SECOND AMENDMENT TO LEASE AGREEMENT This SECOND AMENDMENT TO LEASE (the Second Amendment ) dated this 16th day of December, 2019 (the Effective Date ) is made by and between U.S. REIF CENTRAL PLAZA MASSACHUSETTS, LLC , a

SECOND AMENDMENT TO LEASE AGREEMENT

SECOND AMENDMENT TO LEASE (the Second Amendment ) dated this 16th day of December, 2019 (the Effective Date ) is made by and between U.S. REIF CENTRAL PLAZA MASSACHUSETTS, LLC, a Delaware limited

liability company (the Landlord ), and SPERO THERAPEUTICS, INC., a Delaware corporation (the Tenant ).

A. WHEREAS, Landlord and Tenant are parties to that certain Lease Agreement dated August 24, 2015 (the Original

Lease ), as amended by First Amendment to Lease dated January 17, 2018 (the First Amendment ) (collectively, the Lease ), whereby Tenant leases certain premises from Landlord of approximately:

(i) 7,791 rentable square feet on the fourteenth (14th) and fifteenth (15th) floors; and (ii) approximately

7,800 rentable square feet on the eighth (8th) floor (collectively, the Existing Premises ) in the building located at 675 Massachusetts Avenue, Cambridge,

Massachusetts (the Building );

B. WHEREAS, the Lease Term with respect to the Existing Premises is scheduled to

expire on December 31, 2025; and

C. WHEREAS, Tenant desires to: (i) lease additional space from Landlord consisting of

approximately 7,800 rentable square feet on the twelfth (12th) floor of the Building (the 12th Floor Expansion

Premises ), as more particularly described on EXHIBIT A attached hereto and (ii) extend the Lease Term with respect to the Existing Premises and Landlord desires to accommodate Tenant subject to the terms and conditions set

THEREFORE, in consideration of the promises contained herein and other good and valuable consideration, the receipt of which is hereby acknowledged, the parties agree as follows:

1. Recitals and Defined Term. The recitals set forth above are incorporated herein and made a part of this Second Amendment as

if set forth herein in full. All capitalized terms used in this Second Amendment that are not defined in this Second 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 Second Amendment, the definitions set forth in this Second Amendment shall supersede and control.

2. 12th Floor Expansion Premises. Landlord hereby leases to

Tenant and Tenant hereby leases from Landlord, subject to and with the benefit of the terms, covenants, conditions, agreements, and provisions of the Lease, as amended by this Second Amendment, the

12th Floor Expansion Premises.

2.1 The Lease Term with respect to the 12th Floor Expansion Premises (the 12th Floor Expansion Premises Term ) shall commence on June 1, 2020 (the

12th Floor Expansion Premises Commencement Date ) and shall continue thereafter so as to expire on May 31, 2027.

2.2 For purposes of confirmation herein, Tenant s Proportionate Share of the Building for the Existing Premises is

12.59% which is based on approximately 15,591 rentable square feet in the Existing Premises and approximately 123,810 rentable square feet in the Building. Tenant s Proportionate Share for the

12th Floor Expansion Premises is 6.30% which is based on approximately 7,800 rentable square feet in the 12th Floor Expansion Premises and

approximately 123,810 rentable square feet in the Building. Effective as of the 12th Floor Expansion Premises Commencement Date: (a) the Premises (meaning the Existing

Premises, together with the 12th Floor Expansion Premises) shall be amended to consist of a total of approximately 23,391 rentable square feet; and (b) Tenant s

Proportionate Share shall be amended to be 18.89% which is based on approximately 23,391 rentable square feet in the Premises and 123,810 rentable square feet in the Building.

3. Fixed Rent for 12th Floor Expansion Premises. Tenant

shall pay Fixed Rent with respect to the 12th Floor Expansion Premises in accordance with the schedule below but otherwise in accordance with the terms and conditions of the Lease:

4. Existing Premises Term. The Lease Term with respect to the Existing Premises shall be

extended for an additional period commencing on January 1, 2026 and expiring on May 31, 2027 so as to run and expire coterminous with the 12th Floor Expansion Premises Term.

5. Fixed Rent for Existing Premises. Tenant shall continue to pay Fixed Rent

with respect to the Existing Premises as set forth in the Lease through December 31, 2025. Effective as of January 1, 2026, Tenant shall pay Fixed Rent with respect to the Existing Premises in accordance with the following schedule and

otherwise in accordance with the terms and conditions of the Lease:

6. Utilities. Commencing on the 12th Floor

Expansion Premises Commencement Date, Tenant shall pay for electricity when due directly to the applicable utility supplier.

Additional Rent. For purposes of confirmation herein, from and after the 12th Floor Expansion Premises Commencement Date, Tenant shall be responsible for Additional

Rent with respect to the 12th Floor Expansion Premises in accordance with the terms and conditions of the Lease, except that with respect to Operating Expenses, Tenant shall pay Tenant s

Proportionate Share of Operating Expenses but only to the extent Operating Expenses exceed actual Operating Expenses for the Building for the calendar year 2020, and with respect to Taxes, Tenant shall pay Tenant s Proportionate Share of Taxes

but only to the extent Taxes exceed actual Taxes for the Building for fiscal year 2020. Tenant shall otherwise continue to pay Additional Rent with respect to the Existing Premises through December 31, 2025 in accordance with the provisions of

the Lease. Effective upon January 1, 2026: (a) the Operating Base Year for the Existing Premises shall be amended to mean an amount equal to the actual Operating Expenses for the Building for the calendar year 2026; and

(b) the Tax Base Year for the Existing Premises shall mean an amount equal to the actual Taxes for the Building for fiscal year 2026.

8. Condition of Premises. Except for Tenant Allowance, as described on EXHIBIT B attached hereto, Landlord shall not be

responsible for providing any work or allowances in connection with this Amendment, and Tenant shall take occupancy of the 12th Floor Expansion Premises in its

9. Parking. For purposes of confirmation herein,

Tenant currently leases: (a) eight (8) parking spaces at the rate of $230.00 per space per month; and (b) eight (8) parking spaces at the rate of $210.00 per space per month in accordance with the terms and conditions of the Lease.

Effective as of the 12th Floor Expansion Premises Commencement Date, Tenant shall lease an additional eight (8) parking spaces in the parking facilities at the rate of $250.00 per space per

month which amount shall be paid by at the same time that Fixed Rent is due under the Lease and which rate may be reasonably adjusted from time to time on an annual basis by Landlord. Additional parking may be made available on a tenancy at will

basis upon request. All other terms and conditions of Lease with respect to parking shall apply herein.

10. Extension Option. The option rights afforded Tenant for two

(2) consecutive five (5) year option terms under the First Amendment EXHIBIT C shall remain in place and this Second Amendment shall not be deemed an exercise of such rights with the First Extension Term (as defined under EXHIBIT C

under the First Amendment) commencing on June 1, 2027 (i.e. the day after expiration of the Lease Term) subject to Tenant s timely satisfaction of required conditions to the exercise of such rights.

11. Amendment to Right of Offer. EXHIBIT D RIGHT OF OFFER of the First Amendment shall be deleted in its

entirety and replaced with EXHIBIT C RIGHT OF OFFER attached hereto.

12. Security Deposit. Tenant and

Landlord hereby acknowledge and confirm that Landlord is holding a Security Deposit in the amount of $150,000.00 which amount shall continue to be held by Landlord in accordance with the terms and conditions of the Lease.

13. Brokers. Each party represents and warrants to the other that they have not made any agreement or taken any action which may

cause anyone to become entitled to a commission as a result of the transactions contemplated by this Lease, and each will indemnify and defend the other from any and all claims, actual or threatened, for compensation by any such third person by

reason of such party s breach of their representation or warranty contained in this Section 13 except for JLL, representing Landlord exclusively and JLL, representing Tenant exclusively. Landlord will pay any commission due to the brokers

hereunder pursuant to its separate agreement(s).

14. Tenant s Representations. Tenant hereby represents and warrants

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 Fixed 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 Second Amendment; (e) to the best of Tenant s knowledge, 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 Second 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.

15. Landlord s Representations. Landlord hereby represents and warrants to Tenant

that as of the Effective Date: (a) the Lease has not been modified, supplemented or amended in any way, except as may be set forth in this Second Amendment; (b) to the best of Landlord s knowledge Tenant is not in default under this

Lease and no condition exists with the giving of notice and passage of time would constitute a default of Tenant under this Lease and (c) that this Second Amendment has been duly authorized, executed and delivered by and on behalf of Landlord

and constitutes the valid and binding agreement of Landlord in accordance with the terms hereof.

16. Signage. Tenant, at its sole cost and expense, shall have the right to

install Building Standard signage for the 12th Floor Expansion Premises in the Building directory and at its entrance to the 12th Floor

17. Confirmation of Lease. Except as amended by this Second Amendment, all existing terms and

provisions of the Lease shall remain in full force and effect.

18. Miscellaneous. This Second Amendment may be executed in

one or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same Amendment. Signature pages delivered by pdf, facsimile or other electronic transmission shall be deemed to be an

IN WITNESS WHEREOF, Landlord and Tenant have caused this Second Amendment to be executed as of the Effective Date.

CENTRAL PLAZA MASSACHUSETTS, LLC

a Delaware limited liability company

a Delaware limited liability company, its Manager

a Delaware corporation, its Manager

PLAN OF 12th FLOOR EXPANSION PREMISES

12TH FLOOR EXPANSION PREMISES IMPROVEMENT ALLOWANCE

1. Landlord shall provide to Tenant an allowance of up to $55.00 per rentable square foot of the 12th Floor Expansion Premises (which is $429,000.00 based on 7,800 rentable square feet) (the 12th Floor Expansion Premises

Improvement Allowance ) which shall be applied by Tenant toward hard costs associated with improvements in the 12th Floor Expansion Premises. Landlord shall also provide a test-fit allowance to Tenant in the amount of $0.12 per rentable square foot of the 12th Floor Expansion Premises (which is $936.00 based on 7,800 rentable square

feet) ( 12th Floor Expansion Premises Test Fit Allowance ). In addition, Landlord shall provide to Tenant an allowance of up to $10.00 per rentable square foot of

the Existing Premises (which is $155,910.00 based on 15,591 rentable square feet) (the Additional Improvement Allowance and when referenced with the 12th Floor Expansion

Premises Improvement Allowance and the 12th Floor Expansion Premises Test Fit Allowance, the Tenant Allowance ) which shall be applied by Tenant toward hard costs

associated with improvements in the Existing Premises. The improvements described herein shall be known as Tenant Improvements .

2. Tenant acknowledges that all costs for Tenant Improvements in excess of the Tenant Allowance shall be paid for by Tenant at its sole

cost and expense following the date which is the first to occur of (i) the date the Tenant Allowance has been fully funded by Landlord in accordance with the terms hereof, or (ii) the Outside Requisition Date.

3. The Tenant Improvements shall be shall be: (a) subject to all terms and conditions of the Lease, including but not limited to

Section 10 of the Original Lease; (b) performed by union contractors and subcontractors approved by Landlord in advance, which approval shall not be unreasonably withheld, conditioned or delayed; and (c) based on plans and

specifications reasonably approved by Landlord in advance, which Landlord review shall be completed within ten (10) days of Tenant s submission.

4. So long as it timely submits all requisitions by the Outside Requisition Date, Tenant upon notice to Landlord shall have the right