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Form of Proxy

SPERO THERAPEUTICS, INC.

Notes

No. Proposition For Against Abstain
1

Election of Class II Director to serve until the Companys 2028 Annual Meeting of Stockholders or until their respective successors are elected and qualified: Frank E. Thomas

2

Election of Class II Director to serve until the Companys 2028 Annual Meeting of Stockholders or until their respective successors are elected and qualified: Patrick Vink, M.D.

3

Election of Class II Director to serve until the Companys 2028 Annual Meeting of Stockholders or until their respective successors are elected and qualified: Esther Rajavelu

4

To ratify the appointment of PricewaterhouseCoopers LLP as the Companys independent registered public accounting firm for the fiscal year ending December 31, 2025.

5

To approve by an advisory vote the compensation of the Companys named executive officers, as disclosed in the proxy statement.

6

To approve an amendment to the Companys 2017 Stock Incentive Plan, as amended, to increase the total number of shares of common stock authorized for issuance thereunder by 3,000,000 shares.