Fourth Amendment to Lease, dated June 6, 2018, by and between the Registrant and AG-JCM Wells Avenue Property Owner, LLC and the Registrant

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, 2^nd 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 (2^nd) floor (the “Second Amendment Premises”), (ii) 8,468 rentable square feet located on the third (3^rd) floor (the “Expansion Premises A”), (iii) 7,766 rentable square feet located on the third (3^rd) floor (the “Expansion Premises B”), and (iv) 15,976 rentable square feet located on the third (3^rd) 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 (2^nd) 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:

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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.

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[Signature page follows]

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

LANDLORD:

TENANT:

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EXHIBIT A

RESULTING PREMISES FLOOR PLAN

See attached.

Ex. A

Exhibit A

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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 ###-###-####, 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.