversely affect our business.

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

As of August 6, 2026, we have trademark registrations in the U.S.

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

Outside of the U.S., XPOVIO is registered or pending in 46 additional jurisdictions, and is registered in Katakana in Japan, Hangul in South Korea, and Chinese characters in Taiwan.

Outside of the U.S., XPOVIO is registered in 46 additional jurisdictions, and is registered in Katakana in Japan, Hangul in South Korea, and Chinese characters in Taiwan.

KARYOPHARM, the greyscale logo, KARYOPHARM THERAPEUTICS with the color logo, and the KARYFORWARD logo are each registered in four jurisdictions outside of the U.S.

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

and pending in Cyrillic characters in Russia and Kazakhstan.

and registered in Cyrillic characters in Russia and Kazakhstan.

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

8 unchanged sentences

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

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

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

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

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

13 unchanged sentences

We are highly dependent on the management, technical and scientific expertise of principal members of our management and scientific teams, including our President and Chief Executive Officer.

Although we have entered into formal employment agreements with our executive officers, these agreements do not prevent them from terminating their employment with us at any time.

Although we have entered into formal employment agreements

with our executive officers, these agreements do not prevent them from terminating their employment with us at any time.

We do not maintain “key person” insurance for any of our executives or other employees.

9 unchanged sentences

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

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

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

In addition, concerns about our ability to continue as a going concern or raise sufficient capital to fund our ongoing trials could result in the departure of personnel that are critical to our operations.

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

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

In July 2026 we announced that our board of directors, upon recommendation of its compensation committee, implemented a retention program for certain employees of the Company, including certain executive officers, to incentivize retention of key employees during a period in which the Company is expecting several meaningful catalysts requiring the continued experience and expertise of the designated employees.

The retention program was implemented to replace previously guaranteed amounts under the Company’s annual bonus plan for 2026.

There is no guarantee that such retention program will be successful or reduce the risk of attrition of such employees.

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.

11 unchanged sentences

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.

11 unchanged sentences

Risks Related to Our Common Stock

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.

We must satisfy Nasdaq’s continued listing requirements, including, among other things, a minimum closing bid price of $1.00 per share, or risk delisting, which would have a material adverse effect on our business.

If we fail to maintain compliance with the continued listing requirements and the continued listing standards 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.

We must satisfy Nasdaq’s continued listing requirements and the continued listing standards, including, among other things, a minimum closing bid price of $1.00 per share, or risk delisting, which would have a material adverse effect on our business.

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

1 unchanged sentence

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

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

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

Any potential delisting of our common stock from the Nasdaq Global Select Market would likely result in decreased liquidity and increased volatility for our common stock and would adversely affect our ability to raise additional capital or to enter into strategic transactions.

7 unchanged sentences

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

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

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

As of June 30, 2026, we had outstanding warrants to purchase, without regard to any beneficial ownership limitations, and excluding pre-funded warrants to purchase common stock, up to 14,043,996 shares of common stock at a weighted average exercise price of $11.71 per share.

The exercise of our outstanding warrants could result in significant dilution to existing stockholders, cause

the trading price of our common stock to decline and impair our ability to raise capital through the sale of additional equity securities.

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.

16 unchanged sentences

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 $3.77 to $10.09 in the 52-week period ended May 7, 2026.

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

Our common stock price has ranged from $1.91 to $10.67 in the 52-week period ended August 6, 2026.

On August 6, 2026, the closing sale price of our common stock on the Nasdaq Global Select Market was $1.95 per share.

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

35 unchanged sentences

Other potential liabilities may not be covered by insurance, insurers may dispute coverage or the amount of insurance may not be enough to cover damages awarded.

In addition, certain types of damages may not be covered by insurance, and insurance coverage for all or certain forms of liability may become unavailable or prohibitively expensive in the future.

In addition, certain types of damages may not be covered by insurance, and insurance coverage for all or certain forms of liability may become

unavailable or prohibitively expensive in the future.

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

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

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

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

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

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

Pending their use to fund our operations, we may invest our cash and cash equivalents in a manner that does not produce income or that loses value.

Pending their use to fund our operations, we may invest our cash, cash equivalents, and investments in a manner that does not produce income or that loses value.

We are a “smaller reporting company”, and the reduced disclosure requirements applicable to smaller reporting companies may make our common stock less attractive to investors.

47 unchanged sentences

Further, as of August 2022, the IRA introduced new tax provisions, including a one percent excise tax imposed on certain stock repurchases by publicly traded companies.

The one percent excise tax generally applies to any acquisition of stock by the publicly traded company (or certain of its affiliates) from a stockholder of the company in exchange for money or other property (other than stock of the company itself), subject to a de minimis exception.

The one percent excise tax generally applies to any acquisition of stock by the publicly traded company (or certain of its affiliates) from a stockholder of the company in

exchange for money or other property (other than stock of the company itself), subject to a de minimis exception.

Thus, the excise tax could apply to certain transactions that are not traditional stock repurchases.

2 unchanged sentences

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