Spruce Biosciences Inc. 美股招股说明书（2026年3月9日版）

Common Stock We have entered into an Open Market Sale AgreementSM, dated March 9, 2026 (the “Sales Agreement”), with Jefferies LLC (“Jefferies”), relating to the sale of shares of our common stock offered by this prospectus supplement. In accordance with theterms of the Sales Agreement, under this prospectus supplement we may offer and sell shares of our common stock, $0.0001 parvalue per share, having an aggregate offering price of up to $75.0 million from time to time through Jefferies, acting as our agent. Our common stock is listed on the Nasdaq Capital Market under the symbol “SPRB.” On March 6, 2026, the last reported saleprice of our common stock on the Nasdaq Capital Market was $55.87 per share. Sales of our common stock, if any, under this prospectus supplement may be made by any method deemed to be an “at themarket offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the “Securities Act”),including sales made directly on or through the Nasdaq Capital Market, the existing trading market for our common stock, or anyother existing trading market for our common stock. Jefferies is not required to sell any specific number or dollar amount ofsecurities, but will act as our sales agent using commercially reasonable efforts to sell on our behalf all of the shares of our common Jefferies will be entitled to compensation at a commission rate of 3.0% of the gross proceeds of any shares of common stocksold under the Sales Agreement. In connection with the sale of the common stock on our behalf, Jefferies will be deemed to be an“underwriter” within the meaning of the Securities Act and the compensation paid to Jefferies will be deemed to be underwritingcommissions or discounts. We have also agreed to provide indemnification and contribution to Jefferies with respect to certain We are a “smaller reporting company” under applicable Securities and Exchange Commission rules, and as such, haveelectedto comply with reduced public company reporting requirements for this prospectus supplement and the Investing in our common stock involves a high degree of risk. You should read this prospectus supplement and theaccompanying prospectus as well as the information incorporated herein and therein by reference carefully before youmake your investment decision, including the risks and uncertainties described under the section titled “Risk Factors” Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved ofthese securities or passed upon the accuracy or adequacy of this prospectus supplement or the accompanying prospectus. Jefferies The date of this prospectus supplement is March 9, 2026. TABLE OF CONTENTS Prospectus Supplement Prospectus ABOUT THIS PROSPECTUSPROSPECTUS SUMMARYRISK FACTORSSELECTED FINANCIAL DATA REFLECTING REVERSE STOCK SPLITSPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTSUSE OF PROCEEDSDESCRIPTION OF CAPITAL STOCKDESCRIPTION OF DEBT SECURITIESDESCRIPTION OF WARRANTSLEGAL OWNERSHIP OF SECURITIESPLAN OF DISTRIBUTIONLEGAL MATTERSEXPERTSWHERE YOU CAN FIND MORE INFORMATIONINCORPORATION OF CERTAIN INFORMATION BY REFERENCE Table of Contents ABOUT THIS PROSPECTUS SUPPLEMENT This prospectus supplement and the accompanying prospectus are part of a shelf registration statement on Form S-3 (File No.333-291152)that we filed with the Securities and Exchange Commission (“SEC”). This prospectus supplement describes thespecific terms of the common stock we are offering and also adds to and updates information contained in the accompanyingprospectus and the documents incorporated by reference herein and therein. To the extent there is a conflict between theinformation contained in this prospectus supplement, on the one hand, and the information contained in any document incorporatedby reference into this prospectus supplement or the accompanying prospectus that was filed prior to the date of this prospectus You should rely only on the information contained in, or incorporated by reference into this prospectus supplement, theaccompanying prospectus, and in any free writing prospectus that we may authorize for use in connection with this offering. Wehave not, and Jefferies has not, authorized any other person to provide you with different information. If anyone provides you withdifferent or inconsistent information, you should not rely on it. You should assume that the information appearing in this prospectussupplement, the accompanying prospectus, the documents incorporated by reference herein and therein, and in any free writingprospectus that we may authorize for use in connection with this offering, is accurate only as of the date of those respectivedocuments. Our business, financial condition, results of operations and prospects may have changed since those dates. You should We are offering to sell, and seeking offers to buy, shares of our common stock only in jurisdictions where such offers and salesare pe