Document:

EX-10.1

 Exhibit 10.1 

EXECUTION VERSION 
  
 

 
 85 Wells Ave. Newton, MA 

April 28, 2021 
 Richard Paulson 

Via Email: 
 Dear Richard, 

I am pleased to present you this offer of employment to serve as the President and Chief Executive Officer (“CEO”) of Karyopharm Therapeutics
Inc. (the “Company”). You will report to the Company’s Board of Directors (the “Board”) and will continue to serve as a member of the Board. Your primary place of work shall be out of the Company’s offices in Newton,
Massachusetts. We anticipate your start date to be on May 3, 2021. Please review the details of your offer of employment below. 
 1.
Compensation 
 a. Base Salary. Your semi-monthly base salary will be $27,916.67 ($670,000.00, if annualized) (“Base
Salary”), subject to all applicable taxes and withholdings. This position is classified as Exempt according to the Fair Labor Standards Act (FLSA). Beginning in 2022, your base salary will be reviewed annually and may be increased by the
Compensation Committee of the Board (the “Compensation Committee”) in connection with any such review. 
 b. Bonus Program. Following the
end of each calendar year, and subject to the approval of the Board (or the Compensation Committee), you will be eligible for a retention and performance bonus at a target of 65% of your annualized base salary (the “Target Bonus”),
based solely on the Company’s performance during the applicable calendar year, as determined by the Board (or the Compensation Committee) in its sole discretion in accordance with certain corporate goals determined by the Board (or the
Compensation Committee); provided, however, that the Board or Compensation Committee may approve a bonus amount above target if it determines that the Company’s performance substantially exceeds the established goals. In any event, you must be
an active employee of the Company on the date the bonus is distributed in order to be eligible for and to earn any bonus award, as it also serves as an incentive to remain employed by the Company. Notwithstanding any criteria to the contrary, your
2021 bonus will not be prorated based on your commencement of employment with the Company after the beginning of the calendar year. 

  
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 EXECUTION VERSION 

 

 c. Stock Option Grant. Subject to the approval of the Compensation Committee, the Company will grant
you a stock option to purchase 559,800 shares of the Company’s common stock, $0.0001 par value per share (the “Common Stock”), at an exercise price per share equal to the closing price per share of the Common Stock on the Nasdaq
Global Select Market on the date your employment with the Company commences (the “Grant Date”). The stock option will vest over four years at the rate of 25% on the one-year anniversary of the Grant
Date, subject to your continuing engagement with the Company as of that date, with the remaining shares to vest monthly over the following three years, subject to your continued engagement with the Company. The stock option will be granted either
(i) pursuant to the inducement grant exception under NASDAQ Rule 5635(c)(4) and not pursuant to the Company’s 2013 Stock Incentive Plan or any other equity incentive plan of the Company, as an inducement that is material to your entering
into employment with the Company or (ii) pursuant to the Company’s 2013 Stock Incentive Plan or a successor plan. In either event, the option grant shall also be subject to such other terms and conditions of the applicable Stock Option
Agreement, and if applicable, the Company’s 2013 Stock Incentive Plan or a successor plan. 
 d. RSUs. Subject to the approval of the
Compensation Committee, the Company will grant you 373,200 restricted stock units (“RSUs”) pursuant to the Company’s 2013 Stock Incentive Plan or a successor plan. The RSUs will vest over four years at the rate of 25% on the one-year anniversary of the applicable grant date, subject to your continuing engagement with the Company as of that date, with the remaining RSUs to vest monthly over the following three years, subject to your
continued engagement with the Company. These RSUs shall be subject to the terms and conditions of the Company’s 2013 Stock Incentive Plan and the applicable RSU Agreement. 

e. PTO. You will accrue Paid Time Off (“PTO”), which includes all vacation, sick, and personal time (combined) at a rate of 13.34 hours per
month, accrued on the last day of the month. This is equal to about 160 hours or 4 weeks of PTO per year. You will also receive paid holidays according to the Company’s holiday schedule. 

f. Benefits. Commencing on your first day of employment (subject to eligibility criteria and waiting periods associated with each individual plan), you
may participate in all Company benefits as outlined in the Benefits at a Glance Overview which accompanies this offer letter, subject to the terms and conditions of any applicable plan documents for such benefits. The benefit programs made available
by the Company, and the rules, terms, and conditions for participation in such benefit plans, may be changed by the Company at any time without advance notice. The Company shall reimburse you up to a maximum of $25,000 for your reasonable
professional fees and expenses paid or incurred by you in connection with the negotiation and preparation of this offer letter and other documents related to your employment with the Company. 

g. Sign-On Bonus. The Company agrees to pay you a cash bonus in the amount of $700,000, less applicable taxes
and withholdings, in three separate payments (each a “Milestone Payment”), payable the payroll period following each of the Milestone Dates and in such amounts (each as set forth in the following chart) for a total not exceeding $700,000,
contingent upon your commencement of employment with the Company (with respect to Milestone Payment 1) and, with respect to Milestone Payments 2-3 below, contingent upon your continued employment through such
applicable Milestone Date: 
  

							
	 Milestone Payment
	  	 Milestone Date
	  	Amount	 
	 Milestone Payment 1
	  	 The date upon which you commence employment with the Company (“hire
date”)
	  	$	300,000	 
	 Milestone Payment 2
	  	 The one-year anniversary of your hire
date
	  	$	200,000	 
	 Milestone Payment 3
	  	 The two-year anniversary of your hire
date
	  	$	200,000	 

  
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 EXECUTION VERSION 

 

 If for any reason you terminate your employment with the Company (other than for Good Reason, as defined
below) or are terminated by the Company for Cause (as defined below) prior to the one-year anniversary of each applicable Milestone Date, you will be obligated to repay the net amount of the applicable
Milestone Payment received by you in connection with such Milestone Date. If for any reason you terminate your employment with the Company (other than for Good Reason) or are terminated by the Company for Cause after the one-year anniversary of a Milestone Date but prior to the two-year anniversary of an applicable Milestone Date, you will be obligated to repay to the Company an amount equal to 50% of the Milestone Payment received
by you in connection with such Milestone Date. You agree that any portion of the Milestone Payments owed to the Company will be repaid immediately upon the termination of your employment by you (other than for Good Reason) or the termination of your
employment by the Company for Cause. Notwithstanding the forgoing, in the event that the Company terminates your employment without Cause or you resign from employment with the Company for Good Reason, you will be eligible to receive any unpaid
Milestone Payments in one lump sum as severance pay in accordance with Section 2 of this letter agreement, subject to your timely execution of the release agreement referenced therein. 

2. Severance Benefits 
 If your employment is
terminated without Cause, or you resign for Good Reason, the Company will, provided that you timely execute a severance and release of claims agreement in a form to be provided by the Company (which will include, at a minimum, a release of all
releasable claims, non-disparagement, confidentiality, and cooperation obligations, a reaffirmation of your continuing obligations under the Non-Disclosure, Inventions
Assignment, Non-Competition, and Non-Solicitation Agreement, and an agreement not to compete with the Company for twelve (12) months following your separation from
employment) (the “release agreement”) provide you with the following severance package: (a) pay you severance pay in the form of salary continuation for, eighteen (18) months (the “Severance Period”); (b) pay you, in a
lump sum, a pro-rated Target Bonus for the year in which your termination from employment occurs, calculated by multiplying the Target Bonus by a fraction, the numerator of which is the number of full months
of employment with the Company you completed in such year and the denominator of which is 12; (c) provided you elect to continue you and your eligible dependents’ participation in the Company’s medical and dental benefit plans pursuant to
the Consolidated Omnibus Budget Reconciliation Act of 1986 (“COBRA”), the Company will pay the monthly premium to 

  
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 EXECUTION VERSION 

 

 
continue such coverage for the lesser of (i) the Severance Period and (ii) the end of the calendar month in which you become eligible to receive group health plan coverage under another
employee benefit plan; and (d) an opportunity to enter into a consulting arrangement with the Company, pursuant to the Company’s standard consulting agreement, for an expected term of twelve (12) months, during which term, and subject
to your provision of services during the term, you will be compensated for services performed and any unvested equity awards granted by the Company shall continue to vest. 

Notwithstanding the foregoing, if the Company (which, for the purposes of this paragraph, includes any successor entity) terminates your employment without
Cause, or you resign for Good Reason, each within one year following the consummation of a Change in Control, then the Company (or its successor entity) will, in lieu of the severance benefits set forth in the preceding paragraph and provided that
you timely execute the release agreement, (a) pay you severance pay in the form of salary continuation of your base salary for eighteen (18) months (or such greater amount specified in any Company severance plan under which you are
eligible); (b) pay to you an amount equal to 150% of your target annual bonus for the year in which your termination occurs, which amount shall be payable in a lump sum on the date that the first continued salary payment is made to you under
your currently effective agreement with the Company; and (c) provided you elect to continue you and your eligible dependents’ participation in the Company’s medical and dental benefit plans pursuant to COBRA, the Company will pay the
monthly premium to continue such coverage for the lesser of (i) the Severance Period and (ii) the end of the calendar month in which you become eligible to receive group health plan coverage under another employee benefit plan. 

In each case, the release agreement must be executed and any revocation period with respect to such release agreement must expire no later than 60 days
following your termination of employment. Except as expressly set forth herein, any severance pay under this Section 2 will be paid in the form of salary continuation in accordance with the Company’s payroll procedures. Additionally, any
severance payments under this letter agreement (including, if applicable, with respect to any Milestone Payments in Section 1) will begin, and any lump sum payments will be made, in the first pay period beginning after the release agreement
becomes binding, provided that if the foregoing sixty (60) day period would end in a calendar year subsequent to the year in which Employee’s employment ends, payments will not begin or occur before the first payroll period of the
subsequent year. 
 “Change in Control” shall mean the sale of all or substantially all of the outstanding shares of capital stock, assets
or business of the Company, by merger, consolidation, sale of assets or otherwise (other than a transaction in which all or substantially all of the individuals and entities who were beneficial owners of the capital stock of the Company immediately
prior to such transaction beneficially own, directly or indirectly, more than 50% of the outstanding securities (on an as-converted to Common Stock basis) entitled to vote generally in the election of
directors of the (i) resulting, surviving or acquiring corporation in such transaction in the case of a merger, consolidation or sale of outstanding shares, or (ii) acquiring corporation in the case of a sale of assets; provided that,
where required for compliance with Section 409A, the event described above is also a change in control event as set forth in Treas. Reg. Section 1.409A-3(i)(5). 

  
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 EXECUTION VERSION 

 

 “Cause” shall mean: (i) your conviction by a court of competent jurisdiction of theft
or misappropriation by you of assets of the Company, (ii) your conviction by a court of competent jurisdiction of fraud committed by you or at your direction, (iii) your conviction by a court of competent jurisdiction of, or pleading
“guilty” or “no contest” to, (a) a felony or (b) any other criminal charge that has, or could be reasonably expected to have, a material adverse impact on the Company or the performance of your duties, and/or
(iv) a good faith determination by the Board in its sole discretion of (w) an act or acts of material willful misconduct by you in violation of law or government regulation in the course of your employment by the Company, (x) your
willful, repeated and material failure to perform, or gross negligence in the performance of, the duties which are reasonably assigned to you by the Board, which failure, if curable by you (as determined in good faith by the Board), is not cured to
the reasonable satisfaction of the Board within thirty (30) days after receipt of written notice from the Board of such failure, (y) your material breach of any agreement to which you and the Company are party (including, without
limitation, the Non-Disclosure, Inventions Assignment, Non-Competition, and Non-Solicitation Agreement), and/or (z) your
failure to fully participate in or otherwise cooperate with a Company investigation as may be reasonably requested by the Company. 
 “Good
Reason” shall mean (i) the assignment to you of any duties inconsistent in any adverse, material respect with your position, authority, duties, reporting relationship, or responsibilities as then constituted, or any other action by the
Board which results in a material diminution in such position, authority, duties or responsibilities, (ii) a material reduction in your Base Salary or Target Bonus, except to the extent that any such benefit is replaced with a comparable
benefit, or a reduction in scope or value thereof, other than as a result of across-the board reductions or terminations affecting employees of the Company generally, or (iii) a requirement that you,
without your prior consent, regularly report to work at a location that is thirty (30) miles or more away from your then current place of work; provided, however, that the conditions described immediately above in clauses (i) through (iii)
shall not give rise to a termination for Good Reason, unless you have notified the Board in writing within thirty (30) days of the first occurrence of the facts and circumstances claimed to provide a basis for the termination for Good Reason,
the Company has failed to correct the condition within thirty (30) days after the Board’s receipt of such written notice, and you actually terminate employment with the Company within sixty (60) days of the first occurrence of the
condition. For the avoidance of doubt, your required travel on the Company’s business shall not be deemed a relocation of your principal office under clause (iii), above. 

3. Miscellaneous 
 a.
Section 409A. It is intended that this letter agreement comply with or be exempt from Section 409A of the Internal Revenue Code of 1986, and the Treasury Regulations and IRS guidance thereunder (collectively referred
to as “Section 409A”), and notwithstanding anything to the contrary herein, it shall be administered, interpreted, and construed in a manner consistent with Section 409A. To the extent that any reimbursement, fringe benefit, or
other, similar plan or arrangement in which you participate provides for a “deferral of compensation” within the meaning of Section 409A, (a) the amount of expenses eligible for reimbursement provided to you during any calendar
year shall not affect the amount of expenses eligible for reimbursement or in-kind benefits provided to you in any other calendar year, (b) the reimbursements for

  
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 EXECUTION VERSION 

 

 
expenses for which you are entitled to be reimbursed shall be made on or before the last day of the calendar year following the calendar year in which the applicable expense is incurred,
(c) the right to payment or reimbursement or in-kind benefits hereunder may not be liquidated or exchanged for any other benefit, and (d) the reimbursements shall be made pursuant to objectively
determinable and nondiscretionary Company policies and procedures regarding such reimbursement of expenses. If and to the extent required to comply with Section 409A, no payment or benefit required to be paid under this letter agreement on
account of termination of your employment shall be made unless and until you incur a “separation from service” within the meaning of Section 409A. In the case of any amounts payable to you under this letter agreement that may be
treated as payable in the form of “a series of installment payments”, as defined in Treasury Regulation Section 1.409A-2(b)(2)(iii), your right to receive such payments shall be treated as a
right to receive a series of separate payments for purposes of such Treasury Regulation. If any paragraph of this letter agreement provides for payment within a time period, the determination of when such payment shall be made within such time
period shall be solely in the discretion of the Company. If and to the extent any portion of any payment, compensation or other benefit provided to you in connection with your employment termination is determined to constitute “nonqualified
deferred compensation” within the meaning of Section 409A of the Code, and you are a specified employee as defined in Section 409A(a)(2)(B)(i) of the Code, as determined by the Company in accordance with its procedures, by which
determination you hereby agree that you are bound, such portion of the payment, compensation or other benefit shall not be paid before the earlier of (i) the expiration of the six month period measured from the date of your “separation
from service” (as determined under Section 409A of the Code) or (ii) the tenth day following the date of your death following such separation from service (the “New Payment Date”). The aggregate of any payments that
otherwise would have been paid to you during the period between the date of separation from service and the New Payment Date shall be paid to you in a lump sum in the first payroll period beginning after such New Payment Date, and any remaining
payments will be paid on their original schedule. 
 b. Indemnification. You shall be entitled to indemnification to the maximum extent permitted by
both applicable law and the Company’s charter, with terms no less favorable than provided to any other Company executive officer or director and subject to the terms of any separate written indemnification agreement. At all times during your
employment, the Company shall maintain in effect a directors and officers liability insurance policy with you as a covered officer. 
 c.
Withholding. The Company shall withhold from any compensation or benefits payable under this letter agreement any federal, state and local income, employment or other similar taxes as may be required to be withheld pursuant to any applicable
law or regulation. 
 d. If you accept the terms of this offer, your employment with the Company constitutes at-will
employment, and you are free to resign at any time, and for any or no reason. Similarly, the Company is free to terminate its employment relationship with you at any time, with or without cause. Although your job duties, title, compensation and
benefits, as well as the Company’s personnel policies and procedures, may change from time to time, the “at-will” nature of your employment may only be changed by a written agreement signed by
you and the Board, which expressly states the intention to modify the at-will nature of your employment. Similarly, nothing in this letter shall be construed as an agreement, either express or implied, to
pay you 

  
 6 

 EXECUTION VERSION 

 

 
any compensation or grant you any benefit beyond the end of your employment with the Company. We request that, in the event of resignation, you provide a notice period of at least two weeks. 

e. Your offer is contingent upon the successful completion of an employment, and criminal background check (which will require you to complete and sign all
necessary consent forms authorizing the Company or its designee to perform these background inquiries). The Company may also require that you provide names and contact information so we may conduct reference checks about your past employment. 

f. For purposes of federal immigration law, you will be required to provide to the Company documentary evidence of your identity and eligibility for
employment in the United States. Provided you and the Company do not agree to an alternate interim arrangement with respect to where you perform your services, such documentation must be provided to us within three (3) business days of your
date of hire. The Company agrees to sponsor and pay for the application, administration, and reasonable attorneys’ fees associated with a petition on your behalf to secure valid work authorization for you to work for the Company. 

g. As a condition of your employment, you are also required to sign and comply with a Non-Disclosure, Inventions
Assignment, Non-Competition, and Non-Solicitation Agreement effective your first day of employment. A copy of that agreement accompanies this offer letter. Please
address any concerns you may have with this agreement prior to your first day of employment at the Company. You acknowledge that your receipt of the grant of equity set forth in this offer letter is contingent upon your agreement to the non-competition provisions set forth in the Non-Disclosure, Inventions Assignment, Non-Competition, and
Non-Solicitation Agreement, and that such consideration is fair and reasonable in exchange for your compliance with such non-competition obligations. You further
acknowledge that you were provided with a copy of the Non-Disclosure, Inventions Assignment, Non-Competition, and
Non-Solicitation Agreement prior to your receipt of this letter and more than ten (10) business days prior to your commencement of employment with the Company. 

h. In return for the compensation payments set forth in this letter, you agree to devote your full business time, best efforts, skill, knowledge, attention,
and energies to the advancement of the Company’s business and interests and to the performance of your duties and responsibilities as an employee of the Company and not to engage in any other business activities without prior approval from the
Company. Notwithstanding the foregoing, you may serve on boards of directors for both public and private companies subject to the approval of the Board and otherwise participate in educational, social, religious and civic organizations (including
serving on boards of same) without the prior written approval of the Board, in each case so long as such activities do not interfere or conflict with your obligations to the Company (including, without limitation, the obligations set forth in the
attached Non-Disclosure, Inventions Assignment, Non-Competition, and Non-Solicitation Agreement). 

i. As an employee of the Company, you will be required to comply with all Company policies and procedures. Violations of the Company’s policies may lead
to immediate termination of your employment. Further, the Company’s premises, including all workspaces, furniture, 

  
 7 

 EXECUTION VERSION 

 

 
documents, and other tangible materials, and all information technology resources of the Company (including computers, data and other electronic files, and all internet and email) are subject to
oversight and inspection by the Company at any time. Company employees should have no expectation of privacy with regard to any Company premises, materials, resources, or information. 

j. To accept the Company’s offer, please sign and date this letter in the space provided. By signing this letter, you are representing that you have full
authority to accept this position and perform the duties of the position without conflict with any other legal or contractual obligations, and that you are not involved in any situation that might create, or appear to create, a conflict of interest
with respect to your loyalty to or duties for the Company. You additionally represent and warrant that you have not taken or shared with the Company any confidential or proprietary information belonging to any former employer or other third party,
and that you will at no time during the course of your employment with the Company use or disclose any such confidential or proprietary information of another party without that party’s express consent. 

This letter, together with the other documents and agreements referenced herein, sets forth all of the terms of your employment with the Company, and
supersedes any prior representations or agreements including, but not limited to, any representations made during your recruitment, interviews or pre-employment negotiations, whether written or oral. This
letter may not be modified or amended except by a written agreement signed by the Company and you. This offer of employment will terminate if it is not accepted, signed and returned by close of business on April 30, 2021. 

  
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 EXECUTION VERSION 

 

 We look forward to your favorable reply and to working with you at Karyopharm! 

Sincerely, 
  

			
	Signature:	 	 /s/ Michael Mano

	
	Michael Mano
	Senior Vice President and General Counsel, Karyopharm Therapeutics

			
		
	Date:	 	 April 28, 2021

 The foregoing correctly sets forth the terms of my employment by Karyopharm Therapeutics Inc. I am not relying on any
representations pertaining to my employment other than those set forth above. 
  

			
	Signature:	 	 /s/ Richard Paulson

	
	Richard Paulson

			
		
	Date:	 	 April 28, 2021

  
 9EX-10.2

 Exhibit 10.2 

EXECUTION VERSION 
 KARYOPHARM
THERAPEUTICS INC. 
 April 28, 2021 
 Michael
Kauffman, M.D., Ph.D. 
 c/o Karyopharm Therapeutics Inc. 
 85
Wells Avenue 
 Newton, MA 02459 
 Dear Michael: 

Subject to your execution below, this letter hereby amends the employment letter, dated December 6, 2010, as amended on January 23,
2015 and August 28, 2020, between you and Karyopharm Therapeutics Inc. (the “Company”) and provides for the following terms of employment, effective May 3, 2021 (the “Effective Date”). For the avoidance of
doubt, nothing herein supersedes the Non-Disclosure and Inventions Assignment Agreement you previously executed with the Company, which remains in effect, unaltered, in all respects. 

1. Position. You will serve as Senior Clinical Advisor, reporting to the Company’s Chief Executive Officer
(“CEO”). In this role you will have the responsibilities customarily associated with such position and such additional responsibilities consistent with your senior executive status that are assigned to you by the Company’s CEO.
During the term of your employment with the Company, you will devote the required professional time and efforts to the business of the Company, and you may engage in other activities that may be approved in advance by the Company’s Board of
Directors (the “Board”), including, but not limited to, those activities described in Exhibit A which have been approved by the Board prior to the Effective Date. You will remain a director on the Board and
the Board will nominate you as a candidate for election as a director until no earlier than the second anniversary of the Effective Date. 

2. Compensation. 
 a.
Base Salary. You will be paid an annual base salary of $388,125. Your base salary will be payable pursuant to the Company’s regular payroll policy. Your salary will be reviewed annually and may be increased by the Board in connection
with any such review. 
 b. Bonus Program. You will be eligible for an annual bonus that targets fifty percent (50%) of the total
annual base salary payable to you for the applicable calendar year based upon achievement of certain performance goals and corporate milestones established by the Board in consultation with you. Achievement of goals will be determined in the sole
discretion of the Board or a Compensation Committee of the Board. To earn any part of the bonus, you must be employed on December 31st of the applicable bonus year, and such bonus shall be paid no later than March 15th of the year immediately
following the year to which the applicable annual bonus relates. Your bonus target will be reviewed annually and may be modified by the Board in connection with any such review. 

c. Equity Grants. You are eligible for annual equity grants in the Company’s sole discretion, beginning in calendar year 2022.

 EXECUTION VERSION 
  

 d. Withholding. The Company shall withhold from any compensation or benefits payable
under this letter agreement any federal, state, and local income, employment or other similar taxes as may be required to be withheld pursuant to any applicable law or regulation. 

3. Benefits. 
 a.
Vacation and Holidays. You will be eligible to accrue five weeks of paid vacation each year and take Company paid holidays consistent with the Company’s vacation policy offered to other executive level employees of the Company. 

b. Other. You will be eligible to participate in such medical, retirement and other benefits as are approved by the Board and made
available to other executive level employees of the Company. As is the case with all employee benefits, such benefits will be governed by the terms and conditions of applicable plans or policies, which are subject to change or discontinuation at any
time. 
 4. At-Will Employment. Your employment with the Company is and shall at all times
during your employment hereunder be “at-will” employment. The Company or you may terminate your employment at any time for any reason, with or without Cause, as defined in Section 5, and with or
without notice. The “at-will” nature of your employment shall remain unchanged during your tenure as an employee of the Company and may only be changed by an express written agreement that is signed
by you and the Board. 
 5. Termination of Employment. 

a. Upon your separation from employment with the Company for any reason, you will receive: (i) any unpaid base salary for services
rendered prior to the date of termination or resignation; (ii) any earned but unpaid annual bonus for any year prior to the year in which termination of employment occurs; (iii) reimbursement of any
un-reimbursed business expenses incurred as of the date of termination or resignation in accordance with the Company’s ,)reimbursement policy; (iv) accrued but unused vacation (if applicable) earned
through the effective resignation or termination date; and (v) all other payments, benefits or fringe benefits to which you shall be entitled under the terms of any applicable compensation arrangement or benefit, equity or fringe benefit plan
or program or grant or this letter agreement (collectively, clauses (i) through (v) shall be referred herein as the “Accrued Benefits”), and, except as set forth in paragraph (b) or (c) below, you will not be entitled to
any other compensation except as the Board may otherwise agree in its sole discretion. If the Company terminates your employment for Cause, at any time, then you will receive no additional compensation other than the Accrued Benefits, except that
the benefits described in Section 5(a)(ii) shall not be paid to you. 
 b. If, on or before the second anniversary of the Effective
Date, the Company terminates your employment other than for “Cause” or if you terminate your employment for “Good Reason,” as such terms are defined below, subject to you providing the Company with a fully effective separation
agreement that includes a general release of claims in a form and manner reasonably satisfactory to the Company (the “Release”) within the 60-day period

 EXECUTION VERSION 
  

 
following the date of termination (or such shorter period, not shorter than twenty-one (21) days, as may be directed by the Company), the Company
shall, in addition to the amounts payable under paragraph (a): (i) in the case of such termination that does not occur within the twelve (12) month period following a Change of Control, (x) pay you severance pay in the form of continuation
of base salary at the rate of $646,875 per annum for eighteen (18) months (the “Non-COC Severance Period”) in accordance with the Company’s payroll practice; and (y) provided
you elect to continue your and your eligible dependents’ participation in the Company’s medical and dental benefit plans pursuant to the Consolidated Omnibus Budget Reconciliation Act of 1986 (“COBRA”), pay the monthly
premium to continue such coverage for the lesser of the eighteen (18) full calendar months immediately following the month in which the termination of your employment occurs and the end of the calendar month in which you become eligible to
receive group health plan coverage under another employee benefit plan; or (ii) in the case of such termination that occurs in the twelve (12) month period following a Change of Control, (x) pay you severance pay in the form of
continuation of base salary at the rate of $646,875 per annum for eighteen (18) months (the “COC Severance Period”) in accordance with the Company’s payroll practice; (y) pay to you an amount equal to 150% of your
target annual bonus for the year in which your termination occurs, less applicable taxes and withholdings, which amount shall be payable in a lump sum on the date that the first continued salary payment is made to you under this letter agreement;
and (z) provided you elect to continue your and your eligible dependents’ participation in the Company’s medical and dental benefit plans pursuant to COBRA, pay the monthly premium to continue such coverage for the lesser of the
eighteen (18) full calendar months immediately following the month in which the termination of your employment occurs and the end of the calendar month in which you become eligible to receive group health plan coverage under another employee
benefit plan. 
 c. If, following the second anniversary of the Effective Date, the Company terminates your employment other than for
“Cause” or if you terminate your employment for “Good Reason”, as such terms are defined below, subject to you providing the Company with the Release within the 60-day period following the
date of termination (or such shorter period, not shorter than twenty-one (21) days, as may be directed by the Company), the Company shall, in addition to the amounts payable under paragraph (a), pay you
severance pay in a lump sum in the amount of $323,500, less applicable taxes and withholdings, in the first payroll period after the Release becomes fully effective. 

d. Except as expressly set forth herein, any severance pay will be paid ratably in accordance with the Company’s regular payroll
practices beginning in the Company’s first regular payroll cycle after the Release becomes effective. Notwithstanding anything to the contrary, if the 60th day referenced in (b) or (c) above occurs in the calendar year following the date
of your termination, then any severance pay shall be paid or begin no earlier than January 1 of such subsequent calendar year. 
 e.
Solely for purposes of Section 409A of the Internal Revenue Code of 1986, as amended (the “Code”), each salary continuation payment is considered a separate payment. To the extent that any severance benefit constitutes “non-qualified deferred compensation” under Section 409A of the Code, then such payments or benefits shall be payable only upon your “separation from service.” The determination of whether
and when a separation from service has occurred shall be made in accordance with the presumptions set forth in 

 EXECUTION VERSION 
  

 
Treasury Regulation Section 1.409A-l(h). Solely for this purpose, “Company” shall include all persons with whom the Company would be
considered a single employer under Section 414(b) and 414(c) of the Internal Revenue Code. If, as of the date of your “separation from service” from the Company, you are not a “specified employee” (within the meaning of
Section 409A), then each installment of the severance payments shall be made on the dates and terms set forth in this letter agreement. 
 If, as of
the date of your “separation from service” from the Company, you are a “specified employee” (within the meaning of Section 409A), then: (A) each installment of the severance payments due under this letter agreement
that, in accordance with the dates and terms set forth herein, will in all circumstances, regardless of when your separation from service occurs, be paid within the short-term deferral period (as defined under Section 409A) shall be treated as
a short-term deferral within the meaning of Treasury Regulation Section 1.409A-1(b)(4) to the maximum extent permissible under Section 409A and shall be paid on the dates and terms set forth in this
letter agreement; and (B) each installment of the severance payments due under this letter agreement that is not described the foregoing clause (A) and that would, absent this subsection, be paid within the
six-month period following your “separation from service” from the Company shall not be paid until the date that is six months and one day after such separation from service (or, if earlier, your
death) (the “New Payment Date”), with any such installments that are required to be delayed being accumulated during the six-month period and paid in a lump sum on the New Payment Date and any
subsequent installments, if any, being paid in accordance with the dates and terms set forth herein; provided, however, that the preceding provisions of this sentence shall not apply to any installment of payments if and to the maximum extent that
such installment is deemed to be paid under a separation pay plan that does not provide for a deferral of compensation by reason of the application of Treasury Regulation 1.409A-1(b)(9)(iii) (relating to
separation pay upon an involuntary separation from service). Any installments that qualify for the exception under Treasury Regulation Section 1.409A-1(b)(9)(iii) must be paid no later than the last day
of your second taxable year following the taxable year in which the separation from service occurs. 
 f. For purposes of this
Section 5, the following terms will have the following meanings: 
 (i) “Good Reason” shall mean that you have
complied with the “Good Reason Process,” as defined below, following the occurrence of any of the following events: (i) you are not elected to, or are removed from the Board; (ii) you are made to report to anyone other than the
Company’s Chief Executive Officer; (iii) the Company’s corporate headquarters or your primary work location are located outside Massachusetts; or (iv) a material breach by the Company of this letter agreement or any other
material agreement between you and the Company. 
 (ii) “Good Reason Process” shall mean that (i) you
reasonably determine in good faith that a “Good Reason” condition has occurred; (ii) you notify the Company in writing of the first occurrence of the Good Reason condition within ten (10) days of the first occurrence of such
condition; (iii) you cooperate in good faith with the Company’s efforts, for a period not less than thirty (30) days following such notice (the “Cure Period”), to remedy the condition; (iv) notwithstanding such
efforts, the Good Reason condition continues to 

 EXECUTION VERSION 
  

 
exist; and (v) you terminate your employment within thirty (30) days after the end of the Cure Period. If the Company cures the Good Reason condition during the Cure Period, Good Reason
shall be deemed not to have occurred. 
 (iii) “Change of Control” shall mean any of the following: 

1. any “person,” as such term is used in Sections 13(d) and 14(d) of the Securities Exchange Act of 1934, as amended
(the “Act”) (other than the Company, any of its subsidiaries, or any trustee, fiduciary or other person or entity holding securities under any employee benefit plan or trust of the Company or any of its subsidiaries), together with
all “affiliates” and “associates” (as such terms are defined in Rule 12b-2 under the Act) of such person, shall become the “beneficial owner” (as such term is defined in Rule 13d-3 under the Act), directly or indirectly, of securities of the Company representing fifty percent (50%) or more of the combined voting power of the Company’s then outstanding securities having the right to
vote in an election of the Board (“Voting Securities”) in such case other than as a result of an acquisition of securities directly from the Company; 

2. the date a majority of the members of the Board is replaced during any 12-month
period by directors whose appointment or election is not endorsed by a majority of the members of the incumbent Board before the date of the appointment or election, provided further, that directors whose initial assumption of office is in
connection with an actual or threatened election contest related to the election of directors of the Company will not be considered as members of the incumbent Board for purposes of this paragraph for a period of twelve (12) months following
such initial assumption; or 
 3. the consummation of (A) any consolidation or merger of the Company where the
stockholders of the Company, immediately prior to the consolidation or merger, would not, immediately after the consolidation or merger, beneficially own (as such term is defined in Rule 13d-3 under the (Act),
directly or indirectly, shares representing in the aggregate more than fifty percent (50%) of the voting shares of the Company issuing cash or securities in the consolidation or merger (or of its ultimate parent corporation, if any), or (B) any
sale or other transfer (in one transaction or a series of transactions contemplated or arranged by any party as a single plan) of all or substantially all of the assets of the Company. 

Notwithstanding the foregoing, a “Change in Control” shall not be deemed to have occurred for purposes of the foregoing clause (i) solely as
the result of an acquisition of securities by the Company which, by reducing the number of shares of Voting Securities outstanding, increases the proportionate number of Voting Securities beneficially owned by any person to fifty percent (50%) or
more of the combined voting power of all of the then outstanding Voting Securities; provided, however, that if any person referred to in this sentence shall thereafter become the beneficial owner of any additional shares of Voting Securities (other
than pursuant to a stock split, stock dividend, or similar transaction or as a result of an acquisition of securities directly 

 EXECUTION VERSION 
  

 
from the Company) and immediately thereafter beneficially owns fifty percent (50%) or more of the combined voting power of all of the then outstanding Voting Securities, then a “Change in
Control” shall be deemed to have occurred for purposes of this letter agreement. Further, and solely to the extent necessary to comply with Section 409A of the Code, such event must constitute a “change in control” within the
meaning of Treasury Regulation Section 1.409A-3(i)(5) in order for the payments and benefits hereunder to become payable. 

g. If your employment terminates because of your death or Disability, then you will receive the Accrued Benefits. For purposes of this letter
agreement, “Disability” shall be defined as your inability to have performed your material duties hereunder due to a physical or mental injury, infirmity or incapacity for one hundred eighty (180) days (including weekends and
holidays) in any 365-day period. 
 h. For purposes of this letter agreement,
“Cause” shall mean: (i) dishonesty, embezzlement, misappropriation of assets or property of the Company; (ii) gross negligence, willful misconduct, neglect of duties, theft, fraud or breach of fiduciary duty to the
Company; (iii) violation of federal or state securities law; (iv) the conviction of a felony or any crime involving moral turpitude, including a plea of guilty or nolo contendre; (v) a material breach of any of the
Company’s written policies related to conduct or ethics; or (vi) a material breach of the Nondisclosure and Inventions Assignment Agreement, dated January 1, 2011, between you and the Company (the “Confidentiality
Agreement”). 
 6. Employee Confidentiality Agreement. As an employee of the Company, you will continue to have access to
certain Company and third party confidential information, and you may during the course of your employment develop certain information or inventions which will be the property of the Company. You acknowledge the continuing effectiveness of the
Confidentiality Agreement, and you further acknowledge that the changes to your responsibilities, duties, compensation, and title, as contemplated by this letter agreement (and which may occur hereafter), do not nullify or otherwise alter your
obligations under the Confidentiality Agreement, which remain in full force and effect. 
 7. Equity Forfeiture and Vesting.
Effective as of the Effective Date, you hereby agree to, and do, fully and irrevocably surrender all right, title, and interest in the portions of the equity awards set forth on Exhibit B to this letter agreement. Any equity awards that are
outstanding on the date hereof and that you continue to hold following such surrender are herein referred to as the “Remaining Equity Awards.” Your Remaining Equity Awards will continue to vest, become exercisable and free from
early termination or forfeiture in accordance with their existing terms, provided that if the Company terminates your employment without Cause or you resign for Good Reason on or prior to March 1, 2025, then any of the remaining unvested
portions of your Remaining Equity Awards will, subject to your execution of, and the effectiveness of, the Release required by Section 5 of this letter agreement, become vested, exercisable and free from early termination or forfeiture and, if
such awards are stock options, will remain exercisable until the earlier of (x) March 1, 2026, and (y) the expiration date of such stock option. 

8. Resolution of Disputes. Any controversy or claim arising out of or relating to your employment, this letter agreement, its
enforcement or interpretation, or because of an 

 EXECUTION VERSION 
  

 
alleged breach, default, or misrepresentation in connection with any of its provisions, shall be submitted to arbitration in Boston, Massachusetts before a single arbitrator (applying
Massachusetts law), in accordance with the National Rules for the Resolution of Employment Disputes then in effect of the American Arbitration Association (“AAA”) as modified by the terms and conditions of this Section 8;
provided, however, that provisional injunctive relief may, but need not, be sought in a court of law while arbitration proceedings are pending, and any provisional injunctive relief granted by such court shall remain effective until the matter is
finally determined by the arbitrator. The arbitrator shall be selected by mutual agreement of the parties or, if the parties cannot agree, by striking from a list of arbitrators supplied by AAA. The arbitrator shall issue a written opinion
revealing, however briefly, the essential findings and conclusions upon which the award is based. Final resolution of any dispute through arbitration may include any remedy or relief which the arbitrator deems just and equitable. Any award or relief
granted by the arbitrator hereunder shall be final and binding on the parties hereto and may be enforced by any court of competent jurisdiction. 
 The
parties acknowledge that they are hereby waiving any rights to trial by jury in any action, proceeding or counterclaim brought by either of the parties against the other in connection with any matter whatsoever arising out of or in any way connected
with this letter agreement or your employment. 
 The Company shall pay the arbitrator’s fees and arbitration expenses and any other costs associated
with the arbitration or arbitration hearing that are unique to arbitration. The Company and you each shall separately pay its or your own deposition, witness, expert and attorneys’ fees and other expenses as and to the same extent as if the
matter were being held in court unless otherwise provided by law. The arbitrator shall have the sole and exclusive power and authority to decide any and all issues of or related to whether this letter agreement or any provision of this letter
agreement is subject to arbitration. 
 9. Attorneys’ Fees. The Company shall reimburse you for your reasonable
attorneys’ fees incurred in connection with the negotiation of this letter agreement. 
 10. No Inconsistent Obligations. By
accepting this offer of employment, you represent and warrant to the Company that you are under no obligations or commitments, whether contractual or otherwise, that are inconsistent with your obligations set forth in this letter agreement or that
would be violated by your employment by the Company. You agree that you will not take any action on behalf of the Company or cause the Company to take any action that will violate any agreement that you have with a prior employer. 

11. Indemnification and Liability Insurance. The Company will provide you certain rights to indemnification as set forth in the
Company’s standard form of indemnification agreement for executive officers and directors. 
 12. Miscellaneous. 

a. This letter agreement may be executed in several counterparts, each of which shall be deemed to be an original but all of which together
will constitute one and the same instrument. 

 EXECUTION VERSION 
  

 b. The Company may only assign this letter agreement to a successor (whether direct or
indirect, by purchase, merger, consolidation or otherwise) to all or substantially all of the business and/or assets of the Company, provided, that such successor expressly agrees to assume and perform this letter agreement in the same manner and to
the same extent that the Company would have been required to perform it if no such assignment had taken place, and “Company” shall include any such successor that assumes and agrees to perform this letter agreement, by operation of law or
otherwise. 
 c. No provision of this letter agreement may be modified, waived, or discharged unless such waiver, modification or discharge
is agreed to in writing and signed by you and such officer or director as may be designated by the Board. No waiver by either party hereto at any time of any breach by the other party hereto of, or compliance with, any condition or provision of this
letter agreement to be performed by such other party shall be deemed a waiver of similar or dissimilar provisions or conditions at the same or at any prior or subsequent time. 

d. The validity, interpretation, construction, and performance of this letter agreement shall be governed by the laws of the Commonwealth of
Massachusetts without regard to the choice of law principles thereof. 
 If you have any further questions or require additional
information, please feel free to contact me. 
 [Signatures appear on following page] 

 EXECUTION VERSION 
  

 Sincerely, 
  

			
	Signature:	 	 /s/ Michael Mano

	
	Michael Mano
	Senior Vice President and General Counsel, Karyopharm Therapeutics

			
		
	Date:	 	 April 28, 2021

 The foregoing correctly sets forth the terms of my employment by Karyopharm Therapeutics Inc. I am not relying on any
representations pertaining to my employment other than those set forth above. 
  

			
	Signature:	 	 /s/ Michael Kauffman

	
	Michael Kauffman, M.D., Ph.D.

			
		
	Date:	 	 April 28, 2021

 EXECUTION VERSION 
  

 Exhibit A 

You may (i) engage in charitable, civic, educational, professional, community or industry affairs; (ii) serve on the boards of directors or advisory
boards of other companies; and/or (iii) subject to written approval from the Nominating and Governance Committee, serve as a part-time employee or consultant for another company, so long as all such activities in this Exhibit A, either
individually and/or in the aggregate, do not (x) materially detract from your ability to perform your duties; or (ii) violate your obligations pursuant to the Confidentiality Agreement. 

 EXECUTION VERSION 
  

 Exhibit B 
  

																									
	 Name
	  	Grant
Number	 	  	Grant
Date	 	  	Exercise
Price	 	  	Outstanding
as of the
Effective
Date	 	  	Options
to be
Forfeited
Under
Agreement	 	  	Remaining
Equity
Awards	 
	 Michael Kauffman
	  	 	I000139	 	  	 	12/18/2013	 	  	$	23.66	 	  	 	16,904	 	  	 	—  	 	  	 	16,904	 
	 Michael Kauffman
	  	 	N000139	 	  	 	12/18/2013	 	  	$	23.66	 	  	 	123,096	 	  	 	90,000	 	  	 	33,096	 
	 Michael Kauffman
	  	 	I000235	 	  	 	1/19/2015	 	  	$	26.65	 	  	 	7,504	 	  	 	7,504	 	  	 	—  	 
	 Michael Kauffman
	  	 	N000235	 	  	 	1/19/2015	 	  	$	26.65	 	  	 	192,496	 	  	 	192,496	 	  	 	—  	 
							
	 Total
	  				  				  				  	 	340,000	 	  	 	290,000	 	  	 	50,000

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