X0306 4 2017-11-06 0 0001701108 Spero Therapeutics, Inc. SPRO 0001720875 Sendek Joel C/O SPERO THERAPEUTICS, INC. 675 MASSACHUSETTS AVENUE, 14TH FLOOR CAMBRIDGE MA 02139 0 1 0 0 Chief Financial Officer Common Stock 2017-11-06 4 C 0 10181 A 10181 I Joel D. Sendek Retained Annuity Trust No. 1 Common Stock 2017-11-06 4 P 0 5000 14.00 A 15181 D Series C Preferred Stock 2017-11-06 4 C 0 61880 0.00 D Common Stock 10181 0 I Joel D. Sendek Retained Annuity Trust No. 1 Amount of underlying securities reflects the application of the applicable conversion ratio as set forth in the Issuer's Amended and Restated Certificate of Incorporation in effect immediately prior to the closing of the initial public offering (as adjusted by the 1-for-6.0774 reverse stock split of the Issuer's common stock effected on October 20, 2017). The preferred stock had no expiration date. Reflects shares that were purchased through a directed share program in connection with the Issuer's initial public offering. /s/ Matthew Tikonoff, Attorney-in-Fact for Joel Sendek 2017-11-07