X0306 4 2021-05-20 0 0001683553 SPRUCE BIOSCIENCES, INC. SPRB 0001822557 SIMPSON CAMILLA V C/O SPRUCE BIOSCIENCES, INC. 2001 JUNIPERO SERRA BLVD., SUITE 640 DALY CITY CA 94014 1 0 0 0 Common Stock 2021-05-20 4 M 0 334 0.85 A 334 D Common Stock 2021-05-20 4 S 0 334 15.29 D 0 D Stock Option (Right to Buy) 0.85 2021-05-20 4 M 0 334 0.00 D 2027-10-18 Common Stock 2007 1673 D Stock Option (Right to Buy) 15.24 2021-05-20 4 A 0 10000 0.00 A 2031-05-19 Common Stock 10000 10000 D The sales reported in this Form 4 were effected pursuant to a Rule 10b5-1 trading plan previously adopted by the Reporting Person. The shares subject to the stock option vest over a four-year period commencing October 19, 2017, with 1/4th of the shares vesting on October 19, 2018 and 1/36th of the remaining shares vesting on a monthly basis. The shares vest on the first anniversary of the Grant Date, provided that the Option will in any case be fully vested on the date of Company's 2022 annual stockholder meeting, subject to the Reporting Person's Continuous Service (as defined in the 2020 Equity Incentive Plan (the "Plan")) through such vesting date and will vest in full upon a Change in Control (as defined in the Plan). /s/ Samir Gharib, Attorney-in-Fact 2021-05-20