UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13D

Under the Securities Exchange Act of 1934

(Amendment No. 4)*

Spruce Biosciences, Inc.

(Name of Issuer)

Common Stock, par value $0.0001 per share

(Title of Class of Securities)

85209E 109

(CUSIP Number)

Barbara Fiorini Due

Novo Holdings A/S

Tuborg Havnevej 19

Hellerup, Denmark DK-2900

+45 3527 6592

Copy to:

B. Shayne Kennedy, Esq.

Latham & Watkins LLP

650 Town Center Drive, 20^th Floor

Costa Mesa, CA 92626

Telephone: (714) 540-1235

(Name, Address and Telephone Number of Person Authorized to Receive Notices and Communications)

February 16, 2023

(Date of Event which Requires Filing of this Statement)

If the filing person has previously filed a statement on Schedule 13G to report the acquisition which is subject of this Schedule 13D, and is filing this statement because of Rule 13d-1(e), 13d-1(f) or 13d-1(g), check the following box.  ☐

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See Rule 13d-7(b) for other parties to whom copies are to be sent.

The information required on the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (the “Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

CUSIP No.: 85209E 109

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This amendment (“Amendment No. 4”) amends the Schedule 13D originally filed with the SEC on October 16, 2020, as subsequently amended by Amendment No. 1 filed on May 21, 2021, Amendment No. 2 filed on November 22, 2022, and Amendment No. 3 on September 30, 2022 (collectively, the “Schedule”), and relates to the Common Stock. All capitalized terms contained herein but not otherwise defined shall have the meanings ascribed to such terms in the Schedule.

Item 2 is amended and replaced in its entirety as follows:

The name of each director and executive officer of both Novo Holdings A/S and the Foundation is set forth on the updated Schedule I to this Amendment No. 4.

The residence or business address of each director and executive officer of both Novo Holdings A/S and the Foundation is set forth on the updated Schedule I to this Schedule 13D.

The Foundation is a Danish self-governing and profit-making foundation, whose objectives are to provide a stable basis for commercial and research activities undertaken by the group of Novo companies and to support scientific, humanitarian and social purposes through grants.

Item 3 amends and supplements Item 3 in the Schedule as follows:

On February 8, 2023, Novo Holdings A/S, among other parties, entered into a Securities Purchase Agreement with the Issuer. Pursuant to the Securities Purchase Agreement, Novo Holdings A/S purchased 2,208,000 shares of the Common Stock (“Shares”) and 1,656,000 warrants to purchase the Common Stock with an exercise price of $3.96 per Share (“Warrants”), for a combined price of $3.17 per share of common stock, and total consideration of $6,999,360. At the closing of the transaction on February 16, 2023, the Issuer sold and issued, in a private placement, the Shares and Warrants to Novo Holdings A/S. The foregoing description is qualified in its entirety by the Securities Purchase Agreement incorporated by reference in this filing.

Novo Holdings A/S purchased the Shares and Warrants set forth in this Schedule 13D using funds from working capital.

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Item 4. Purpose of Transaction

Item 4 of the Schedule 13D is supplemented as follows:

The information set forth in Item 3 and Item 6 of this Schedule 13D is incorporated by reference to this Item 4.

Item 5 is amended and replaced in its entirety as follows:

Item 6. Contracts, Arrangements, Understandings or Relationships with Respect to Securities of the Issuer

Item 6 is amended and supplemented as follows:

On February 8, 2023, the Issuer and certain other purchasers including Novo Holdings A/S entered into a Securities Purchase Agreement pursuant to which the Issuer agreed to sell and issue (i) 16,116,000 of the Common Stock, (ii) pre-funded warrants to purchase 800,000 Shares of the Common Stock, and (iii) 12,687,000 standard warrants to purchase the Common Stock in a private placement transaction. Pursuant to the Securities Purchase Agreement, Novo Holdings A/S purchased the securities set forth in Item 3 of this Amendment No. 4.

Under the Securities Purchase Agreement, the Issuer is required to file one or more registration statements (the “Registration Statements”) covering the resale of the Common Stock and the shares of Common Stock issuable upon conversion of the Warrants issued under the Securities Purchase Agreement as soon as reasonably practicable, but in no event later than 30 days after the closing of the transaction (the “Filing Deadline”) and to cause the applicable Registration Statements to become effective within a specified period after the Filing Deadline. The Issuer is required to use its best efforts to keep the Registration Statements continuously effective until the earlier of: February 16, 2026 or the date the covered shares and warrant shares held by or issuable to such Holder may be sold under Rule 144 without being subject to any volume, manner of sale or publicly available information requirements. Certain cash penalties will apply to the Issuer in the event of registration failures, as described in the Securities Purchase Agreement. All registration expenses incurred shall be borne by the Issuer. From February 8, 2023 and until 90 days following the effectiveness of the Registration Statements, the Issuer may not issue shares of Common

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Stock or file a registration statement with the SEC for equity other than the Registration Statements, unless all securities sold under the Securities Purchase Agreement are sold or may be sold under Rule 144 during the 90 day period. The foregoing description is qualified in its entirety by the Securities Purchase Agreement incorporated by reference in this filing.

Pursuant to the Common Stock Purchase Warrant, dated February 16, 2023, the Warrants are currently exercisable, with an exercise price of $3.96 per share, subject to adjustment, and expire February 16, 2028. The Common Stock Purchase Warrant permits cashless exercises in certain circumstances, and contains certain anti-dilution adjustments and an obligation of the Issuer, at the election of the holder in the event of a Fundamental Transaction (as defined), to purchase the warrants from the holder.

Pursuant to the Securities Purchase Agreement and the Common Stock Purchase Warrant, certain exercise limitations apply. Novo Holdings A/S may not exercise any portion of its Warrants if after the exercise Novo Holdings A/S would beneficially own more than 19.99% of the Common Stock, unless shareholder approval from the stockholders of the Issuer is obtained prior to issuance. The foregoing description is qualified in its entirety by the Form of Common Stock Purchase Warrant incorporated by reference in this filing.

Item 7. Material to be Filed as Exhibits

Exhibit A – Securities Purchase Agreement, dated February 8, 2023, by and among Spruce Biosciences, Inc. and Purchasers (incorporated by reference to Exhibit 10.1 of the Issuer’s Current Report on Form 8-K, filed with the Securities and Exchange Commission on February 9, 2023).

Exhibit B – Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.2 of the Issuer’s Current Report on Form 8-K, filed with the Securities and Exchange Commission on February 9, 2023).

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SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.

Schedule I

Information regarding each director and executive officer of both Novo Holdings A/S and the Novo Nordisk Foundation is set forth below.

Novo Holdings A/S

Novo Nordisk Foundation

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Novo Nordisk Foundation

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