X0202 SCHEDULE 13G/A 0001104659-25-100138 0001423053 XXXXXXXX LIVE 3 Common Stock, par value $0.0001 per share (the "Shares") 06/30/2026 0001683553 Spruce Biosciences, Inc. 85209E208 611 Gateway Boulevard, Suite 740 South San Francisco CA 94080 Rule 13d-1(c) Citadel Advisors LLC DE 0.00 46960.00 0.00 46960.00 46960.00 N 1.7 IA HC OO The percentages reported in this Schedule 13G are based upon 2,752,278 Shares outstanding as of May 11, 2026 (according to the issuer's Form 10-Q as filed with the Securities and Exchange Commission on May 13, 2026). Citadel Advisors Holdings LP DE 0.00 46960.00 0.00 46960.00 46960.00 N 1.7 HC PN Citadel GP LLC DE 0.00 46960.00 0.00 46960.00 46960.00 N 1.7 HC OO Citadel Securities LLC DE 0.00 1684.00 0.00 1684.00 1684.00 N 0.1 BD OO Citadel Securities Group LP DE 0.00 4959.00 0.00 4959.00 4959.00 N 0.2 HC PN Citadel Securities GP LLC DE 0.00 4959.00 0.00 4959.00 4959.00 N 0.2 HC OO Kenneth Griffin X1 0.00 51919.00 0.00 51919.00 51919.00 N 1.9 HC IN Spruce Biosciences, Inc. 611 Gateway Boulevard, Suite 740, South San Francisco, CA 94080 This Schedule 13G is being jointly filed by Citadel Advisors LLC ("Citadel Advisors"), Citadel Advisors Holdings LP ("CAH"), Citadel GP LLC ("CGP"), Citadel Securities LLC ("Citadel Securities"), Citadel Securities Group LP ("CALC4"), Citadel Securities GP LLC ("CSGP") and Mr. Kenneth Griffin (collectively with Citadel Advisors, CAH, CGP, Citadel Securities, CALC4 and CSGP, the "Reporting Persons") with respect to the Shares of the above-named issuer held of record by Citadel Multi-Strategy Equities Master Fund Ltd., a Cayman Islands company ("CM"), Citadel CEMF Investments Ltd., a Cayman Islands limited company ("CCIL"), Citadel Quantitative Strategies Master Fund Ltd., a Cayman Islands limited company ("CQ"), Citadel Securities and CRBU Holdings LLC, a Delaware limited liability company ("CRBH"). Such Shares may include other instruments exercisable for or convertible into Shares. Citadel Advisors is the portfolio manager for CM, CCIL and CQ. CAH is the sole member of Citadel Advisors. CGP is the general partner of CAH. CALC4 is the non-member manager of Citadel Securities and CRBH. CSGP is the general partner of CALC4. Mr. Griffin is the President and Chief Executive Officer of CGP, and owns a controlling interest in CGP and CSGP. The address of each of the Reporting Persons is 830 Brickell Plaza, Miami, Florida 33131. Each of Citadel Advisors, CGP, Citadel Securities and CSGP is organized as a limited liability company under the laws of the State of Delaware. Each of CALC4 and CAH is organized as a limited partnership under the laws of the State of Delaware. Mr. Griffin is a U.S. citizen. Y 1. Each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC may be deemed to beneficially own 46,960 Shares. 2. Citadel Securities LLC may be deemed to beneficially own 1,684 Shares. 3. Each of Citadel Securities Group LP and Citadel Securities GP LLC may be deemed to beneficially own 4,959 Shares. 4. Mr. Griffin may be deemed to beneficially own 51,919 Shares. 1. The number of Shares that each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC may be deemed to beneficially own constitutes 1.7% of the Shares outstanding. 2. The number of Shares that Citadel Securities LLC may be deemed to beneficially own constitutes 0.1% of the Shares outstanding. 3. The number of Shares that each of Citadel Securities Group LP and Citadel Securities GP LLC may be deemed to beneficially own constitutes 0.2% of the Shares outstanding. 4. The number of Shares that Mr. Griffin may be deemed to beneficially own constitutes 1.9% of the Shares outstanding. 1. Each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC: 0 2. Citadel Securities LLC: 0 3. Each of Citadel Securities Group LP and Citadel Securities GP LLC: 0 4. Mr. Griffin: 0 1. Each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC: 46,960 2. Citadel Securities LLC: 1,684 3. Each of Citadel Securities Group LP and Citadel Securities GP LLC: 4,959 4. Mr. Griffin: 51,919 1. Each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC: 0 2. Citadel Securities LLC: 0 3. Each of Citadel Securities Group LP and Citadel Securities GP LLC: 0 4. Mr. Griffin: 0 1. Each of Citadel Advisors LLC, Citadel Advisors Holdings LP and Citadel GP LLC: 46,960 2. Citadel Securities LLC: 1,684 3. Each of Citadel Securities Group LP and Citadel Securities GP LLC: 4,959 4. Mr. Griffin: 51,919 N Y Y Y Y Y N By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under § 240.14a-11. Citadel Advisors LLC /s/ Seth Levy 08/14/2026 Citadel Advisors Holdings LP /s/ Seth Levy 08/14/2026 Citadel GP LLC /s/ Seth Levy 08/14/2026 Citadel Securities LLC /s/ Seth Levy 08/14/2026 Citadel Securities Group LP /s/ Seth Levy 08/14/2026 Citadel Securities GP LLC /s/ Seth Levy 08/14/2026 Kenneth Griffin /s/ Seth Levy 08/14/2026 * Seth Levy is signing on behalf of Kenneth Griffin as attorney-in-fact pursuant to a power of attorney previously filed with the Securities and Exchange Commission, and hereby incorporated by reference herein. The power of attorney was filed as an attachment to a filing by Citadel Advisors LLC on Schedule 13G for Allakos Inc. on October 13, 2023.