SECOND AMENDMENT TO CREDIT AND GUARANTY AGREEMENT

SECOND AMENDMENT TO CREDIT AND GUARANTY AGREEMENT, dated as of February 27, 2026 (this “Amendment”), made by and among Karyopharm Therapeutics Inc., a Delaware corporation (“Company”) as borrower, the Lenders party hereto from time to time, and Wilmington Savings Fund Society, FSB (“WSFS”), as administrative agent for the Lenders (in such capacity, “Administrative Agent”) and collateral agent for the Secured Parties (in such capacity, “Collateral Agent”).

RECITALS:

WHEREAS, reference is hereby made to the Credit and Guaranty Agreement, dated as of May 8, 2024, as amended by that certain First Amendment and Waiver to Credit and Guaranty Agreement, dated as of October 7, 2025 (as further amended, restated, amended and restated, supplemented or otherwise modified from time to time and immediately prior to the Second Amendment Effective Date, the “Existing Credit Agreement”), by and among the Company, as borrower and certain of its Subsidiaries from time to time party thereto as Guarantors, the Administrative Agent, each Lender from time to time party thereto, the Collateral Agent and the other parties party thereto (capitalized terms used but not defined herein having the meaning provided in the Amended Credit Agreement (as defined below));

WHEREAS, the Company has requested that, pursuant to Section 10.5(b) of the Existing Credit Agreement, and the Administrative Agent and each Lender party hereto (constituting all Lenders as of the date hereof under the Existing Credit Agreement) has agreed, to effect the amendments set forth herein, and agree to the terms of this Amendment and the Amended Credit Agreement, on the terms and subject to the conditions set forth in this Amendment;

WHEREAS, the Company and each other Credit Party expects to realize substantial direct and indirect benefits as a result of this Amendment becoming effective and the consummation of the transactions contemplated hereby and thereby and agrees to reaffirm its obligations pursuant to the Collateral Documents, and the other Credit Documents to which it is a party.

NOW, THEREFORE, in consideration of the premises and agreements, provisions and covenants herein contained, the parties hereto agree as follows:

“2026 Forbearance Agreement” means that certain Forbearance Agreement, dated as of February 27, 2026, made by and among the Company and the other parties thereto.

“Capital Raise Trigger” means the consummation of a sale and issuance by the Company of Common Stock (including the issuance of any warrants exercised (or, in the case of pre-funded warrants, exercisable) directly into Common Stock) occurring at any time after February 27, 2026 that results in unrestricted (including, not subject to any redemption, clawback, escrow or similar encumbrance or restriction) gross proceeds actually received in cash by the Company of not less than $25,000,000, in one

or more transactions, before June 10, 2026. The Company shall notify the Administrative Agent promptly, and in any event no later than one (1) Business Day after the occurrence of the Capital Raise Trigger.

“Second Amendment” means that certain Second Amendment to Credit and Guaranty Agreement, dated as of February 27, 2026, made by and among the Company, the Lenders party thereto, the Administrative Agent and the Collateral Agent.

“Prepayment Premium” means the amount set forth in the chart below, determined by reference to the date of prepayment:

Except as otherwise set forth herein, interest on each Loan (i) shall accrue on a daily basis and shall be payable in arrears, in Cash, on each Interest Payment Date with respect to interest accrued on and to each such Interest Payment Date; (ii) shall accrue on a daily basis and shall be payable in arrears upon any prepayment of that Loan, whether voluntary or mandatory, to the extent accrued on the amount being prepaid; and (iii) shall accrue on a daily basis and shall be payable in arrears at maturity of the Loans, including final maturity of the Loans, provided, that (x) the interest on the Loans that was due on September 30, 2025 shall be paid in kind by being capitalized, added to, and made part of, the outstanding principal

amount of the Loans on the First Amendment Effective Date (for the avoidance of doubt, at the Applicable Margin for such Interest Payment Date after giving effect to the First Amendment), (y) from and after the First Amendment Effective Date, for any Interest Payment Date or portion of any Interest Period on or prior to March 31, 2026, interest on the Loans, shall be payable in kind which such in-kind interest shall be capitalized, added to, and made part of, the outstanding principal amount of the Loans on the applicable Interest Payment Date and payable as part of the outstanding principal amounts of the Loans upon any prepayment of the Loans, whether voluntary or mandatory, and shall be payable as part of the outstanding principal amount of Loans upon the Maturity Date and (z) solely to the extent the Capital Raise Trigger has occurred, the Interest Payment due on June 30, 2026, shall be paid in kind by being capitalized, added to, and made part of, the outstanding principal amount of the Loans on June 30, 2026 and payable upon any prepayment of the Loans, whether voluntary or mandatory, and shall be payable as part of the outstanding principal amount of Loans upon the Maturity Date.

Scheduled Payments. The principal amounts of the Term Loans shall be repaid in consecutive quarterly installments (each such payment, an “Installment”) on the tenth day of each March, June, September and December commencing on June 10, 2026 (each such date, an “Installment Payment Date”), in an amount equal to the product of (x) 6.25% multiplied by (y) the aggregate original stated principal amount of all Term Loans made under this Agreement prior to such Installment Payment Date (without reducing any such Installment to reflect payments of the outstanding principal of any Term Loan after the initial funding thereof); provided that, notwithstanding the foregoing, solely to the extent the Capital Raise Trigger has occurred, no Installment shall be due on June 10, 2026 and the Installment due on September 10, 2026 shall be increased by the amount that would have been due on June 10, 2026 but for the occurrence of the Capital Raise Trigger. Notwithstanding the foregoing, the Term Loans, together with all other amounts owed hereunder with respect thereto, shall, in any event, be Paid in Full on the Maturity Date.

Minimum Consolidated Liquidity. The Company shall not permit Consolidated Liquidity at any time to be (i) for the period commencing on the Closing Date, to but excluding the First Amendment Effective Date, less than $25,000,000, (ii) for the period commencing on the First Amendment Effective Date through and including October 10, 2026, less than the lesser of (A) sum of (x) $10,000,000 and (y) 50% of the net cash proceeds of any issuance of Indebtedness for borrowed money or Capital Stock of the Company or any of its Subsidiaries (but not including the issuance of Indebtedness or Capital Stock to the Company or any of its Subsidiaries) occurring after the First Amendment Effective Date and prior to October 10, 2026 (not including (x) for the avoidance of doubt, any net cash proceeds of any First Amendment Transaction and (y) any net cash proceeds in connection with a Capital Raise Trigger) and (B) $25,000,000 and (iii) at any time after October 10, 2026, less than $25,000,000.

[signature pages to follow]

IN WITNESS WHEREOF, each of the undersigned has caused its duly authorized officer to execute and deliver this Amendment as of the date first set forth above.

COMPANY:

KARYOPHARM THERAPEUTICS INC.

ADMINISTRATIVE AGENT:

WILMINGTON SAVINGS FUND SOCIETY, FSB

COLLATERAL AGENT:

WILMINGTON SAVINGS FUND SOCIETY, FSB

LENDERS:

1992 Master Fund Co-Invest SPC - Series 4 Segregated Portfolio, as a Lender

By: Highbridge Capital Management, LLC,

as Trading Manager and not in its individual capacity

HIGHBRIDGE TACTICAL CREDIT INSTITUTIONAL FUND, LTD., as a Lender

By: Highbridge Capital Management, LLC,

as Trading Manager and not in its individual capacity

HIGHBRIDGE TACTICAL CREDIT MASTER FUND, L.P., as a Lender

By: Highbridge Capital Management, LLC,

as Trading Manager and not in its individual capacity

Highbridge SCF II Loan SPV, L.P., as a Lender

By: Highbridge Capital Management, LLC,

as Trading Manager and not in its individual capacity

BRAIDWELL TRANSACTION HOLDINGS
LLC – SERIES 7, as a Lender

By: Braidwell LP, its Investment Manager

Context Partners Master Fund, L.P., as a Lender

By: Context Capital Management, LLC,

Investment Adviser

Midtown Acquisitions, L.P., as a Lender

By: Midtown Acquisitions GP LLC, its general partner

GARX I, L.P., as a Lender

HEALTHCARE ROYALTY PARTNERS IV, L.P., as a Lender

By: HealthCare Royalty GP IV, LLC, its general partner

HCRX INVESTMENT HOLDCO, L.P., as a Lender

By: HCRX Master GP, LLC, its general partner

HCR CANARY FUND, L.P., as a Lender

By: HCR Canary Fund GP, LLC, its general partner

HCR MOLAG FUND, L.P.

By: HCR Molag Fund GP, LLC, its general partner