SecProbe.io

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 S PRUCE B IOSCIENCES , I NC .
 611 Gateway Boulevard, Suite 740
 South San Francisco, California 94080
 November 24, 2025 VIA EDGAR
 Securities and Exchange Commission Office of Finance
 Division of Corporation Finance 100 F. Street N.E.
 Washington, D.C. 20549-3010

 RE:
 Spruce Biosciences, Inc.
 Registration Statement on Form S-3 (File No. 333-291153)
 Request for Acceleration of Effective Date
 Ladies and Gentlemen: Spruce Biosciences, Inc.
(the “ Registrant ”) hereby requests that the U.S. Securities and Exchange Commission (the “ Commission ”) take appropriate action to cause the above-referenced Registration Statement on Form S-3 (File
No. 333-291153) (the “ Registration Statement ”) to become effective on Wednesday, November 26, 2025, at 4:30 p.m., Eastern Time, or as soon thereafter as is practicable or at such later time as the Registrant may orally
request via telephone call to the staff of the Commission. The Registrant hereby authorizes each of Katherine Denby and Alexander Gefter of Cooley LLP, counsel to the Registrant, to make such request on its behalf.
 Once the Registration Statement has been declared effective, please orally confirm that event with Katherine Denby of Cooley LLP, counsel to
the Registrant, at (202) 776-2070, or in her absence, Alexander Gefter at (310) 883-6438. [Remainder of page intentionally
left blank]

 Very truly yours,

 S PRUCE B IOSCIENCES , I NC .

 By:

 /s/ Samir Gharib

 Name:

 Samir Gharib

 Title:

 President and Chief Financial Officer

 cc:
 Katherine Denby, Cooley LLP
 Alexander Gefter, Cooley LLP

CORRESP
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 CORRESP

 S PRUCE B IOSCIENCES , I NC .
 611 Gateway Boulevard, Suite 740
 South San Francisco, California 94080
 November 24, 2025 VIA EDGAR
 Securities and Exchange Commission Office of Finance
 Division of Corporation Finance 100 F. Street
N.E. Washington, D.C. 20549-3010

 RE:
 Spruce Biosciences, Inc.
 Registration Statement on Form S-3 (File
 No. 333-291152) Request for Acceleration of Effective Date
 Ladies and Gentlemen:
 Spruce Biosciences, Inc. (the “ Registrant ”) hereby requests that the U.S. Securities and Exchange Commission
(the “ Commission ”) take appropriate action to cause the above-referenced Registration Statement on Form S-3 (File No. 333-291152) (the
“ Registration Statement ”) to become effective on Wednesday, November 26, 2025, at 4:30 p.m., Eastern Time, or as soon thereafter as is practicable or at such later time as the Registrant may orally request via telephone call
to the staff of the Commission. The Registrant hereby authorizes each of Katherine Denby and Alexander Gefter of Cooley LLP, counsel to the Registrant, to make such request on its behalf.
 Once the Registration Statement has been declared effective, please orally confirm that event with Katherine Denby of Cooley
LLP, counsel to the Registrant, at (202) 776-2070, or in her absence, Alexander Gefter at (310) 883-6438.
 [Remainder of page intentionally left blank]

 Very truly yours,

 S PRUCE B IOSCIENCES , I NC .

 By:

 /s/ Samir Gharib

 Name:

 Samir Gharib

 Title:

 President and Chief Financial Officer

 cc:
 Katherine Denby, Cooley LLP
 Alexander Gefter, Cooley LLP

CORRESP
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  CORRESP

  Spruce Biosciences, Inc.

  611 Gateway Blvd, Suite 740

  South San Francisco, California 94080

  April 5, 2023

  Via EDGAR

  Division of Corporation Finance

  U.S. Securities and Exchange Commission

  100 F Street, N.E.

  Washington, D.C. 20549

  Attn: Jason Drory

  RE:  Spruce Biosciences, Inc.

  Registration Statement on Form S-3

  Filed March 16, 2023

  File No. 333-270612

  Ladies and Gentlemen:

  Pursuant to Rule 461 under the Securities Act of 1933, as amended, the undersigned registrant hereby requests that the Securities and Exchange Commission take appropriate action to cause the above-referenced Registration Statement on Form S-3 to become effective at 4:30 p.m. Eastern Time on April 7, 2023, or as soon thereafter as is practicable.

  Once the above-referenced Registration Statement has been declared effective, please orally confirm that event with Alexa Smith of Cooley LLP, counsel to the Registrant, at (858) 550-6183.

  Spruce Biosciences, inc.

  By:   /s/ Samir Gharib                                  _

  Samir Gharib

  President and Chief Financial Officer

United States securities and exchange commission logo
March 21, 2023
Javier Szwarcberg, M.D., MPH
Chief Executive Officer
Spruce Biosciences, Inc.
611 Gateway Boulevard, Suite 740
South San Francisco, CA 94080
Re:Spruce Biosciences, Inc.
Registration Statement on Form S-3
Filed March 16, 2023
File No. 333-270612
Dear Javier Szwarcberg:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Jason Drory at 202-551-8342 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Alexa Smith

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Spruce Biosciences, Inc.

2001 Junipero Serra Boulevard, Suite 640

Daly City, CA 94014

February 9, 2022

Via Edgar

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attn:Chris Edwards

RE:

Spruce Biosciences, Inc.

Registration Statement on Form S-3

File No. 333-261960

Acceleration Request

Requested Date:

February 11, 2022

Requested Time:

4:00 p.m. Eastern Time

Ladies and Gentlemen:

Pursuant to Rule 461 under the Securities Exchange Act of 1933, as amended, the undersigned registrant hereby requests that the Securities and Exchange Commission take appropriate action to cause the above-referenced Registration Statement on Form S-3 (File No. 333-261960) (the “Registration Statement”) to become effective at 4:00 p.m. Eastern Time on Friday, February 11, 2022, or as soon thereafter as is practicable.

Once the Registration Statement has been declared effective, please orally confirm that event with Alexa Ekman of Cooley LLP, counsel to the registrant, at (858) 550-6183.

[Signature page follows]

Sincerely,

Spruce Biosciences, Inc.

By:

/s/ Javier Szwarcberg, M.D., MPH

Javier Szwarcberg, M.D., MPH

Chief Executive Officer

cc:

Samir Gharib, President and Chief Financial Officer, Spruce Biosciences, Inc.

Michael Grey, Executive Chairman, Spruce Biosciences, Inc.

Alexa Ekman, Cooley LLP

Daniel P. Eitutis, Cooley LLP

United States securities and exchange commission logo
January 6, 2022
Michael Grey
Interim Chief Executive Officer
Spruce Biosciences, Inc.
2001 Junipero Serra Boulevard, Suite 640
Daly City, California 94014
Re:Spruce Biosciences, Inc.
Registration Statement on Form S-3
Filed December 30, 2021
File No. 333-261960
Dear Mr. Grey:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Chris Edwards at 202-551-6761 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Daniel P. Eitutis

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CORRESP

 SPRUCE BIOSCIENCES, INC.

2001 Junipero Serra Boulevard, Suite 640

Daly City, California 94014

 October 6, 2020

 VIA EDGAR

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, D.C. 20549

Attn:
 Jessica Livingston

David Lin

 Eric Atallah

Angela Connell

Re:
 Spruce Biosciences, Inc.

Registration Statement on Form S-1, as amended (File
No. 333-248924)

 Request for Acceleration of Effective Date

Ladies and Gentlemen:

 Pursuant
to Rule 461 under the Securities Act of 1933, as amended, Spruce Biosciences, Inc. (the “Company”) hereby requests that the Securities and Exchange Commission (the “Commission”) accelerate the effective date of the
above-referenced Registration Statement on Form S-1 (as amended, the “Registration Statement”) and declare the Registration Statement effective as of 4:30 p.m. Eastern time, on October 8,
2020, or as soon thereafter as possible, or at such other time as the Company or its counsel may request by telephone to the staff of the Commission. The Company hereby authorizes each of Kristin VanderPas and Alexa Ekman of Cooley LLP, counsel to
the Company, to make such a request on its behalf. This request for acceleration is subject, however, to your receiving a telephone call prior to such time from Cooley LLP confirming this request.

Once the Registration Statement has been declared effective, please orally confirm that event with Kristin VanderPas of Cooley LLP at (415) 693-2097, or in her absence, Alexa Ekman of Cooley LLP at (858) 550-6183.

Under separate cover, you will receive today a letter from the managing underwriters of the proposed offering joining in the Company’s
request for acceleration of the effectiveness of the Registration Statement.

 [Signature page follows]

Very truly yours,

Spruce Biosciences, Inc.

 /s/ Richard King

By:

Richard King

Title:

Chief Executive Officer

 [Signature Page to Acceleration Request]

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CORRESP

 October 6, 2020

VIA EDGAR

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, D.C. 20549

Re:
 Spruce Biosciences, Inc.

Registration Statement on Form S-1, as amended (File
No. 333-248924)

 Ladies and Gentlemen:

Pursuant to Rule 461 under the Securities Act of 1933, as amended (the “Act”), we, as the representatives of the several
underwriters, hereby join in the request of Spruce Biosciences, Inc. (the “Company”) for acceleration of the effective date of the above-referenced Registration Statement on Form S-1 so that
it becomes effective at 4:30 p.m. Eastern time, on October 8, 2020, or as soon thereafter as practicable.

 Pursuant to Rule 460 under
the Act, we, as the representatives of the several underwriters, wish to advise you that between October 5, 2020 through the date hereof we have distributed approximately 2,141 copies of the Company’s Preliminary Prospectus dated
October 5, 2020 to prospective underwriters, dealers, institutional investors and others.

 We, the undersigned, as the
representatives of the several underwriters, have complied and will comply, and we have been informed by participating underwriters that they have complied and will comply, with the requirements of Rule 15c2-8
under the Securities Exchange Act of 1934, as amended.

 [Signature page follows]

Very truly yours,

 COWEN AND COMPANY, LLC

 SVB LEERINK
LLC

 CREDIT SUISSE SECURITIES (USA) LLC

RBC CAPITAL MARKETS, LLC

Acting severally on behalf of themselves and the several underwriters

COWEN AND COMPANY, LLC

By:

 /s/ Bill Follis

Name:

Bill Follis

Title:

Managing Director

SVB LEERINK LLC

By:

 /s/ Murphy Gallagher

Name:

Murphy Gallagher

Title:

Managing Director

CREDIT SUISSE SECURITIES (USA) LLC

By:

 /s/ Rebecca Kotkin

Name:

Rebecca Kotkin

Title:

Director

RBC CAPITAL MARKETS, LLC

By:

 /s/ Jennifer Caruso

Name:

Jennifer Caruso

Title:

Managing Director

 [Signature Page to Acceleration Request]

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CORRESP

 Kristin VanderPas

 +1 415 693 2097

kvanderpas@cooley.com

VIA EDGAR AND FEDEX

 *FOIA Confidential Treatment Request*

Confidential Treatment Requested by Spruce Biosciences, Inc.

in connection with its Registration Statement on Form S-1 (File No. 333-248924)

September 18, 2020

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, D.C. 20549

Attn:

Jessica Livingston

David Lin

Eric Atallah

Angela Connell

 Re:

Spruce Biosciences, Inc.

Registration Statement on Form S-1

Filed September 18, 2020

File No. 333-248924

 Ladies and Gentlemen:

On behalf of Spruce Biosciences, Inc. (the “Company”), in response to comments from the staff (the
“Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) received by letter dated September 3, 2020 (the “Comment Letter”), relating to the Company’s
draft Registration Statement on Form S-1 confidentially submitted to the Commission on August 7, 2020 (the “DRS”), which was subsequently updated by the Company with a Registration
Statement on Form S-1 filed with the Commission on September 18, 2020 (the “Registration Statement”), we are submitting this supplemental letter to further address Comment
No. 6 of the Comment Letter. For the convenience of the Staff, we have incorporated the text of Comment No. 6 into this letter.

Due to the commercially sensitive nature of information contained in this letter, this submission is accompanied by the Company’s request
for confidential treatment for selected portions of this letter. The Company has filed a separate letter with the Office of Freedom of Information and Privacy Act Operations in connection with the confidential treatment request pursuant to Rule 83
of the Commission’s Rules on Information and Requests (17 C.F.R. § 200.83).

 Cooley
LLP    101 California Street, 5th Floor    San Francisco, CA    94111-5800

 t:
(415) 693-2000  f: (415) 693-2222  cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Two

 Staff Comment

General

20.
 Once you have an estimated offering price or range, please explain to us how you determined the fair value
of the common stock underlying your equity issuances and the reasons for any differences between the recent valuations of your common stock leading up to the IPO and the estimated offering price. This information will help facilitate our review of
your accounting for equity issuances including stock-based compensation.

 Response:

Preliminary Price Range

 The
Company advises the Staff that the Company currently expects a price range of approximately $[***] to $[***] per share (the “Preliminary Price Range”) for the initial public offering
(“IPO”) of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), which Preliminary Price Range does not reflect the impact of a reverse stock split of the Common Stock that
the Company anticipates will be effected prior to the effectiveness of the Registration Statement (the “Reverse Stock Split”). This Preliminary Price Range implies a pre-money valuation
range for the Company of $[***] million to $[***] million.

 The Preliminary Price Range is based in part upon the Company’s
prospects, prospects for the biopharmaceutical industry, the general condition of the securities markets and the recent market prices of, and the demand for, publicly traded shares of generally comparable companies in the biopharmaceutical industry,
as well as input received from Cowen and Company, LLC, SVB Leerink LLC, Credit Suisse Securities (USA) LLC, and RBC Capital Markets, LLC, the representatives of the several underwriters for the Company’s IPO (the
“Representatives”). The Company notes that, as is typical in IPOs, the Preliminary Price Range for the Company’s IPO was not derived using a formal determination of fair value or single valuation methodology, but was
determined based on a variety of considerations and methodologies, including the assessment of the aforementioned factors.

 The Company
will include a narrower bona fide price range of the Common Stock as adjusted for the Reverse Stock Split, as well as the terms of the Reverse Stock Split, in an amendment to the Registration Statement that will be filed prior to the commencement of
the Company’s road show. However, the parameters of the bona fide price range will be subject to then-current market conditions, continuing discussions with the Representatives and material business developments impacting the Company. As a
result of these factors and due to the volatility in the securities markets, there is a possibility that the bona fide price range for the IPO may fall outside of the Preliminary Price Range. In any event, the Company confirms to the Staff that the
bona fide price range will comply with Item 501(b)(3) of Regulation S-K and C&DI 134.04.

 Common Stock
Valuation Methodologies

 As there has been no public market for the Common Stock to date, the estimated fair value of Common Stock
for purposes of granting equity awards has been determined by the Company’s board of directors (the “Board”), as of the date of each option grant, with input from management, considering the Company’s
(i) issuances and sales of its redeemable convertible preferred stock, and (ii) the most recent third-party valuation of its Common Stock, as well as the Board’s assessment of additional objective and

 *FOIA Confidential
Treatment Requested by Spruce Biosciences, Inc.*

 Cooley LLP    101 California Street, 5th
Floor    San Francisco, CA    94111-5800

 t: (415) 693-2000  f: (415)
693-2222  cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Three

 subjective factors that the Board believed were relevant and which may have changed from
the date of the most recent third-party valuation through the date of the grant. The Board considered various objective and subjective factors to determine the fair value of the Common Stock as of each grant date, including:

•

 external market conditions affecting the pharmaceutical and biotechnology industry and trends within the
industry;

•

 the Company’s stage of development;

•

 the prices at which the Company sold shares of its redeemable convertible preferred stock and the rights,
preferences and privileges of its redeemable convertible preferred stock relative to those of the Common Stock;

•

 the Company’s financial condition and operating results, including its levels of available capital
resources;

•

 the progress of the Company’s research and development efforts and business strategy;

•

 the timing and probability of future financings;

•

 equity market conditions affecting comparable public companies;

•

 general U.S. market conditions; and

•

 the lack of marketability of the Common Stock.

The third-party valuations of Common Stock that the Board considered in making its determinations were prepared in accordance with the
American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (the “Practice Aid”), which prescribes several
valuation approaches for determining the value of an enterprise, such as the cost, market and income approaches, and various methodologies for allocating the value of an enterprise to its capital structure and specifically its common stock.

In accordance with the Practice Aid, the Company considered the following methods for allocating the enterprise value across its classes and
series of capital stock to determine the estimated fair value of the Common Stock at each valuation date.

•

 Option Pricing Method (the “OPM”). The OPM is an allocation method that considers
the current value of equity and then allocates that equity value to the various equity interests considering their rights and preferences. The OPM treats common stock and preferred stock as call options on the company’s equity value, with
exercise prices based on the liquidation preferences of the preferred stock. Thus, the value of the common stock can be determined by estimating the value of its portion of each of these call option rights. Under this method, the common stock has
value only if the funds available for distribution to stockholders exceed the value of the liquidation preference at the time of a liquidity event, such as a merger or sale.

•

 Probability-Weighted Expected Return Method (the “PWERM”). The PWERM is a
scenario-based analysis that estimates the value per share based on the probability-weighted present value of expected future investment returns, considering each of the possible outcomes considered by a company, as well as the economic and control
rights of each share class.

 *FOIA Confidential
Treatment Requested by Spruce Biosciences, Inc.*

 Cooley LLP    101 California Street, 5th
Floor    San Francisco, CA    94111-5800

 t: (415) 693-2000  f: (415)
693-2222  cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Four

•

 Hybrid Method. The hybrid method is a weighted-average method that combines both OPM and PWERM. Weighting
allocations are assigned to the OPM and PWERM factoring in possible future liquidity events.

 In order for the Board to
determine the estimated fair value of the Common Stock, the OPM was utilized for the independent third-party valuations of the Common Stock as of February 15, 2019 (the “February 2019 Valuation”) and as of March 31,
2020 (the “March 2020 Valuation”), each as discussed below. The Hybrid Method was utilized for the independent third-party valuations of the Common Stock as of June 30, 2020 (the “June 2020
Valuation”) and as of August 31, 2020 (the “August 2020 Valuation”), each as discussed below, as a result of the increasing likelihood of the occurrence of certain discrete events, such as an IPO, improving
market conditions and the receptivity of the market to IPOs. In addition, and with respect to the August 2020 Valuation, the Company had commenced substantial preparations for an IPO at such time and therefore had better visibility into the timing
of a potential IPO. In that IPO scenario, the Company assumed that all outstanding shares of its redeemable convertible preferred stock would be converted into shares of Common Stock. In addition, given the Common Stock represents a non-marketable equity interest in a private enterprise, an adjustment to the preliminary value estimates had to be made in each of the OPM and Hybrid Method to account for the lack of liquidity that a stockholder
experiences. This adjustment is commonly referred to as a discount for lack of marketability (“DLOM”).

 At each
grant date, the Board evaluated any recent events and their potential impact on the estimated fair value per share of the Common Stock. For grants of stock awards made on dates for which there was no contemporaneous independent third-party
valuation, the Board determined the estimated fair value of the Common Stock on the date of grant taking into consideration the immediately preceding valuation report as well as other pertinent information available to it at the time of the grant.
In connection with the valuations prior to June 30, 2020, the Company considered an implied equity value from the closings of the issuances and sales of its redeemable convertible preferred stock prior to the issuance of any stock option
grants, as the basis for the value of its Common Stock at the date of the stock option grant. On and after June 30, 2020, the valuation methodology changed to the use of a Hybrid Method incorporating the stay private scenario (using the OPM,
specifically, the backsolve method) and the PWERM, as the Company had obtained better visibility into the timing of a potential IPO as indicated above, but still considered the uncertainty around the Company’s value should an IPO not occur. The
Hybrid Method is commonly used in these situations and is consistent with guidance from the Practice Aid.

 *FOIA Confidential
Treatment Requested by Spruce Biosciences, Inc.*

 Cooley LLP    101 California Street, 5th
Floor    San Francisco, CA    94111-5800

 t: (415) 693-2000  f: (415)
693-2222  cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Five

 Common Stock Valuations and Stock Option Grants

During the previous 12 months, the Company has granted stock options as follows:

 Date of Grant

Numbers of Shares
Subject to Stock
Options Granted

Exercise Price
Per Share of
Common Stock

Estimated Fair
Value Per Share
of Common
Stock at Date of
Grant

 October 14, 2019

[***]

$[***]

$[***]

 June 8, 2020

[***]

$[***]

$[***]

 August 7, 2020

[***]

$[***]

$[***]
*

 September 9, 2020

[***]

$[***]

$[***]
*

 Total

[***]

 February 2019 Valuation and October 14, 2019 Stock Option Grants

On October 14, 2019, the Company granted stock options to purchase a total of [***] shares of Common Stock at an exercise price of $[***]
per share. On the date of grant, the Board determined the estimated fair value of the Common Stock was $[***] per share based on a number of factors, including the February 2019 Valuation.

For the February 2019 Valuation, the Company utilized the OPM to derive the implied equity value for the Company. Specifically, the Company
utilized the backsolve method to determine the implied total equity value of the Company by accounting for all share class rights and preferences. The backsolve method takes into account the economic rights of recently issued securities in relation
to the rights of other equity securities within the capital structure.

 For purposes of the February 2019 Valuation, the backsolve method
reflected the Company’s closing of the issuance and sale of its Series A redeemable convertible preferred stock in May 2016 of 20,000,000 shares at a price of $1.00 per share (the “Series A Financing”). Although the
Series A Financing occurred in 2016, it was still considered the best indication of value for use in the backsolve method after reviewing the Company’s financial performance and management’s assessment of the lack of any material changes
in the Company’s business prospects since the completion of the Series A Financing. In determining the total implied equity value under the backsolve method, and to account for market changes subsequent to the Series A Financing, an equity
adjustment of [***]% based on the market performance of peer public companies between the Series A Financing and the February 2019 Valuation was applied.

In addition, in determining the total implied equity value under the backsolve method, the Company used an estimated volatility of [***]% and
an estimated time to liquidity of [***] years, based on management’s best estimates of a liquidity event at such time.

 After
applying a DLOM of [***]%, the fair value of the Common Stock was estimated to be $[***] per share in the February 2019 Valuation.

 For
the period from the date of the February 2019 Valuation to October 14, 2019, the Board determined there were no internal or external developments since the February 2019 Valuation that warranted a change in the estimated fair value of the
Common Stock. During this period, the Company was inwardly focused on the research, development and regulatory approval pathway of its product candidate, tildacerfont. As a result, the Board determined the estimated fair value of the Common Stock
for the October 14, 2019 stock option grants was $[***] per share.

*
 Subject to adjustment based on the future reassessment described herein.

 *FOIA Confidential
Treatment Requested by Spruce Biosciences, Inc.*

 Cooley LLP    101 California Street, 5th
Floor    San Francisco, CA    94111-5800

 t: (415) 693-2000  f: (415)
693-2222  cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Six

 March 2020 Valuation and June 8, 2020 Stock
Option Grants

 On June 8, 2020, the Company granted stoc

CORRESP
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CORRESP

 Kristin VanderPas

 +1 (415) 693-2097

 kvanderpas@cooley.com

Via EDGAR and Courier

 September 18, 2020

 U.S.
Securities and Exchange Commission

 Division of Corporation Finance

100 F Street, N.E.

 Washington, D.C. 20549

Attn:
 Jessica Livingston

 David Lin

 Eric Atallah

 Angela Connell

Re:
 Spruce Biosciences, Inc.

 Draft Registration Statement on Form S-1

 Submitted August 7, 2020

 CIK No. 0001683553

Ladies and Gentlemen:

 On behalf of Spruce Biosciences, Inc.
(the “Company”), we submit this letter in response to comments received from the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) by letter
dated September 3, 2020 (the “Comment Letter”) with respect to the Company’s draft Registration Statement on Form S-1 confidentially submitted to the Commission on
August 7, 2020. Concurrently with the submission of this response letter, the Company is filing its Registration Statement on Form S-1 (the “Registration Statement”) with the
Commission. In addition to addressing the comments raised by the Staff in the Comment Letter, the Company has included other revisions and updates to its disclosure in the Registration Statement.

For the convenience of the Staff, the numbering of the paragraphs below corresponds to the numbering of the comment in the Comment Letter, the text of which
we have incorporated into this response letter for convenience in italicized type and which is followed by the Company’s response. Page references in the text of this response letter correspond to the page numbers of the Registration Statement.

 Prospectus Summary, page 1

1.
 Please ensure that the information you include in your summary is balanced. For example, we note the risk
disclosure on pages 6 and 13 that you have a limited operating history, have incurred significant net losses since inception, anticipate that you will continue to do so for the foreseeable future and expect these losses to increase as you continue
clinical development and seek regulatory approvals. Please provide a more detailed and prominent discussion of the most material risks you face.

Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 6 and 7 of the Registration Statement
to provide an expanded, a more detailed and prominent discussion of the most material risks the Company faces.

Cooley LLP 101 California Street, 5th Floor San Francisco, CA 94111-5800

t: (415) 693-2000 f: (415) 693-2222 cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Two

2.
 On page 5, please revise the table to disclose all remaining stages you must successfully complete before
you could seek FDA approval. For example, please revise to reference Phase 3 trials and any estimated timetable. In this regard, we note your disclosure on pages 132 - 133 regarding Phase 1, Phase 2, and Phase 3 clinical trials.

 Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 5, 15, and 112
of the Registration Statement to reference the possibility that the Company may be required by the U.S. Food and Drug Administration (“FDA”) and comparable foreign regulatory authorities to initiate one or more additional
clinical trials, including a Phase 3 clinical trial or trials. However, the Company advises the Staff that the estimated timing or scope of any such future clinical trials is not currently ascertainable, as the design, duration, and scope of
such clinical trials will be decided upon after further discussions with the FDA or comparable foreign regulatory authorities. The Company has expanded the disclosure on page 15 of the Registration Statement to more clearly address this uncertainty.

 Risk Factors

 Our amended and restated
certificate of incorporation and amended and restated bylaws will provide that..., page 76

3.
 Please revise your disclosure on pages 76 and 185 regarding choice of forum for consistency. In particular,
please revise the first sentence under “Choice of Forum” on page 185 to clarify that both your amended and restated bylaws and amended and restated certificate of incorporation include such provision, and similarly, revise the second
paragraph of the risk factor to clarify that both documents provide that the federal district courts of the United States of America will be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities
Act.

 Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 77,
78, and 188 of the Registration Statement.

 Management’s Discussion and Analysis of Financial Condition and Results of Operations

License Agreement with Eli Lilly and Company, page 92

4.
 You disclose on pages 92 and F-44 that in May 2016, you entered into
a License Agreement with Lilly, which could require you to pay Lilly up to an aggregate of $23.0 million upon the achievement of certain clinical and commercialization milestones. Please revise to describe such milestones in
greater detail, including how they will be calculated and any timeframe, as applicable.

 Response: In response
to the Staff’s comment, the Company has revised the disclosure on pages 94, 129, F-21, and F-45 of the Registration Statement.

Loan Agreement, page 97

5.
 Please expand to provide more detailed disclosure of any material financial covenants contained in your Loan
Agreement, including quantifying any ratios, as applicable. If any of such covenants could materially impact your ability to obtain additional debt financing, please revise your “Funding Requirements” disclosure on page 98 to disclose the
same, and expand your risk factor disclosure as appropriate.

Cooley LLP 101 California Street, 5th Floor San Francisco, CA 94111-5800

t: (415) 693-2000 f: (415) 693-2222 cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Three

 Response: The Company respectfully acknowledges the Staff’s comment and advises
the Staff that the Loan and Security Agreement, dated September 23, 2019, between the Company and Silicon Valley Bank (the “Loan Agreement”), contains a negative covenant impacting the Company’s ability to obtain
additional debt financing and certain remedies that Silicon Valley Bank may pursue upon the occurrence of an Event of Default (as defined in the Loan Agreement), including a material adverse change in the Company’s business, operations, or
condition (financial or otherwise). However, the Loan Agreement does not contain any material financial covenants, including financial ratios. Accordingly, in response to the Staff’s comment, the Company has revised the disclosure on pages 41,
and 99 of the Registration Statement to reference the aforementioned negative covenant regarding the Company’s ability to obtain additional debt financing and that a material adverse change in the Company’s business constitutes an Event of
Default under the Loan Agreement.

 Management’s Discussion and Analysis of Financial Condition and Results of Operations Critical Accounting
Policies, Significant Judgments and Use of Estimates

 Stock-Based Compensation Expense, page 103

6.
 Once you have an estimated offering price or range, please explain to us how you determined the fair value
of the common stock underlying your equity issuances and the reasons for any differences between the recent valuations of your common stock leading up to the IPO and the estimated offering price. This information will help facilitate our review of
your accounting for equity issuances including stock-based compensation.

 Response: Following the submission
of this response letter, the Company will provide the Staff with the requested information.

 Internal Control Over Financial Reporting, page 106

7.
 We note from your disclosures on page 71 that you identified a material weakness in internal control over
financial reporting primarily related to a lack of timely review over the financial statement close process and you were unable to adequately conduct review and analysis of certain routine transactions. Additionally you disclose that the measures
you have taken to date may not be sufficient to remediate the material weakness in your internal control over financial reporting. Please revise to clarify what remains to be completed in your remediation plan, if anything. Also, if the material
weakness has not been fully remediated, please revise to disclose how long you estimate it will take to complete your plan and disclose any material costs you have, or expect to be, incurred.

Response: In response to the Staff’s comment, the Company has revised the disclosure on page 73 of the Registration Statement.

General

8.
 Please supplementally provide us with copies of all written communications, as defined in Rule 405 under the
Securities Act, that you, or anyone authorized to do so on your behalf, present to potential investors in reliance on Section 5(d) of the Securities Act, whether or not they retain copies of the communications. Please contact the
staff member associated with the review of this submission to discuss how to submit the materials, if any, to us for our review.

Cooley LLP 101 California Street, 5th Floor San Francisco, CA 94111-5800

t: (415) 693-2000 f: (415) 693-2222 cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Four

 Response: The Company is providing to the Staff, on a supplemental basis, copies of
the written communications, as defined in Rule 405 under the Securities Act of 1933, as amended (the “Securities Act”), that have been used in meetings with potential investors in reliance on Section 5(d) of the
Securities Act. These materials were only made available for viewing by potential investors during the Company’s presentations, and no copies were retained by any potential investor. Pursuant to Rule 418 under the Securities Act, the copies
supplementally provided shall not be deemed to be filed with, or a part of, or included in, the Registration Statement.

 To the extent the
Company conducts additional meetings, it expects to use the same or similar materials, and the Company undertakes to provide the Staff with copies of any additional written communications that are presented to potential investors in the future by it
or anyone authorized to do so on its behalf in reliance on Section 5(d) of the Securities Act, whether or not such potential investors retain copies of such communications.

 Cooley LLP 101 California Street, 5th Floor San Francisco, CA 94111-5800

 t: (415) 693-2000 f: (415) 693-2222 cooley.com

 U.S. Securities and Exchange Commission

September 18, 2020

 Page Five

 Please contact me at (415) 693-2097 or Alexa Ekman at
(858) 550-6183 with any questions or further comments regarding the Company’s response to the Staff’s comments.

Sincerely,

/s/ Kristin VanderPas

Kristin VanderPas

Cooley LLP

cc:
 Richard King, Spruce Biosciences, Inc.

 Samir Gharib, Spruce Biosciences, Inc.

 Alexa Ekman, Cooley LLP

 Brian J. Cuneo, Latham & Watkins LLP

 Drew Capurro, Latham & Watkins LLP

 Cooley LLP 101 California Street, 5th Floor San Francisco, CA 94111-5800

 t: (415) 693-2000 f: (415) 693-2222 cooley.com

United States securities and exchange commission logo
September 3, 2020
Richard King
Chief Executive Officer
Spruce Biosciences, Inc.
2001 Junipero Serra Boulevard, Suite 640
Daly City, CA 94014
Re:Spruce Biosciences, Inc.
Draft Registration Statement on Form S-1
Submitted August 7, 2020
CIK No. 0001683553
Dear Mr. King:
            We have reviewed your draft registration statement and have the following comments.  In
some of our comments, we may ask you to provide us with information so we may better
understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Draft Registration Statement on Form S-1
Prospectus Summary, page 1
1.Please ensure that the information you include in your summary is balanced.  For
example, we note the risk disclosure on pages 6 and 13 that you have a limited operating
history, have incurred significant net losses since inception, anticipate that you will
continue to do so for the foreseeable future and expect these losses to increase as you
continue clinical development and seek regulatory approvals.  Please provide a more
detailed and prominent discussion of the most material risks you face.
2.On page 5, please revise the table to disclose all remaining stages you must successfully
complete before you could seek FDA approval.  For example, please revise to reference
Phase 3 trials and any estimated timetable.  In this regard, we note your disclosure on

 FirstName LastNameRichard King
 Comapany NameSpruce Biosciences, Inc.
 September 3, 2020 Page 2
 FirstName LastNameRichard King
Spruce Biosciences, Inc.
September 3, 2020
Page 2
pages 132 - 133 regarding Phase 1, Phase 2, and Phase 3 clinical trials.
Risk Factors
Our amended and restated certificate of incorporation and amended and restated bylaws will
provide that..., page 76
3.Please revise your disclosure on pages 76 and 185 regarding choice of forum for
consistency.  In particular, please revise the first sentence under "Choice of Forum" on
page 185 to clarify that both your amended and restated bylaws and amended and restated
certificate of incorporation include such provision, and similarly, revise the second
paragraph of the risk factor to clarify that both documents provide that the federal district
courts of the United States of America will be the exclusive forum for resolving any
complaint asserting a cause of action arising under the Securities Act.
Management’s Discussion and Analysis of Financial Condition and Results of Operations
License Agreement with Eli Lilly and Company, page 92
4.You disclose on pages 92 and F-44 that in May 2016, you entered into a License
Agreement with Lilly, which could require you to pay Lilly up to an aggregate of $23.0
million upon the achievement of certain clinical and commercialization milestones.
Please revise to describe such milestones in greater detail, including how they will be
calculated and any timeframe, as applicable.
Loan Agreement, page 97
5.Please expand to provide more detailed disclosure of any material financial covenants
contained in your Loan Agreement, including quantifying any ratios, as applicable.  If any
of such covenants could materially impact your ability to obtain additional debt financing,
please revise your "Funding Requirements" disclosure on page 98 to disclose the same,
and expand your risk factor disclosure as appropriate.
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Critical Accounting Policies, Significant Judgments and Use of Estimates
Stock-Based Compensation Expense, page 103
6.Once you have an estimated offering price or range, please explain to us how you
determined the fair value of the common stock underlying your equity issuances and the
reasons for any differences between the recent valuations of your common stock leading
up to the IPO and the estimated offering price. This information will help facilitate our
review of your accounting for equity issuances including stock-based compensation.
Internal Control Over Financial Reporting, page 106
7.We note from your disclosures on page 71 that you identified a material weakness in
internal control over financial reporting primarily related to a lack of timely review over
the financial statement close process and you were unable to adequately conduct review

 FirstName LastNameRichard King
 Comapany NameSpruce Biosciences, Inc.
 September 3, 2020 Page 3
 FirstName LastName
Richard King
Spruce Biosciences, Inc.
September 3, 2020
Page 3
and analysis of certain routine transactions.   Additionally you disclose that the measures
you have taken to date may not be sufficient to remediate the material weakness in your
internal control over financial reporting.  Please revise to clarify what remains to be
completed in your remediation plan, if anything.  Also, if the material weakness has not
been fully remediated, please revise to disclose how long you estimate it will take to
complete your plan and disclose any material costs you have, or expect to be, incurred.
General
8.Please supplementally provide us with copies of all written communications, as defined in
Rule 405 under the Securities Act, that you, or anyone authorized to do so on your behalf,
present to potential investors in reliance on Section 5(d) of the Securities Act, whether or
not they retain copies of the communications.  Please contact the staff member associated
with the review of this submission to discuss how to submit the materials, if any, to us for
our review.
            You may contact Eric Atallah at 202-551-3663 or Angela Connell at 202-551-3426 if you
have questions regarding comments on the financial statements and related matters.  Please
contact Jessica Livingston at 202-551-3448 or David Lin at 202-551-3552 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences