X0306 4 2022-02-01 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 2022-02-01 4 A 0 134168 0.00 A 278204 D Stock Option (Right to Buy) 11.18 2022-02-01 4 A 0 187730 0.00 A 2032-02-01 Common Stock 187730 187730 D Consists of restricted stock units ("RSUs"). Each RSU represents the right to receive one share of common stock upon vesting. The RSUs vest in four equal annual installments beginning on February 1, 2023, subject to the Reporting Person's continued service through the applicable vesting date. 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 212,387 RSUs held by the Reporting Person. The shares underlying this option vest as to 25% on February 1, 2023, with the remainder vesting in 36 equal monthly installments thereafter, subject to the Reporting Person's continued service through the applicable vesting date. /s/ Tamara Joseph, Attorney-in-Fact for Ankit Mahadevia 2022-02-03