X0306 4 2023-02-03 0 0001701108 Spero Therapeutics, Inc. SPRO 0001720974 Mahadevia Ankit C/O SPERO THERAPEUTICS, INC. 675 MASSACHUSETTS AVENUE, 14TH FLOOR CAMBRIDGE MA 02139 1 1 0 0 CEO and President Common Stock 2023-02-03 4 S 0 12286 1.81 D 797832 D The reported transaction is a sale of common stock effected to cover tax withholding obligations in connection with the vesting of restricted stock units ("RSUs") that were granted to the Reporting Person on February 1, 2022 pursuant to a "sell to cover" provision included in the RSU Agreement. Amount includes 65,817 shares of common stock held by the Mahadevia-Mehta Family Trust, of which the Reporting Person is a trustee. Amount also includes 691,205 RSUs held by the Reporting Person. /s/ Tamara Joseph, Attorney-in-Fact for Ankit Mahadevia 2023-02-06