SPERO THERAPEUTICS, INC.

MODIFICATION P00021 THIS MODIFICATION IS BEING ISSUED TO DE-OBLIGATE CANCELLING FUNDS IN THE AMOUNT OF $61,887.86.

MODIFICATION P00019 THE PURPOSE OF THIS BILATERAL MODIFICATION IS TO: A) CHANGE ARTICLE F.2. DELIVERABLES, ARTICLE G.2. CONTRACTING OFFICER'S REPRESENTATIVE (COR), AND ARTICLES G.5. INVOICE/FINANCING REQUEST AND CONTRACT FINANCIAL REPORTING TO

TO ADVANCE CLINICAL AND NON-CLINICAL DEVELOPMENT OF AN ANTIBIOTIC CANDIDATE.

MODIFICATION P00015 THE PURPOSE OF THIS BILATERAL MODIFICATION IS TO: A) INCREASE THE US GOVERNMENT FUNDING FOR CLIN 0005 OPTION 4 FROM $12,498,467 BY $11,697,110 TO $24,195,577 AND THE SPERO COST SHARE FROM $63,204,595 BY $14,683,133 TO $77,887,

ADVANCE THE DEVELOPMENT OF SPR994 AS AN ORAL THERAPY FOR USE IN ADULTS TO TREAT COMPLICATED URINARY TRACT INFECTIONS (CUTIS), INCLUDING THOSE CAUSED BY DRUG RESISTANT BACTERIA

TO ADVANCE CLINICAL AND NON-CLINICAL DEVELOPMENT OF AN ANTIBIOTIC CANDIDATE.

TO ADVANCE CLINICAL AND NON-CLINICAL DEVELOPMENT OF AN ANTIBIOTIC CANDIDATE.

TO ADVANCE CLINICAL AND NON-CLINICAL DEVELOPMENT OF AN ANTIBIOTIC CANDIDATE.

TO ADVANCE CLINICAL AND NON-CLINICAL DEVELOPMENT OF AN ANTIBIOTIC CANDIDATE.

THIS MOD SHOULD INCLUDE UPDATED SOW, GO/NO-GO MILESTONES, GANTT CHART) CHANGE THE CO FROM KATHY TO JONATHAN GONZALEZ; CHANGE KEY PERSONNEL CMO FROM DAVID TO KAMAL; REFLECT CHANGES TO IPP SYSTEM FOR INVOICING.

CHANGE COR

DEVELOPMENT OF A SECOND GENERATION POLYMYXIN FOR THERAPY OF MDR GRAM-NEGATIVE INFECTIONS

EXERCISE OPTION 3/CLIN0004