Document:

EX-10.3

 Exhibit 10.3 

FOURTH AMENDMENT TO LEASE 

This FOURTH AMENDMENT TO LEASE (this “Amendment”) is dated as of June 6, 2018 (the “Effective Date”)
and is hereby entered into by and between AG-JCM Wells Avenue Property Owner, LLC (“Landlord”), a Delaware limited liability company, with an address of c/o Jumbo Capital Management, LLC, 1900
Crown Colony Drive, 4th Floor, Quincy, Massachusetts 02169, and Karyopharm Therapeutics Inc. (“Tenant”), a Delaware corporation, with an address of 85 Wells Avenue, 2nd Floor,
Newton, Massachusetts 02459. 
 RECITALS 

WHEREAS, Landlord, as successor-in-interest to NS Wells
Acquisition LLC, and Tenant are parties to that certain Office Lease Agreement dated March 27, 2014 (the “Office Lease Agreement”), as amended by that First Amendment to Lease dated December 31, 2014 (the “First
Amendment”), as amended by that Second Amendment to Lease dated October 22, 2015 (the “Second Amendment”), and as amended by that Third Amendment to Lease dated February 28, 2018 (the “Third
Amendment”, and together with the Office Lease Agreement, the First Amendment, and the Second Amendment, the “Lease”), pursuant to which Landlord leases to Tenant approximately 62,143 rentable square feet of office space
being comprised of (i) 29,933 rentable square feet on the second (2nd) floor (the “Second Amendment Premises”), (ii) 8,468 rentable square feet located on the third (3rd) floor (the “Expansion Premises A”), (iii) 7,766 rentable square feet located on the third (3rd) floor (the “Expansion
Premises B”), and (iv) 15,976 rentable square feet located on the third (3rd) floor (the “New Expansion Premises”, and together with the Second Amendment Premises, the
Expansion Premises A, and Expansion Premises B, the “Existing Premises”), located in the building located at 75-95 Wells Avenue, Newton, Massachusetts 02459 (the “Building”);

 WHEREAS, Tenant desires to increase the size of the Existing Premises and lease additional space in the Building consisting of
approximately 36,359 rentable square feet on the second (2nd) floor of the Building (as shown on Exhibit A attached hereto the “Fourth Amendment Expansion Premises”); and

 WHEREAS, Landlord and Tenant further agree to amend, modify and/or supplement other provisions of the Lease, all as set forth herein on
the following terms and conditions. 
 AGREEMENT 

NOW, THEREFORE, in consideration of the mutual covenants contained herein and for other good and valuable consideration, the receipt and
sufficiency of which is hereby acknowledged, Landlord and Tenant hereby agree, as of the Effective Date, as follows: 
  

	 	1.	Incorporation of Recitals. The recitals set forth above are true and correct, incorporated herein and made a part of this Amendment as if set forth herein in full. 

 

	 	2.	Incorporation of Exhibits. The exhibits attached hereto are incorporated herein and made a part of this Amendment as if set forth herein in full. 

  
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	 	3.	Capitalized Terms and Conflicts. All capitalized terms used in this Amendment that are not defined in this Amendment shall have the meanings ascribed to such terms in the Lease. In the event of any conflict
between the terms of the Lease and the terms of this Amendment, the definitions set forth in this Amendment shall supersede and control. 

  

	 	4.	Addition of Fourth Amendment Expansion Premises. As of the later of the date Landlord delivers the Premises to Tenant in the condition required by this Section 4 or July 1, 2018 (the “Fourth
Amendment Expansion Premises Commencement Date”), the Existing Premises shall hereby be expanded to include the Fourth Amendment Expansion Premises. Accordingly, as of the Fourth Amendment Expansion Premises Commencement Date: (a) the
total premises to be leased by Tenant in the Building shall consist of approximately 98,502 rentable square feet (the “Resulting Premises”); and (b) all references in the Lease to the Premises shall mean the “Resulting
Premises”. Landlord hereby agrees to deliver the Fourth Amendment Expansion Premises in broom-clean condition, free and clear of all occupants, tenants, and furniture on or before the Fourth Amendment Expansion Premises Commencement Date. The
Fourth Amendment Expansion Premises Commencement Date shall not occur until Landlord delivers the Fourth Amendment Expansion Premises to Tenant in the condition required in the preceding sentence. Subject to Force Majeure (as such term is defined in
Section 26.03 of the Lease), if Landlord does not deliver the Fourth Amendment Expansion Premises to Tenant on or before July 1, 2018, then Tenant shall receive a
day-for-day abatement of Base Rent hereunder solely with respect to the Reduced Fourth Amendment Expansion Premises (as hereinafter defined) as a penalty for such delay
for the period of time from July 1, 2018 until August 31, 2018. If Landlord does not deliver the Fourth Amendment Expansion Premises to Tenant on or before September 1, 2018, then, commencing on September 1, 2018 until the date
Landlord delivers the Fourth Amendment Expansion Premises, Tenant shall receive an additional two (2) days’ credit for Base Rent hereunder for each day solely with respect to the Reduced Fourth Amendment Expansion Premises as a penalty for
such delay. Landlord shall make good faith efforts to deliver the Fourth Amendment Expansion Premises to Tenant on or before July 1, 2018 (all such delay credits referred to in the two (2) immediately preceding sentences, the
“Delay Rent Credits”). All accrued Delay Rent Credits shall be applied to the first amounts of Base Rent that actually accrue and are owed by Tenant with respect to the Fourth Amendment Expansion Premises strictly in accordance with
the Base Rent table set forth in Section 6(e) herein. In the event Landlord does not deliver the Fourth Amendment Expansion Premises to Tenant in the condition required by this Section 4 by November 30, 2018, as extended due to delays
caused by Tenant, but not delays caused by Force Majeure, Tenant shall have the right, but not the obligation, to terminate this Amendment on December 1, 2018, or thereafter, by written notice to Landlord given prior to Landlord’s delivery
of the Fourth Amendment Expansion Premises to Tenant, in which event, the Delay Rent Credits shall cease to accrue as of the date of such notice to Landlord, and Tenant may apply up to a maximum amount of Two Hundred Twenty Five Thousand and 00/100
Dollars ($225,000.00) (the “Termination Delay Rent Credits Cap”) to Base Rent obligations as to the Existing Premises, and Tenant thereafter shall have no right, title, or interest to any such accrued Delay Rent Credits in excess of
the Termination Delay Rent Credits Cap. 

  
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	 	5.	Coterminous Lease Term. The term of the Lease with respect to the Fourth Amendment Expansion Premises shall be coterminous with the Term (as same may be extended pursuant to the terms and conditions of the Lease)
with respect to the Existing Premises. 

  

	 	6.	Base Rent. From and after the Effective Date, Tenant shall pay Base Rent with respect to the Resulting Premises in accordance with the schedules below but otherwise in accordance with the terms and conditions of
the Lease. 

  

	 	a.	Base Rent for Second Amendment Premises. From and after the Effective Date, Tenant shall pay Base Rent with respect to the Second Amendment Premises in accordance with the schedule below but otherwise in
accordance with the terms and conditions of the Lease: 

  

									
	 Period (Months)
	  	Monthly Base Rent	 	  	Annual Base Rent	 
	 Effective Date – November 30, 2018
	  	$	71,090.88	 	  	$	853,090.50	* 
	 December 1, 2018 – November 30, 2019
	  	$	72,338.08	 	  	$	868,057.00	 
	 December 1, 2019 – November 30, 2020
	  	$	73,585.29	 	  	$	883,023.50	 
	 December 1, 2020 – November 30, 2021
	  	$	74,832.50	 	  	$	897,990.00	 
	 December 1, 2021 – September 30, 2022
	  	$	78,574.13	 	  	$	942,889.50	* 
	 October 1, 2022 – September 30, 2023
	  	$	93,540.63	 	  	$	1,122,487.50	 
	 October 1, 2023 – September 30, 2024
	  	$	96,035.04	 	  	$	1,152,420.50	 
	 October 1, 2024 – September 30, 2025
	  	$	98,529.46	 	  	$	1,182,353.50	 

  

	*	Annualized figure. 

  
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	 	b.	Base Rent for Expansion Premises A. In addition to the foregoing, from and after the Effective Date, Tenant shall pay Base Rent with respect to the Expansion Premises A in accordance with the schedule below but
otherwise in accordance with the terms and conditions of the Lease. 

  

									
	 Period (Months)
	  	Monthly
Base Rent	 	  	Annual Base
Rent	 
	 Effective Date – September 30, 2018
	  	$	20,817.17	 	  	$	249,806.00	* 
	 October 1, 2018 – September 30, 2019
	  	$	21,170.00	 	  	$	254,040.00	 
	 October 1, 2019 – September 30, 2020
	  	$	21,522.83	 	  	$	258,274.00	 
	 October 1, 2020 – September 30, 2021
	  	$	21,875.67	 	  	$	262,508.00	 
	 October 1, 2021 – September 30, 2022
	  	$	22,228.50	 	  	$	266,742.00	 
	 October 1, 2022 – September 30, 2023
	  	$	26,462.50	 	  	$	317,550.00	 
	 October 1, 2023 – September 30, 2024
	  	$	27,168.17	 	  	$	326,018.00	 
	 October 1, 2024 – September 30, 2025
	  	$	27,873.83	 	  	$	334,486.00	 

  

	*	Annualized figure. 

  

	 	c.	Base Rent for Expansion Premises B. In addition to the foregoing, from and after the Effective Date, Tenant shall pay Base Rent with respect to the Expansion Premises B in accordance with the schedule below but
otherwise in accordance with the terms and conditions of the Lease. 

  

									
	 Period (Months)
	  	Monthly
Base Rent	 	  	Annual Base
Rent	 
	 Effective Date – September 30, 2018
	  	$	19,091.42	 	  	$	229,097.00	* 
	 October 1, 2018 – September 30, 2019
	  	$	19,415.00	 	  	$	232,980.00	 
	 October 1, 2019 – September 30, 2020
	  	$	19,738.58	 	  	$	236,863.00	 
	 October 1, 2020 – September 30, 2021
	  	$	20,062.17	 	  	$	240,746.00	 
	 October 1, 2021 – September 30, 2022
	  	$	20,385.75	 	  	$	244,629.00	 
	 October 1, 2022 – September 30, 2023
	  	$	24,268.75	 	  	$	291,225.00	 
	 October 1, 2023 – September 30, 2024
	  	$	24,915.92	 	  	$	298,991.00	 
	 October 1, 2024 – September 30, 2025
	  	$	25,563.08	 	  	$	306,757.00	 

  

	**	Annualized figure. 

  
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	 	d.	Base Rent for New Expansion Premises. In addition to the foregoing, from and after the Effective Date, Tenant shall pay Base Rent with respect to the New Expansion Premises in accordance with the schedule below
but otherwise in accordance with the terms and conditions of the Lease. 

  

									
	 Period (Months)
	  	Monthly
Base Rent	 	  	Annual Base
Rent	 
	 NEP Rent Commencement Date (as defined in the Third Amendment) – September 30,
2018
	  	$	43,268.33	 	  	$	519,220.00	* 
	 October 1, 2018 – September 30, 2019
	  	$	44,599.67	 	  	$	535,196.00	 
	 October 1, 2019 – September 30, 2020
	  	$	45,931.00	 	  	$	551,172.00	 
	 October 1, 2020 – September 30, 2021
	  	$	47,262.33	 	  	$	567,148.00	 
	 October 1, 2021 – September 30, 2022
	  	$	48,593.67	 	  	$	583,124.00	 
	 October 1, 2022 – September 30, 2023
	  	$	49,925.00	 	  	$	599,100.00	 
	 October 1, 2023 – September 30, 2024
	  	$	51,256.33	 	  	$	615,076.00	 
	 October 1, 2024 – September 30, 2025
	  	$	52,587.67	 	  	$	631,052.00	 

  

	*	Annualized figure 

	**	During the entire Term of the Lease, including any free Base Rent period as applicable, Tenant shall be responsible for payment of Additional Rent, including, without limitation, charges for electricity as set forth in
Section 7.02 of the Lease. 

  
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	 	e.	Base Rent for Fourth Amendment Expansion Premises. In addition to the foregoing, from and after the Effective Date, Tenant shall pay Base Rent with respect to the Fourth Amendment Expansion Premises in accordance
with the schedule below but otherwise in accordance with the terms and conditions of the Lease. 

  

									
	 Period (Months)
	  	Monthly Base
Rent	 	 	Annual Base Rent	 
	 Fourth Amendment Free Rent Period
	  	$	0.00	* 	 	$	0.00	* 
	 FAEP Rent Commencement Date – until the date that is six (6) months following said date
(see footnote *** below)
	  	$	57,248.71	*** 	 	$	686,984.50	**^ 
	 Month 7 – September 30, 2019
	  	$	101,502.21	 	 	$	1,218,026.50^	 
	 October 1, 2019 – September 30, 2020
	  	$	104,532.13	 	 	$	1,254,385.50	 
	 October 1, 2020 – September 30, 2021
	  	$	107,562.04	 	 	$	1,290,744.50	 
	 October 1, 2021 – September 30, 2022
	  	$	110,591.96	 	 	$	1,327,103.50	 
	 October 1, 2022 – September 30, 2023
	  	$	113,621.88	 	 	$	1,363,462.50	 
	 October 1, 2023 – September 30, 2024
	  	$	116,651.79	 	 	$	1,399,821.50	 
	 October 1, 2024 – September 30, 2025
	  	$	119,681.71	 	 	$	1,436,180.50	 

  

	*	During the entire Term of the Lease, including any free Base Rent period as applicable, Tenant shall be responsible for payment of Additional Rent, including, without limitation, charges for electricity as set forth in
Section 7.02 of the Lease; provided, however, that with respect to the Fourth Amendment Expansion Premises, charges shall not accrue and Tenant shall not be responsible for payment of Additional Rent, including, without limitation, charges for
electricity as set forth in Section 7.02 of the Lease, until the occurrence of the Fourth Amendment Expansion Premises Commencement Date. 

	**	 “Fourth Amendment Free Rent Period” shall commence on the Fourth Amendment Expansion Premises
Commencement Date and continue through the day immediately preceding the “FAEP Rent Commencement Date”, which shall be the earlier of (i) one (1) month after the date of Substantial Completion (as defined below) of Tenant’s
Fourth Amendment Expansion Premises Work, or (ii) either December 1, 2018 or, if the Fourth Amendment Expansion Premises Commencement Date occurs on or after July 10, 2018, then the one hundred fifty-third (153rd) day following the Fourth Amendment Expansion Premises Commencement Date. For the purposes of this Fourth Amendment, the term “Substantially Complete” or “Substantial Completion”
shall mean, with respect to the Fourth Amendment Expansion Premises Work, such work is completed, other than minor work which does not materially affect Tenant’s use of, or access to, the Fourth Amendment Expansion Premises, and Tenant has
obtained such evidence as is customarily 

  
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provided by the City of Newton to lawfully occupy the Fourth Amendment Expansion Premises. In the event that Substantial Completion of Tenant’s Fourth Amendment Expansion Premises Work
occurs on a date other than the first day of a calendar month, Tenant shall not be liable for the payment of Base Rent during the period of time beginning on Substantial Completion of Tenant’s Fourth Amendment Expansion Premises Work and ending
on the date that is thirty (30) days following the Substantial Completion of Tenant’s Fourth Amendment Expansion Premises Work. Thereafter, Base Rent for such partial calendar month shall be
pro-rated through the final day of such calendar month and for subsequent months Base Rent shall commence on the first day of each calendar month, all in accordance with the Base Rent tables set forth herein,
and otherwise in accordance with the terms and conditions of the Lease. 

	***	For the period of time commencing on the FAEP Rent Commencement Date until the date that is six (6) months following said date, Tenant shall be responsible for the payment of Base Rent to Landlord for only a
portion of the Fourth Amendment Expansion Premises, such portion consisting of a total of 20,507 rentable square feet (the “Reduced Fourth Amendment Expansion Premises”). 

	^	Annualized figure. 

  

	 	7.	Tenant’s Pro Rata Share. Effective as of the Fourth Amendment Expansion Premises Commencement Date, Tenant’s Pro Rata Share with respect to (i) the Fourth Amendment Expansion Premises shall be
15.05%, (ii) the Existing Premises shall be 25.72%, and (iii) the Resulting Premises shall be 40.77%. 

  

	 	8.	Fourth Amendment Expansion Premises Base Year Expenses and Taxes. 

  

	 	a.	Tenant shall continue to pay its Pro Rata Share of increases to Expenses and Taxes in accordance with the terms of the Lease; provided, however, that with respect to the Resulting Premises, for the period commencing on
the Fourth Amendment Expansion Premises Commencement Date and ending on Lease expiration: 

  

	 	i.	With respect to the Resulting Premises, Base Year Expenses shall be actual Expenses incurred with respect to the period commencing on January 1, 2018 and ending on December 31, 2018; and 

 

	 	ii.	With respect to the Resulting Premises, Base Year Taxes shall be actual Taxes for the twelve-month period commencing on July 1, 2018 and ending on June 30, 2019. 

 

	 	b.	 The provisions of Section 11.b of the Third Amendment shall continue to apply with respect to the Resulting
Premises as increased by the Fourth Amendment Expansion Premises, that is, notwithstanding anything to the contrary contained in the Lease or herein, commencing on the New Expansion Premises Commencement Date, Tenant’s Pro Rata Share of
increases to Expenses (as adjusted based on 95% occupancy in accordance with Exhibit B, Section 2.03 of the Lease) shall not exceed Tenant’s Pro Rata Share of Controllable Operating Expenses (as hereinafter defined) for the immediately
preceding calendar year, as such Controllable Operating Expenses may be increased by no more than four percent (4%) per calendar year on a cumulative and compounded basis. For purposes hereof,

  
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“Controllable Operating Expenses” shall mean all Expenses other than Taxes, insurance premiums, and utility costs and utility expenses. Tenant’s audit rights provided for in
Exhibit B, Section 4 of the Lease shall include the right to inspect any of Landlord’s records necessary to verify the increase in any Controllable Operating Expenses as described herein. 

 

	 	c.	Unless otherwise modified herein, Tenant shall pay its Pro Rata Share of Expenses and Taxes in accordance with all terms and conditions of the Lease, including, without limitation, Section 11 of the Third
Amendment. Beginning on the Fourth Amendment Expansion Premises Commencement Date, the Base Year for Expenses and Taxes with respect to the Existing Premises shall change to be the same as the Base Years for Expenses and Taxes with respect to the
Fourth Amendment Expansion Premises. 

  

	 	9.	Condition of Existing Premises. Tenant acknowledges that Tenant is in possession of the Existing Premises and accepts the same “as is”, without any obligation on the part of Landlord to refurbish the
Existing Premises, and without any representation by Landlord to Tenant as to the condition of the Existing Premises or the Building, and Tenant is satisfied with the condition of the Existing Premises as it relates to the suitability of the
Existing Premises for Tenant’s purposes. Nothing contained herein shall in any way diminish or affect Landlord’s on-going repair, maintenance and/or replacement obligations under Section 9.02 of
the Lease or Landlord’s service obligations under Section 7 of the Lease. 

  

	 	10.	Condition of Fourth Amendment Expansion Premises. Tenant shall perform Tenant’s Fourth Amendment Expansion Premises Work described on Exhibit B (“Fourth Amendment Work Letter”), and
Exhibit B-1 attached hereto, and incorporated herein by reference. The Fourth Amendment Work Letter shall govern the Tenant’s Fourth Amendment Expansion Premises Work and Landlord’s provision
of the Fourth Amendment Expansion Premises TI Allowance. Landlord shall deliver the Fourth Amendment Expansion Premises with all structural elements of the Building and all mechanical, electrical and plumbing systems in good operating condition and
repair. Tenant acknowledges that Tenant has examined the Fourth Amendment Expansion Premises, and, upon delivery by Landlord in the condition required by Section 4 of this Amendment, accepts the same “as is”, without any obligation on
the part of Landlord to refurbish the Fourth Amendment Expansion Premises, and without any representation by Landlord to Tenant as to the condition of the Fourth Amendment Expansion Premises or the Building, and Tenant is satisfied with the
condition of the Fourth Amendment Expansion Premises as it relates to the suitability of the Fourth Amendment Expansion Premises for Tenant’s purposes. Nothing contained herein shall in any way diminish or affect Landlord’s on-going repair, maintenance and/or replacement obligations under Section 9.02 of the Lease or Landlord’s service obligations under Section 7 of the Lease. Notwithstanding the foregoing, Landlord will
deliver the Fourth Amendment Expansion Premises in conformity with all applicable building codes, permits, laws and regulations, including, without limitation, Americans with Disabilities Act. Landlord would also be responsible, at its expense, for
any necessary improvements to the Building to deliver the Fourth Amendment Expansion Premises to comply with Americans with Disabilities Act requirements prior to the Fourth Amendment Expansion Premises Commencement Date, including the restroom
facilities. 

  
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	 	11.	Resulting Premises Floor Plan. As of the Fourth Amendment Expansion Premises Commencement Date, the Resulting Premises Floor Plan attached to the Third Amendment shall be deleted and removed in its entirety and
replaced with the Resulting Premises Floor Plan attached hereto as Exhibit A. 

  

	 	12.	Right of First Refusal. 

  

	 	a.	Subject to the terms and conditions set forth below and subject to the existing rights, if any, of other tenants or occupants in the Building or other buildings owned by Landlord with respect to the ROFR Space
(defined below), all of such existing rights described in this sentence being listed on Exhibit C attached hereto and made a part hereof, Tenant shall have an ongoing “Right of First Refusal” to lease any space on the
third (3rd) floor of the Building (the “ROFR Space”). 

  

	 	b.	If Tenant shall timely exercise its Right of First Refusal for such ROFR Space strictly in accordance with this Section 12, then the term of the Lease with respect to the Resulting Premises shall be for the same
term as contained in the Offer (as hereinafter defined) with respect to the ROFR Space, such ROFR Amendment (as hereinafter defined) to incorporate all such terms and conditions relating to both the Resulting Premises and the ROFR Space.

  

	 	c.	 If Landlord receives a bona fide offer (the “Offer”) from a prospective tenant to lease all or
any part of the ROFR Space, Landlord shall give Tenant written notice of such fact. Landlord’s notice shall specify all material terms and conditions of the Offer. Tenant, by written notice to Landlord, will notify Landlord within five
(5) Business Days of Landlord’s notice if Tenant wishes to lease such ROFR Space from Landlord on the terms and conditions so specified in the Offer. If the term for the ROFR Space set forth in the Offer is longer than the current
Term under the Lease, Tenant shall lease such ROFR Space and the Resulting Premises for the term set forth in the Offer, in which event the term for the Resulting Premises shall extend to be coterminous with the ROFR Space. If Tenant notifies
Landlord that it wishes to lease the ROFR Space, Landlord and Tenant shall execute an amendment to this Lease in a form provided by Landlord incorporating the ROFR Space into the Resulting Premises upon the terms contained in the Offer within ten
(10) Business Days of Tenant receipt of the draft amendment from Landlord (the “ROFR Amendment”), and the term of the Lease with respect to the Resulting Premises shall be for the same term as contained in the Offer with
respect to the ROFR Space, and the amendment shall contain any other specific terms of the Offer (including terms relating to the Resulting Premises) that are inconsistent with the then terms of this Lease. If Tenant exercises the Right of First
Refusal, Landlord will deliver such space to Tenant at the time the space was to be delivered to the prospective tenant under the Offer. If Tenant fails to notify Landlord within said five (5) Business Day period that Tenant intends to lease
such ROFR Space, or fails to execute a lease amendment for such ROFR Space within 

  
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ten (10) Business Days of Tenant’s receipt of a draft lease amendment from Landlord (provided Landlord worked in good faith and with diligence to attempt to reach agreement with Tenant
on the lease amendment), Tenant shall be deemed to have waived its rights with respect to the ROFR Space and Landlord shall be entitled to lease, at its sole discretion and without any further notice to Tenant, in whole or in part, the ROFR Space to
the prospective tenant identified in such Offer on the terms set forth in the Offer or on terms for a Net Effective Rate (as defined hereinafter) which is not lower than that offered to Tenant pursuant to the Offer by more than seven and one-half percent (7.5%); it being hereby agreed that, as used herein, the term “Net Effective Rate” shall mean the actual rental rate to be received per year, on the average, during the proposed term
determined by deducting from the face rental value for the term thereof the dollar value of all inducements, free rent, tenant improvements and other concessions proposed to be given. 

 

	 	d.	Notwithstanding any contrary provision of this Section or any other provision of the Lease, any Right of First Refusal and any exercise by Tenant of any Right of First Refusal shall be void and of no effect unless on
the date Tenant notifies Landlord that it is exercising the Right of First Refusal and on the commencement date of the amendment for the ROFR Space (i) the Lease is in full force and effect and (ii) no Default has occurred under the Lease
and (iii) Tenant shall not have assigned the Lease, nor subleased more than thirty-three percent (33%) of the total rentable square footage of the Resulting Premises. 

 

	 	13.	Extension Option. Landlord and Tenant hereby acknowledge and agree that Tenant shall retain the right to extend the Term of the Lease for the Resulting Premises then demised to Tenant in accordance with the terms
and conditions set forth in Section 1 (Extension Option) of Exhibit F of the Lease. 

  

	 	14.	Electricity. Tenant shall continue to pay electricity charges for the Existing Premises as set forth in Section 7.02 of the Lease. Commencing on the Fourth Amendment Expansion Premises Commencement Date,
Tenant shall pay electricity charges for the Fourth Amendment Expansion Premises in accordance with the provisions of Section 7.02 of the Lease. 

  

	 	15.	Parking. Effective as of the Fourth Amendment Expansion Premises Commencement Date, Tenant shall have the right to use on a non reserved, first come, first served basis, parking on the surface parking lot located
adjacent to the Building at a ratio of three and two-tenths (3.2) vehicle spaces per each one thousand (1,000) rentable square feet of the Resulting Premises (equaling three hundred fifteen (315) parking
spaces for Tenant’s occupancy of 98,502 rentable square feet) and otherwise upon the same terms and conditions as specified in the Lease. There shall be no additional charges to Tenant for the parking rights granted herein or under this Lease.

  

	 	16.	 Security Deposit. As of the Effective Date, the amount of the Security Deposit shall be increased by
$350,000.00 (the “Security Deposit Increased Amount”), for a total Security Deposit of $550,000.00 (the “New Security Deposit Amount”), subject to the terms and conditions contained herein and the Lease. From and
after the Effective Date, all references 

  
 10 

	 	
in the Lease to the Security Deposit shall be deemed to refer to the “New Security Deposit Amount”. The Security Deposit Increased Amount shall be timely delivered to Landlord in the
form of an irrevocable letter of credit in accordance with all terms and conditions of Section 6.01 of the Lease, and all other applicable provisions of the Lease. Provided that (x), there then exists no Default of Tenant, as defined in
Section 18 of the Lease, and (y) Tenant is then in full compliance with its obligations under this Lease, and provided Tenant holds 65 million dollars in cash, cash equivalents, and short term investments in the aggregate
(“Liquid Asset Test”), then there shall be a reduction in the Security Deposit Increased Amount in accordance with the schedule below (in the event Tenant exceeds 50 million dollars in the Liquid Asset Test, but does not meet
the 65 million dollars threshold, the Tenant may present additional financial documentation to the Landlord and the parties will have a good faith discussion as to the reasonableness of reducing the Security Deposit Increased Amount.

  

	 	a.	On January 1, 2021, the Security Deposit Increased Amount shall be reduced by $150,000.00, and that amount shall be returned to Tenant; and 

	 	b.	On January 1, 2022, the Security Deposit Increased Amount shall be reduced by $100,000.00, and that amount shall be returned to Tenant. 

In the event that Tenant does not meet the Liquid Asset Test on January 1, 2021 and the Security Deposit Increased Amount is not reduced,
but Tenant does meet the Liquid Asset Test on January 1, 2022, the Security Deposit Increased Amount shall be reduced by $150,000.00, and that amount shall be returned to Tenant. 

 

	 	17.	Signage. Notwithstanding any provision of the Lease to the contrary, Landlord shall install, at Landlord’s sole cost and expense, all Tenant identification and suite number signage in the lobby of the
Building and in the Fourth Amendment Expansion Premises, such signage to be to be consistent with that for other tenants in the Building and in accordance with all lawful ordinances, regulations and orders of governmental authority, and subject to
Landlord’s reasonable approval. 

  

	 	18.	Brokers. Landlord and Tenant represent and warrant to the other that except for Jones Lang LaSalle and Newmark Knight Frank (the “Brokers”) they have not made any agreement or taken any action
which may cause any other party to become entitled to a commission as a result of the transactions contemplated by this Amendment. Furthermore, each party will indemnify and defend the other from any and all claims, actual or threatened, for
compensation by any other such third person by reason of such party’s breach of their representation or warranty contained in this Section. Landlord will pay any commission due to the Brokers pursuant to its separate agreement with the Brokers.

  

	 	19.	Representations. 

  

	 	a.	Landlord’s Representations. As of the Effective Date, Landlord hereby represents and warrants that: (a) to the best of Landlord’s knowledge all Building systems serving the Fourth Amendment
Expansion Premises, including without limitation all building fire protection, HVAC, electrical, and mechanical systems, are in good working order; and (b) to the best of Landlord’s knowledge, the Fourth Amendment Expansion Premises is in
conformity with all applicable building codes, permits, laws, and regulations, including, without limitation, the Americans with Disabilities Act. 

  
 11 

	 	b.	Tenant’s Representations. Tenant hereby represents and warrants, to best of Tenant’s knowledge, to Landlord that as of the Effective Date: (a) all of Tenant’s estate, right, title and interest
in and to the Lease is free and clear of assignments, sublettings, liens and encumbrances; (b) the Lease is in full force and effect; (c) Tenant is presently in possession of the Existing Premises and is paying the Base Rent, Additional
Rent and any other charges or sums due under the Lease with respect to the Existing Premises; (d) the Lease has not been modified, supplemented or amended in any way, except as may be set forth in this Amendment; (e) Tenant is not aware of
any actionable defenses, claims or set-offs under the Lease against rents or charges due or to become due thereunder; and (f) that this Amendment has been duly authorized, executed and delivered by and on
behalf of Tenant and constitutes the valid and binding agreement of Tenant in accordance with the terms hereof. 

  

	 	20.	Hazardous Materials. Landlord represents that, as of the Effective Date, Landlord, to the best of its knowledge, has not received notice from any governmental agencies or other third parties alleging that the
Building or Premises is in violation of any Laws or regulations relating to Hazardous Materials, which violation is still in effect, and, except as previously disclosed to Tenant in writing, Landlord, to the best of its knowledge, is not aware of
any Hazardous Materials have been released upon any portion of the Property and remain unremediated. Landlord and Tenant’s obligations and responsibilities with respect to Hazardous Materials shall remain in accordance with Section 26.14
of the Lease. 

  

	 	21.	SNDA. As to any future mortgage, ground lease, and/or underlying lease or deed of trust, Landlord shall use commercially reasonable efforts to obtain from such mortgagee, ground lessor, or trustee therein a
Nondisturbance Agreement (as such term is defined in Section 23 of the Lease) in accordance with and subject to the terms and conditions of the Lease. 

  

	 	22.	Ratification of Lease. Except as amended and modified by this Amendment, all the terms, provisions, agreements, covenants and conditions of the Lease are hereby affirmed and ratified. In the event that any
provision of this Amendment conflicts with the provisions of the Lease, the provisions of this Amendment shall control. 

  

	 	23.	Execution/Entire Agreement. This Amendment, together with the Lease as affected hereby, constitutes the entire agreement of the parties, and may not be amended except by written instrument signed by all parties.
This Amendment shall have the effect of an agreement under seal and shall be binding upon and inure to the benefit of the parties hereto and their respective successors and assigns. 

 

	 	24.	Counterparts. This Amendment may be executed in multiple counterparts, each of which shall be deemed an original and all of which together shall constitute one and the same document. 

[Signature page follows] 

  
 12 

 IN WITNESS WHEREOF, Landlord and Tenant have caused this Amendment to be executed as of the date
set forth above. 
 LANDLORD: 
  

			
	 AG-JCM WELLS AVENUE PROPERTY OWNER, LLC,

a Delaware limited liability company

		
	By:	 	/s/ Jay O. Hirsh
	Name:	 	Jay O. Hirsh
	Title:	 	Authorized Signatory

 TENANT: 
  

			
	 KARYOPHARM THERAPEUTICS INC.,

a Delaware corporation

		
	By:	 	/s/ Christopher B. Primiano
	Name:	 	Christopher B. Primiano
	Title:	 	EVP, Chief Business Officer, General Counsel and Secretary

  
 13 

 EXHIBIT A 

RESULTING PREMISES FLOOR PLAN 

See attached. 

  
 Ex. A 

 Exhibit A 
  

 

  
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 Page 3 of 3 

 EXHIBIT B 

FOURTH AMENDMENT WORK LETTER 

This Exhibit is attached to and made a part of the Fourth Amendment to Lease by and between AG-JCM
Wells Avenue Property Owner, LLC, a Delaware limited liability company, (“Landlord”), and Karyopharm Therapeutics Inc., a Delaware corporation (“Tenant”), for space in the Building located at 75-95 Wells Avenue, Newton, Massachusetts 02459 (the “Building”). 
 1. Tenant’s Fourth Amendment
Expansion Premises Work. Subject to the terms of this Work Letter, other applicable provisions of this Amendment, the Lease, and Landlord’s consent, which consent shall not be unreasonably withheld, delayed or conditioned, Tenant may engage
its own architects, engineers, consultants, general contractor and subcontractors to perform certain commercially reasonable improvements (“Tenant’s Fourth Amendment Expansion Premises Improvements”) to the Fourth Amendment
Expansion Premises in accordance with the Fourth Amendment Expansion Premises Plans (as hereinafter after defined) (“Tenant’s Fourth Amendment Expansion Premises Work”). Tenant may enter the Fourth Amendment Expansion Premises
commencing on the Fourth Amendment Expansion Premises Commencement Date to perform Tenant’s Fourth Amendment Expansion Premises Work. Tenant’s Fourth Amendment Expansion Premises Work shall be performed in a good and workmanlike manner and
in compliance with all applicable laws, as well as all terms and conditions of this Amendment and the Lease. As part of Tenant’s Fourth Amendment Expansion Premises Work, Tenant’s contractor shall use commercially reasonable efforts to
mitigate sound emanating from the Fourth Amendment Expansion Premises and install appropriate ventilation so that Tenant’s use of the Fourth Amendment Expansion Premises shall minimize noise and/or odors being transmitted outside the Fourth
Amendment Expansion Premises. Prior to commencing Tenant’s Fourth Amendment Expansion Premises Work, Tenant shall deliver to Landlord the plans (the “Fourth Amendment Expansion Premises Plans”), as described on Exhibit B-1 attached hereto, detailing Tenant’s Fourth Amendment Expansion Premises Work, and obtain Landlord’s approval of the same. Landlord’s approval of the Fourth Amendment Expansion Premises Plans
shall not be unreasonably withheld, conditioned, or delayed. Before commencing Tenant’s Fourth Amendment Expansion Premises Work, Tenant shall (a) obtain (and deliver to Landlord copies of) all required permits and authorizations of any
state, federal or municipal governing body for such work, and (b) deliver to Landlord certificates (in form reasonably acceptable to Landlord) evidencing the following insurance coverages from each contractor and subcontractor:
(i) worker’s compensation insurance covering all persons to be employed in the performance of Tenant’s Fourth Amendment Expansion Premises Work, and (ii) commercial general liability insurance on a primary and non-contributory basis with a limit of liability reasonably approved by Landlord, and with contractual liability coverage, naming Landlord, Landlord’s managing agent, Landlord’s property manager and any
designated mortgagee of the Building as additional insureds, and (iii) builders risk insurance for the full value of Tenant’s Fourth Amendment Expansion Premises Work performed by such contractor and subcontractor. 

(a) Any reasonable out-of-pocket expenses incurred by Landlord in connection
with Landlord’s review of the Fourth Amendment Expansion Premises Plans and inspection of Tenant’s Fourth Amendment Expansion Premises Work, including outside experts retained by Landlord for that purpose shall be included in the Fourth
Amendment Expansion Premises TI Allowance (as 

  
 Ex. B 

 
hereinafter defined) after Landlord provides to Tenant a written invoice detailing such charges and proposed deduction from the Fourth Amendment Expansion Premises TI Allowance. Landlord’s
consent to Tenant’s Fourth Amendment Expansion Premises Work and Landlord’s approval of the Fourth Amendment Expansion Premises Plans shall be without liability to or recourse against Landlord, shall not release Tenant from its obligations
to comply strictly with the provisions of this Amendment and the Lease, and shall not constitute any representation or warranty by Landlord regarding the adequacy for any purpose of Tenant’s Fourth Amendment Expansion Premises Work or the
Fourth Amendment Expansion Premises Plans or their compliance with applicable law, and shall not relieve Tenant from obtaining Landlord’s express written approval to revisions thereto. Promptly after completion of Tenant’s Fourth Amendment
Expansion Premises Work, Tenant shall, at Tenant’s expense, obtain and deliver to Landlord copies of all sign-offs, letters of completion, approvals and certificates of any government authority required upon the completion of Tenant’s
Fourth Amendment Expansion Premises Work and “as-built” plans and specifications for Tenant’s Fourth Amendment Expansion Premises Work prepared as reasonably required by Landlord. 

(b) If, in connection with Tenant’s Fourth Amendment Expansion Premises Work or any other act or omission of Tenant or Tenant’s employees, agents or
contractors, a mechanic’s lien, financing statement or other lien or violation of any applicable law, is filed against Landlord or all or any part of the Building or Property (as such term is defined in Section 1.15 of the Lease), Tenant
shall, at Tenant’s expense, have such lien removed by bonding or otherwise within thirty (30) days after Tenant receives notice of the filing. 

(c) All construction managers, contractors and subcontractors performing work for which a license is required by applicable laws, shall be licensed by the
appropriate government authorities and approved by Landlord, which approval shall not be unreasonably withheld or delayed. Landlord’s approval of such construction managers, contractors and subcontractors shall be without liability to or
recourse against Landlord, shall not release Tenant from its obligations to comply strictly with the provisions of this Amendment and the Lease, shall not constitute any warranty by Landlord regarding the adequacy, professionalism, competence or
experience of the approved construction manager, contractor, or subcontractor, and shall not relieve Tenant from obtaining Landlord’s express prior written approval if Tenant seeks to employ any other or additional construction manager,
contractor or subcontractor. Promptly following completion of the Tenant’s Fourth Amendment Expansion Premises Work, Tenant shall furnish to Landlord lien waivers and releases, in form reasonably satisfactory to Landlord, from all construction
managers, contractors, subcontractors, and materialmen furnishing work, services or materials in connection with Tenant’s Fourth Amendment Expansion Premises Work. 

(d) At Tenant’s request, Landlord shall join in any applications for any authorizations required from any government authority in connection with
Tenant’s Fourth Amendment Expansion Premises Work to which Landlord has consented, and otherwise cooperate with Tenant in connection with Tenant’s Fourth Amendment Expansion Premises Work, but Landlord shall not be obligated to incur any out-of-pocket expense or obligation in connection with any such applications or cooperation. 

  
 Ex. B 

 (e) Tenant shall not place a load on any floor of the Fourth Amendment Expansion Premises exceeding the floor
load per square foot placed on any portion of the Existing Premises prior to the date hereof and which is allowed by any applicable laws. 
 (f) Tenant
shall be liable for any damage caused to any part of the Building, including its fixtures and equipment, arising from, or as a result of, Tenant’s Fourth Amendment Expansion Premises Work and/or its installation and/or removal of its signs. If
Tenant performs with Landlord’s approval any work on the roof of the Building (for example, in connection with repair, maintenance, or installation of any air conditioning system), Tenant shall use only a contractor approved by Landlord for
such work and shall not do or cause anything to be done which would invalidate Landlord’s then effective roof warranty for the Building. Tenant shall also be responsible for promptly repairing (including any necessary replacement) any damage to
the roof or Building caused by such work; provided that Landlord may, at its option, upon seven (7) Business Days’ written notice to Tenant, complete any such repair or replacement, in which event Tenant shall reimburse Landlord for all
actual and reasonable out-of-pocket costs incurred by Landlord in connection therewith within thirty (30) days after Tenant is billed therefor. 

(g) On or before the expiration date of the Lease or sooner termination of the Lease, if applicable, Tenant shall, at Tenant’s expense, remove from the
Building (a) all Tenant’s Fourth Amendment Expansion Premises Improvements which Landlord designates for removal in a notice given by Landlord to Tenant at the time of Landlord’s approval of the plans for such Fourth Amendment
Expansion Premises Improvements, provided, however, that in no event shall Landlord require the removal of Fourth Amendment Expansion Premises Improvements that consist of standard office improvements; and (b) Tenant’s trade fixtures,
equipment and personal property which are removable without material damage to the Tenant’s Fourth Amendment Expansions Premises or the Building (“Tenant’s Fourth Amendment Expansion Premises Property”). Tenant shall
repair any damage to the Fourth Amendment Expansion Premises, and/or the Property, caused by the installation or removal of Tenant’s Fourth Amendment Expansion Premises Property, signs or Tenant’s Fourth Amendment Expansion Premises
Improvements. Except as expressly provided in this Section, Tenant’s Fourth Amendment Expansions Premises Improvements shall not be removed. Any Tenant’s Fourth Amendment Expansion Premises Property or Tenant’s Fourth Amendment
Expansion Premises Improvements that Tenant was required to remove and which is not removed by Tenant by the expiration date of the Lease or sooner termination of the Lease shall be deemed abandoned and may, at Landlord’s option, be retained as
Landlord’s property or disposed of by Landlord at Tenant’s expense. 
 2. Fourth Amendment Expansion Premises TI Allowance. 

(a) Subject to the terms of this Section and the Lease, Landlord shall reimburse or credit to Tenant, as applicable, up to a maximum contribution of One
Million Three Hundred Ninety-Nine Thousand Eight Hundred Twenty-One and 50/100 Dollars ($1,399,821.50) (the “Fourth Amendment Expansion Premises TI Allowance”). The Fourth Amendment Expansion
Premises TI Allowance will be provided as a reimbursement of money actually expended by Tenant. In lieu of reimbursement, at Tenant’s option, the Fourth Amendment Expansion Premises TI Allowance shall be paid to Tenant, or at Tenant’s
election directly to the contractor, in installments (with five percent (5%) retainage), as construction progresses no more frequently than once every thirty (30) 

  
 Ex. B 

 
day period as certified by Tenant’s architect pursuant to AIA Document G702-1992, Application and Certificate for Payment. Landlord shall fund each installment to Tenant, or at Tenant’s
election, directly to the contractor within thirty (30) days following Landlord’s receipt of Tenant’s written draw request, accompanied by a certification of the construction progress to date from Tenant’s architect and
supporting detail for the costs incurred and paid by Tenant reasonably acceptable to Landlord. Subject strictly to the Fourth Amendment Expansion Premises TI Allowance Deadline (as hereinafter defined), the final installment of the Fourth Amendment
Expansion Premises TI Allowance shall be paid to Tenant, or at Tenant’s election directly to the contractor within thirty (30) days Landlord’s receipt of Tenant’s written request therefor, accompanied by a certificate of final
completion from Tenant’s architect, a final lien waiver from the contractor and, if to be funded to Tenant, supporting detail for the costs incurred and paid by Tenant reasonably acceptable to Landlord. In the event Tenant completes the Fourth
Amendment Expansion Premises Work after the Fourth Amendment Expansion Premises TI Allowance Deadline, Tenant shall furnish to Landlord such documents in accordance with the immediately preceding sentence on the date Tenant completes such Fourth
Amendment Expansion Premises Work. The Fourth Amendment Expansion Premises TI Allowance may be applied by Tenant for the following: costs of design, preparation, renovation and construction of the Fourth Amendment Expansion Premises in connection
with Tenant’s Fourth Amendment Expansion Premises Work (the “Hard Costs”). Tenant may use up to a maximum of Two Hundred Ninety Thousand Eight Hundred Seventy-Two and 00/100 Dollars
($290,872.00) towards non-building related costs, including, without limitation, permitting, space plans, moving, and the purchase of Tenant’s furniture, fixtures, and equipment (however, specifically
excluding Base Rent), such amount, as applicable, to be deducted from the Fourth Amendment Expansion Premises TI Allowance (the “Soft Costs”); provided, however, that any portion of the Fourth Amendment Expansion Premises TI
Allowance that exceeds the cost of the Tenant’s Fourth Amendment Expansion Premises Work or is otherwise remaining after September 30, 2019 (the “Fourth Amendment Expansion Premises TI Allowance Deadline”) shall accrue to
the sole benefit of Landlord, it being agreed that Tenant shall not be entitled to any credit, offset, abatement or payment with respect thereto. Notwithstanding anything contained herein to the contrary, Tenant shall be solely responsible for any
costs of Tenant’s Fourth Amendment Expansion Premises Work in excess of the Fourth Amendment Expansion Premises TI Allowance and shall pay for any out-of-pocket
costs in excess of the Fourth Amendment Expansion Premises TI Allowance expended by Landlord for Tenant’s Fourth Amendment Expansion Premises Work. 

In addition, Tenant may use any Landlord allowances remaining under the Third Amendment, if any, including, and limited to, the Existing Premises TI
Allowance, the New Expansion Premises TI Allowance, and Landlord’s Plans Contribution (as such terms are defined in the Third Amendment), up to a maximum amount of $346,252.50 in the aggregate for Tenant’s performance of Tenant’s
Fourth Amendment Expansion Premises Work. Such amounts in connection with the immediately preceding sentence may be used by Tenant solely for the Hard Costs incurred by Tenant with respect to the Fourth Amendment Expansion Premises Work. For the
purposes of clarity, any such amounts of the Existing Premises TI Allowance, the New Expansion Premises TI Allowance, or the Landlord’s Plans Contribution used by Tenant in connection with the immediately preceding two (2) sentences, as
applicable, shall be reduced from the Existing Premises TI Allowance, the New Expansion Premises TI Allowance, or the Landlord’s Plans Contribution, as applicable. The right in the preceding sentence shall be in addition to and not in

  
 Ex. B 

 
lieu of Tenant’s right under Exhibit B, Section 2 of the Third Amendment to apply any outstanding portion of the Base Rent Credit Amount, if any, on the same terms and conditions
otherwise applicable to the Base Rent Credit Amount, it being agreed that any portion of said Base Rent Credit Amount used by Tenant towards the Fourth Amendment Expansion Premises Work shall be reduced from said Base Rent Credit Amount. 

(b) Provided Tenant has delivered to Landlord documentation detailing the applicable costs, including, without limitation, invoices, bills or statements for
the work completed or services rendered, and the materials and supplies used, Landlord shall make payment directly to Tenant within a commercially reasonable time period for the Fourth Amendment Expansion Premises TI Allowance. 

(c) In addition to the Fourth Amendment Expansion Premises TI Allowance, Landlord shall contribute (i) a maximum amount of Five Thousand Four Hundred
Fifty-Three and 85/100 Dollars ($5,453.85) (i.e., $0.15 per rentable square foot of the Fourth Amendment Expansion Premises) (“Landlord’s Electrical Contribution”) towards Tenant’s removal of any wiring and cabling in the
Fourth Amendment Expansion Premises, and (ii) Four Thousand Three Hundred Sixty-Three and 08/100 Dollars ($4,363.08) (i.e., $0.12 per rentable square foot of the Fourth Amendment Expansion Premises) (the “Landlord’s Fourth
Amendment Plans Contribution”) towards the cost of the Fourth Amendment Expansion Premises Plans. Landlord shall reimburse Tenant for Landlord’s Fourth Amendment Plans Contribution and Landlord’s Electrical Contribution within
thirty (30) days of the Fourth Amendment Expansion Premises Commencement Date, provided that Tenant has delivered to Landlord documentation detailing the applicable costs, including, without limitation, invoices, bills or statements for the
work completed or services rendered, and the materials and supplies used. 

  
 Ex. B 

 EXHIBIT B-1 

FOURTH AMENDMENT EXPANSION PREMISES PLANS 

  
 Ex. B-1 

 Exhibit B1 
  

 

  
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 EXHIBIT C 

EXISTING RIGHTS WITH RESPECT TO ROFR SPACE 

None.EX-10.4

 Exhibit 10.4 
  

 
 June 7, 2018 
 Anand
Varadan 
 Dear Anand: 
 On behalf of
Karyopharm Therapeutics Inc., (the “Company”), I am very pleased to inform you that subject to the approval of the Board of Directors of the Company (the “Board”), the Company anticipates appointing you to the position of
Executive Vice President, Chief Commercial Officer. 
 The terms of your position with the Company are as set forth below: 

1. Position. As of June 22, 2018 (the “Commencement Date”), subject to the approval of the Board, you will become
Executive Vice President, Chief Commercial Officer of the Company, reporting to the Company’s Chief Executive Officer. In your role you will have the responsibilities customarily associated with such position as well as those
responsibilities consistent with your role that are assigned to you by the Company’s Chief Executive Officer. During the term of your employment with the Company, you will devote your full professional time and efforts to the business of
the Company, except that you may engage in other activities that may be approved in advance by the Company’s Board of Directors (the “Board”), including continuation of your role as strategic advisor to Chiasma, Inc. and Geron
Corporation. 
 2. Compensation. 

a. Base Salary. You will be paid a semi-monthly salary of $16,875 ($405,000, if annualized), subject to tax and other
withholdings required by law, pursuant to the Company’s regular payroll policy. Your salary may be adjusted from time to time in accordance with normal business practices and in the sole discretion of the Company. 

b. Bonus Program. You will be eligible for an annual bonus that targets forty percent (40%) of your annualized base
salary based upon achievement of certain individual performance goals and corporate milestones established by the Company; provided, however, that any such bonus for calendar year 2018 will be prorated. Achievement of goals will be determined in the
sole discretion of the Board or a Compensation Committee of the Board the (“Compensation Committee”). To earn any part of the bonus, you must be employed on the December 31st of the
applicable bonus year and such bonus will be paid no later than March 15th of the year immediately following the year to which the applicable annual bonus relates. Your bonus target may be
adjusted from time to time in accordance with normal business practices and in the sole discretion of the Company. 

  
 

 

 c. Sign-On Bonus.
Contingent upon the commencement of your employment and subject to the terms and conditions set forth herein, the Company agrees to pay you a one-time sign-on
bonus of $25,000 (the “Sign-On Bonus”), less all applicable taxes and withholdings, which will be paid no later than the second pay period following the commencement of your employment. If for any
reason you voluntarily terminate your employment with the Company or are terminated by the Company for Cause (as defined below) prior to the one-year anniversary of your start date, you will be obligated to
repay the entire net amount of the Sign-On Bonus received by you. You agree that any portion of the net amount of the Sign-On Bonus owed to the Company will be repaid
immediately upon the voluntary termination of your employment by you or the termination of your employment by the Company for Cause (as defined below.) 

d. Stock Option Grant. Subject to the approval of the Compensation Committee, the Company will grant you a stock
option to purchase 150,000 (one hundred fifty thousand) shares of the Company’s common stock at a price per share equal to the Company’s closing price per share on the Nasdaq Global Select Market on the date of grant (the “Initial
Option Grant”). The Initial Option Grant will vest over four years at the rate of 25% on the one-year anniversary of the Commencement Date, subject to your continuing employment with the Company as of
that date. The remaining shares shall vest monthly over the following three years, subject to your continued engagement with the Company. The stock option will be granted 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 employment with the Company. This option grant shall also be subject to such other terms and
conditions of the applicable Stock Option Agreement. 
 e. Payments due upon termination. In the event of termination,
regardless for the reason of such termination, the Company shall pay you: (i) any unpaid base salary for services rendered prior to the date of termination of employment; (ii) reimbursement of any unreimbursed business expenses incurred as
of the date of termination of employment in accordance with the Company’s expense reimbursement policy, (iii) accrued but unused vacation (if applicable) through the date of termination of employment, (iv) any earned but unpaid bonus
payment for the year immediately preceding the year in which your employment is terminated, 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. 
 f. Eligibility for Severance
Benefits. 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, and further provided that you timely execute, return, and do not revoke
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 and non-disparagement, confidentiality, and cooperation
obligations) (the “release agreement”), the Company will: (a) pay you, as severance pay, the equivalent of six (6) months of your base salary as of the date of 

  
 2 

 
your termination from employment (or such greater amount specified in any Company severance plan under which you are eligible); and (b) 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
six (6) 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. Notwithstanding the foregoing, if your employment is terminated 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, provided you
timely execute, return, and do not revoke the release agreement, and in lieu of the foregoing severance benefits: (a) pay you, as severance pay, the equivalent of twelve (12) months of your base salary as of the date of your termination
from employment (or such greater amount specified in any Company severance plan under which you are eligible); and (b) 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 twelve (12) 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. Any severance pay will be paid in the form of salary
continuation in accordance with the Company’s payroll procedures, with payments beginning 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 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). 

“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

  
 3 

 
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 determination by the Company 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) willful, repeated and material failure to perform, or gross negligence in the performance of, the duties which are reasonably assigned to you by the Company, (y) material
breach of any agreement to which you and the Company are party and/or (z) failure to fully participate in a Company investigation as may be reasonably requested by the Company; provided, however, that you shall have a period of thirty
(30) days to cure any act constituting Cause (unless the Company determines that such act is not reasonably subject to cure)) under clauses (iv) of this paragraph, following the Company’s delivery to you of written notice, setting
forth in reasonable detail the facts and circumstances claimed to provide a basis for the termination for Cause. 

“Good Reason” shall mean (i) the assignment to you of any duties inconsistent in any adverse,
material respect with your position, authority, duties or responsibilities as then constituted, or any other action by the Company which results in a material diminution in such position, authority, duties or responsibilities, (ii) a reduction
in the aggregate of your base salary or incentive compensation by greater than ten percent (10%) or the termination of your rights to any employee benefits, 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, (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 or (iv) the material breach by the Company of any agreement to which you
and the Company are party; provided, however, that the conditions described immediately above in clauses (i) through (iv) shall not give rise to a termination for Good Reason, unless you have notified the Company 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 Company’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 from time to time on the Company’s business shall
not be deemed a relocation of your principal office under clause (iii), above. 
 g. 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. 

4. Benefits. You will be eligible to participate in such healthcare related, retirement and other benefits as are approved by
the Board and made available to other 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 

 5. 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, 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 Company. Similarly, nothing in this letter shall be construed as an agreement, either express or implied, to pay you any compensation or grant you any benefit beyond the end of your employment with the Company, except to the
extent set forth in Sections 2(e) or 2(f) hereof. 
 6. Employee Confidentiality Agreement. As an employee of the Company, you
will 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. To protect the interest of the Company
you agree to sign the Company’s standard “Non-Disclosure, Inventions Assignment, Non-Competition, and Non-Solicitation
Agreement” as a condition of your employment, a copy of which has been provided. 
 7. 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 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 7; 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 any 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 Company shall pay the
arbitrator’s fees and all AAA costs and administrative fees in excess of the amount of filing and other court-related fees you would have been required to pay if you initiated claims in a court of law. 

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. 

  
 5 

 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. 
 8. 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. 
 9. 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. 
 b. The Company may only assign this letter agreement to, and
this letter agreement shall be binding upon, 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 the Company. 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. 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. 
 e. 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. Such documentation must be provided to us within three (3) business days of your date of hire, or our employment relationship with you will be
terminated. 

  
 6 

 f. 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, 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. 
 g. 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. 

10. 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 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 

  
 7 

 
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. 

11. Modified Section 280G Cutback. 

(a) Notwithstanding any other provision of this Agreement, except as set forth in Section 11(b), in the event that the Company undergoes
a “Change in Ownership or Control” (as defined below), the Company shall not be obligated to provide to you a portion of any “Contingent Compensation Payments” (as defined below) that you would otherwise be entitled to receive to
the extent necessary to eliminate any “excess parachute payments” (as defined in Section 280G(b)(1) of the Code) for you. For purposes of this Section 11(a), the Contingent Compensation Payments so eliminated shall be referred to
as the “Eliminated Payments” and the aggregate amount (determined in accordance with Treasury Regulation Section 1.280G-1, Q/A-30 or any successor
provision) of the Contingent Compensation Payments so eliminated shall be referred to as the “Eliminated Amount.” 
 (b)
Notwithstanding the provisions of Section 11(a), no such reduction in Contingent Compensation Payments shall be made if (1) the Eliminated Amount (computed without regard to this sentence) exceeds (2) 100% of the aggregate present value
(determined in accordance with Treasury Regulation Section 1.280G-1, Q/A-31 and Q/A-32 or any successor provisions) of the
amount of any additional taxes that would be incurred by you if the Eliminated Payments (determined without regard to this sentence) were paid to you (including, state and federal income taxes on the Eliminated Payments, the excise tax imposed by
Section 4999 of the Code payable with respect to all of the Contingent Compensation Payments in excess of your “base amount” (as defined in Section 280G(b)(3) of the Code), and any withholding taxes). The override of such
reduction in Contingent Compensation Payments pursuant to this Section 11(b) shall be referred to as a “Section 11(b) Override.” For purpose of this paragraph, if any federal or state income taxes would be attributable to the
receipt of any Eliminated Payment, the amount of such taxes shall be computed by multiplying the amount of the Eliminated Payment by the maximum combined federal and state income tax rate provided by law. Any determination required under this
Section shall be made in writing by a third party expert (the “Expert”) that is selected by the Company, subject to your consent (not to be unreasonably conditioned, delayed or withheld), prior to the Change in Ownership or Control and the
determinations of such Expert shall be final and binding on all persons. 

  
 8 

 (c) For purposes of this Section 11 the following terms shall have the following respective
meanings: 
 (i) “Change in Ownership or Control” shall mean a change in the ownership or effective control of the
Company or in the ownership of a substantial portion of the assets of the Company determined in accordance with Section 280G(b)(2) of the Code. 

(ii) “Contingent Compensation Payment” shall mean any payment (or benefit) in the nature of compensation that is made
or made available (under this Agreement or otherwise) to a “disqualified individual” (as defined in Section 280G(c) of the Code) and that is contingent (within the meaning of Section 280G(b)(2)(A)(i) of the Code) on a Change in
Ownership or Control of the Company. 
 (d) Any payments or other benefits otherwise due to you following a Change in Ownership or Control
that could reasonably be characterized (as determined by the Expert) as Contingent Compensation Payments (the “Potential Payments”) shall be made within three business days following receipt by the Company of the Expert’s final
determination of (1) which Potential Payments constitute Contingent Compensation Payments, (2) the Eliminated Amount and (3) whether the Section 11(b) Override is applicable (except for any Potential Payments which are not due to
be made until after such date, which Potential Payments shall be made on the date on which they are due). 
 (e) The Contingent Compensation
Payments to be treated as Eliminated Payments shall be determined by the Expert by determining the “Contingent Compensation Payment Ratio” (as defined below) for each Contingent Compensation Payment and then reducing the Contingent
Compensation Payments in order beginning with the Contingent Compensation Payment with the highest Contingent Compensation Payment Ratio. For Contingent Compensation Payments with the same Contingent Compensation Payment Ratio, such Contingent
Compensation Payment shall be reduced based on the time of payment of such Contingent Compensation Payments with amounts having later payment dates being reduced first. For Contingent Compensation Payments with the same Contingent Compensation
Payment Ratio and the same time of payment, such Contingent Compensation Payments shall be reduced on a pro rata basis (but not below zero) prior to reducing Contingent Compensation Payment with a lower Contingent Compensation Payment Ratio. The
term “Contingent Compensation Payment Ratio” shall mean a fraction the numerator of which is the value of the applicable Contingent Compensation Payment that must be taken into account by you for purposes of Section 4999(a) of the
Code, and the denominator of which is the actual amount to be received by you in respect of the applicable Contingent Compensation Payment. For example, in the case of an equity grant that is treated as contingent on the Change in Ownership or
Control because the time at which the payment is made or the payment vests is accelerated, the denominator shall be determined by reference to the fair market value of the equity at the acceleration date, and not in accordance with the methodology
for determining the value of accelerated payments set forth in Treasury Regulation Section 1.280G-1Q/A-24(b) or (c)). 

  
 9 

 The provisions of this Section 11 are intended to apply to any and all payments or benefits
available to you under this Agreement or any other agreement or plan of the Company under which you receive Contingent Compensation Payments. 

12. 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. 
 13. 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 June 14, 2018. 
 [Signatures appear on following page]

  
 10 

 
			
	Sincerely,
	
	KARYOPHARM THERAPEUTICS INC.
		
	By:	 	/s/ Michael Kauffman
		 	Name: Michael Kauffman, M.D., Ph.D.
		 	Title: CEO

  

			
	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.
		
	Agreed:	 	/s/ Anand Varadan
		 	Anand Varadan
		
	Date:	 	6/8/18

  
 11

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