May 9, 2025

Scott Burrows
Chief Financial Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23
Suite 105
Waltham, MA 02453

       Re: Spyre Therapeutics, Inc.
           Form 10-K for the fiscal year ended December 31, 2024
           Filed February 27, 2025
           File No. 001-37722
Dear Scott Burrows:

       We have limited our review of your filing to the financial statements
and related
disclosures and have the following comment.

       Please respond to this letter within ten business days by providing the
requested
information or advise us as soon as possible when you will respond. If you do
not believe
our comment applies to your facts and circumstances, please tell us why in your
response.

       After reviewing your response to this letter, we may have additional
comments.

Form 10-K for the fiscal year ended December 31, 2024
Management's Discussion and Analysis of Financial Condition and Results of
Operations,
page 81
Results of Operations, page 88

1.     We note the discussion of research and development (R&D) expenses,
including
       external and internal components, on page 89. Please revise your
disclosure in future
       filings to provide:
       i) a breakout of external R&D expenses by program and functional area or
indication,
       or state that such information cannot be tracked on those bases and the
reason(s)
       therefore;
       ii) a breakout of internal costs by function, type or category; and
       iii) a discussion of the factor(s) impacting the changes in these
disaggregated amounts
       for the periods presented.
 May 9, 2025
Page 2

       We note this information is particularly relevant to investors as your
candidates are
       being evaluated to address multiple indications and given your
expectation that you
       will invest "significant funds" into R&D in order to advance your
product candidates
       through clinical trials (per pages 40 and 42). As part of your response,
please provide
       what this disclosure would have looked like had it been included in your
December
       31, 2024 Form 10-K.
        In closing, 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 Jenn Do at 202-551-3743 or Kevin Vaughn at 202-551-3494
with any
questions.



                                                            Sincerely,

                                                            Division of
Corporation Finance
                                                            Office of Life
Sciences