What changed in Karyopharm Therapeutics Inc.'s 2025 10-K compared to 2024?

Across the narrative sections we track, Karyopharm Therapeutics Inc. (KPTI) added 767 paragraphs, removed 743, and edited 550 between the 2024 and 2025 10-K filings. The biggest movers are Item 7. Management's Discussion & Analysis (+652/−648), Item 6. [Reserved] (+90/−72), Item 1. Business (+19/−16).

What changed in Karyopharm Therapeutics Inc.'s MD&A (Item 7) in 2025?

Item 7 Management's Discussion & Analysis shows 652 new/edited paragraphs and 648 removed paragraphs year-over-year. Read the side-by-side diff to see exactly which revenue, margin, and outlook commentary was rewritten.

Did Karyopharm Therapeutics Inc. update its Cybersecurity disclosure (Item 1C) in 2025?

Item 1C Cybersecurity has 2 paragraph-level changes between the 2024 and 2025 filings.

Did Karyopharm Therapeutics Inc.'s Legal Proceedings (Item 3) change in 2025?

Item 3 shows 1 added/edited paragraphs and 1 removed paragraphs — usually indicating new litigation disclosed or settled cases removed.

Where does this KPTI 10-K diff come from?

The source filings are Karyopharm Therapeutics Inc.'s official 2024 and 2025 Form 10-K annual reports from SEC EDGAR. 10q10k.net parses each filing, aligns paragraphs by section (Item 1, 1A, 1C, 2, 3, 7, 7A), and highlights every added, removed and edited sentence side-by-side.

What changed in Karyopharm Therapeutics Inc.'s 10-K — 2024 vs 2025

Paragraph-level year-over-year comparison of Karyopharm Therapeutics Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+767 added−743 removedSource: 10-K (2026-02-13) vs 10-K (2025-02-19)

Top changes in Karyopharm Therapeutics Inc.'s 2025 10-K

767 paragraphs added · 743 removed · 550 edited across 8 sections

Item 7. Management's Discussion & Analysis+652 / −648 · 478 edited
Item 6. [Reserved]+90 / −72 · 57 edited
Item 1. Business+19 / −16 · 9 edited
Item 1C. Cybersecurity+2 / −2 · 2 edited
Item 2. Properties+1 / −2 · 1 edited

Item 1. Business

Business — how the company describes what it does

9 edited+10 added−7 removed7 unchanged

2024 filing

2025 filing

Biggest changeWe had net losses of $76.4 million and $143.1 million for the years ended December 31, 2024 and 2023, respectively. We recognized total revenue of $145.2 million in 2024, including $112.8 million of XPOVIO net product revenue and $32.4 million of license revenue. As of December 31, 2024, we had $108.7 million in cash, cash equivalents and investments.

Biggest changeAs of December 31, 2025, we had an accumulated deficit of $1.8 billion. We had net losses of $196.0 million, $76.4 million, and $143.1 million for the years ended December 31, 2025, 2024 and 2023, respectively. We recognized total revenue of $146.1 million in 2025, including $114.9 million of XPOVIO net product revenue and $31.2 million of license revenue.

Approval in this indication was based on the results from the BOSTON ( Bo rtezomib, S elinexor and Dexame t has on e) trial (the “BOSTON Trial”); • 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 (“PIs”), at least two immunomodulatory agents (“IMiDs”), and an anti-CD38 monoclonal antibody (“mAb”).

Approval in this indication was based on the results from the BOSTON ( Bo rtezomib, S elinexor and Dexame t has on e) trial (the “BOSTON Trial”; NCT03110562); • 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 (“PIs”), at least two immunomodulatory agents (“IMiDs”), and an anti-CD38 monoclonal antibody (“mAb”).

Approval in this indication was based on the results from the STORM ( S elinexor T reatment of R efractory M yeloma) trial (the “STORM Trial”); and • For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (“DLBCL”), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

Approval in this indication was based on the results from the STORM ( S elinexor T reatment of R efractory M yeloma) trial (the “STORM Trial”; NCT02336815); and • For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (“DLBCL”), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

This indication was approved under accelerated approval based on response rate and was based on the results from the SADAL ( S elinexor A gainst D iffuse A ggressive L ymphoma) trial (the “SADAL Trial”). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

This indication was approved under accelerated approval based on response rate and was based on the results from the SADAL ( S elinexor A gainst D iffuse A ggressive L ymphoma) trial (the “SADAL Trial”; NCT04442022). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Our primary focus is on marketing XPOVIO in its currently approved indications as well as developing and seeking the regulatory approval of selinexor as an oral agent targeting multiple high unmet need cancer indications, including our lead clinical programs in myelofibrosis and our other late-stage clinical programs in endometrial cancer and multiple myeloma.

Our primary focus is on marketing XPOVIO in its currently approved indications as well as developing and seeking regulatory approval of selinexor as an oral agent targeting multiple high unmet need cancer indications, including our lead clinical programs in myelofibrosis and endometrial cancer and our other late-stage clinical program in multiple myeloma.

We have discovered and are developing and commercializing novel, small molecule Selective Inhibitor of Nuclear Export (“SINE”) compounds that inhibit the nuclear export protein exportin 1 (“XPO1”). These SINE compounds represent a new class of drug candidates with a novel mechanism of action that have the potential to treat a variety of diseases with high unmet medical need.

We have discovered and are developing and commercializing novel, small molecule XPO1 inhibitor compounds that inhibit the nuclear export protein exportin 1 (“XPO1”). These compounds represent a new class of drug candidates with a novel mechanism of action that have the potential to treat a variety of diseases with high unmet medical need.

XPOVIO/NEXPOVIO has received regulatory approval in various indications in over 45 countries outside the U.S. and is commercially available in a growing number of countries as our partners continue to secure reimbursement approvals.

XPOVIO/NEXPOVIO has received regulatory approvals in various indications in 50 territories and countries outside the U.S. and is commercially available in a growing number of countries as our partners continue to secure reimbursement approvals.

Based on our current business plan and current capital resources, combined with the uncertainty regarding the availability of additional funding and considering our debt obligations, including a requirement to maintain cash, cash equivalents and investments of at least $25.0 million at all times, we have concluded that there is substantial doubt regarding our ability to continue as a going concern within one year after the date the accompanying consolidated financial statements are issued.

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 and financial covenant to maintain minimum liquidity, 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.

In May 2024, we entered into a series of transactions (the “Refinancing Transactions”) to limit our aggregate indebtedness, extend the maturity of certain of our indebtedness and provide us with additional working capital.

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 6 Table of Contents Transactions”).

Removed

We plan to continue to educate physicians, other healthcare providers and patients about XPOVIO’s clinical profile and unique mechanism of action as we continue to expand XPOVIO use.

Added

Depending on the data in our Phase 3 myelofibrosis and/or endometrial cancer programs and the availability of capital resources, we plan to explore opportunities to develop our leading next-generation XPO1 inhibitor, eltanexor, in additional myeloproliferative neoplasms and TP53 wild-type tumors.

Removed

We plan to continue to conduct clinical trials and to seek additional approvals for the use of selinexor as a single agent or in combination with other oncology therapies to expand the patient populations that are eligible for treatment with selinexor.

Added

In September 2025, we completed enrollment in our ongoing Phase 3 clinical trial to evaluate the efficacy and safety of once-weekly selinexor in combination with ruxolitinib versus placebo plus ruxolitinib in JAK2 inhibitor (“JAKi”)-naive myelofibrosis patients (the “SENTRY Trial”; NCT04562389). We expect to report top-line data from the SENTRY Trial in March 2026.

Removed

As announced in January 2024, further clinical development of our eltanexor program continues to remain on hold in an effort to focus our resources on our prioritized late-stage programs.

Added

We continue to enroll JAKi-naïve myelofibrosis patients in the Phase 2 clinical trial to evaluate the safety and efficacy of selinexor as a monotherapy in patients with JAKi-naïve myelofibrosis with moderate thrombocytopenia (the “SENTRY-2 Trial”; NCT05980806). The protocol, as amended in 2025, includes patients with platelet counts above 50,000 per microliter.

Removed

Pursuant to these transactions, we borrowed $100.0 million from existing lenders and certain entities managed by HealthCare Royalty Management, LLC (“HCRx”) under a new, senior secured term loan facility and used a portion of the proceeds of that loan to repay obligations under our existing financing arrangement with HCRx pursuant to an amendment that made other changes to our existing financing arrangement with HCRx.

Added

We expect to report top-line data from all patients in the 60 mg cohort with at least 24 weeks of follow-up in the second half of 2026.

Removed

We also exchanged, pursuant to privately negotiated agreements, an aggregate principal amount of $148.0 million of our existing 3.00% unsecured convertible senior notes for (i) $111.0 million aggregate principal amount of new 6.00% secured convertible senior notes and (ii) warrants to purchase up to 45.8 million shares of our common stock.

Added

We are continuing to enroll patients in a global, Phase 3, randomized, double-blind trial evaluating selinexor as a maintenance-only therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “XPORT-EC-042 Trial”; NCT05611931). We expect to report top-line data from this event-driven trial in mid-2026.

Removed

In addition, HCRx purchased $5.0 million aggregate principal amount of new 6.00% secured convertible senior notes through satisfaction of $5.0 million of our existing 6 Table of Contents obligations to HCRx.

Added

The Financing Transactions included the following key components: (i) $27.5 million in new term loan borrowings and new convertible debt; (ii) $25.4 million of near-term deferrals of interest and royalty payments; (iii) a temporary reduction of $15.0 million in our minimum liquidity covenant; (iv) an exchange of $15.0 million aggregate principal amount of our convertible notes due 2029 for shares of common stock; (v) an exchange of $24.3 million aggregate principal amount of our convertible notes due October 15, 2025 for shares of our common stock and warrants to purchase shares of our common stock; and (vi) a private placement of shares of our common stock and warrants to purchase shares of our common stock for gross proceeds of approximately $8.8 million.

Removed

Please refer to Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K for additional details of the Refinancing Transactions. As of December 31, 2024, we had an accumulated deficit of $1.6 billion.

Added

In connection with the Financing Transactions, we issued an aggregate of 7,223,982 shares of common stock, pre-funded warrants to purchase an aggregate of 2,913,136 shares of common stock, and warrants to purchase an aggregate of 5,918,358 shares of common stock with an exercise price of $6.64 per share.

Added

In addition, we reduced the exercise price of outstanding warrants to purchase 3,068,417 shares from $16.50 to $6.64 per share.

Added

Following consummation of the Financing Transactions, we had $116.5 million outstanding under our senior secured term loan with a maturity date in May 2028 (the “Amended Term Loan”), $15.0 million aggregate principal amount of 9.00% senior secured convertible notes due October 2028, $103.5 million aggregate principal amount of 9.00% senior secured convertible notes due May 2029, and $116.2 million of maximum remaining payments payable under our revenue interest financing agreement.

Added

License revenue included $15.0 million of revenue for the reimbursement of development related expenses from the Menarini Group (“Menarini”). As of December 31, 2025, we had $63.7 million in cash, cash equivalents and investments.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

2 edited+0 added−0 removed0 unchanged

2024 filing

2025 filing

Biggest changeItem 1C. Cybersecurity 103 Item 2. Properties 105 Item 3. Legal Proceedings 105 Item 4. Mine Safety Disclosures 105 PART II 106 Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 106 Item 6. [Reserved] 106 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 107 Item 7A.

Biggest changeItem 1C. Cybersecurity 105 Item 2. Properties 107 Item 3. Legal Proceedings 107 Item 4. Mine Safety Disclosures 107 PART II 108 Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities 108 Item 6. [Reserved] 108 Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations 109 Item 7A.

Quantitative and Qualitative Disclosures about Market Risk 115 Item 8. Financial Statements and Supplementary Data 115

Quantitative and Qualitative Disclosures about Market Risk 118 Item 8. Financial Statements and Supplementary Data 118

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−1 removed0 unchanged

2024 filing

2025 filing

Biggest changeItem 2. Pro perties Our headquarters are located in Newton, Massachusetts, where we currently lease a total of 98,502 square feet of office and research space through September 30, 2025, which will be reduced to 52,224 square feet of solely office space from October 1, 2025 through September 30, 2030.

Biggest changeItem 2. Pro perties Our headquarters are located in Newton, Massachusetts, where we currently lease a total of 52,224 square feet of office space through September 30, 2030. We also lease approximately 3,681 square feet of office space in Munich, Germany.

Removed

We also lease approximately 3,681 square feet of office space in Munich, Germany.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

1 edited+0 added−0 removed0 unchanged

2024 filing

2025 filing

Biggest changeItem 3. Le gal Proceedings The information required by this Item is provided under “ Litigation ” in Note 12, “ Commitments and Contingencies”, of the consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K.

Biggest changeItem 3. Le gal Proceedings The information required by this Item is provided under “ Litigation ” in Note 13, “ Commitments and Contingencies”, of the consolidated financial statements included in Part II, Item 8 of this Annual Report on Form 10-K.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

1 edited+0 added−0 removed2 unchanged

2024 filing

2025 filing

Biggest changeMa rket for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock, $0.0001 par value per share, began trading on the Nasdaq Global Select Market on November 6, 2013, where its prices are quoted under the symbol “KPTI.” Holders As of February 14, 2025, there were nine holders of record of our common stock.

Biggest changeMa rket for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities Market Information Our common stock, $0.0001 par value per share, began trading on the Nasdaq Global Select Market on November 6, 2013, where its prices are quoted under the symbol “KPTI.” Holders As of February 5, 2026, there were 16 holders of record of our common stock.

Item 6. [Reserved]

Selected Financial Data — reserved (removed by SEC in 2021)

57 edited+33 added−15 removed33 unchanged

2024 filing

2025 filing

Biggest changeSee Note 6, “ Fair Value Measurements”, and Note 10, “ Long-Term Obligations”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K for additional information. 109 Table of Contents Results of Operations The following table summarizes our results of operations (in thousands, except for percentages): For the Years Ended December 31, 2024 2023 $ Change % Change Product revenue, net $ 112,806 $ 112,011 $ 795 1 % License and other revenue 32,431 34,022 (1,591 ) (5 )% Total revenue 145,237 146,033 (796 ) (1 )% Operating expenses: Cost of sales 6,007 4,942 1,065 22 % Research and development 143,232 138,750 4,482 3 % Selling, general and administrative 115,441 131,881 (16,440 ) (12 )% Loss from operations (119,443 ) (129,540 ) 10,097 (8 )% Other income (expense), net 43,078 (13,236 ) 56,314 (>100)% Loss before income taxes (76,365 ) (142,776 ) 66,411 (47 )% Income tax provision (57 ) (323 ) 266 (82 )% Net loss $ (76,422 ) $ (143,099 ) $ 66,677 (47 )% Product Revenue, net (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Product revenue, net $ 112,806 $ 112,011 $ 795 1 % Net product revenue from U.S. commercial sales of XPOVIO for the year ended December 31, 2024 was relatively consistent as compared to the year ended December 31, 2023.

Biggest changeResults of Operations The following table summarizes our results of operations (in thousands, except for percentages): For the Years Ended December 31, 2025 2024 $ Change % Change Product revenue, net $ 114,857 $ 112,806 $ 2,051 2 % License and other revenue 31,210 32,431 (1,221 ) (4 )% Total revenue 146,067 145,237 830 1 % Operating expenses: Cost of sales 5,949 6,007 (58 ) (1 )% Research and development 125,617 143,232 (17,615 ) (12 )% Selling, general and administrative 105,208 115,441 (10,233 ) (9 )% Loss from operations (90,707 ) (119,443 ) 28,736 (24 )% Other (expense) income, net (105,289 ) 43,078 (148,367 ) (>100)% Loss before income taxes (195,996 ) (76,365 ) (119,631 ) >100% Income tax provision (43 ) (57 ) 14 (25 )% Net loss $ (196,039 ) $ (76,422 ) $ (119,617 ) >100% Product Revenue, net (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Product revenue, net $ 114,857 $ 112,806 $ 2,051 2 % To date, our only source of product revenue has been from the U.S. sales of XPOVIO.

We track our external clinical trial and related costs on a program-by-program basis. Our major programs include our lead clinical programs in myelofibrosis and our other late-stage clinical programs in endometrial cancer and multiple myeloma.

We track our external clinical trial and related costs on a program-by-program basis. Our major programs include our lead clinical programs in myelofibrosis and endometrial cancer and our other late-stage clinical program in multiple myeloma.

The estimates for our product revenue allowances and accruals are most significantly affected by chargebacks, which are contractual commitments to provide products to qualified healthcare entities at prices lower than the list prices charged to our customers who purchase XPOVIO directly from us, and rebates that represent discount obligations under government programs, including Medicaid, Medicare, the Department of Veterans Affairs, the Department of Defense, and others.

The estimates for our product revenue allowances and accruals are most significantly affected by chargebacks, which are contractual commitments to provide products to qualified healthcare entities at prices lower than the list prices charged to our customers who purchase XPOVIO directly from us, and rebates that represent discount obligations under government programs, including Medicaid, Medicare, Tricare , the Department of Veterans Affairs, the Department of Defense, and others.

We base our expenses related to CROs and CMOs on our estimates of the services performed and efforts expended pursuant to quotes and contracts with CROs and CMOs that conduct research and development activities on our behalf. The payment terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows.

We base our expenses related to CROs on our estimates of the services performed and efforts expended pursuant to quotes and contracts with CROs that conduct research and development activities on our behalf. The payment terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows.

Food and Drug Administration (“FDA”) in July 2019, and is currently approved and marketed in the U.S. for the following indications: • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

Food and Drug Administration in July 2019, and is currently approved and marketed in the U.S. for the following indications: • In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

These reserves are based on the amounts earned, or to be claimed on the related sales, and are generally classified as reductions of accounts receivable (if the amount is payable to the customer) or a current liability (if the amount is payable to a party other than a customer).

These reserves are based on the amounts earned, or to be claimed on the related sales, and are generally classified as reductions of accounts receivable (if the amount is payable to the customer) or a current or long-term liability (if the amount is payable to a party other than a customer).

Results of Operations - Years Ended December 31, 2023 and 2022 Discussion and analysis of the results of operations for the year ended December 31, 2023 as compared to the results of operations for the year ended December 31, 2022 is included under the heading “ Item 7.

Results of Operations - Years Ended December 31, 2024 and 2023 Discussion and analysis of the results of operations for the year ended December 31, 2024 as compared to the results of operations for the year ended December 31, 2023 is included under the heading “ Item 7.

The significant estimates in our accrued research and development costs include fees to be paid to contract research organizations (“CROs”) and contract manufacturing organizations (“CMOs”) in connection with research and development activities, as well as fees to be paid to investigative sites in connection with clinical studies, for which we have not yet been invoiced.

The significant estimates in our accrued research and development costs include fees incurred with contract research organizations (“CROs”) in connection with research and development activities, as well as fees to be paid to investigative sites in connection with clinical studies, for which we have not yet been invoiced.

There can be no assurance as to the amount or timing of any such revenue, and we may not achieve profitability for several years, if at all, as described more fully in the risk factor entitled “ We have incurred significant losses since inception, expect to continue to incur significant losses, and may never achieve or maintain profitability ,” under the heading “ Risk Factors ” in this Annual Report on Form 10-K.

There can be no assurance as to the amount or timing of any such revenue, and we may not achieve profitability in the near-term, if at all, as described more fully in the risk factor entitled “ We have incurred significant losses since inception, expect to continue to incur significant losses, and may never achieve or maintain profitability ,” under the heading “ Risk Factors ” in this Annual Report on Form 10-K.

Under the 2023 Open Market Sale Agreement, we may issue and sell shares of our common stock having an aggregate offering price of up to $100.0 million (the “Shares”) from time to time through Jefferies. We did not sell any Shares under the 2023 Open Market Sales Agreement during the year ended December 31, 2024.

Under the Open Market Sale Agreement, we may issue and sell shares of our common stock having an aggregate offering price of up to $100.0 million (the “Shares”) from time to time through Jefferies. We did not sell any Shares under the Open Market Sale Agreement during the year ended December 31, 2025.

License revenue included $15.0 million of revenue for the reimbursement of development related expenses from the Menarini Group (“Menarini”). As of December 31, 2024, we had $108.7 million in cash, cash equivalents and investments.

For additional information, see Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K. 113 Table of Contents On February 17, 2023, we entered into an Open Market Sale Agreement (the “2023 Open Market Sale Agreement”) with Jefferies LLC, as agent (“Jefferies”).

For additional information, see Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K. In February 2023, we entered into an Open Market Sale Agreement (the “Open Market Sale Agreement”) with Jefferies LLC, as agent (“Jefferies”).

As of December 31, 2024, $100.0 million of Shares was available for issuance and sale under the 2023 Open Market Sale Agreement.

As of December 31, 2025, $100.0 million of Shares was available for issuance and sale under the Open Market Sale Agreement.

During the year ended December 31, 2024, we received $19.6 million in milestone and upfront payments under our license and distribution arrangements pursuant to which we are entitled to receive additional milestone payments, if certain development goals and sales milestones are achieved, as well as royalties on future net sales of the licensed and sold products in the territories under such arrangements.

During the year ended December 31, 2025, we received $8.2 million in milestone under our license and distribution arrangements pursuant to which we are entitled to receive additional milestone payments, if certain development goals and sales milestones are achieved, as well as royalties on future net sales of the licensed and sold products in the territories under such arrangements.

Management’s Discussion and Analysis of Financial Condition and Results of Operations ” in our Annual Report on Form 10-K for the year ended December 31, 2023 as filed with the SEC on February 29, 2024 (“2023 Form 10-K”).

Management’s Discussion and Analysis of Financial Condition and Results of Operations ” in our Annual Report on Form 10-K for the year ended December 31, 2024 as filed with the SEC on February 19, 2025 (“2024 Form 10-K”).

As of December 31, 2024, our principal source of liquidity was $108.7 million of cash, cash equivalents and investments. We have had recurring losses since inception and incurred a loss of $76.4 million for the year ended December 31, 2024. 112 Table of Contents We anticipate that we will continue to incur significant operating losses in the foreseeable future.

As of December 31, 2025, our principal source of 114 Table of Contents liquidity was $63.7 million of cash, cash equivalents and investments. We have had recurring losses since inception and incurred an operating loss of $90.7 million for the year ended December 31, 2025. We anticipate that we will continue to incur significant operating losses in the foreseeable future.

Commitments, Contingencies and Contractual Obligations Operating Leases We are party to an operating lease of office and research space in Newton, Massachusetts, which was amended in November 2024 and under which we currently lease a total of 98,502 square feet of research and office space through September 30, 2025, which will be reduced to 52,224 square feet of solely office space from October 1, 2025 through September 30, 2030.

Commitments, Contingencies and Contractual Obligations Operating Leases We are party to an operating lease of office and research space in Newton, Massachusetts, which was amended in November 2024 and under which we currently lease a total of 52,224 square feet of office space through September 30, 2030.

Certain amounts are known at the time of sale based on contractual terms and are recorded pursuant to the most likely amount method, which is the single most likely amount in a range of possible considerations. Other amounts are estimated pursuant to the expected value method, which is the sum of probability-weighted amounts in a range of possible consideration amounts.

As of December 31, 2024, we had an accumulated deficit of $1.6 billion. We had net losses of $76.4 million, $143.1 million, and $165.3 million for the years ended December 31, 2024, 2023 and 2022, respectively. We recognized total revenue of $145.2 million in 2024, including $112.8 million of XPOVIO net product revenue and $32.4 million of license revenue.

As of December 31, 2025, we had an accumulated deficit of $1.8 billion. We had net losses of $196.0 million, $76.4 million, and $143.1 million for the years ended December 31, 2025, 2024 and 2023, respectively. We recognized total revenue of $146.1 million in 2025, including $114.9 million of XPOVIO net product revenue and $31.2 million of license revenue.

For additional information on the Amended Revenue Interest Agreement, see Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K.

The total amount payable under the Revenue Interest Financing Agreement will remain capped at $263.3 million. For additional information, see Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K.

Sources of Liquidity On September 14, 2019, we and certain of our subsidiaries entered into the Revenue Interest Financing Agreement with HCRx, which was subsequently amended on June 23, 2021, August 1, 2023 and May 8, 2024 (the “Revenue Interest Agreement” and, as amended, the “Amended Revenue Interest Agreement”), pursuant to which, HCRx paid us a total of $135.0 million, less certain transaction expenses.

In September, 2019, we and certain of our subsidiaries entered into the Revenue Interest Financing Agreement with certain entities managed by HCRx, which was subsequently 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 in July 2025 by HCRx to KKR in connection with its acquisition of a majority ownership stake in HCRx (the “Revenue Interest Agreement” and, as amended, the “Amended Revenue Interest Agreement”), pursuant to which, HCRx paid us a total of $135.0 million, less certain transaction expenses.

Based on our current business plan and current capital resources, combined with the uncertainty regarding the availability of additional funding or other strategic transactions and considering our debt service obligations and financial covenant to maintain minimum liquidity, 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.

If we are unable to raise capital 114 Table of Contents when needed or on acceptable terms, we would be forced to delay, reduce or eliminate our research and development programs and/or commercialization efforts ,” under the heading “ Risk Factors ” in this Annual Report on Form 10-K.

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 ,” under the heading “ Risk Factors ” in this Annual Report on Form 10-K.

If they are not distinct, they are combined with other promised goods or services to create a bundle of promised goods or services that are distinct. Distinct goods or services and distinct bundles of goods or services are considered performance obligations.

At contract inception, we evaluate all goods or services in the agreement to determine if they are distinct. If they are not distinct, they are combined with other promised goods or services to create a bundle of promised goods or services that are distinct. Distinct goods or services and distinct bundles of goods or services are considered performance obligations.

Item 6. [Reserved] 106 Table of Contents Item 7. Management’s D iscussion and Analysis of Financial Condition and Results of Operations The following discussion of our financial condition and results of operations should be read in conjunction with our consolidated financial statements and related notes included elsewhere in this report.

You should read the following discussion and analysis of our financial condition and results of operations in conjunction with our consolidated financial statements and related notes included elsewhere in this report.

Refinancing Transactions Our estimated value of the gain on extinguishment of debt, the embedded derivatives in the 2029 Notes (as defined above) and the liability-classified common stock warrants related to the Refinancing Transactions, were valued using methodologies that incorporate certain unobservable inputs including (i) the volatility of our common stock price, (ii) our estimated credit spread and (iii) an estimate of when the warrants will be exercised based on an option pricing model.

To date, our estimates have not been materially different than amounts actually incurred. 111 Table of Contents Financing Transactions Our estimated value of the gain or loss on extinguishment of debt, the embedded derivatives in our convertible notes and the liability-classified common stock warrants on our consolidated balance sheets were valued using methodologies that incorporate certain unobservable inputs including (i) the volatility of our common stock price, (ii) our estimated credit spread and (iii) an estimate of when the warrants will be exercised based on an option pricing model.

On May 8, 2024, we entered into a credit and guaranty agreement (the “Credit Agreement”) with certain existing lenders and HCRx, which provides for a senior secured term loan facility of $100.0 million.

In May 2024, we entered into a credit and guaranty agreement (the “Credit Agreement”) with certain existing lenders and HCRx, which was subsequently assigned by HCRx to KKR in connection with its acquisition of a majority ownership stake in HCRx in July 2025, which provides for a senior secured term loan facility of $100.0 million (the “Term Loan”).

Our future long-term capital requirements will depend on many factors, as described more fully in the risk factor entitled “ We will need additional funding to achieve our business objectives.

Additionally, the negotiation and consummation of a financing transaction or strategic alternative may be costly and time-consuming. Our future long-term capital requirements will depend on many factors, as described more fully in the risk factor entitled “ We will need additional funding or to enter into strategic alternatives to achieve our business objectives.

The future impact from remeasurements of the embedded derivatives and liability-classified common stock warrants will depend on a variety of factors, including movements in our stock price, and cannot be forecasted.

We also expect interest expense to increase as a result of higher debt balances and interest rates in 2026 following the Financing Transactions. The future impact of remeasurements of embedded derivatives and liability-classified common stock warrants will depend on a variety of factors, including movements in our stock price, and cannot be forecasted.

These costs represent expenses incurred across multiple programs or to support our general research and development operations. Research and development expenses for the year ended December 31, 2024 increased by $4.5 million as compared to the year ended December 31, 2023.

These costs represent expenses incurred across multiple programs or to support our general research and development operations. Research and development expenses for the year ended December 31, 2025 decreased by $17.6 million as compared to the year ended December 31, 2024, primarily due to lower personnel and stock-based compensation costs and reduced clinical trial spending.

License and Other Revenue (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Menarini $ 28,014 $ 24,360 $ 3,654 15 % Antengene 1,680 2,713 (1,033 ) (38 )% Other 2,737 6,949 (4,212 ) (61 )% Total license and other revenue $ 32,431 $ 34,022 $ (1,591 ) (5 )% License and other revenue for the year ended December 31, 2024 decreased by $1.6 million as compared to the year ended December 31, 2023 primarily due to a decrease in milestone-related revenue from our other license agreements, offset by an increase in milestone-related and royalty revenue from Menarini.

License and Other Revenue (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Menarini $ 28,308 $ 28,014 $ 294 1 % Antengene 2,330 1,680 650 39 % Other 572 2,737 (2,165 ) (79 )% Total license and other revenue $ 31,210 $ 32,431 $ (1,221 ) (4 )% License and other revenue for the year ended December 31, 2025 decreased by $1.2 million as compared to the year ended December 31, 2024 primarily due to a decrease in milestone-related revenue from our other license agreements.

In addition to the expenses required to fund our operations described above, our funding requirements as of December 31, 2024 also include the following: • Lease costs for our headquarters in Newton, Massachusetts of $10.9 million through September 30, 2030; • Future obligations related to the 2025 Notes of $25.2 million through October 2025; • Future obligations related to the 2029 Notes of $146.4 million through May 2029; • Future obligations related to the Credit Agreement of $142.7 million through May 2028 in addition to our requirement to maintain cash, cash equivalents and investments of at least $25.0 million at all times; and • Future royalty obligations to HCRx under the Amended Revenue Interest Agreement of $119.9 million by October 1, 2031.

In addition to the expenses required to fund our operations described above, our funding requirements as of December 31, 2025 also include the following: • Lease costs for our headquarters in Newton, Massachusetts of $9.4 million through September 30, 2030; • Future obligations related to the Amended Credit Agreement of $153.2 million through May 8, 2028 in addition to the financial covenant to maintain minimum liquidity; • Future obligations related to the 2028 Notes of $19.2 million through October 15, 2028; 117 Table of Contents • Future obligations related to the New 2029 Notes of $138.2 million through May 13, 2029; • Future royalty obligations to KKR under the Amended Revenue Interest Agreement of $116.2 million by September 26, 2035.

Research and Development Expenses (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Clinical trial and related costs: Selinexor in myelofibrosis $ 32,093 $ 13,319 $ 18,774 >100% Selinexor in multiple myeloma 17,320 15,287 2,033 13 % Selinexor in endometrial cancer 15,444 14,271 1,173 8 % Other programs 3,102 12,877 (9,775 ) (76 )% Non-program specific clinical trial and related costs 7,522 9,939 (2,417 ) (24 )% Total clinical trial and related costs 75,481 65,693 9,788 15 % Unallocated costs: Personnel costs 44,252 49,907 (5,655 ) (11 )% Consulting, professional and other 18,658 16,621 2,037 12 % Stock-based compensation 4,841 6,529 (1,688 ) (26 )% Total unallocated costs 67,751 73,057 (5,306 ) (7 )% Total research and development expenses $ 143,232 $ 138,750 $ 4,482 3 % At any one time, we have a number of ongoing clinical development programs that we are conducting independently or in collaboration with third parties.

Research and Development Expenses (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Clinical trial and related costs: Selinexor in myelofibrosis $ 37,054 $ 32,093 $ 4,961 15 % Selinexor in multiple myeloma 8,657 17,320 (8,663 ) (50 )% Selinexor in endometrial cancer 16,589 15,444 1,145 7 % Other programs 1,950 3,102 (1,152 ) (37 )% Non-program specific clinical trial and related costs 6,176 7,522 (1,346 ) (18 )% Total clinical trial and related costs 70,426 75,481 (5,055 ) (7 )% Unallocated costs: Personnel 35,325 44,252 (8,927 ) (20 )% Consulting, professional and other 15,768 18,658 (2,890 ) (15 )% Stock-based compensation 4,098 4,841 (743 ) (15 )% Total unallocated costs 55,191 67,751 (12,560 ) (19 )% Total research and development expenses $ 125,617 $ 143,232 $ (17,615 ) (12 )% At any one time, we have a number of ongoing clinical development programs that we are conducting independently or in collaboration with third parties.

We plan to continue to educate physicians, other healthcare providers and patients about XPOVIO’s clinical profile and unique mechanism of action as we continue to expand XPOVIO use. The commercialization of XPOVIO and NEXPOVIO ® (selinexor) (the brand name for selinexor in Europe and the United Kingdom) outside of the U.S. is managed by our partners in their respective territories.

The commercialization of XPOVIO and NEXPOVIO ® (selinexor) (the brand name for selinexor in Europe and the United Kingdom) outside of the U.S. is managed by our partners in their respective territories.

A discussion of changes in our financial condition for the year ended December 31, 2023 as compared to the year ended December 31, 2022 is included under the heading “ Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations ” in the 2023 Form 10-K.

The decrease was primarily driven by lower net proceeds from debt and equity financing in 2025 compared to 2024. A discussion of changes in our financial condition for the year ended December 31, 2024 as compared to the year ended December 31, 2023 is included under the heading “ Item 7.

A 10% increase or decrease in these estimates would impact net product revenue by a corresponding increase or decrease of approximately $4.0 million.

A 10% increase or decrease in these estimates would impact net product revenue by a corresponding increase or decrease of approximately $4.0 million. License Agreements We generate revenue from license or similar agreements with pharmaceutical companies for the development and commercialization of certain of our products and product candidates.

Funding Requirements We expect to continue to incur costs related to our clinical development programs as we continue to advance our lead clinical programs in myelofibrosis and our other late-stage clinical programs in endometrial cancer and multiple myeloma, as well as commercialization expenses related to sales, marketing, manufacturing and distribution of our approved products, to the extent that these functions are not the responsibility of our collaborators.

Contractual Obligations We have contractual obligations under our (i) Amended Credit Agreement; (ii) 2028 Notes; (iii) 9.00% convertible senior notes due 2029; and (iv) Amended Revenue Interest Agreement as disclosed in Note 10, “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K. 116 Table of Contents Funding Requirements We expect to continue to incur costs related to our clinical development programs as we continue to advance our lead clinical programs in myelofibrosis and endometrial cancer and our other late-stage clinical program in multiple myeloma, as well as commercialization expenses related to sales, marketing, manufacturing and distribution of our approved products, to the extent that these functions are not the responsibility of our collaborators.

We expect that our cash, cash equivalents and investments as of December 31, 2024 will be sufficient to fund our current operating plans and debt obligation requirements into the fourth quarter of 2025.

We expect that our existing liquidity, including cash, cash equivalents and investments as of December 31, 2025 as well as cash flow from net product revenue and license and other revenue, will enable us to fund our current operating plans into the second quarter of 2026.

The following table provides information regarding our cash flows (in thousands): For the Years Ended December 31, 2024 2023 $ Change % Change Net cash used in operating activities $ (127,486 ) $ (92,723 ) $ (34,763 ) 37 % Net cash provided by investing activities 95,473 7,940 87,533 >100% Net cash provided by financing activities 41,646 1,124 40,522 >100% Effect of exchange rates on cash, cash equivalents and restricted cash (11 ) (34 ) 23 (68 )% Net increase (decrease) in cash, cash equivalents and restricted cash $ 9,622 $ (83,693 ) $ 93,315 (>100)% Net Cash Used in Operating Activities The $34.8 million increase in net cash used in operating activities during the year ended December 31, 2024 as compared to the year ended December 31, 2023 was primarily driven by working capital changes, including the collection of $27.3 million of milestone payments from Antengene in 2023.

The following table provides information regarding our cash flows (in thousands): For the Years Ended December 31, 2025 2024 $ Change % Change Net cash used in operating activities $ (75,369 ) $ (127,486 ) $ 52,117 (41 )% Net cash provided by investing activities 43,378 95,473 (52,095 ) (55 )% Net cash provided by financing activities 30,048 41,646 (11,598 ) (28 )% Effect of exchange rates on cash, cash equivalents and restricted cash 20 (11 ) 31 (>100)% Net (decrease) increase in cash, cash equivalents and restricted cash $ (1,923 ) $ 9,622 $ (11,545 ) (>100)% Net Cash Used in Operating Activities Net cash used in operating activities decreased by $52.1 million during the year ended December 31, 2025 compared to the year ended December 31, 2024.

We expect license and other revenue to slightly decrease in 2025 as compared to 2024 primarily due to a decrease in milestone-related revenue from our partners. 110 Table of Contents Operating Expenses (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Cost of sales $ 6,007 $ 4,942 $ 1,065 22 % Research and development 143,232 138,750 4,482 3 % Selling, general and administrative 115,441 131,881 (16,440 ) (12 )% Total operating expenses $ 264,680 $ 275,573 $ (10,893 ) (4 )% Cost of Sales Cost of sales for the year ended December 31, 2024 was relatively consistent with the year ended December 31, 2023.

We expect license and other revenue to decrease as a result of the expiration of Menarini’s reimbursement of development-related expenses, which had previously provided up to $15.0 million in other revenue annually. 112 Table of Contents Operating Expenses (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Cost of sales $ 5,949 $ 6,007 $ (58 ) (1 )% Research and development 125,617 143,232 (17,615 ) (12 )% Selling, general and administrative 105,208 115,441 (10,233 ) (9 )% Total operating expenses $ 236,774 $ 264,680 $ (27,906 ) (11 )% Cost of Sales Cost of sales for the year ended December 31, 2025 was relatively consistent with the year ended December 31, 2024.

Relevant factors used in the expected value method include: current contractual and statutory requirements, specific known market events and trends, industry data, and forecasted customer buying and payment patterns. These reserves reflect our best estimates of the variable consideration based on the terms of the respective underlying contracts.

Other amounts are estimated pursuant to the expected value method, which is the 110 Table of Contents sum of probability-weighted amounts in a range of possible consideration amounts. Relevant factors used in the expected value method include: current contractual and statutory requirements, specific known market events and trends, industry data, and forecasted customer buying and payment patterns.

We expect our research and development expenses to decrease in 2025 as compared to 2024 due primarily to full enrollment in mid-2024 of our Phase 3 multiple myeloma study and decreased headcount costs, partially offset by an increase in expenses in connection with our ongoing Phase 3 trials in myelofibrosis and endometrial cancer. 111 Table of Contents Selling, General and Administrative Expenses (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Personnel costs $ 57,711 $ 66,465 $ (8,754 ) (13 )% Consulting, professional and other costs 44,371 50,606 (6,235 ) (12 )% Stock-based compensation 13,359 14,810 (1,451 ) (10 )% Total selling, general and administrative expenses $ 115,441 $ 131,881 $ (16,440 ) (12 )% Selling, general and administrative expenses for the year ended December 31, 2024 decreased by $16.4 million as compared to the year ended December 31, 2023.

In the event of positive top-line data in any of our trials, we would expect to incur incremental costs primarily associated with regulatory filings. 113 Table of Contents Selling, General and Administrative Expenses (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Personnel costs $ 51,535 $ 57,711 $ (6,176 ) (11 )% Consulting, professional and other costs 43,864 44,371 (507 ) (1 )% Stock-based compensation 9,809 13,359 (3,550 ) (27 )% Total selling, general and administrative expenses $ 105,208 $ 115,441 $ (10,233 ) (9 )% Selling, general and administrative expenses for the year ended December 31, 2025 decreased by $10.2 million as compared to the year ended December 31, 2024, primarily due to reductions in personnel-related costs.

In addition, HCRx purchased $5.0 million aggregate principal amount of the 2029 Notes through satisfaction of $5.0 million of our existing obligations to HCRx. Please refer to Note 10 “ Long-Term Obligations ”, to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K for additional details of the Refinancing Transactions.

See the notes to the consolidated financial statements included under Part II, Item 8 of this Annual Report on Form 10-K for additional information.

Proceeds from the maturities of investments decreased by $12.7 million in 2024, which was significantly offset by a decrease of $100.3 million in purchases of investments in 2024, due to liquidity needs to fund our operations.

Proceeds from the maturities of investments decreased by $111.1 million, partially offset by a $58.8 million decrease in purchases of investments, reflecting liquidity needs to fund our operations. Net Cash Provided by Financing Activities Net cash provided by financing activities decreased by $11.6 million during the year ended December 31, 2025 compared to the year ended December 31, 2024.

In addition, under the Menarini Agreement, Menarini will reimburse us for 25% of all development related expenses we incur for selinexor from 2022 through 2025, provided that such reimbursements shall not exceed $15.0 million per calendar year. We received $15.0 million of reimbursements for development related expenses under the Menarini Agreement during the year ended December 31, 2024.

In addition, Menarini reimbursed us $15.0 million per calendar year, or $60 million in total, for development related expenses we incurred for selinexor from 2022 through 2025.

Other Income (Expense), net (in thousands, except for percentages) For the Years Ended December 31, 2024 2023 $ Change % Change Interest expense $ (37,422 ) $ (23,823 ) $ (13,599 ) 57 % Interest income 7,400 10,943 (3,543 ) (32 )% Gain on extinguishment of debt 44,702 — 44,702 100 % Other income (expense), net 28,398 (356 ) 28,754 (>100)% Total other income (expense), net $ 43,078 $ (13,236 ) $ 56,314 (>100)% Other income (expense), net for the year ended December 31, 2024 increased by $56.3 million as compared to the year ended December 31, 2023, primarily due to a $44.7 million gain on extinguishment of debt from the Refinancing Transactions and a $28.7 million gain from the remeasurement of embedded derivatives and liability-classified common stock warrants, both of which are non-cash items.

Other Income (Expense), net (in thousands, except for percentages) For the Years Ended December 31, 2025 2024 $ Change % Change Interest expense $ (45,849 ) $ (37,422 ) $ (8,427 ) 23 % Interest income 2,773 7,400 (4,627 ) (63 )% (Loss) gain on extinguishment of debt (62,365 ) 44,702 (107,067 ) (>100)% Other income, net 152 28,398 (28,246 ) (99 )% Total other (expense) income, net $ (105,289 ) $ 43,078 $ (148,367 ) (>100)% Total other (expense) income, net for the year ended December 31, 2025 increased by $148.4 million compared to the year ended December 31, 2024.

The $9.8 million increase in clinical trial and related costs was primarily due to increased activity in each of our ongoing Phase 3 trials, including increased purchases of comparator drugs. These increases were partially offset by a $9.8 million decrease in clinical trial and related costs in other programs.

These decreases were partially offset by a $5.0 million increase in clinical trial and related costs for selinexor in myelofibrosis, primarily driven by increased trial activity and higher patient enrollment. We expect our research and development expenses to increase as we continue to support our ongoing Phase 3 trials as they progress from the enrollment phase to the maintenance phase.

We currently expect that cash, cash equivalents and investments as of December 31, 2024 will be sufficient to fund our current operating plans and debt obligation requirements into the fourth quarter of 2025 while we continue to commercialize XPOVIO in the U.S. and continue the clinical trials of our product candidates.

We currently 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 the second quarter of 2026.

We also exchanged, pursuant to privately negotiated agreements, an aggregate principal amount of $148.0 million of our existing 3.00% unsecured convertible senior notes due 2025 (the “2025 Notes”) for (i) $111.0 million aggregate principal amount of new 6.00% secured convertible senior notes due 2029 (the “2029 Notes”) and (ii) warrants to purchase up to 45.8 million shares of our common stock.

We received aggregate gross proceeds of approximately $8.8 million. In October 2025, we entered into a note purchase agreement pursuant to which issued and sold, in a private placement, $15.0 million aggregate principal amount of new 9.00% senior secured convertible notes due 2028 (the “2028 Notes”) to certain holders of our existing 6.00% senior secured convertible notes due 2029.

We expect other income (expense), net to decrease in 2025 as compared to 2024 due to the $44.7 million gain on extinguishment of debt being a one-time, non-recurring item.

Lastly, interest income decreased by $4.6 million due to lower investment balances in 2025 compared to 2024. We expect total other (expense) income, net to decrease, primarily due to the debt extinguishment recorded in 2025 in connection with the Financing Transactions.

Net Cash Provided by Financing Activities The $40.5 million increase in net cash provided by financing activities during the year ended December 31, 2024 as compared to the year ended December 31, 2023 was primarily driven by $83.3 million of proceeds from the Term Loan, partially offset by a $40.5 million payment of our deferred royalty obligation to HCRx and a $2.6 million payment of debt issuance costs related to the Refinancing Transactions.

The decrease was primarily driven by lower cash disbursements resulting from reduced operating expenses and the deferral of cash interest and royalty payments associated with the Financing Transactions. Net Cash Provided by Investing Activities Net cash provided by investing activities decreased by $52.1 million during the year ended December 31, 2025 compared to the year ended December 31, 2024.

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Item 6. [Reserved] 108 Table of Contents Item 7.

Removed

As announced in January 2024, further clinical development of our eltanexor program continues to remain on hold in an effort to focus our resources on our prioritized late-stage programs.

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Management’s D iscussion and Analysis of Financial Condition and Results of Operations The following discussion and analysis of our financial condition and results of operations is meant to provide material information relevant to an assessment of the financial condition and results of operations of our company, including an evaluation of the amounts and uncertainties of cash flows from operations and from outside resources, so as to allow investors to better view our company from management’s perspective.

Removed

Pursuant to these transactions, we borrowed $100.0 million from existing lenders and certain entities managed by HealthCare Royalty Management, LLC (“HCRx”) under a $100.0 million senior secured term loan facility (the “Term Loan”) and used a portion of the proceeds of the Term Loan to repay obligations under our existing financing arrangement with HCRx pursuant to an amendment that made other changes to our 107 Table of Contents existing financing arrangement with HCRx.

Added

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License Agreements We generate revenue from license or similar agreements with pharmaceutical companies for the development and commercialization of certain of our products and product candidates. 108 Table of Contents At contract inception, we evaluate all goods or services in the agreement to determine if they are distinct.

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In September 2025, we completed enrollment in our ongoing Phase 3 clinical trial to evaluate the efficacy and safety of once-weekly selinexor in combination with ruxolitinib versus placebo plus ruxolitinib in JAK2 inhibitor (“JAKi”)-naive myelofibrosis patients (the “SENTRY Trial”). We expect to report top-line data from the SENTRY Trial in March 2026.

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To date, our estimates have not been materially different than amounts actually incurred.

Added

We continue to enroll JAKi-naïve myelofibrosis patients in the Phase 2 clinical trial to evaluate the safety and efficacy of selinexor as a monotherapy in patients with JAKi-naïve myelofibrosis with moderate thrombocytopenia (the “SENTRY-2 Trial”). The protocol, as amended in 2025, 109 Table of Contents includes patients with platelet counts above 50,000 per microliter.

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XPOVIO net product revenue was adversely impacted year-over-year by higher gross-to-net adjustments in 2024, driven primarily by 340B discounts and Medicare rebates. We expect net product revenue to increase in 2025 as compared to 2024 due to demand growth.

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We expect to report top-line data from all patients in the 60 mg cohort with at least 24 weeks of follow-up in the second half of 2026.

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We expect cost of sales to remain relatively consistent in 2025 as compared to 2024.

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We are continuing to enroll patients in a global, Phase 3, randomized, double-blind trial evaluating selinexor as a maintenance-only therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “XPORT-EC-042 Trial”). We expect to report top-line data from this event-driven trial in mid-2026.

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The decrease in personnel costs of $5.7 million was primarily due to a reduction in headcount and contractors for the year ended December 31, 2024 as compared to the year ended December 31, 2023 due to the realization of previously implemented cost reduction initiatives.

Added

Removed

The decrease in personnel costs of $8.8 million and the decrease in stock-based compensation of $1.5 million were primarily due to a reduction in headcount and contractors for the year ended December 31, 2024 as compared to the year ended December 31, 2023 due to our ongoing cost reduction initiatives.

Added

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The decrease in consulting, professional and other costs of $6.2 million was primarily due to lower commercial-related activities in connection with cost optimization efforts during 2024. We expect our selling, general and administrative expenses to slightly decrease in 2025 as compared to 2024 due to continued realization of previously implemented cost reduction initiatives.

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In addition, we reduced the exercise price of outstanding warrants to purchase 3,068,417 shares from $16.50 to $6.64 per share.

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These gains were partially offset by an increase in interest expense related to the Term Loan and the 2029 Notes and a decrease in interest income resulting from lower investment balances in 2024 as compared to 2023.

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We also expect increased interest expense in 2025 as compared to 2024 on the Term Loan and the 2029 Notes, as both of these instruments were issued in May 2024, and 2025 will include a full year of interest expense on these instruments.

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Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

478 edited+174 added−170 removed956 unchanged

2024 filing

2025 filing

Biggest changeOur ability to become and remain profitable depends significantly on our success in many areas, including: • effectively commercializing XPOVIO or any future products either on our own or with a collaborator, including by maintaining a full commercial organization required to market, sell and distribute our products, and achieving an adequate level of market acceptance; • the impact of current or future competing products on product sales of XPOVIO or any of our future products; • obtaining sufficient pricing, coverage and reimbursement, including government pricing and reimbursement policies or a change in the mix of our business effecting rebates related to 340B Programs, Medicare and Medicaid, for XPOVIO and any of our other approved products from private and government payers and the impact of any pricing changes, any of which can impact our gross-to-net provisions related to product sales; • initiating and successfully completing clinical trials required to file for, obtain and maintain marketing approval for our product candidates; • obtaining and maintaining regulatory approvals, either by us or our collaborators, and the timing of such approvals; • manufacturing at commercial scale; • establishing and managing any collaborations for the development, marketing and/or commercialization of our products and product candidates, including the level of success of our collaborators’ efforts and the timing and amount of any milestone or royalty payments we may receive; • obtaining, maintaining and protecting our intellectual property rights; • the willingness of patients to pay out-of-pocket in the absence of third-party coverage or as co-pay amounts under third-party coverage; for example, multiple myeloma foundation closures during 2023 resulted in significantly increased use of our PAP, which adversely impacted our 2023 revenues; and • navigating the negative impacts to healthcare systems, the ability of our clinical trial sites to conduct current or future trials and the regulatory review process as the result of pandemics or other public health emergencies. 83 Table of Contents We anticipate that our operating expenses will continue to be significant and increase as we continue to: • commercialize XPOVIO in the U.S., including maintaining our commercial infrastructure, and engage in activities to prepare for the potential approval and commercialization of additional indications for selinexor; • obtain and/or maintain regulatory approval for XPOVIO and our product candidates, including completing any required post-marketing requirements to the satisfaction of the FDA or other regulatory agencies; • expand our research and development programs, identify additional product candidates and initiate and conduct clinical trials, including clinical trials required by the FDA or other regulatory agencies in addition to those that have been or are currently expected to be conducted; • maintain, expand and protect our intellectual property portfolio; • manufacture XPOVIO and our product candidates; and • acquire or in-license other products, product candidates or technologies.

Biggest changeOur ability to become and remain profitable depends significantly on our success in many areas, including: • effectively commercializing XPOVIO or any future products either on our own or with a collaborator, including by maintaining a full commercial organization required to market, sell and distribute our products, and achieving an adequate level of market acceptance; • the impact of current or future competing products on product sales of XPOVIO or any of our future products; • obtaining sufficient pricing, coverage and reimbursement, including government pricing and reimbursement policies or a change in the mix of our business 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 trials in myelofibrosis and endometrial cancer, with top-line data from both trials anticipated in 2026; • obtaining and maintaining regulatory approvals, either by us or our collaborators, and the timing of such approvals; • placement of selinexor in the treatment recommendations adopted by the National Comprehensive Cancer Network and similar guidelines; • manufacturing at commercial scale; • establishing and managing any collaborations for the development, marketing and/or commercialization of our products and product candidates, including the level of success of our collaborators’ efforts and the timing and amount of any milestone or royalty payments we may receive; • obtaining, maintaining and protecting our intellectual property rights; 55 Table of Contents • the willingness of patients to pay out-of-pocket in the absence of third-party coverage or as co-pay amounts under third-party coverage; for example, multiple myeloma foundation closures during 2023 resulted in significantly increased use of our Patient Assistance Program, which adversely impacted our 2023 revenues; and • navigating the negative impacts to healthcare systems, the ability of our clinical trial sites to conduct current or future trials and the regulatory review process.

We are building upon our existing U.S. multiple myeloma foundation as we continue to expand the breadth and depth of XPOVIO’s use across lines of therapy in the relapsed/refractory setting, focusing on growing sales in our approved U.S. indications by establishing XPOVIO as a novel effective modality.

We are building upon our existing U.S. multiple myeloma foundation as we continue to expand the breadth and depth of XPOVIO’s use across lines of therapy in the relapsed/refractory setting, focusing on growing sales in our approved U.S. multiple myeloma indications by establishing XPOVIO as a novel effective modality.

Manufacturing We do not own or operate, and have no plans to establish, any manufacturing facilities for our products or product candidates. We currently rely, and expect to continue to rely, on third-party contract manufacturers to manufacture our products and product candidates for our commercial and clinical use.

We do not own or operate, and currently have no plans to establish, any manufacturing facilities for our products or product candidates. We currently rely, and expect to continue to rely, on third-party contract manufacturers to manufacture our products and product candidates for our commercial and clinical use.

Moreover, FDORA established expedited procedures authorizing the FDA to withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence demonstrates the product is not shown to be safe or effective under the conditions of use.

Moreover, FDORA established expedited procedures authorizing FDA to withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence demonstrates the product is not shown to be safe or effective under the conditions of use.

Arrangements with providers, consultants, third-party payors, and customers are subject to broadly applicable fraud and abuse, anti-kickback, false claims laws, reporting of payments to healthcare providers and patient privacy laws and regulations and other healthcare laws and regulations that may constrain our business and/or financial arrangements.

Arrangements with providers, consultants, third-party payors, and customers are subject to broadly applicable fraud and abuse, anti-kickback, false claims laws, reporting of payments to healthcare providers, patient privacy laws and regulations, and other healthcare laws and regulations that may constrain our business and/or financial arrangements.

In the U.S., approval and reimbursement decisions are not linked directly, but there is increasing scrutiny from the Congress, regulatory authorities, payers, patients and pathway organizations of the pricing of pharmaceutical products. Adverse pricing limitations may also hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.

In the U.S., approval and reimbursement decisions are not linked directly, but there is increasing scrutiny from Congress, regulatory authorities, payers, patients and pathway organizations of the pricing of pharmaceutical products. Adverse pricing limitations may also hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval.

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

Although single-arm trials have been commonly used to support accelerated approval, a randomized controlled trial is the preferred approach as it provides a more robust efficacy and safety assessment and allows for direct comparisons to an available therapy.

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.

For Fast Track products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a Fast Track product’s application before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a Fast Track product may be effective.

Orphan drug exclusivity may also be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients with the rare disease or condition. In 2017, the Congress passed the FDA Reauthorization Act of 2017 (the “FDARA”).

Orphan drug exclusivity may also be lost if the FDA or EMA determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of the patients with the rare disease or condition. In 2017, Congress passed the FDA Reauthorization Act of 2017 (the “FDARA”).

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

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

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

We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures.

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.

Additionally, OCR is looking to amend the HIPAA Security Rule, which (if and when finalized) could create additional compliance obligations and risk for our business. In addition to potential enforcement by the HHS, we could also be potentially subject to privacy enforcement from the Federal Trade Commission (the “FTC”).

Additionally, OCR is looking to amend the HIPAA Security Rule, which (if and when finalized) could create additional compliance obligations and risk for our business. In addition to potential enforcement by HHS, we could also be potentially subject to privacy enforcement from the Federal Trade Commission (the “FTC”).

The FTC has been particularly focused on the unpermitted processing of health and genetic data through its recent enforcement actions and is expanding the types of privacy violations that it interprets to be “unfair” under Section 5 of the FTC Act, as well as the types of activities it views to trigger the Health Breach Notification Rule (which the FTC also has the authority to enforce).

States are also active in creating specific rules relating to the processing of personal information. In 2018, California passed into law the California Consumer Privacy Act (the “CCPA”), which took effect on January 1, 2020 and imposed many requirements on businesses that process the personal information of California residents.

The CCPA also affords California residents the right to opt-out of “sales” of their personal information. The CCPA contains significant penalties for companies that violate its requirements.

In November 2020, California voters passed a ballot initiative for the California Privacy Rights Act (the “CPRA”), which went into effect on January 1, 2023 and significantly expanded the CCPA to incorporate additional GDPR-like provisions including requiring that the use, retention and sharing of personal information of California residents be reasonably necessary and proportionate to the purposes of collection or processing, granting additional protections for sensitive personal information, and requiring greater disclosures related to notice to residents regarding retention of information.

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.

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

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.

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.

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. 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.

XPOVIO is currently approved and marketed in the U.S. in multiple hematologic malignancy indications, including in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and under accelerated approval as a monotherapy for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (“DLBCL”), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

Collaborations involving our products and product candidates pose the following risks to us: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not perform their obligations as expected or in compliance with applicable local and national laws and regulatory requirements; • collaborators may not pursue development, marketing and/or commercialization of our products or product candidates or may elect not to continue or renew development, marketing or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators may pursue a clinical and/or regulatory strategy for registration outside of the U.S. that would require our assistance and we may not have the resources to meet their or the regulators’ timelines and/or expectations, which could delay or limit the development, commercialization or approval of our products outside the U.S.; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • 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; 89 Table of Contents • 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; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • we may lose certain valuable rights under circumstances identified in any collaboration arrangement that we enter into, such as if we undergo a change of control; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development, marketing and/or commercialization of the applicable products or product candidates or to enter into new collaboration agreements; • collaborators may learn about our discoveries and use this knowledge to compete with us in the future; and • the number and type of our collaborations could adversely affect our attractiveness to other collaborators or acquirers.

Collaborations involving our products and product candidates pose the following risks to us: • collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations; • collaborators may not perform their obligations as expected or in compliance with applicable local and national laws and regulatory requirements; • collaborators may not pursue development, marketing and/or commercialization of our products or product candidates or may elect not to continue or renew development, marketing or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators may pursue a clinical and/or regulatory strategy for registration outside of the U.S. that would require our assistance and we may not have the resources to meet their or the regulators’ timelines and/or expectations, which could delay or limit the development, commercialization or approval of our products outside of the U.S.; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • 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; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • we may lose certain valuable rights under circumstances identified in any collaboration arrangement that we enter into, such as if we undergo a change of control; • collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development, marketing and/or commercialization of the applicable products or product candidates or to enter into new collaboration agreements; • collaborators may learn about our discoveries and use this knowledge to compete with us in the future; and • the number and type of our collaborations could adversely affect our attractiveness to other collaborators or acquirers.

In December 2019, former President Trump signed legislation intended to facilitate the development of generic and biosimilar products. The bill, previously known as the CREATES Act, authorizes sponsors of abbreviated new drug applications (“ANDAs”) and 505(b)(2) applications to file lawsuits against companies holding NDAs that decline to provide sufficient quantities of an approved reference drug on commercially reasonable, market-based terms.

In December 2019, President Trump signed legislation intended to facilitate the development of generic and biosimilar products. The bill, previously known as the CREATES Act, authorizes sponsors of Abbreviated New Drug Applications (“ANDAs”) and 505(b)(2) applications to file lawsuits against companies holding NDAs that decline to provide sufficient quantities of an approved reference drug on commercially reasonable, market-based terms.

In addition to our XPO1 inhibitor, a number of non-chemotherapy drugs such as PIs, IMiDs, mAbs, bispecific antibodies, and chimeric antigen receptor T-cell (“CAR-T”) therapy, have also emerged as treatment options within the last two decades. The introduction of these non-chemotherapeutic novel agents has led to a significant increase in the survival of patients with multiple myeloma.

In addition to our XPO1 inhibitor, a number of non-chemotherapy drugs and biologics such as PIs, IMiDs, mAbs, bispecific antibodies, and chimeric antigen receptor T-cell (“CAR-T”) therapy, have also emerged as treatment options within the last two decades. The introduction of these non-chemotherapeutic novel agents has led to a significant increase in the survival of patients with multiple myeloma.

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

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).

Although we intend to comply fully with the terms of these statutory provisions, we are still exposed to potential litigation and damages by competitors who may claim that we are not providing sufficient quantities of our approved products on commercially reasonable, market-based terms for testing in support of ANDAs and 505(b)(2) applications.

Although we have and intend to comply fully with the terms of these statutory provisions, we are still exposed to potential litigation and damages by competitors who may claim that we are not providing sufficient quantities of our approved products on commercially reasonable, market-based terms for testing in support of ANDAs and 505(b)(2) applications.

Rangwala served as Vice President, Medical, at Genmab Inc., an international biotechnology company, from 2017 to July 2020. Prior to that, Dr. Rangwala served as Executive Clinical Director at Merck & Co., a biopharmaceutical company, from 2012 to 2017. Dr. Rangwala received her B.S. in Biology from Duke University and her M.D./Ph.D. from the University of Cincinnati College of Medicine.

Rangwala served as Vice President, Medical, at Genmab Inc., an international biotechnology company, from 2017 to 2020. Prior to that, Dr. Rangwala served as Executive Clinical Director at Merck & Co., a biopharmaceutical company, from 2012 to 2017. Dr. Rangwala received her B.S. in Biology from Duke University and her M.D./Ph.D. from the University of Cincinnati College of Medicine.

All patients must have received at least two prior lines of therapy, and either have progressed after or are not eligible to receive CAR-T or bispecific antibody treatment. The primary endpoints of this trial are to assess the ORR and the clinical benefit rate. Key secondary endpoints include PFS, OS and DOR.

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

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

We are focused on advancing our lead clinical programs in myelofibrosis and our other late-stage clinical programs in endometrial cancer and multiple myeloma. Our clinical pipeline has been consciously and strategically focused to target cancers with high unmet need based on the potential to provide meaningful clinical benefit to patients and compelling supportive data.

We are focused on advancing our lead clinical programs in myelofibrosis and endometrial cancer and our other late-stage clinical program in multiple myeloma. Our clinical pipeline has been consciously and strategically focused to target cancers with high unmet need based on the potential to provide meaningful clinical benefit to patients and compelling supportive data.

Notably, the FDA acknowledged that the magnitude of benefit achieved from checkpoint inhibitors is less for patients with pMMR tumors compared to patients with dMMR tumors. The FDA recommended that we modify the EC-042 Trial to only enroll patients with TP53 wild-type and pMMR tumors, and redesign the trial to account for the current U.S. treatment landscape.

Notably, the FDA acknowledged that the magnitude of benefit achieved from checkpoint inhibitors is less for patients with pMMR tumors compared to patients with dMMR tumors. The FDA recommended that we modify the XPORT-EC-042 Trial to only enroll patients with TP53 wild-type and pMMR tumors, and redesign the trial to account for the current U.S. treatment landscape.

This CJEU decision resulted in increased scrutiny on data transfers and increased our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners. In October 2022, President Biden signed an executive order to implement the EU-U.S.

This CJEU decision resulted in increased scrutiny on data transfers and increased our costs of compliance with data privacy legislation as well as our costs of negotiating appropriate privacy and security agreements with our vendors and business partners. In October 2022, former President Biden signed an executive order to implement the EU-U.S.

We are also eligible to receive double-digit royalties on future net sales in the Promedico Territory. Promedico received the exclusive rights to commercialize XPOVIO in the Promedico Territory and is responsible for all regulatory filings and obligations required for registering XPOVIO. We have retained exclusive production rights and will supply finished product for commercial use in the Promedico Territory.

We are also eligible to receive double-digit royalties on net sales in the Promedico Territory. Promedico received the exclusive rights to commercialize XPOVIO in the Promedico Territory and is responsible for all regulatory filings and obligations required for registering XPOVIO. We have retained exclusive production rights and will supply finished product for commercial use in the Promedico Territory.

The FDA also imposes requirements for costly post-marketing studies or clinical trials to maintain approval of any products that received accelerated or conditional approval. For drugs approved under the FDA’s Accelerated Approval Program, the FDA typically requires post-marketing confirmatory trials to evaluate the anticipated effect on irreversible morbidity or mortality or other clinical benefit.

The FDA also imposes requirements for costly post-marketing studies or clinical trials to maintain approval of any products that received accelerated approval. For drugs approved under the FDA’s Accelerated Approval Program, the FDA typically requires post-marketing confirmatory trials to evaluate the anticipated effect on irreversible morbidity or mortality or other clinical benefit.

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.

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.

Further, in connection with the EC-042 Trial, we entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne ® CDx, a tissue-based next generation sequencing test to identify and enroll patients whose tumors are TP53 wild-type.

Further, in connection with the XPORT-EC-042 Trial, we entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne ® CDx, a tissue-based next generation sequencing test to identify and enroll patients whose tumors are TP53 wild-type.

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.

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.

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: • need to delay, limit or terminate ongoing or planned clinical trials; • be delayed in obtaining, or not obtain at all, marketing approval for the indication or product candidate; • obtain marketing approval in some countries and not in others; • obtain approval for indications or patient populations that are not as broad as intended or desired; 56 Table of Contents • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings; • be subject to additional post-marketing testing requirements; • not receive royalty or milestone revenue under our collaboration agreements for several years, or at all; or • have the product removed from the market after obtaining marketing approval.

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: • need to delay, limit or terminate ongoing or planned clinical trials; • be delayed in obtaining, or not obtain at all, marketing approval for the indication or product candidate; • obtain marketing approval in some countries and not in others; • obtain approval for indications or patient populations that are not as broad as intended or desired; • obtain approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings; • be subject to additional post-marketing testing requirements; • not receive royalty or milestone revenue under our collaboration agreements for several years, or at all; or • have the product removed from the market after obtaining marketing approval.

Rangwala joined Karyopharm in April 2022 as Executive Vice President, Chief Medical Officer, with more than a decade of experience in oncology and drug development. Dr. Rangwala served as Chief Medical Officer of Aravive, Inc., a public oncology company, from September 2020 to April 2022. Prior to that, Dr.

Our Code of Business Conduct and Ethics, Corporate Governance Guidelines and the charters of the Audit, Compensation, Nominating, Corporate Governance & Compliance and Commercialization and Portfolio Committees of our Board of Directors are all available on our website at https://www.karyopharm.com at the “Investors” section under “Corporate Governance.” Stockholders may request a free copy of any of these documents by writing to Investor Relations, Karyopharm Therapeutics Inc., 85 Wells Avenue, 2 nd floor, Newton, Massachusetts 02459, U.S.A. 52 Table of Contents Item 1A .

Our Code of Ethics and Business Conduct, Corporate Governance Guidelines and the charters of the Audit, Compensation, Nominating, Corporate Governance & Compliance and Commercialization and Portfolio Committees of our Board of Directors are all available on our website at https://www.karyopharm.com at the “Investors” section under “Corporate Governance.” Stockholders may request a free copy of any of these documents by writing to Investor Relations, Karyopharm Therapeutics Inc., 85 Wells Avenue, 2 nd floor, Newton, Massachusetts 02459, U.S.A. 53 Table of Contents Item 1A .

The figure below depicts the process by which our SINE compounds inhibit the XPO1-mediated nuclear export of tumor suppressor proteins, oncoprotein mRNAs and the glucocorticoid receptor. 8 Table of Contents We believe that the unique mechanism of action, oral administration and low levels of major organ toxicities observed to date in patients treated with our SINE compounds, along with encouraging efficacy data, support the potential for their broad use across many cancer types, including both hematological and solid tumor malignancies.

The figure below depicts the process by which our compounds inhibit the XPO1-mediated nuclear export of tumor suppressor proteins, oncoprotein mRNAs and the glucocorticoid receptor. 8 Table of Contents We believe that the unique mechanism of action, oral administration and low levels of major organ toxicities observed to date in patients treated with our XPO1 inhibitor compounds, along with encouraging efficacy data, support the potential for their broad use across many cancer types, including both hematological and solid tumor malignancies.

The underlying causes of primary myelofibrosis are not clear; however, myelofibrosis is associated with specific well-described DNA changes (mutations) in certain genes. There is currently no drug therapy that can cure myelofibrosis.

The underlying causes of myelofibrosis are not clear; however, myelofibrosis is associated with specific well-described DNA changes (mutations) in certain genes. There is currently no drug therapy that can cure myelofibrosis.

These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the EU with the intention to import the active pharmaceutical ingredients into the EU; and • the marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU notably under Directive 2001/83/EC, as amended, and are also subject to EU Member State laws.

These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients (“API”), including the manufacture of APIs outside of the EU with the intention to import the APIs into the EU; and • the marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU notably under Directive 2001/83/EC, as amended, and are also subject to EU Member State laws.

However, a number of patients have 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.

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.

The ESSENTIAL Trial Our evaluation of selinexor to treat myelofibrosis is also supported by data from the ongoing Phase 2 ESSENTIAL trial, an investigator-sponsored open-label, prospective trial evaluating single-agent selinexor at a dose of 80 mg, 60 mg or 40 mg once weekly in adult patients with primary or secondary myelofibrosis with resistance or intolerance to JAKi therapy (the “ESSENTIAL Trial”; NCT03627403).

The ESSENTIAL Trial Our evaluation of selinexor to treat myelofibrosis is also supported by data from the completed Phase 2 ESSENTIAL trial, an investigator-sponsored open-label, prospective trial evaluating single-agent selinexor at a dose of 80 mg, 60 mg or 40 mg once weekly in adult patients with primary or secondary myelofibrosis with resistance or intolerance to JAKi therapy (the “ESSENTIAL Trial”; NCT03627403).

Participants in the SIENDO Trial with advanced or recurrent disease who had a partial response (“PR”) or complete 12 Table of Contents response (“CR”) after at least 12 weeks of standard of care taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression.

Participants in the SIENDO Trial with advanced or recurrent disease who had a partial response (“PR”) or complete response (“CR”) after at least 12 weeks of standard of care taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life- threatening or chronically debilitating condition, (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life- threatening or chronically debilitating condition, (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not 47 Table of Contents generate sufficient return in the EU to justify investment and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition.

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

In the selinexor-treated patients with TP53 wild-type and pMMR and TP53 wild-type and dMMR endometrial cancer, median PFS was 39.5 months and 13.1 months, respectively, compared to 4.9 months and 3.7 months, respectively. The updated analyses also highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (“Q-TWiST”) used to assess quality and toxicity-adjusted PFS.

In the selinexor-treated patients with TP53 wild-type and pMMR and TP53 wild-type and dMMR endometrial cancer, median PFS was 39.5 months and 13.1 months, respectively, compared to 4.9 months and 3.7 months, respectively, for placebo. The updated analyses also highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (“Q-TWiST”) used to assess quality and toxicity-adjusted PFS.

Such conditional approvals may be granted for product candidates (including medicines designated as orphan medicinal products) if (1) the product candidate is intended for the treatment, prevention, or medical diagnosis of seriously debilitating or life-threatening diseases; (2) the product candidate is intended to meet unmet medical needs of patients; (3) the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required; (4) the risk-benefit balance of the product candidate is positive, and (5) it is likely that the sponsor will be in a position to provide the required comprehensive clinical trial data.

Such conditional approvals may be granted for product candidates (including medicines designated as orphan medicinal products) if (1) the product candidate is intended for the treatment, prevention, or medical diagnosis of seriously debilitating or life-threatening diseases; (2) the product candidate is intended to meet unmet medical needs of patients; (3) the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are 45 Table of Contents still required; (4) the risk-benefit balance of the product candidate is positive, and (5) it is likely that the sponsor will be in a position to provide the required comprehensive clinical trial data.

The failure of a sponsor to comply with applicable requirements under the FDCA and other applicable laws at any time during the product development process, approval process or after approval may subject a sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities.

The failure of a sponsor to comply with applicable requirements under the FDCA and other applicable laws at any time during the product development process, approval process or after approval may subject a sponsor to a variety of administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial suspension of production or distribution, 24 Table of Contents injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities.

For example, with the enactment of the Tax Cuts and Jobs Act of 2017 (the “TCJA”), which was signed by President Trump in December 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019. In June 2021, the U.S.

Moreover, FDORA established expedited procedures authorizing FDA to 65 Table of Contents withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence demonstrates the product is not shown to be safe or effective under the conditions of use.

Moreover, FDORA established expedited procedures authorizing the FDA to withdraw an accelerated approval if certain conditions are met, including where a required confirmatory study fails to verify and describe the predicted clinical benefit or where evidence 32 Table of Contents demonstrates the product is not shown to be safe or effective under the conditions of use.

Until such time, if ever, as we can generate substantial revenues from the sale of our products, we expect to finance our cash needs through a combination of equity offerings, debt financings and refinancings, collaborations, strategic alliances and/or licensing arrangements. We do not have any committed external source of funds.

Until such time, if ever, as we can generate substantial revenues from the sale of our products, we expect to finance our cash needs through a combination of equity offerings, debt financings and refinancings, collaborations, strategic alliances and/or licensing arrangements or asset sales. We do not have any committed external source of funds.

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

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

Healthcare Compliance In the U.S., biopharmaceutical manufacturers and their products are subject to extensive regulation at the federal and state level, such as laws intended to prevent fraud and abuse in the healthcare industry. Healthcare providers and third-party payors play a primary role in the recommendation and prescription of pharmaceutical products that are granted marketing approval.

Healthcare Compliance In the U.S., biopharmaceutical manufacturers and their products are subject to extensive regulation at the federal and state level, such as laws intended to prevent fraud and abuse in the healthcare industry. Healthcare providers and third-party payors play a primary role in the recommendation, prescription, coverage, and reimbursement of pharmaceutical products that are granted marketing approval.

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

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

Some of our 2024 initiatives included continuing support for the scientific, medical, patient, and local communities in which we operate, including patient education, public health, quality of healthcare, and disease awareness. We also enable our employees to participate in various charity events, including walks, races, and other events that impact change in the communities of the patients we serve.

Some of our 2025 initiatives included continuing support for the scientific, medical, patient, and local communities in which we operate, including patient education, public health, quality of healthcare, and disease awareness. We also enable our employees to participate in various charity events, including walks, races, and other events that impact change in the communities of the patients we serve.

The primary endpoint of the EC-042 Trial is progression-free survival (“PFS”) as assessed by an investigator and OS as the key secondary endpoint.

The primary endpoint of the XPORT-EC-042 Trial is progression-free survival (“PFS”) as assessed by an investigator and OS is the key secondary endpoint.

Other T-cell engaging therapies, bispecifics with different targets, and immunomodulators are in clinical development and may be introduced into the multiple myeloma market in 2025 and beyond. CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) and Abecma ® (idecabtagene vicleucel; ide-cel) were approved in April 2024 for the treatment of multiple myeloma in earlier lines.

Other T-cell engaging therapies, bispecifics with different targets, and immunomodulators are in clinical development and may be introduced into the multiple myeloma market in 2026 and beyond. CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) and Abecma ® (idecabtagene vicleucel; ide-cel) were approved in April 2024 for the treatment of multiple myeloma in earlier lines.

Other T-cell engaging therapies, bispecifics with different targets, and immunomodulators are in clinical development and may be introduced into the multiple myeloma market in 2025 and beyond. CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) and Abecma® (idecabtagene vicleucel; ide-cel) were approved in April 2024 for the treatment of multiple myeloma in earlier lines.

Other T-cell engaging therapies, bispecifics with different targets, and immunomodulators are in clinical development and may be introduced into the multiple myeloma market in 2026 and beyond. CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) and Abecma ® (idecabtagene vicleucel; ide-cel) were approved in April 2024 for the treatment of multiple myeloma in earlier lines.

The SIENDO Trial Our evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from our SIENDO trial, a multi-center, randomized, double-blinded Phase 3 trial evaluating the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (the “SIENDO Trial”; NCT03555422).

The SIENDO Trial Our evaluation of selinexor as a maintenance therapy to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from our SIENDO trial, a multi-center, randomized, double-blinded Phase 3 trial, which evaluated the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (the “SIENDO Trial”; NCT03555422).

Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies have suffered significant setbacks in late-stage clinical trials after achieving positive results in earlier development, and we could face similar setbacks. We may publicly disclose preliminary, interim or top-line data from our clinical trials.

The EMN29 Trial is designed to evaluate a 40 mg once weekly dose of selinexor compared to standard dosing of elotuzumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma as the immediate next line of therapy after treatment with anti-CD38 antibodies.

The EMN29 Trial was designed to evaluate a 40 mg once weekly dose of selinexor compared to standard dosing of elotuzumab in combination with pomalidomide and dexamethasone in relapsed or refractory multiple myeloma as the immediate next line of therapy after treatment with anti-CD38 antibodies.

The TCJA, as amended by the CARES Act, among other things, contained significant changes to corporate taxation, including reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of 21% and, for taxable years beginning after December 31, 2020, limitation of the deduction for net operating losses to 80% of current year taxable income for losses arising in taxable years beginning after December 31, 2017 (though any such net operating losses may be carried forward indefinitely).

The TCJA, as amended by the CARES Act, among other things, contained significant 104 Table of Contents changes to corporate taxation, including reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of 21% and, for taxable years beginning after December 31, 2020, limitation of the deduction for net operating losses to 80% of current year taxable income for losses arising in taxable years beginning after December 31, 2017 (though any such net operating losses may be carried forward indefinitely).

In addition, blood cell production commonly moves to the spleen (causing spleen enlargement) or to other areas of the body. It is estimated that there are approximately 5,000 new cases of myelofibrosis each year in the U.S. and approximately 20,000 patients in the U.S. living with myelofibrosis.

In addition, blood cell production commonly moves to the spleen (causing spleen enlargement) or to other areas of the body. It is estimated that there are approximately 6,000 new cases of myelofibrosis each year in the U.S. and approximately 20,000 patients in the U.S. living with myelofibrosis.

Currently, we maintain complete development and commercial rights to our products and product candidates in the U.S. and Japan and have entered into the following key agreements: Menarini In December 2021, we entered into a license agreement with the Menarini Group (“Menarini”), an Italian pharmaceutical company (the “Original Menarini Agreement”).

Currently, we maintain complete development and commercial rights to our products and product candidates in the U.S. and Japan and have entered into the following key agreements: Menarini In December 2021, we entered into a license agreement with Menarini, an Italian pharmaceutical company (the “Original Menarini Agreement”).

Myelofibrosis The current standard of care for patients with myelofibrosis who are not candidates for allogeneic HSCT, which is currently the only treatment for myelofibrosis that can provide a clinical cure, is to treat the patients with JAKi’s, the only currently approved drug therapy for treatment for myelofibrosis to reduce spleen volume and improve symptoms.

Myelofibrosis The current standard of care for patients with myelofibrosis who are not candidates for allogeneic HSCT, which is currently the only treatment for myelofibrosis that can provide a clinical cure, is to treat the patients with a JAKi, the only currently approved drug therapy for treatment for myelofibrosis to reduce spleen volume and improve symptoms.

Ongoing clinical trials, such as those involving imetelstat, bomedemstat, navtemadlin, siremadlin, and zilurgisertib are studying the treatment of myelofibrosis either with JAKi therapy, non-JAKi therapy or a combination of JAKi and drug treatment. Endometrial Cancer The treatment landscape for endometrial cancer has undergone considerable change since 2023.

Ongoing clinical trials, such as those involving imetelstat, bomedemstat, navtemadlin, siremadlin, and pelabresib are studying the treatment of myelofibrosis either with JAKi therapy, non-JAKi therapy or a combination of JAKi and drug treatment. Endometrial Cancer The treatment landscape for endometrial cancer has undergone considerable change since 2023.

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 88 Table of Contents 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.

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.

Post-approval discovery of previously unknown problems with our products, including AEs of unanticipated severity or frequency, or relating to our manufacturing processes, data integrity issues with regulatory filings, or failure to comply with regulatory requirements, may yield various results, including: • litigation involving patients taking our drug; 67 Table of Contents • restrictions on our manufacturers or manufacturing processes; • restrictions on the labeling or marketing of our products; • restrictions on the distribution or use of our products; • requirements to conduct post-marketing studies or clinical trials; • warning letters or untitled letters; • withdrawal, recall or seizure of our products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • fines, restitution or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • damage to relationships with our current or potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; or • injunctions or the imposition of civil or criminal penalties.

Post-approval discovery of previously unknown problems with our products, including AEs of unanticipated severity or frequency, reduced effectiveness of our products, or relating to our manufacturing processes, data integrity issues with regulatory filings, or failure to comply with regulatory requirements, may yield various results, including: • litigation involving patients taking our drug; • restrictions on our manufacturers or manufacturing processes; • restrictions on the labeling or marketing of our products; • restrictions on the distribution or use of our products; • requirements to conduct post-marketing studies or clinical trials; • warning letters or untitled letters; • withdrawal, recall or seizure of our products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • fines, restitution or disgorgement of profits or revenues; • suspension or withdrawal of marketing approvals; • damage to relationships with our current or potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; or • injunctions or the imposition of civil or criminal penalties.

It is not always possible to identify and deter employee or third-party misconduct, and the precautions we take to detect and prevent these activities may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from significant penalties, governmental investigations or other 79 Table of Contents actions or lawsuits stemming from a failure to be in compliance with such laws, standards, regulations, guidance or codes of conduct.

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

Numerous unforeseen events during, or as a result of, clinical trials could delay or prevent our or our collaborators’ ability to complete such clinical trials or receive marketing approval of our product candidates, including, but not limited to, the following: • delays or failure to reach agreement with regulatory authorities on a trial design or the receipt of feedback requiring us to modify the design of our clinical trials, perform additional or unanticipated clinical trials to obtain approval or alter our regulatory strategy, as is the case in connection with the feedback we received from the FDA in February 2022 on our SIENDO trial and the feedback from the FDA that we announced in December 2024 regarding the appropriateness of our global, Phase 3 trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “EC-042 Trial”) given the evolving treatment landscape for patients with advanced or recurrent endometrial cancer; • clinical trials of our product candidates may produce negative or inconclusive results or other patient safety concerns, including undesirable side effects or other unexpected characteristics, and we may decide, or regulatory authorities may require us, to conduct additional clinical trials, suspend ongoing clinical trials or abandon drug development programs, including as a result of a finding that the participants are being exposed to unacceptable health risks; • enrollment in our clinical trials may be slower than we anticipate, including as a result of competition with other ongoing clinical trials or recently approved agents, which could decrease the overall supply of patients, or decreasing interest from selected clinical trial sites, delays in site activation, higher than expected screen failure rates, newly approved competitive products for the same indications as our product candidates or new or amended regulations; for example, in August 2024, we announced expected delays in our top-line data readout for our EC-042 Trial due primarily to higher than expected screen failure rates, which has required us to screen a larger number of patients than originally planned; • 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 55 Table of Contents 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; • strategic revisions to clinical trial designs, including a change in primary endpoints or a reduction in the total number of patients targeted for enrollment, which could negatively impact our ability to submit and/or receive regulatory approval for the indication sought; for example, we recently decreased the number of total patients to be enrolled in the ongoing Phase 3 trial evaluating selinexor in combination with pomalidomide and dexamethasone versus elotuzumab, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma; • regulators may revise the requirements for approving our product candidates, even after providing a positive opinion on or otherwise reviewing and providing comments to a clinical trial protocol, and/or such requirements may not be as we anticipate; • delays or failure in obtaining the necessary authorization from regulatory authorities or ethics committees, including institutional review boards, to permit us, our collaborators or our investigators to commence a clinical trial, conduct a clinical trial at a prospective trial site, or the suspension or termination of a clinical trial once commenced; • delays or failure to reach agreement on acceptable terms with prospective clinical trial sites or contract research organizations (“CROs”); • the number of patients required for clinical trials of our product candidates may be larger than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate, which can increase the cost of our trials, extend clinical trial timelines and provide competitors with additional time to seek regulatory approval for their products prior to the finalization of our trials; • our third-party contractors, including manufacturers or CROs, may fail to comply with regulatory requirements, perform effectively, or meet their contractual obligations to us in a timely manner, or at all; • we or our investigators might be found to be non-compliant with regulatory requirements; • the cost of clinical trials of our product candidates may be greater than we anticipate; • 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; and • negative impacts resulting from a pandemic or other public health emergency, including impacts to healthcare systems and our trial sites’ ability to conduct trial.

Numerous unforeseen events during, or as a result of, clinical trials could delay or prevent our or our collaborators’ ability to complete such clinical trials or receive marketing approval of our product candidates, including, but not limited to, the following: • delays or failure to reach agreement with regulatory authorities on a trial design or the receipt of feedback requiring us to modify the design of our clinical trials, perform additional or unanticipated clinical trials to obtain approval or alter our regulatory strategy, as is the case in connection with the feedback we received from the FDA in February 2022 on our SIENDO trial and the feedback from the FDA that we announced in December 2024 regarding the appropriateness of our global, Phase 3 trial evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer (the “XPORT-EC-042 Trial”) given the evolving treatment landscape for patients with advanced or recurrent endometrial cancer; • clinical trials of our product candidates may produce negative or inconclusive results or other patient safety concerns, including undesirable side effects or other unexpected characteristics, and we may decide, or regulatory authorities may require us, to conduct additional clinical trials, suspend ongoing clinical trials or abandon drug development programs, including as a result of a finding that the participants are being exposed to unacceptable health risks; • enrollment in our clinical trials may be slower than we anticipate, including as a result of competition with other ongoing clinical trials or recently approved agents, which could decrease the overall supply of patients, or decreasing interest from selected clinical trial sites, delays in site activation, higher than expected screen failure rates, newly approved competitive products for the same indications as our product candidates or new or amended regulations; for example, in August 2024, we announced expected delays in our top-line data readout for our XPORT-EC-042 Trial due primarily to higher than expected screen failure rates, which has required us to screen a larger number of patients than originally planned; • changes in the treatment landscape on which a clinical development plan was based, such as the approval of new therapies during the course of a clinical trial, can change the potential approvability of a drug even if the results of a pivotal, Phase 3 clinical trial are considered clinically meaningful and the primary endpoints achieve statistical significance since global regulatory agencies, including the FDA, often consider approvability in light of the current treatment landscape at the time of approval, and not at the time when a clinical trial is first designed; for example, in recent years three new novel agents (dostarlimab-gxly, pembrolizumab and durvalumab) have been approved for treatment in patients with endometrial cancer, which has evolved the treatment landscape; • modifications of clinical trial protocols impacting the patient population under study, including any modifications to the eligibility criteria or the total number of patients targeted for enrollment; • strategic revisions to clinical trial designs, including a change in primary endpoints or the total number of patients targeted for enrollment, which could negatively impact our ability to submit and/or receive regulatory approval for the indication sought; for example, in 2024 we decreased the number of total patients to be enrolled in the ongoing Phase 3 trial evaluating selinexor in combination with pomalidomide and dexamethasone versus elotuzumab, pomalidomide, and dexamethasone in patients with relapsed or refractory multiple myeloma; • regulators may revise the requirements for approving our product candidates, even after providing a positive opinion on or otherwise reviewing and providing comments to a clinical trial protocol, and/or such requirements may not be as we anticipate; • delays or failure in obtaining the necessary authorization from regulatory authorities or ethics committees, including institutional review boards, to permit us, our collaborators or our investigators to commence a clinical trial, conduct a clinical trial at a prospective trial site, or the suspension or termination of a clinical trial once commenced; • delays or failure to reach agreement on acceptable terms with prospective clinical trial sites or contract research organizations (“CROs”); • the number of patients required for clinical trials of our product candidates may be larger than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate, which can increase the cost of our trials, extend clinical trial timelines and provide competitors with additional time to seek regulatory approval for their products prior to the finalization of our trials; • we, our investigators, or our third-party contractors, including manufacturers or CROs, may fail to comply with regulatory requirements, which include requirements related to the implementation of clinical trials, such as requirements for 64 Table of Contents ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial, perform effectively, or meet their contractual obligations to us in a timely manner, or at all; • the cost of clinical trials of our product candidates may be greater than we anticipate; • 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; and • negative impacts resulting from a pandemic or other public health emergency, including impacts to healthcare systems and our trial sites’ ability to conduct trial.

This approval was based on the results of the SADAL Trial, an open-label Phase 2b clinical trial evaluating single-agent oral selinexor (60 mg, twice weekly) in patients that had relapsed or refractory DLBCL after at least two prior multi-agent therapies and who were ineligible for transplantation, including high dose chemotherapy with stem cell rescue.

The SADAL Trial Accelerated approval of XPOVIO in DLBCL was based on the results of the SADAL Trial, an open-label Phase 2b clinical trial evaluating single-agent oral selinexor (60 mg, twice weekly) in patients that had relapsed or refractory DLBCL after at least two prior multi-agent therapies and who were ineligible for transplantation, including high dose chemotherapy with stem cell rescue.

During the second half of 2024, we amended certain aspects of the design for the EMN29 Trial, including a reduction in the number of patients that are targeted for enrollment from 222 patients to approximately 120 patients and revisions to the trial’s statistical plan and powering assumptions.

During the second half of 2024, we amended certain aspects of the design for the EMN29 Trial, including a reduction in the number of patients that were targeted for enrollment from 222 patients to approximately 120 patients and revisions to the trial’s statistical plan and powering assumptions.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

1 edited+0 added−0 removed5 unchanged

2024 filing

2025 filing

Biggest changeItem 7A. Quantitat ive and Qualitative Disclosures about Market Risk We are exposed to market risk related to changes in interest rates. We had cash, cash equivalents and investments of $108.7 million as of December 31, 2024. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates.

Biggest changeItem 7A. Quantitat ive and Qualitative Disclosures about Market Risk We are exposed to market risk related to changes in interest rates. We had cash, cash equivalents and investments of $63.7 million as of December 31, 2025. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates.

Top changes in Karyopharm Therapeutics Inc.'s 2025 10-K

Item 1. Business

Item 1C. Cybersecurity

Item 2. Properties

Item 3. Legal Proceedings

Item 5. Market for Registrant's Common Equity

Item 6. [Reserved]

Item 7. Management's Discussion & Analysis

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Other KPTI 10-K year-over-year comparisons