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,
                                                            Draft Registration
Statement on Form S-1
                                                            Submitted August 7,
                                                            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

             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

       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
 Richard King
FirstName LastNameRichard    King
Spruce Biosciences, Inc.
Comapany 3,
September NameSpruce
             2020        Biosciences, Inc.
Page 2    3, 2020 Page 2
FirstName LastName
         pages 132 - 133 regarding Phase 1, Phase 2, and Phase 3 clinical
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
Management   s Discussion and Analysis of Financial Condition and Results of
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
         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
         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
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
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
 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.

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

FirstName LastNameRichard King                                 Sincerely,
Comapany NameSpruce Biosciences, Inc.
                                                               Division of
Corporation Finance
September 3, 2020 Page 3                                       Office of Life
FirstName LastName