FIRST AMENDMENT TO LEASE AGREEMENT This FIRST AMENDMENT TO LEASE (the Amendment ) dated this 17th day of January, 2018 (the Effective Date ) is made by and between U.S. REIF CENTRAL PLAZA MASSACHUSETTS, LLC , a Delaware

FIRST AMENDMENT TO LEASE AGREEMENT

FIRST AMENDMENT TO LEASE (the Amendment ) dated this 17th day of January, 2018 (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. (formerly known as Spero Opco, Inc.), a Delaware corporation (the Tenant ).

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

whereby Tenant leases certain premises from Landlord of approximately 7,791 rentable square feet on the fourteenth (14th) and fifteenth (15th)

floors (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 January 31, 2022; and

C. WHEREAS, Tenant desires to: (i) lease additional space from Landlord consisting of approximately 7,800 rentable square feet on

the eighth (8th) floor of the Building (the 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 forth herein.

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 Amendment as if set

forth herein in full. 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.

2. 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 Amendment, the Expansion Premises.

2.1 The Lease Term with respect to the Expansion Premises (the

Expansion Premises Term ) shall commence on the date Landlord has delivered possession of the Expansion Premises to Tenant in the Delivery Condition (as hereinafter defined) (the Expansion Premises Commencement

Date ) and the Lease Term shall continue thereafter so as to expire on the last day of the full eighty-fourth (84th) month following the Expansion Premises Commencement Date. The

Expansion Premises Rent Commencement Date shall be the Expansion Premises Commencement Date. Upon the Expansion Premises Commencement Date, Landlord and Tenant shall enter into an Expansion Premises Commencement Date Certificate

in the form attached hereto as EXHIBIT B. Landlord estimates that the Expansion Premises Commencement Date shall occur on December 1, 2018 (the Estimated Delivery Date ). In the event that the Expansion Premises

Commencement Date does not occur prior to January 15, 2019, then Tenant shall receive a day-for-day credit of Fixed Rent for each day thereafter until the earlier

of (a) the Expansion Premises Commencement Date; and (b) March 15, 2019. In the event that the Expansion Premises Commencement Date does not occur on or before March 15, 2019, then such day-for-day credit of Fixed Rent shall continue from and after March 15, 2019 until the Expansion Premises Commencement Date occurs, except that Tenant shall have the right to terminate this Amendment

upon written notice to Landlord, in which case this Amendment shall be null and void and without any force and effect. In the event that Tenant does not deliver the Construction Drawings to Landlord within the time period required in

Section 2.4, then the January 15 and March 15 dates in the two immediately foregoing sentences shall each be extended by one (1) day respectively for each day such Construction Drawings are overdue.

2.2 For purposes herein, Delivery Condition shall mean that the Expansion Premises are delivered to

Tenant pursuant to and in accordance with a separate and final plan mutually agreed to by Landlord and Tenant (the Final Plan ) and a final and unconditional certificate of occupancy or other legal sign off has been obtained by

Landlord from the City of Cambridge Inspectional Services Department with respect to the Expansion Premises permitting legal occupancy of the Expansion Premises for the Permitted Use and with all mechanical and HVAC systems serving the Expansion

Premises in good operational condition with a remaining useful life as long as the Expansion Premises Term as the same may be extended hereunder and with the common areas of the Building in compliance with all applicable legal requirements, subject

only to mutually agreed schedule of punch list items, which mean those items, the incompleteness of which does not prevent Tenant s use and occupancy of the Expansion Premises for the conduct of Tenant s business without interference.

Landlord agrees to complete any punch list items within thirty (30) days after the Expansion Premises Commencement Date. Notwithstanding the foregoing, Landlord shall not be obligated to contribute more than $55.00 per rentable square foot of

the Expansion Premises (or $429,000.00 in total based on 7,800 rentable square feet in the Expansion Premises) (the Expansion Premises Allowance ) toward the cost of Landlord s Expansion Work, as defined herein. In addition to

the Expansion Premises Allowance, Landlord shall contribute the amount of $.10 per rentable square foot of the Expansion Premises (or $780.00) toward the cost of Tenant s architect to perform a

test-fit with respect to the Expansion Premises ( Test Fit Allowance ).

2.3 In the event Landlord s Expansion Work is in excess of the Expansion Premises Allowance (the

Excess ), Tenant shall reimburse Landlord for such Excess within thirty (30) days of invoice. In the alterative, upon written notice to Landlord, Tenant shall have the option to reimburse Landlord over the Expansion Premises

Term in accordance with the following: Landlord shall amortize the Excess over the Expansion Premises Term at the rate of eight percent (8%) per annum and Tenant shall reimburse Landlord for the Excess over the Expansion Premises Term on a monthly

basis at the same time Fixed Rent is due under the Lease.

2.4 Landlord shall perform all work using its own contractors necessary to

deliver possession of the Expansion Premises to Tenant in Delivery Condition on or before the Estimated Delivery Date ( Landlord s Expansion Work ). Tenant shall deliver a draft of the initial test fit plan (the Draft

Plan ) with respect to Landlord s Expansion Work to Landlord for review and approval not later than April 30, 2018. Landlord shall have seven (7) business days to review and approve the Draft Plan. If Landlord does not

approve the same, Landlord shall provide written notice to Tenant citing the reasons for such disapproval and Tenant shall be required to review and re-submit the same within five (5) business days. This

process shall continue until the Final Plan has been mutually approved in writing by Landlord and Tenant. Within forty-five (45) days of mutual approval of the Final Plan, Tenant shall deliver to Landlord final construction drawings based on

the Final Plan (the Construction Drawings ). Notwithstanding the foregoing, in the event that Tenant does not deliver the Draft Plan to Landlord by May 31, 2018, Landlord shall have the right to terminate the Lease with

respect to the Expansion Premises upon written notice to Tenant.

2.5 For purposes of confirmation herein,

Tenant s Proportionate Share of the Building for the Existing Premises is 6.29% which is based on approximately 7,791 rentable square feet in the Existing Premises and approximately 123,810 rentable square feet in the Building. Tenant s

Proportionate Share of the Building for the Expansion Premises is 6.30% which is based on approximately 7,800 rentable square feet in the Expansion Premises and approximately 123,810 rentable square feet in the Building. Effective as of the

Expansion Premises Commencement Date: (a) the Premises (meaning the Existing Premises, together with the Expansion Premises) shall be amended to consist of a total of approximately 15,591 rentable square feet; and (b)

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

3. Fixed Rent for Expansion Premises. Tenant shall pay Fixed Rent with respect to the 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 so as to run and expire coterminous with the Expansion Premises Term.

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, 2021. Effective as of January 1, 2022, Tenant shall pay Fixed Rent with respect to the

Existing Premises at the same rate per square foot as then in effect for the Expansion Premises, which rate shall increase at the same rate and on the same dates as applicable to the Expansion Premises.

6. Utilities. The Expansion Premises, as part of Landlord s Expansion Work, shall be separately metered for electricity and

commencing on the 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 Expansion Premises Rent Commencement Date, Tenant shall be responsible for Additional Rent with respect to the 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 2018, 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 2018. Tenant shall continue to pay

Additional Rent with respect to the Existing Premises through December 31, 2021 in accordance with the provisions of the Lease. Effective upon January 1, 2022: (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 2022; and (b) the Tax Base Year for the Existing Premises shall mean an amount equal to the actual Taxes for the

Building for the fiscal year 2022.

8. Condition of Premises. Except for the (a) Expansion Premises Allowance;

(b) Test Fit Allowance; and (c) Landlord s Expansion Work, Landlord shall not be responsible for providing any work or allowances in connection with this Amendment, and Tenant shall take occupancy of the Expansion Premises in its as-is condition.

9. Parking. For purposes of confirmation herein, Tenant

currently leases eight (8) parking spaces at the rate of $230.00 per space per month in accordance with the terms and conditions of the Lease. Effective as of the Expansion Premises Commencement Date, Tenant shall lease an additional eight

(8) parking spaces in the parking facilities on the Land at the rate of $210.00 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. EXHIBIT G EXTENSION OPTION of the Lease is

hereby deleted in its entirety and replaced with EXHIBIT C EXTENSION OPTIONS attached hereto.

Offer. EXHIBIT H RIGHT OF OFFER of the Lease is hereby deleted in its entirety and replaced with EXHIBIT D 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 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 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

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 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 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. Landlord, at its sole cost and expense, shall provide Tenant with

Building Standard signage for the Expansion Premises in the Building directory and at its entrance to the Expansion Premises. Tenant shall have the right, but not the obligation, to maintain such signage at its entrance to the Existing Premises.

16. Confirmation of Lease. Except as amended by this Amendment, all existing terms and provisions of the Lease shall remain

in full force and effect.

17. Miscellaneous. This 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 facsimile or other electronic transmission shall be deemed to be an original.

[Signature Page Follows]

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

CENTRAL PLAZA MASSACHUSETTS, LLC

a Delaware limited liability company

a Delaware limited liability