1 Pursuant to Rule 416(a) promulgated under the Securities Act of 1933, as amended (the “Securities Act”), this Registration Statement shall also cover any additional shares of common stock of Spruce Biosciences, Inc. (the “Registrant”) that become issuable under the Registrant’s 2026 Inducement Plan (the “Inducement Plan”) by reason of any stock dividend, stock split, recapitalization, or other similar transaction effected that results in an increase to the number of outstanding shares of the Registrant’s common stock, as applicable. The amount registered represents shares of common stock that are available for issuance pursuant to the Inducement Plan. The proposed maximum aggregate offering price per unit and proposed maximum aggregate offering price for the 75,000 shares of common stock reserved for grant under the Inducement Plan are estimated in accordance with Rules 457(c) and 457(h) solely for the purpose of calculating the registration fee on the basis of $55.76 per share, which is the average of the high and low selling prices per share of the Registrant’s common stock on May 12, 2026 as reported on the Nasdaq Capital Market.