SecProbe.io

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 June 2, 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 completed our review of your filing. 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.

 Sincerely,

 Division of Corporation
Finance
 Office of Life Sciences
</TEXT>
</DOCUMENT>

CORRESP
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 Document May 21, 2025 Securities and Exchange Commission Division of Corporation Finance Office of Life Sciences 100 F Street, N.E. Washington, D.C. 20549 Attn: Jenn Do and Kevin Vaughn VIA EDGAR Re: Spyre Therapeutics, Inc. Form 10-K for Fiscal Year Ended December 31, 2024 Filed February 27, 2025 File No. 001-37722 Dear Ms. Do and Mr. Vaughn, This letter is in response to your letter dated May 9, 2025, regarding Spyre Therapeutics, Inc.’s (the “Company”) Annual Report on Form 10-K for the fiscal year ended December 31, 2024. Your comment from the May 9, 2025 letter is set forth below, followed by our related response. 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. 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. The Company acknowledges the Staff’s comment. In future filings, including any Form 10-K or Form 10-Q, beginning with the quarter ending June 30, 2025, the Company will revise its disclosure regarding R&D expenses to provide additional disaggregation of external and internal R&D expenses, with discussion of the factor(s) impacting the changes in these disaggregated amounts. The Company plans to disaggregate its R&D expenses into the following categories — Preclinical, IBD, Rheumatology, Legacy Aeglea, Compensation, and Stock-based compensation. Please see below for the aforementioned disclosure had it been included in the Company’s Form 10-K for the year ended December 31, 2024. In 2023, the Company’s R&D expense was primarily related to its early preclinical activities, including antibody development and nonhuman studies, and also included expenses related to legacy Aeglea Biotherapeutics programs. In 2024, the Company’s R&D expense was related to continued preclinical activities, as well as the preparation and/or execution of its Phase 1 clinical trials of SPY001, SPY002 and SPY003 for the treatment of Inflammatory Bowel Disease (“IBD”), including related manufacturing costs. As disclosed in the Company’s Current Report on Form 8-K filed on January 13, 2025, the Company is now pursuing an additional indication, rheumatoid arthritis (RA), with SPY002. As a result of this expansion and the potential for future indication expansions in IBD and rheumatology, the Company expects that its R&D expense for the year ended December 31, 2025 will be focused on both IBD indication(s) and rheumatology indication(s), as well as ongoing preclinical activities. For its initial IBD indication, the Company plans to initiate a platform trial, which is designed to study SPY001, SPY002 and SPY003 as monotherapies and in combination with each other as SPY120 (a combination of SPY001 and SPY002), SPY130 (a combination of SPY001 and SPY003) and SPY230 (a combination of SPY002 and SPY003). This platform trial is designed to help the Company determine which monotherapies or combination therapies will continue in future development. This platform trial is expected to comprise a large and growing portion of the Company’s R&D costs in 2025 through 2027. It is not possible to track costs of the trial to the individual monotherapies and combination therapies over time given most of the platform study arms are blinded, which means that the Company is not able to determine which patients are receiving a specific monotherapy or combination therapy. For its initial rheumatology indication, the Company plans to initiate a Phase 2 study in rheumatoid arthritis in 2025. In order to preserve/promote comparability across periods, the Company intends to disclose its external R&D expenses for past and future periods on a disaggregated basis for expenses related to its preclinical activities, IBD indication(s), rheumatology indication(s), and legacy Aeglea Biotherapeutics programs, as applicable. * * * The following table summarizes our research and development expenses incurred for the periods presented (in thousands): Year Ended December 31, Dollar Change % Change 2024 2023 External research and development expenses: Preclinical $ 62,235  $ 37,130  $ 25,105  68%  IBD 64,919  6,017  58,902  979%  Stock-based compensation (1) 14,459  11,328  3,131  28%  Legacy Aeglea assets (906) 18,187  (19,093) (105) % Total external research and development expense 140,707  72,662  68,045  94%  Internal research and development expenses: Compensation 11,728  6,802  4,926  72%  Stock-based compensation 9,112  2,910  6,202  213%  Other (2) 1,243  7,130  (5,887) (83) % Total internal research and development expenses 22,083  16,842  5,241  31  % Total research and development expense $ 162,790  $ 89,504  $ 73,286  82  % (1) For the years ended December 31, 2024 and 2023, $14.5 million and $11.3 million, respectively, was recognized as stock compensation expense related to the Parapyre Option Obligation. (2) The year ended December 31, 2023 includes $3.2 million of restructuring expenses consisting of cash severance payments and $2.1 million of impairment losses related to the operating lease right-of-use asset and related leasehold improvements. External research and development expenses include costs associated with third parties contracted to conduct research and development activities on behalf of the Company, including through Paragon, contract research organizations, contract manufacturing organizations, and third-party laboratories. For the years ended December 31, 2024 and 2023, external research and development costs accounted for $140.7 million and $72.7 million, respectively. Preclinical expenses increased due to antibody development, nonhuman studies, and other preclinical development activities for the Company’s product candidates. IBD expenses increased primarily due to a $43.3 million and $15.6 million increase in manufacturing and clinical development costs, respectively, related to ongoing or planned clinical trials. Stock-based compensation increased due to the higher valuation of the Parapyre Option Obligation in 2024. Expenses associated with Aeglea’s legacy rare disease pipeline decreased year-over-year as those programs were discontinued. Internal research and development expenses include compensation and related costs associated with our research and development employees, as well as costs associated with the Company's on-premises research laboratory. For the years ended December 31, 2024 and 2023, internal research and development costs accounted for $22.1 million and $16.8 million, respectively. Compensation and stock-based compensation expenses increased primarily due to higher research and development headcount. Other internal research and development expenses decreased primarily due to no restructuring expenses incurred in 2024 compared with $5.3 million of restructuring expenses incurred in 2023 related to legacy Aeglea employee separation and impairment costs. * * * We appreciate the Staff’s responsiveness with respect to the Company’s filing and look forward to resolving any concerns the Staff may have. If you have any questions, please contact me at (213) 886-9419 or Melanie E. Neary of Gibson, Dunn & Crutcher LLP at (415) 393-8243. Sincerely, /s/ Scott Burrows Scott Burrows Chief Financial Officer cc: Heidy King-Jones, Spyre Therapeutics, Inc. (via electronic mail) Melanie E. Neary, Gibson, Dunn & Crutcher LLP (via electronic mail)

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 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
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Document

March 5, 2025

VIA EDGAR AND EMAIL

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, DC 20549

Attn: Jessica Dickerson

Re: Spyre Therapeutics, Inc.

 Registration Statement on Form S-3

 Filed February 27, 2025

 File No. 333-285341

To Whom it May Concern:

Pursuant to Rules 460 and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced Registration Statement on Form S-3 filed by the Company be accelerated to 5:00 p.m., Eastern Time, on March 7, 2025 or as soon thereafter as practicable, unless we or our outside counsel, Gibson, Dunn & Crutcher LLP, request by telephone that such Registration Statement be declared effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by calling Branden Berns at (415) 393-4631.

Very truly yours,

SPYRE THERAPEUTICS, INC.

By: /s/ Cameron Turtle

Name: Cameron Turtle

Title: Chief Executive Officer

cc: Scott Burrows, Spyre Therapeutics, Inc.

 Heidy King-Jones, Spyre Therapeutics, Inc.

 Ryan A. Murr, Gibson, Dunn & Crutcher LLP

 Branden C. Berns, Gibson, Dunn & Crutcher LLP

 Melanie E. Neary, Gibson, Dunn & Crutcher LLP

March 4, 2025
Heidy King-Jones
Chief Legal Officer and Corporate Secretary
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Registration Statement on Form S-3
Filed February 27, 2025
File No. 333-285341
Dear Heidy King-Jones:
            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 Jessica Dickerson at 202-551-8013 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Branden C. Berns, Esq.

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September 30, 2024

VIA EDGAR AND EMAIL

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, DC 20549

Attn:  Doris Stacey Gama

 Re: Spyre Therapeutics, Inc.

  Registration Statement on Form S-3

  Filed September 20, 2024

  File No. 333-282252

To Whom it May Concern:

Pursuant to Rules 460 and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced Registration Statement on Form S-3 filed by the Company be accelerated to 4:15 p.m., Eastern Time, on October 2, 2024 or as soon thereafter as practicable, unless we or our outside counsel, Gibson, Dunn & Crutcher LLP, request by telephone that such Registration Statement be declared effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by calling Branden Berns at (415) 393-4631.

Very truly yours,

SPYRE THERAPEUTICS, INC.

By: /s/ Cameron Turtle

Name: Cameron Turtle

Title: Chief Executive Officer

cc: Scott Burrows, Spyre Therapeutics, Inc.

Heidy King-Jones, Spyre Therapeutics, Inc.

Ryan A. Murr, Gibson, Dunn & Crutcher LLP

Branden C. Berns, Gibson, Dunn & Crutcher LLP

September 26, 2024
Cameron Turtle
Chief Executive Officer
Spyre Therapeutics, Inc.
221 Crescent Street, Bldg 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Registration Statement on Form S-3
Filed September 20, 2024
File No. 333-282252
Dear Cameron Turtle:
            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 Doris Stacey Gama at 202-551-3188 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Branden C. Berns, Esq.

CORRESP
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September 13, 2024

VIA EDGAR AND EMAIL

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, DC 20549

Attn: Tamika Sheppard

Re: Spyre Therapeutics, Inc.

 Registration Statement on Form S-3

 Filed September 6, 2024

 File No. 333-281975

To Whom it May Concern:

Pursuant to Rules 460 and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced Registration Statement on Form S-3 filed by the Company be accelerated to 4:15 p.m., Eastern Time, on September 18, 2024 or as soon thereafter as practicable, unless we or our outside counsel, Gibson, Dunn & Crutcher LLP, request by telephone that such Registration Statement be declared effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by calling Branden Berns at (415) 393-4631.

Very truly yours,

SPYRE THERAPEUTICS, INC.

By: /s/ Cameron Turtle

Name: Cameron Turtle

Title: Chief Executive Officer

cc: Scott Burrows, Spyre Therapeutics, Inc.

 Heidy King-Jones, Spyre Therapeutics, Inc.

 Ryan A. Murr, Gibson, Dunn & Crutcher LLP

 Branden C. Berns, Gibson, Dunn & Crutcher LLP

September 12, 2024
Heidy King-Jones
Chief Legal Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Registration Statement on Form S-3
Filed September 6, 2024
File No. 333-281975
Dear Heidy King-Jones:
            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 Tamika Sheppard at 202-551-8346 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Branden Berns

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CORRESP

 April 25, 2024

VIA EDGAR AND EMAIL

 United States Securities and
Exchange Commission

 Division of Corporation Finance

 100 F
Street, N.E.

 Washington, DC 20549

Attn:
 Jimmy McNamara

Re:
 Spyre Therapeutics, Inc.

 
 Registration Statement on Form S-1

 
 Filed April 19, 2024

 
 File No. 333-278810

To Whom it May Concern:

 Pursuant to Rules 460
and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Spyre Therapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced
Registration Statement on Form S-1 filed by the Company be accelerated to 4:15 p.m., Eastern Time, on April 29, 2024 or as soon thereafter as practicable, unless we or our outside counsel, Gibson,
Dunn & Crutcher LLP, request by telephone that such Registration Statement be declared effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by
calling Branden Berns at (415) 393-4631.

 Very truly yours,

 SPYRE THERAPEUTICS, INC.

By:

/s/ Cameron Turtle

 Name:

 Cameron Turtle

 Title:

 Chief Executive Officer

cc:
 Scott Burrows, Spyre Therapeutics, Inc.

 
 Heidy King-Jones, Spyre Therapeutics, Inc.

 
 Ryan A. Murr, Gibson, Dunn & Crutcher LLP

 
 Branden C. Berns, Gibson, Dunn & Crutcher LLP

United States securities and exchange commission logo
April 25, 2024
Heidy King-Jones
Chief Legal Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Registration Statement on Form S-1
Filed April 19, 2024
File No. 333-278810
Dear Heidy King-Jones:
            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 Jimmy McNamara at 202-551-7349 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden Berns

CORRESP
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CORRESP

 March 28, 2024

VIA EDGAR AND EMAIL

 United States Securities and
Exchange Commission

 Division of Corporation Finance

 100 F
Street, N.E.

 Washington, DC 20549

 Attn: Lauren Hamill and
Jason Drory

Re:
 Spyre Therapeutics, Inc.

Registration Statement on Form S-1

Filed March 27, 2024

File No. 333-276251

 Ladies and
Gentlemen:

 Pursuant to Rules 460 and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Spyre
Therapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced Registration Statement on Form S-1 filed by the Company be
accelerated to 4:01 p.m., Eastern Standard Time, on April 1, 2024 or as soon thereafter as practicable, unless we or our outside counsel, Gibson, Dunn & Crutcher LLP, request by telephone that such Registration Statement be declared
effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by
calling Branden Berns at (415) 393-4631.

Very truly yours,

SPYRE THERAPEUTICS, INC.

By:

 /s/ Cameron Turtle

Name:

Cameron Turtle

Title:

Chief Executive Officer

cc:
 Scott Burrows, Spyre Therapeutics, Inc.

Heidy King-Jones, Spyre Therapeutics, Inc.

Ryan A. Murr, Gibson, Dunn & Crutcher LLP

Branden C. Berns, Gibson, Dunn & Crutcher LLP

Melanie Neary, Gibson, Dunn & Crutcher LLP

CORRESP
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 Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 2600

 San Francisco, CA
94111-3715

 Tel 415.393.8200

 gibsondunn.com

 March 26, 2024

 EDGAR
CORRESPONDENCE

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, D.C. 20549

Attn: Lauren Hamill and Jason Drory

Re:
 Spyre Therapeutics, Inc.

Amendment No. 3 to Registration Statement on Form S-1 filed on March 14, 2024 (File No. 333-276251) and Post-Effective Amendment No. 2 to Registration Statement on Form S-1 filed on March 14, 2024 (File
No. 333-273769)

 Ladies and Gentlemen:

On behalf of Spyre Therapeutics, Inc. (the “Company”), this letter responds to the oral comments of the staff of the U.S.
Securities and Exchange Commission – Division of Corporation Finance (the “Staff”) provided to the Company’s outside counsel on March 21, 2024 regarding the above-referenced Registration Statement on Form S-1 (File No. 333-273769) (the “Pre-effective Registration Statement”) and Registration Statement on Form S-1 (File No. 333-276251) (the “Effective Registration Statement”). The Staff’s comments are set forth below, followed by the Company’s
responses. For ease of reference, the headings and numbered paragraphs below correspond to the Staff’s two oral comments. The Company’s responses are set forth in ordinary type below the Staff’s comments, which are set forth in bold
type. References are made to the Company’s Pre-effective Amendment No. 4 to the Pre-effective Registration Statement (the “Pre-effective
Amendment”) and the Post-effective Amendment No. 3 to the Effective Registration Statement (the “Post-effective Amendment”), each filed on March 26, 2024.

1.
 Please update the disclosure in the Prospectus Summary to describe the patent life of the SPY002 program.

 In response to the Staff’s comment, the Company has revised its disclosure on pages 4, 52 and 69 of the Pre-effective Amendment
and on pages 4, 52 and 69 of the Post-effective Amendment, in each case, to describe the expected patent life of the SPY002 program if such research program is pursued non-provisionally and matures into issued
patents.

 Abu
Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong
Kong • Houston • London • Los Angeles

 Munich • New
York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

 U.S. Securities and Exchange Commission

March 26, 2024

2.
 Please include a new subsection titled “Intellectual Property” under the heading
“Business” containing disclosures regarding intellectual property rights associated with the Company’s programs and technologies.

In response to the Staff’s comment, the Company has revised its disclosure on pages 76-78 of the Pre-effective Amendment and on pages 76-78 of
the Post-effective Amendment, in each case, to add a new subsection titled “Intellectual Property” under the heading “Business” containing disclosures regarding certain intellectual property rights associated with the
Company’s programs and technologies.

 ***

Thank you for your consideration of this response. If you have any questions regarding the response set forth above, please do not hesitate to call me at
(415) 393-8373 or Branden C. Berns at (415) 393-4631.

 Sincerely,

 /s/ Ryan A. Murr

 Ryan A. Murr

cc:
 Branden C. Berns, Gibson, Dunn & Crutcher LLP

Melanie Neary, Gibson, Dunn & Crutcher LLP

Dr. Cameron Turtle, Spyre Therapeutics, Inc.

Scott Burrows, Spyre Therapeutics, Inc.

Heidy King-Jones, Spyre Therapeutics, Inc.

 2

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Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 2600

San Francisco, CA 94111-3715

 Tel 415.393.8200

 gibsondunn.com

 March 14, 2024

 EDGAR
CORRESPONDENCE

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, D.C. 20549

Attn: Lauren Hamill and Jason Drory

Re:
 Spyre Therapeutics, Inc.

 
 Amendment No. 2 to Registration Statement on Form S-1 filed on
March 1, 2024 (File No. 333-276251) and Post-Effective Amendment No. 1 to Registration Statement on Form S-1 filed on March 5, 2024 (File No. 333-273769)

 Ladies and Gentlemen:

On behalf of Spyre Therapeutics, Inc. (the “Company” or “Spyre”), this letter responds to the written comment
of the staff of the U.S. Securities and Exchange Commission – Division of Corporation Finance (the “Staff”) contained in your letter, dated March 8, 2024 (the “Comment Letter”), and an oral comment
provided to the Company’s outside counsel on March 8, 2024 regarding the above-referenced Registration Statement on Form S-1 (File No. 333-273769) (the
“Pre-effective Registration Statement”) and Registration Statement on Form S-1 (File No. 333-276251) (the
“Effective Registration Statement”). The Staff’s comments are set forth below, followed by the Company’s responses. For ease of reference, the headings and numbered paragraphs below correspond to the Staff’s written
comment, followed by the oral comment. The Company’s responses are set forth in ordinary type below the Staff’s comments, which are set forth in bold type. References are made to the Company’s Pre-effective Amendment No. 3 to the
Pre-effective Registration Statement (the “Pre-effective Amendment”) and the Post-effective Amendment No. 2 to the Effective Registration Statement
(the “Post-effective Amendment”), each filed on March 14, 2024.

 Amendment No. 2 to Registration Statement on
Form S-1 filed March 1, 2024

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

 Results of Operations

Comparison of the Years Ended December 31, 2023 and 2022, page 58

Abu Dhabi • Beijing • Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong •
Houston • London • Los Angeles

 Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San
Francisco • Singapore • Washington, D.C.

 U.S. Securities and Exchange Commission

March 14, 2024

1.
 Please include an explanation for the increase in Other expense, net.

In response to the Staff’s comment, the Company has revised its disclosure on page 59 of the Pre-effective Amendment and on page 59 of the Post-effective
Amendment, in each case, to provide an explanation for the increase in Other expense, net.

2.
 Please include the material terms that are anticipated to be reflected in the SPY001 License Agreement and
the SPY002 License Agreement, which are expected to be entered into between the Company and Paragon Therapeutics, Inc. but which have not been entered into as of the date hereof.

In response to the Staff’s comment, the Company has revised its disclosure on pages 65 and 66 of the Pre-effective Amendment and on pages 65 and 66 of
the Post-effective Amendment, in each case, to provide the material terms that are anticipated to be reflected in the SPY001 License Agreement and the SPY002 License Agreement, which are expected to be entered into between the Company and Paragon
Therapeutics, Inc. but which have not been entered into as of the date hereof.

 ***

Thank you for your consideration of this response. If you have any questions regarding the response set forth above, please do not hesitate to call me at
(415) 393-8373 or Branden C. Berns at (415) 393-4631.

Sincerely,

 /s/ Ryan A. Murr

Ryan A. Murr

cc:
 Branden C. Berns, Gibson, Dunn & Crutcher LLP

Melanie Neary, Gibson, Dunn & Crutcher LLP

Dr. Cameron Turtle, Spyre Therapeutics, Inc.

Scott Burrows, Spyre Therapeutics, Inc.

Heidy King-Jones, Spyre Therapeutics, Inc.

 2

United States securities and exchange commission logo
March 8, 2024
Cameron Turtle
Chief Executive Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Amendment No. 2 to Registration Statement on Form S-1
Filed March 1, 2024
File No. 333-276251
Dear Cameron Turtle:
            We have reviewed your registration statement and have the following comment.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies to your facts and circumstances
or do not believe an amendment is appropriate, please tell us why in your response.
            After reviewing any amendment to your registration statement and the information you
provide in response to this letter, we may have additional comments.
Amendment No. 2 to Registration Statement on Form S-1 filed March 1, 2024
Management's Discussion and Analysis of Financial Condition and Results of Operations
Results of Operations
Comparison of the Years Ended December 31, 2023 and 2022, page 58
1.Please include an explanation for the increase in Other expense, net.
            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.
            Refer to Rules 460 and 461 regarding requests for acceleration. Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.

 FirstName LastNameCameron  Turtle
 Comapany NameSpyre Therapeutics, Inc.
 March 8, 2024 Page 2
 FirstName LastName
Cameron  Turtle
Spyre Therapeutics, Inc.
March 8, 2024
Page 2
            Please contact Christine Torney at 202-551-3652 or Vanessa Robertson at 202-551-3649
if you have questions regarding comments on the financial statements and related matters. Please
contact Lauren Sprague Hamill at 303-844-1008 or Jason Drory at 202-551-8342 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden Berns

CORRESP
1
filename1.htm

CORRESP

 Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 2600

 San Francisco, CA
94111-3715

 Tel 415.393.8200

 gibsondunn.com

 March 1, 2024

 EDGAR
CORRESPONDENCE

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, D.C. 20549

Attn: Lauren Hamill and Jason Drory

Re:
 Spyre Therapeutics, Inc.

Amendment No. 1 to Registration Statement on Form S-1

Filed February 5, 2024

 File
No. 333-276251

 Ladies and Gentlemen:

On behalf of Spyre Therapeutics, Inc. (the “Company” or “Spyre”), this letter responds to the comments of
the staff of the U.S. Securities and Exchange Commission – Division of Corporation Finance (the “Staff”) contained in your letter, dated February 16, 2024 (the “Comment Letter”) regarding the
above-referenced Registration Statement on Form S-1 (the “Registration Statement”). The Staff’s comments are set forth below, followed by the Company’s responses. For ease of
reference, the heading and numbered paragraphs below correspond to the heading and numbered comments in the Comment Letter. The Company’s responses are set forth in ordinary type beneath the Staff comment, which is set out in bold type.
References are made to the Company’s Amendment No. 2 to the Registration Statement (the “Amendment”), filed on March 1, 2024.

Prospectus Summary

 Company Overview, page 4

1.
 We note your response to prior comment 6. Please revise to address the part of that comment requesting
certain balancing disclosures to be included in the Summary.

 In response to the Staff’s comment, the Company has revised its
disclosure on pages 4, 5, 53 and 72 of the Amendment by providing certain balancing disclosures regarding its development strategy and candidate programs in the Summary.

 Abu Dhabi • Beijing
• Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles

Munich • New York • Orange County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington,
D.C.

 U.S. Securities and Exchange Commission

March 1, 2024

 Risk Factor Summary, page 10

2.
 Please revise your summary risk factors to disclose, if true, that additional time may be required to obtain
regulatory approval for your product candidates and future product candidates because of their status as combination therapies. In this regard, we note your disclosure on page 88 that the FDA indicated it intends to assess each potential combination
on a case-by-case basis.

 In response to the
Staff’s comment, the Company respectfully advises the Staff that the disclosure requested above was previously added to the summary risk factors on page 10 of the Amendment.

Our Relationship with Paragon and Parapyre, page 53

3.
 Please revise the last paragraph of this section to clarify how the provisions of the Parapyre Option
Obligation relate to the term of the Paragon Agreement. In this regard, we note based on your disclosure on page F-40 that the Parapyre Option Obligation provides for an annual equity grant of options for
Parapyre to purchase 1% of the then outstanding shares of Spyre’s common stock, on a fully diluted basis, on the last business day of each calendar year “during the term of the Paragon Agreement.”

In response to the Staff’s comment, the Company has revised its disclosure on pages 53 and 54 of the Amendment to clarify how the provisions of the
Parapyre Option Obligation relate to the term of the Paragon Agreement.

 Business, page 73

4.
 In your Business section, please revise your disclosure where appropriate to:

•
 Better explain the meaning of “complementary diagnostics” and explain how such term differs from
“companion diagnostics,” including with respect to the regulatory approval pathways.

•
 Discuss the advantages and disadvantages of potentially using patient selection strategies based on
development and use of a complementary diagnostic. Explain how your plan to develop and use a complementary diagnostic may impact your overall clinical development plan, including your clinical trial design and regulatory strategy, as well as your
commercialization strategy, if ultimately approved.

 In response to the Staff’s comment, the Company has revised its disclosure
on pages 70 and 71 of the Amendment.

 2

 U.S. Securities and Exchange Commission

March 1, 2024

 Our Strategy, page 73

5.
 With respect to the patient selection and complementary diagnostics pillar of your development strategy,
please revise in an appropriate place to explain what a genetic- or biomarker-based complementary diagnostic is, and how you plan to develop and use such complementary diagnostics to match treatment targets to IBD
sub-populations to implement a precision immunology approach.

 In response to the
Staff’s comment, the Company has revised its disclosure on pages 70 and 71 of the Amendment.

 Our Combination Therapy Approach, page 74

6.
 You disclose that you plan to investigate combinations of your proprietary antibody therapies in preclinical
studies in 2024 and in clinical studies beginning in 2025.

•
 Please revise to clarify that commencement of clinical trials is subject to approval of an IND or equivalent
foreign regulatory submission.

•
 Further, you state that your preclinical studies and preclinical trials involving your combination therapies
are expected to initially include SPY120. Please disclose when you plan to submit an IND or foreign regulatory submission for SPY120 or otherwise advise. Also, please make conforming revisions to the section captioned “SPY120 – combination
anti-4ß7 and anti-TL1A mAbs” on page 79.

 In response to the
Staff’s comment, the Company has revised its disclosure on pages 70, 75 and 76 of the Amendment.

 Our Portfolio, page 75

7.
 We note your response to prior comment 23. Your response letter and other disclosures suggest that SPY-003 and at least some of your combination product candidates are not currently material to your business given the early stage of discovery. With respect to SPY003, we note:

•
 Your disclosures regarding SPY003 are limited in comparison with your discussion of co-lead product candidates SPY001 and SPY002.

•
 Your disclosure on page 19 indicates that you are investing a majority of your efforts and financial
resources into optioned co-lead product candidates SPY001 and SPY002.

 3

 U.S. Securities and Exchange Commission

March 1, 2024

•

 It appears that under the terms of the Paragon Agreement, (a) Paragon has granted you only
a limited license to the antibody technology arising from the non-optioned research programs solely to evaluate the Option and for the purpose of allowing you to determine whether to exercise the Option with
respect to each such program; and (b) unless and until you exercise the Option with respect to SPY003, the execution of a SPY003 License Agreement will not occur.

•

 You state in the response letter and on page 79 that (i) the Company is still in the
process of narrowing down potential clones to select a development candidate for SPY003, which is not expected to occur until at least mid-2024, if at all; and (ii) the Company will not
exercise the Option to acquire IP rights for the SPY003 program until after such candidate nomination occurs.

 In addition to the
foregoing, we note the following with respect to your combination product candidates:

•

 Your disclosures regarding your combination product programs remain limited in comparison with your discussion
of co-lead product candidates SPY001 and SPY002.

•

 You disclose on page 79 that each of SPY130 and SPY230 include combination with
non-optioned SPY003, for which no development candidate has been nominated.

•

 You disclose on page 74 that with respect to your combination therapies, your preclinical studies and clinical
trials planned for 2024 and 2025, respectively, are expected to initially include SPY120, which combines optioned product candidates SPY001 and SPY002.

As such, please limit the product candidates and programs included in your pipeline table to those that are currently material to you and your operations,
and for which you have exercised the Option to exclusively license all of Paragon’s right, title, and interest in, including all intellectual property license rights thereto. Please remove the references to SPY003 and combination programs that
include SPY003 from your pipeline table. We will not object to your discussion of your development plans for SPY003, SPY004, and your combination programs including SPY003 in the narrative discussion in the Business section.

In response to the Staff’s comment, the Company has revised its disclosure on page 72 of the Amendment.

 4

 U.S. Securities and Exchange Commission

March 1, 2024

 SPY001 - anti-4ß7 mAb, page 76

8.
 You state on page 76: “The JDC is the decision-making body for SPY001 and our other pipeline programs
prior to the execution of the SPY-001 License Agreement and we will control and lead the development process once the SPY001 License Agreement is executed.” For the avoidance of doubt, please clarify
whether you will control and lead the development process for each of SPY002, non-optioned programs SPY003 and SPY004, and each of the combination programs once the SPY001 license agreement is executed, or
otherwise revise.

 In response to the Staff’s comment, the Company has revised its disclosure on page 73 of the Amendment to
clarify that the Company will control and lead the development process for each of SPY002, non-optioned programs SPY003 and SPY004, and each of the combination programs once the respective license agreements
are executed.

9.
 We note your response to prior comment 26, which we reissue with respect to portions of the second bullet.
In this subsection and in others as appropriate, please further revise your discussion of completed preclinical studies to disclose when preclinical studies were conducted, as well as the number of tests conducted in each study.

 In response to the Staff’s comment, the Company has revised its disclosure on pages
73-75 of the Amendment.

10.
 Please review and revise the Figures included in this section to ensure that the text in each, including
subscript or other notations, are clearly legible without need for magnification.

 In response to the Staff’s comment, the
Company has revised its disclosure on pages 72, 74 and 75 of the Amendment to revise the Figures in this section to ensure that the text in each are clearly legible.

 5

 U.S. Securities and Exchange Commission

March 1, 2024

 Notes to the Financial Statements

8. Paragon Agreement, page F-58

11.
 We acknowledge your response to comment 33. Please revise your disclosure on pages F-56 and F-59 to clarify that the $22.0 million is also upon the achievement of regulatory milestones as your current disclosure only refers to development and clinical
milestones.

 In response to the Staff’s comment, the Company submits that it filed its Annual Report on Form 10-K for the year-ended December 31, 2023, on February 29, 2024, and, accordingly, has included updated F-pages in the Amendment reflecting the financials from such
report.

 General

12.
 Please file the offer letter with Ms. King-Jones as an exhibit to the registration statement, or tell
us why you believe it is not required to be filed.

 In response to the Staff’s comment, the Company has revised the exhibit
index and filed the offer letter with Ms. King-Jones as an exhibit to the registration statement.

 ***

Thank you for your consideration of this response. If you have any questions regarding the response set forth above, please do not hesitate to call me at
(415) 393-8373 or Branden C. Berns at (415) 393-4631.

Sincerely,

 /s/ Ryan A. Murr

Ryan A. Murr

cc:
 Branden C. Berns, Gibson, Dunn & Crutcher LLP

 
 Melanie Neary, Gibson, Dunn & Crutcher LLP

 
 Dr. Cameron Turtle, Spyre Therapeutics, Inc.

 
 Scott Burrows, Spyre Therapeutics, Inc.

 
 Heidy King-Jones, Spyre Therapeutics, Inc.

 6

United States securities and exchange commission logo
February 16, 2024
Cameron Turtle
Chief Executive Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Amendment No. 1 to Registration Statement on Form S-1
Filed February 5, 2024
File No. 333-276251
Dear Cameron Turtle:
            We have reviewed your registration statement and have the following comments.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies to your facts and circumstances
or do not believe an amendment is appropriate, please tell us why in your response.
            After reviewing any amendment to your registration statement and the information you
provide in response to this letter, we may have additional comments.
Amendment No. 1 to Registration Statement on Form S-1 filed February 5, 2024
Prospectus Summary
Company Overview, page 4
1.We note your response to prior comment 6.  Please revise to address the part of that
comment requesting certain balancing disclosures to be included in the Summary.
Risk Factor Summary, page 10
2.Please revise your summary risk factors to disclose, if true, that additional time may be
required to obtain regulatory approval for your product candidates and future product
candidates because of their status as combination therapies.  In this regard, we note your
disclosure on page 88 that the FDA indicated it intends to assess each potential
combination on a case-by-case basis.
Our Relationship with Paragon and Parapyre, page 53

 FirstName LastNameCameron  Turtle
 Comapany NameSpyre Therapeutics, Inc.
 February 16, 2024 Page 2
 FirstName LastNameCameron  Turtle
Spyre Therapeutics, Inc.
February 16, 2024
Page 2
3.Please revise the last paragraph of this section to clarify how the provisions of the Papyre
Option Obligation relate to the term of the Paragon Agreement.  In this regard, we note
based on your disclosure on page F-40 that the Parapyre Option Obligation provides for
an annual equity grant of options for Parapyre to purchase 1% of the then outstanding
shares of Spyre’s common stock, on a fully diluted basis, on the last business day of each
calendar year "during the term of the Paragon Agreement."
Business, page 73
4.In your Business section, please revise your disclosure where appropriate to:
•Better explain the meaning of "complementary diagnostics" and explain how such
term differs from "companion diagnostics," including with respect to the regulatory
approval pathways.
•Discuss the advantages and disadvantages of potentially using patient selection
strategies based on development and use of a complementary diagnostic.  Explain
how your plan to develop and use a complementary diagnostic may impact your
overall clinical development plan, including your clinical trial design and regulatory
strategy, as well as your commercialization strategy, if ultimately approved.
Our Strategy, page 73
5.With respect to the patient selection and complementary diagnostics pillar of your
development strategy, please revise in an appropriate place to explain what a genetic- or
biomarker-based complementary diagnostic is, and how you plan to develop and use such
complementary diagnostics to match treatment targets to IBD sub-populations to
implement a precision immunology approach.
Our Combination Therapy Approach, page 74
6.You disclose that you plan to investigate combinations of your proprietary antibody
therapies in preclinical studies in 2024 and in clinical studies beginning in 2025.
•Please revise to clarify that commencement of clinical trials is subject to approval of
an IND or equivalent foreign regulatory submission.
•Further, you state that your preclinical studies and preclinical trials involving your
combination therapies are expected to initially include SPY120.  Please disclose
when you plan to submit an IND or foreign regulatory submission for SPY120 or
otherwise advise.  Also, please make conforming revisions to the section captioned
"SPY120 – combination anti-4ß7 and anti-TL1A mAbs" on page 79.
Our Portfolio, page 75
7.We note your response to prior comment 23. Your response letter and other disclosures
suggest that SPY-003 and at least some of your combination product candidates are not
currently material to your business given the early stage of discovery.  With respect to
SPY003, we note:

 FirstName LastNameCameron  Turtle
 Comapany NameSpyre Therapeutics, Inc.
 February 16, 2024 Page 3
 FirstName LastNameCameron  Turtle
Spyre Therapeutics, Inc.
February 16, 2024
Page 3
•Your disclosures regarding SPY003 are limited in comparison with your discussion
of co-lead product candidates SPY001 and SPY002.
•Your disclosure on page 19 indicates that you are investing a majority of your efforts
and financial resources into optioned co-lead product candidates SPY001 and
SPY002.
•It appears that under the terms of the Paragon Agreement, (a) Paragon has granted
you only a limited license to the antibody technology arising from the non-optioned
research programs solely to evaluate the Option and for the purpose of allowing you
to determine whether to exercise the Option with respect to each such program; and
(b) unless and until you exercise the Option with respect to SPY003, the execution of
a SPY003 License Agreement will not occur.
•You state in the response letter and on page 79 that (i) the Company is still in the
process of narrowing down potential clones to select a development candidate for
SPY003, which is not expected to occur until at least mid-2024, if at all; and (ii) the
Company will not exercise the Option to acquire IP rights for the SPY003 program
until after such candidate nomination occurs.

In addition to the foregoing, we note the following with respect to your combination
product candidates:
•Your disclosures regarding your combination product programs remain limited in
comparison with your discussion of co-lead product candidates SPY001 and SPY002.
•You disclose on page 79 that each of SPY130 and SPY230 include combination with
non-optioned SPY003, for which no development candidate has been nominated.
•You disclose on page 74 that with respect to your combination therapies, your
preclinical studies and clinical trials planned for 2024 and 2025, respectively, are
expected to initially include SPY120, which combines optioned product candidates
SPY001 and SPY002.

As such, please limit the product candidates and programs included in your pipeline table
to those that are currently material to you and your operations, and for which you have
exercised the Option to exclusively license all of Paragon's right, title, and interest in,
including all intellectual property license rights thereto.  Please remove the references to
SPY003 and combination programs that include SPY003 from your pipeline table.  We
will not object to your discussion of your development plans for SPY003. SPY004, and
your combination programs including SPY003 in the narrative discussion in the Business
section.
SPY001 - anti-4ß7 mAb, page 76
8.You state on page 76:  "The JDC is the decision-making body for SPY001 and our other
pipeline programs prior to the execution of the SPY-001 License Agreement and we will
control and lead the development process once the SPY001 License Agreement is
executed."  For the avoidance of doubt, please clarify whether you will control and lead
the development process for each of SPY002, non-optioned programs SPY003 and

 FirstName LastNameCameron  Turtle
 Comapany NameSpyre Therapeutics, Inc.
 February 16, 2024 Page 4
 FirstName LastName
Cameron  Turtle
Spyre Therapeutics, Inc.
February 16, 2024
Page 4
SPY004, and each of the combination programs once the SPY001 license agreement is
executed, or otherwise revise.
9.We note your response to prior comment 26, which we reissue with respect to portions of
the second bullet.  In this subsection and in others as appropriate, please further revise
your discussion of completed preclinical studies to disclose when preclinical studies were
conducted, as well as the number of tests conducted in each study.
10.Please review and revise the Figures includes in this section to ensure that the text in each,
including subscript or other notations, are clearly legible without need for magnification.

Notes to the Financial Statements
8. Paragon Agreement, page F-58
11.We acknowledge your response to comment 33. Please revise your disclosure on pages F-
56 and F-59 to clarify that the $22.0 million is also upon the achievement of regulatory
milestones as your current disclosure only refers to development and clinical milestones.
General
12.Please file the offer letter with Ms. King-Jones as an exhibit to the registration statement,
or tell us why you believe it is not required to be filed.
            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.
            Refer to Rules 460 and 461 regarding requests for acceleration. Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Christine Torney at 202-551-3652 or Vanessa Robertson at 202-551-3649
if you have questions regarding comments on the financial statements and related matters. Please
contact Lauren Sprague Hamill at 303-844-1008 or Jason Drory at 202-551-8342 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden Berns

CORRESP
1
filename1.htm

CORRESP

 Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 2600

 San Francisco, CA
94111-3715

 Tel 415.393.8200

 gibsondunn.com

 February 2, 2024

 EDGAR
CORRESPONDENCE

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, D.C. 20549

Attn: Lauren Hamill and Jason Drory

Re:
 Spyre Therapeutics, Inc.

Registration Statement on Form S-1

Filed on December 22, 2023

File No. 333-276251

Ladies and Gentlemen:

 On behalf of Spyre
Therapeutics, Inc. (the “Company” or “Spyre”), this letter responds to the comments of the staff of the Securities and Exchange Commission Division of Corporation Finance (the “Staff”) contained in
your letter, dated January 18, 2024 (the “Comment Letter”) regarding the above-referenced Registration Statement on Form S-1 (the “Registration Statement”). The
Staff’s comments are set forth below, followed by the Company’s responses. For ease of reference, the heading and numbered paragraphs below correspond to the heading and numbered comments in the Comment Letter. The Company’s responses
are set forth in ordinary type beneath the Staff comment, which is set out in bold type. References are made to the Company’s Amendment No. 1 to the Registration Statement (the “Amendment”), filed on February 2, 2024.

 Company Overview, page 4

1.
 On page 4 and in your Business section, please revise your disclosure to:

•

 Disclose the meaning of “combinations of proprietary antibodies,” “patient enrichment
strategies,” and “companion diagnostics;”

•

 With reference to your disclosure on page F-58, explain how you plan
to develop your portfolio of individual treatments to create therapeutic combination candidates, and clarify whether you plan to develop any of your candidates for use both as monotherapies and combination therapies;

•

 Explain how you plan to develop and use each of patient enrichment strategies and companion diagnostics in
your development strategy; and

 Abu Dhabi • Beijing • Brussels • Century City • Dallas •
Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles

 Munich • New York • Orange
County • Palo Alto • Paris • Riyadh • San Francisco • Singapore • Washington, D.C.

 U.S. Securities and Exchange Commission

February 2, 2024

•

 Explain how your plan to use combination candidates and patient enrichment strategies via companion
diagnostics may “enhance efficacy” in your programs. Further, please qualify your statements on pages 4, 49, and 66 to clarify that your ability to execute your strategy to “enhance efficacy” is currently aspirational.

 In response to the Staff’s comment, the Company has further clarified its plans for the development of its product candidates.
The Company submits that in addition to its plan to develop its product candidates as potential monotherapies, the Company also plans to investigate combinations of its proprietary antibodies in preclinical and clinical studies to evaluate whether
combination therapy (co-administration or co-formulation of multiple monoclonal antibodies) can lead to greater efficacy, less frequent dosing, or the enhanced
identification of patients with responsive profiles, in each case, as compared to monotherapies in IBD. This is expected to initially include SPY120, which combines SPY001 (α4ß7) and SPY002 (TL1A), and is anticipated to be followed by
combinations that include SPY003 (IL-23), SPY130 (a combination of SPY001 and SPY003) and SPY230 (a combination of SPY002 and SPY003). The Company also submits that it has no existing plans to develop
companion diagnostics restricting usage of its products to a specific sub-population of patients; instead, it intends to examine patient selection strategies via complementary diagnostics utilized in its proof-of-concept clinical studies in order to
evaluate whether patients may be matched to the optimal therapy based on genetic background and/or other biomarker signatures. Accordingly, the Company has revised its disclosure on pages 4 and 5 of the Amendment and deleted references to
“enhance efficiency” on pages 4, 52 and 73.

2.
 With respect to your strategy to use patient enrichment strategies via companion diagnostics:

•

 Please disclose in an appropriate place in the Summary and Business sections whether you anticipate that any
or all of your programs will require you to develop and obtain FDA approval of a companion diagnostic.

•

 Include balancing disclosure regarding any material risks or challenges that the development and/or use of
companion diagnostics might pose to your business and/or development strategy.

 In response to the Staff’s comment, the Company
submits that it currently intends to examine patient selection strategies via complementary diagnostics utilized in its proof-of-concept clinical studies rather than pursuing companion diagnostics. Accordingly, the Company has added disclosure on
the regulatory pathway of approval for complementary diagnostics and has balanced such disclosure with a discussion of material risks or challenges inherent in the development of complementary diagnostics on pages 4, 52 and 73 of the Amendment,
respectively.

3.
 Please revise to qualify the following statement that appears on pages 4 and 66: “We have purposely
engineered our product candidates to bind potently and selectively to target epitopes with extended half-lives.” In this regard, we note your disclosure on page 48 indicating that potent binding and selectivity are “the aim” of your
product engineering.

 2

 U.S. Securities and Exchange Commission

February 2, 2024

 In response to the Staff’s comment, the Company has revised its disclosure on pages 4 and 73 of the
Amendment to remove “purposely” from the referenced statement and added additional clarifying language.

4.
 We note that your statement on page 17 that your success is “dependent on observing a longer half-life
of your programs in humans than other mAbs currently marketed and in development” lacks sufficient context in the Summary and Business sections.

•

 Please revise pages 4 and 66 to clearly describe your strategy to engineer “long-acting” product
candidates that will exhibit extended pharmacokinetic half-lives.

•

 In your revisions, please also specifically explain the meaning of the term “extended half-life” and
how your focus on half-life extension relates to potential dosing convenience or otherwise advise.

 In response to the Staff’s
comment, the Company has revised its disclosure on pages 4, 52 and 74 of the Amendment by providing additional detail regarding its strategy of engineering its product candidates. In doing so, the Company has explained that “extended
half-life” means extended pharmacokinetic half-lives that are achieved through modifications in the Fc domain that increase affinity to human FcRn and increase antibody recycling. Furthermore, the Company has explained that it anticipates that
half-life extension will enable less frequent administration compared to marketed or development-stage monoclonal antibodies that do not incorporate half-life extension modifications.

5.
 We note your stated intention to deliver your product candidates through self-administered, subcutaneous
injection via a pre-filled pen. Please revise your Summary and Business sections to disclose whether you anticipate that your product candidates may be regulated by the FDA as drug/device combination products.
Explain the implications of drug/device combination product classification with respect to the regulatory approval process, including how this process differs from the process of obtaining FDA approval for drugs.

In response to the Staff’s comment, the Company submits that while a pre-filled pen is an industry-standard
approach for subcutaneously-delivered monoclonal antibodies that is not typically regulated as a drug/device combination and is frequently utilized by other drug developers, the specific delivery mechanism or technology that the Company intends to
use to deliver its product candidates is currently under review and has not yet been selected. Accordingly, the Company has revised its disclosure on pages 5 and 52 of the Amendment. Furthermore, the Company has added disclosure under the Summary
and Business on pages 4, 5 and 74 of the Amendment regarding the regulation of combination products on page 88 of the Amendment.

 3

 U.S. Securities and Exchange Commission

February 2, 2024

6.
 Please balance the discussion of your Company’s development strategy and candidate programs by
prominently highlighting in the Summary that:

•

 the drug and/or device development process is inherently uncertain, your development approach is unproven,
preclinical evidence to support your approach is preliminary and limited, and you have yet to test any product candidate in humans; and

•

 there can be no guarantee that you will be able to develop product candidates that will be found to be safe
and effective so as to obtain necessary regulatory approvals.

 In response to the Staff’s comment, the Company has revised its
disclosure on page 76 of the Amendment to balance the discussion of its development strategy and candidate programs with additional bold-faced disclaimer language.

Risk Factor Summary, page 9

7.
 We note your stated plan to use patient enrichment strategies via companion diagnostics in your product
development. If material, please add summary risk and corresponding risk factor disclosure addressing the risks and challenges related to your proposed use of companion diagnostic tools needed to leverage your strategy.

In response to the Staff’s comment, the Company submits that development of companion diagnostics is not currently core to its plans; instead, it intends
to focus on examining patient selection strategies via complementary diagnostics in its clinical studies to evaluate whether patients can be matched to the optimal therapy based on genetic background and/or other biomarker signatures. Accordingly,
the Company has revised its disclosures on pages 10, 20, 23 and 24 of the Amendment.

8.
 Given your stated intention to deliver your product candidates through injection via a prefilled pen, please
add summary risk and corresponding risk factor disclosure discussing any risks or challenges related to the development and/or regulatory approval of your product candidates if the FDA may consider your product candidates to be drug/device
combination products.

 In response to the Staff’s comment, the Company submits that while a
pre-filled pen is an industry-standard approach for subcutaneously delivered monoclonal antibodies that is not typically regulated as a drug/device combination and is frequently utilized by other drug
developers, the specific delivery mechanism for its product candidates is currently under review and has not yet been selected. Accordingly, the Company has revised its disclosure on pages 5, 10, 23 and 52 of the Amendment to clarify that it is
evaluating delivery mechanisms and has not yet selected a final delivery mechanism and to add risk factor disclosure discussing the risks or challenges related to the development and/or regulatory approval of our product candidates in conjunction
with the development and/or regulatory approval of drug delivery device(s) through which we intend to deliver our product candidates.

 4

 U.S. Securities and Exchange Commission

February 2, 2024

 Risk Factors

We will need to raise additional capital…, page 11

9.
 On page 12, please remove the reference to being subject to the limitations set forth in Instruction I.B.6
of Form S-3, or otherwise advice.

 In response to the Staff’s comment, the Company has
revised its disclosure on page 13 of the Amendment to remove the reference.

 We have historically incurred losses, have a limited operating
history…, page 13

10.
 In the first sentence of the third paragraph, please revise to clarify whether the reference to
“conducting clinical trials” pertains only to your legacy product candidates. In this regard, it appears from your disclosure throughout that all of your current programs are in preclinical stages of development and have not yet been
tested in humans.

 In response to the Staff’s comment, the Company confirms that the reference to “conducting clinical
trials” pertains only to its legacy product candidates. Accordingly, the Company has revised its disclosure on page 15 of the Amendment to clarify the development status of its current product candidates.

11.
 We note your disclosure that the holders of your Series B Preferred Stock may be entitled to require you to
settle their shares of Series B Preferred Stock for cash at a price per share equal to the fair value of the Series B Preferred Stock, as described in your Series B Certificate of Designation. Please revise your disclosure to describe how the fair
value is determined and quantify the aggregate amount of the potential cash redemption as of a recent date or otherwise advise.

 In
response to the Staff’s comment, the Company has revised its disclosure on page 15 of the Amendment to add a discussion of how fair value is determined in connection with a hypothetical cash settlement of Series B Preferred Stock and the
aggregate amount of a potential cash settlement, for illustrative purposes, if the Company was obligated to settle the conversion of all outstanding Series B Preferred Stock as of January 2, 2024, pursuant to the terms of the Series B
Certificate of Designation.

 5

 U.S. Securities and Exchange Commission

February 2, 2024

 Our Certificate of Incorporation provides that…, page 42

12.
 We note the exclusive forum provisions in your certificate of incorporation and bylaws. Please clarify
whether these provisions apply to actions arising under the Securities Act or Exchange Act. In that regard, please note that while Section 27 of the Exchange Act creates exclusive federal jurisdiction over all suits brought to enforce any duty
or liability created by the Exchange Act, Section 22 of the Securities Act creates concurrent jurisdiction for federal and state courts over all suits brought to enforce any duty or liability created by the Securities Act or the rules and
regulations thereunder.

 In response to the Staff’s comment, the Company has revised its disclosure on page 46 of the Amendment
to affirmatively state that, “These choice of forum provisions will not apply to claims brought to enforce a duty or liability created by the Exchange Act.” Additionally, the Company has made parallel revisions to its disclosure in the
section titled “Description Of Capital Stock–Certificate of Incorporation and Bylaw Provisions” on page 138 of the Amendment.

Our relationship with Paragon and Parapyre, page 49

13.
 We note your disclosure describing the Parapyre Option Obligation, “which provided for an annual equity
grant of options to purchase 1% of the then outstanding shares of Pre-Merger Spyre’s common stock, on a fully diluted basis, on the last business day of each calendar year during the term of the Paragon
Agreement.” Please update your disclosure to clarify the term of the Paragon Agreement.

 In response to the Staff’s
comment, the Company has revised its disclosure on page 53 of the Amendment to clarify the terms of the Parapyre Option Obligation.

 Research and
Development Expenses, page 53

14.
 Please revise the disclosure to break out the dollar amount of external research and development expenses
incurred for each period presented. Alternatively, disaggregate research and development expenses by nature or type of expense for each period presented.

In response to the Staff’s comment, the Company has revised its disclosure on pages 58-60 of the Amendment to break out the respective dollar amounts of
internal and external research and development expenses incurred for each period presented.

 6

 U.S. Securities and Exchange Commission

F

United States securities and exchange commission logo
January 18, 2024
Cameron Turtle
Chief Executive Officer
Spyre Therapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Spyre Therapeutics, Inc.
Registration Statement on Form S-1
Filed December 22, 2023
File No. 333-276251
Dear Cameron Turtle:
            We have reviewed your registration statement and have the following comments.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies to your facts and circumstances
or do not believe an amendment is appropriate, please tell us why in your response.
            After reviewing any amendment to your registration statement and the information you
provide in response to this letter, we may have additional comments.
Registration Statement on Form S-1 filed December 22, 2023
Company Overview, page 4
1.On page 4 and in your Business section, please revise your disclosure to:
•Disclose the meaning of "combinations of proprietary antibodies," "patient
enrichment strategies," and "companion diagnostics;"
•With reference to your disclosure on page F-58, explain how you plan to develop
your portfolio of individual treatments to create therapeutic combination candidates,
and clarify whether you plan to develop any of your candidates for use both as
monotherapies and combination therapies;
•Explain how you plan to develop and use each of patient enrichment strategies and
companion diagnostics in your development strategy; and
•Explain how your plan to use combination candidates and patient enrichment
strategies via companion diagnostics may "enhance efficacy" in your programs.
Further, please qualify your statements on pages 4, 49, and 66 to clarify that your

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 January 18, 2024 Page 2
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ability to execute your strategy to "enhance efficacy" is currently aspirational.
2.With respect to your strategy to use patient enrichment strategies via companion
diagnostics:
•Please disclose in an appropriate place in the Summary and Business sections
whether you anticipate that any or all of your programs will require you to develop
and obtain FDA approval of a companion diagnostic.
•Include balancing disclosure regarding any material risks or challenges that the
development and/or use of companion diagnostics might pose to your business and/or
development strategy.
3.Please revise to qualify the following statement that appears on pages 4 and 66:  "We have
purposely engineered our product candidates to bind potently and selectively to target
epitopes with extended half-lives."  In this regard, we note your disclosure on page 48
indicating that potent binding and selectivity are "the aim" of your product engineering.
4.We note that your statement on page 17 that your success is "dependent on observing
a longer half-life of your programs in humans than other mAbs currently marketed and in
development" lacks sufficient context in the Summary and Business sections.
•Please revise pages 4 and 66 to clearly describe your strategy to engineer "long-
acting" product candidates that will exhibit extended pharmacokinetic half-lives.
•In your revisions, please also specifically explain the meaning of the term "extended
half-life" and how your focus on half-life extension relates to potential dosing
convenience or otherwise advise.
5.We note your stated intention to deliver your product candidates through self-
administered, subcutaneous injection via a pre-filled pen.  Please revise your Summary
and Business sections to disclose whether you anticipate that your product candidates may
be regulated by the FDA as drug/device combination products.  Explain the implications
of drug/device combination product classification with respect to the regulatory approval
process, including how this process differs from the process of obtaining FDA approval
for drugs.
6.Please balance the discussion of your Company's development strategy and candidate
programs by prominently highlighting in the Summary that:
•the drug and/or device development process is inherently uncertain, your
development approach is unproven, preclinical evidence to support your approach is
preliminary and limited, and you have yet to test any product candidate in humans;
and
•there can be no guarantee that you will be able to develop product candidates that will
be found to be safe and effective so as to obtain necessary regulatory approvals.

Risk Factor Summary, page 9
7.We note your stated plan to use patient enrichment strategies via companion diagnostics in

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your product development.  If material, please add summary risk and corresponding risk
factor disclosure addressing the risks and challenges related to your proposed use of
companion diagnostic tools needed to leverage your strategy.
8.Given your stated intention to deliver your product candidates through injection via a pre-
filled pen, please add summary risk and corresponding risk factor disclosure discussing
any risks or challenges related to the development and/or regulatory approval of your
product candidates if the FDA may consider your product candidates to be drug/device
combination products.
Risk Factors
We will need to raise additional capital..., page 11
9.On page 12, please remove the reference to being subject to the limitations set forth in
Instruction I.B.6 of Form S-3, or otherwise advise.
We have historically incurred losses, have a limited operating history..., page 13
10.In the first sentence of the third paragraph, please revise to clarify whether the reference to
"conducting clinical trials" pertains only to your legacy product candidates.  In this regard,
it appears from your disclosure throughout that all of your current programs are in
preclinical stages of development and have not yet been tested in humans.
11.We note your disclosure that the holders of your Series B Preferred Stock may be entitled
to require you to settle their shares of Series B Preferred Stock for cash at a price per share
equal to the fair value of the Series B Preferred Stock, as described in your Series B
Certificate of Designation. Please revise your disclosure to describe how the fair value is
determined and quantify the aggregate amount of the potential cash redemption as of a
recent date or otherwise advise.
Our Certificate of Incorporation provides that..., page 42
12.We note the exclusive forum provisions in your certificate of incorporation and bylaws.
Please clarify whether these provisions apply to actions arising under the Securities Act or
Exchange Act. In that regard, please note that while Section 27 of the Exchange Act
creates exclusive federal jurisdiction over all suits brought to enforce any duty or liability
created by the Exchange Act, Section 22 of the Securities Act creates concurrent
jurisdiction for federal and state courts over all suits brought to enforce any duty or
liability created by the Securities Act or the rules and regulations thereunder.
Our Relationship with Paragon and Parapyre, page 49
13.We note your disclosure describing the Parapyre Option Obligation, "which provided for
an annual equity grant of options to purchase 1% of the then outstanding shares of Pre-
Merger Spyre’s common stock, on a fully diluted basis, on the last business day of each
calendar year during the term of the Paragon Agreement ." Please update your disclosure

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 January 18, 2024 Page 4
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January 18, 2024
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to clarify the term of the Paragon Agreement.
Research and Development Expenses, page 53
14.Please revise the disclosure to break out the dollar amount of external research and
development expenses incurred for each period presented. Alternatively, disaggregate
research and development expenses by nature or type of expense for each period presented
.
Management's Discussion and Analysis of Financial Condition and Results of Operations
Future Funding Requirements and Operational Plan, page 59
15.Please update the final paragraph in this section consistent with your disclosure in the
"Recent Developments" section and elsewhere regarding shareholder approval of the
conversion of your Series A Preferred Stock.  In addition, please update your "Recent
Developments" section to discuss the December 2023 SPA for Series B Preferred Stock.
Contractual Obligations and Other Commitments, page 63
16.You state here and on page 66 that as of the date of this prospectus, the Option remains
unexercised with respect to three research programs under the Paragon Agreement.
•Such disclosures are inconsistent with statements on pages 17, 49, and 116
indicating that you exercised your Option for the PSY001 and SPY002 programs in
July 2023 and December 2023, respectively, and the remaining two options for the
SPY003 and SPY004 programs remain outstanding.  Please reconcile or advise.
•Also, please update this section as appropriate to clarify the current status of your
expected obligations under the Paragon Agreement based on your exercise of the
Option to date.
Management's Discussion and Analysis of Financial Condition and Results of Operations
Contractual Obligations and Other Commitments, page 63
17.You disclose that as of the date of the filing of this prospectus, the Option remains
unexercised with respect to the three remaining research programs under the Paragon
Agreement. However, on pages 48 and 49 you disclose that in December 2023 you
exercised the Option for the SPY002 program. Please clarify.
Business
Company Overview, page 66
18.We note your disclosure "[f]or more information on the Paragon Agreement, see
discussion under the heading “Paragon Agreement” below." However, we are unable to
locate the heading. Please revise your disclosure to describe all the material terms of the
Paragon Agreement as amended.
Our Strategy, page 66

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19.We note your statements on pages 66 and 67 that your antibodies have "best-in-class"
potential.  Given the development stage of your programs and length of the drug approval
process, it is premature and inappropriate to speculate or imply that any Spyre product
candidates will ultimately be approved or become best-in-class.  Please remove these
statements and any similar statements throughout.
20.Please revise in an appropriate place to explain what a genetic- or biomarker-based
companion diagnostic is, and how you plan to develop and use such companion
diagnostics to match treatment targets to IBD sub-populations.
21.With respect to the half-life extension pillar of your development strategy, please revise
your Business section in the appropriate place(s) to:
•explain the basic operation of half-life extension technologies including YTE and LS
amino acid substitutions, and describe your efforts to develop programs using such
technologies, as mentioned on page 18;
•explain how your focus on half-life extension/optimization has the potential to confer
a more favorable dosing schedule for your programs, assuming they successfully
complete clinical development; and
•if material, describe the non-human primate study referenced on page 18, including
quantitative information regarding the range of results observed regarding the
increased half-life properties of your programs or otherwise.
Our Portfolio, page 67
22.Please remove or revise your statement that you are advancing a "broad pipeline" of
antibodies for the treatment of IBD, or advise.  In this regard, we note your disclosure that
you are initially focused and substantially dependent on the success of the SPY001 and
SPY002 programs that each address IBD.  We also refer to disclosure on page F-36
stating that the Company determined that the pipeline candidates within its portfolio are
"similar in nature."
23.We note the inclusion of SPY003, SPY004 and combination programs SPY120, SPY130
and SPY230 in your pipeline table. In this regard:
•It is seemingly premature to highlight the SPY003 and SPY004 programs in
the pipeline table given your disclosure that you are investing a majority of your
efforts and financial resources into optioned co-lead programs SPY001 and SPY002,
disclosure that you have not exercised the Option with respect to SPY003 and
SPY004, and your limited disclosures regarding SPY003 and SPY004 in the
registration statement.  Please remove SPY003 and SPY004 from the table, or
explain why these programs are currently material to your business so as to warrant
inclusion therein.
•It is also seemingly premature to highlight your combination programs in the pipeline
table given that your individual programs appear to be in early preclinical stages,
certain of your combination programs purport to involve combination

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 January 18, 2024 Page 6
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Page 6
with SPY003 (IL-23) which you have not yet exercised the Option on, and you have
provided only limited disclosures regarding your combination programs in the
registration statement.  Please remove your combination programs from the pipeline
table or advise as to the materiality of each such program.

Please note that we do not object to your narrative discussion of SPY003, SPY004, and
your combination programs in the Business section.
24.Please also revise the pipeline table on page 67 as follows:
•Disclose the indication for which you are currently developing each program.
•Disclose whether you have nominated a development candidate for each program.
•Revise the columns so they are clearly delineated from each other.  Include columns
of equal width for each of Phase 1, Phase 2 and Phase 3 of clinical testing.
•The table should not be used to prematurely project or imply successful completion
of the stages required prior to regulatory approval.  To the extent that you disclose
the next anticipated milestone for a candidate in the table, only provide the next
material step in the regulatory review process (e.g., development candidate
nomination, intended timing of IND submissions, etc.).  The narrative discussion
following the pipeline table is more appropriate for discussing aspirational plans for
your product candidates beyond the immediate next step, such as expected interim
data from any future Phase 1 trials.
•Ensure the font and type used is clearly legible.  For example only, we note that the
information currently presented under the column titled "Clinical" is not clearly
readable even with enhanced pixelation.
•With respect to footnote 1 to the table, revise to explain that the SPY001 and SPY002
License Agreements are still being finalized and clarify the expected timing for
entering into these agreements.
25.In the narrative discussion following the pipeline table, you discuss the potential timing of
Phase 1 clinical trials of SPY001 and SPY002 without addressing the necessary
submission of INDs to the FDA.  For each of SPY001 and SPY002, clarify when you plan
to submit an IND and specify the indication(s) to be covered.
26.Please expand your narrative disclosure following the pipeline table to provide a more
fulsome discussion of each of your individual and combination programs and clarify the
status of development activities to date. In your revisions, please:
•Clarify your role and involvement in completed or ongoing development efforts

CORRESP
1
filename1.htm

CORRESP

 November 17, 2023

VIA EDGAR AND EMAIL

 United States Securities and
Exchange Commission

 Division of Corporation Finance

 100 F
Street, N.E.

 Washington, DC 20549

Attn: Laura Crotty and Dillon Hagius

Re:
 Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-1

Filed August 7, 2023

File No. 333-273769

 Ladies and
Gentlemen:

 Pursuant to Rules 460 and 461 promulgated under the Securities Act of 1933, as amended (the “Act”), Aeglea
BioTherapeutics, Inc., a Delaware corporation (the “Company”), hereby respectfully requests that the effective time of the above referenced Registration Statement on Form S-1 filed by the Company be
accelerated to 4:01 p.m., Eastern Standard Time, on November 20, 2023 or as soon thereafter as practicable, unless we or our outside counsel, Gibson, Dunn & Crutcher LLP, request by telephone that such Registration Statement be
declared effective at some other time. In making this acceleration request, the Company acknowledges that it is aware of its obligations under the Act.

Once the Registration Statement is effective, please orally confirm the event with our counsel, Gibson, Dunn & Crutcher LLP by
calling Branden Berns at (415) 393-4631.

 Very truly yours,

 AEGLEA BIOTHERAPEUTICS, INC.

By:

/s/ Cameron Turtle

Name:

Cameron Turtle

Title:

Chief Operating Officer

cc:

 Scott Burrows, Aeglea BioTherapeutics, Inc.

Heidy King-Jones, Aeglea BioTherapeutics, Inc.

 Ryan A. Murr,
Gibson, Dunn & Crutcher LLP

 Branden C. Berns, Gibson, Dunn & Crutcher LLP

CORRESP
1
filename1.htm

CORRESP

 November 15, 2023

EDGAR CORRESPONDENCE

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 Office of Life
Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

Attn: Laura Crotty and Dillon Hagius

Re:
 Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-1

Filed on August 7, 2023

File No. 333-273769

Ladies and Gentlemen:

 On behalf of Aeglea
BioTherapeutics, Inc. (the “Company” or “Aeglea”), this letter responds to the comments of the staff of the Securities and Exchange Commission Division of Corporation Finance (the “Staff”) contained
in your letter, dated October 20, 2023 (the “Comment Letter”) regarding the above-referenced Registration Statement on Form S-1 (the “Amended Registration Statement”),
which was originally filed on Form S-3 on August 7, 2023. The Staff’s comments are set forth below, followed by the Company’s responses following our call with Staff on November 9, 2023.
For ease of reference, the heading and numbered paragraphs below correspond to the heading and numbered comments in the Comment Letter. The Company’s responses are set forth in ordinary type beneath the Staff comment, which is set out in bold
type. References are made to the Company’s Amendment No. 1 to the Amended Registration Statement (“Amendment No. 1”).

General

1.
 We note the representation in Section 2.4 of the Agreement and Plan of Merger, filed on June 23,
2023 as exhibit 2.1 to Aeglea’s Form 8-K, that Spyre’s holders were required to consent to the merger. We further note your Form S-1 seeks to registers the
resale of securities issued and issuable to Spyre’s security holders as consideration for the merger. Please revise to identify all former affiliates of Spyre reselling pursuant to this Form S-1 as
underwriters and fix a selling price for the duration of their offering. See Securities Act Rule 145(c).

 In response to the
Staff’s comment, the Company has removed all former affiliates of Spyre from the selling stockholder table in Amendment No. 1. Specifically, the Company has removed as selling stockholders Fairmount Healthcare Fund L.P., Fairmount
Healthcare Fund II L.P., Fairmount Healthcare Co-Invest L.P., Paragon Therapeutics, Inc., Parapyre Holding LLC and

 U.S. Securities and Exchange Commission

November 15, 2023

Spyre Advisors LLC, which were the only former affiliates of Spyre listed as selling security holders in the Registration Statement (including both shares acquired as merger consideration and
shares purchased for cash from the Company in the concurrent private placement).1 Additionally, the Company has elected to remove Cameron Turtle, Ph.D. as a selling stockholder from the
Registration Statement. Dr. Turtle was not an affiliate of Spyre at the time of the merger, but is currently an officer of the Company and was a consultant of Spyre at the time of the merger. None of the remaining selling stockholders set forth
in Amendment No. 1 were officers, directors or greater-than-10% holders of Spyre capital stock at the time of the Spyre stockholder vote or as of the consummation of the merger with Aeglea.

2.
 Please revise to remove all incorporation by reference from the Form
S-1 and file a complete prospectus with your amendment. See General Instruction VII.D.1.b to Form S-1.

In response to the Staff’s comment, the Company has amended the Amended Registration Statement by removing all information previously incorporated by
reference and has filed a complete prospectus with Amendment No. 1.

 ***

Thank you for your consideration of this response. If you have any questions regarding the response set forth above, please do not hesitate to
call me at (415) 393-8373 or Branden Berns at (415) 393-4631.

Sincerely,

/s/ Ryan A. Murr

Ryan A. Murr

cc:
 Thomas Kim, Gibson, Dunn & Crutcher LLP

Brian Lane, Gibson, Dunn & Crutcher LLP

Cameron Turtle, Aeglea BioTherapeutics, Inc.

Scott Burrows, Aeglea BioTherapeutics, Inc.

Heidy King-Jones, Aeglea BioTherapeutics, Inc.

1
 For purposes of this response, we have defined “affiliates” of Spyre at the time of the merger as all
officers, directors and holders of at least 10% of the issued and outstanding capital stock of Spyre. As Fairmount and entities controlled by Fairmount or under common control with Fairmount owned approximately 93% of Spyre at the time of the
merger, these Fairmount-affiliated entities were in “control” of Spyre for purposes of affiliate status under Rule 405 under the Securities Act. No parties remaining listed as selling stockholders are controlled by Fairmount or under
common control with Fairmount.

 2

CORRESP
1
filename1.htm

CORRESP

 October 26, 2023

 EDGAR
CORRESPONDENCE

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, D.C. 20549

Attn: Laura Crotty and Dillon Hagius

Re:
 Aeglea BioTherapeutics, Inc.

 
 Registration Statement on Form S-1

 
 Filed on August 7, 2023

 
 File No. 333-273769

Ladies and Gentlemen:

 On behalf of Aeglea
BioTherapeutics, Inc. (the “Company” or “Aeglea”), this letter responds to the comments of the staff of the Securities and Exchange Commission Division of Corporation Finance (the “Staff”) contained
in your letter, dated October 20, 2023 (the “Comment Letter”), regarding the above-referenced Registration Statement on Form S-1, which was originally filed on Form S-3 on August 7, 2023 (the “Registration Statement”). The Staff’s comments are set forth below, followed by the Company’s responses. For ease of reference, the heading and numbered
paragraphs below correspond to the heading and numbered comments in the Comment Letter. The Company’s responses are set forth in ordinary type beneath the Staff comment, which is set out in bold type.

General

1.
 We note the representation in Section 2.4 of the Agreement and Plan of Merger, filed on June 23,
2023 as exhibit 2.1 to Aeglea’s Form 8-K, that Spyre’s holders were required to consent to the merger. We further note your Form S-1 seeks to registers the
resale of securities issued and issuable to Spyre’s security holders as consideration for the merger. Please revise to identify all former affiliates of Spyre reselling pursuant to this Form S-1 as
underwriters and fix a selling price for the duration of their offering. See Securities Act Rule 145(c).

 We note that the foregoing
comment follows prior comments issued by the Staff on August 28, 2023 and September 29, 2023 (reissuing Comment No. 1 from the August 28, 2023 letter), both of which are predicated on the question of whether the Company was a
shell company and thus ineligible to use Form S-3. Having elected to convert the Registration Statement to Form S-1 following the September 29, 2023 comment letter
and subsequent discussion with the Staff, the Company is now faced with a request to identify affiliated selling stockholders as presumptive

 Abu Dhabi • Beijing
• Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles

Munich • New York • Orange County • Palo Alto • Paris • San Francisco • Singapore • Washington, D.C.

 U.S. Securities and Exchange Commission

October 26, 2023

 underwriters under Securities Act Rule 145(c). As noted in the Company’s response to the
September 29, 2023 comment letter, the Company reaffirms its view that at no time has it been a shell company. In light of the Staff’s most recent comments, the Company would like to take this opportunity to provide its analysis of the
shell company question, both under the existing framework set forth in Rule 4051 under the Securities Act (as elucidated by Release No. 33-8407 (the
“Proposing Release”) and No. 33-8587 (the “Adopting Release”)), as well as the “totality of the transactions” standard set forth in the Staff’s
September 29, 2023 comment letter, as further articulated in subsequent calls with the Staff.

 Current Legal Standard

The test for what constitutes a “shell company” is set forth in Rule 405 under the Securities Act, which defines a shell company as a registrant that
has both:

(i)
 no or nominal operations; and

(2)
 either: (i) no or nominal assets; or (ii) assets consisting solely of cash and cash equivalents; or
(iii) assets consisting of any amount of cash and cash equivalents and nominal other assets.

 As described below, the Company
believes that it has, at all times since its initial public offering in 2016, maintained both substantive operations and assets and thus cannot be properly characterized as a shell company at any point in time.

No or nominal operations

 Prior to the acquisition
of Spyre in June 2023, the Company operated as a clinical-stage biotechnology company focused on human enzyme therapeutics for the treatment of rare metabolic diseases. As a result of an interim review of clinical data in April 2023 for the
Company’s homocystinuria program, the Company observed mixed results at the doses and treatment durations tested. The Company believed that while this drug candidate could potentially show a clinically meaningful benefit at higher doses and/or
longer treatment durations, the Company was not in a position to continue to study the drug in this indication. Accordingly, the Company began a process of exploring strategic alternatives to preserve and create value for its stockholders. This
process included considering in-licenses, acquisitions, business combinations and/or the sale of clinical programs.

1
 Rule 12b-2 under the Exchange Act sets forth the same test for shell
company status. For convenience, we have referred in this letter to the shell company test under Rule 405, although the analysis applies as well to Rule 12b-2 under the Exchange Act.

 2

 U.S. Securities and Exchange Commission

October 26, 2023

 At the same time the Company was exploring strategic alternatives, the Company continued to invest resources
in its clinical programs to preserve the value of the assets in any future disposition. These activities included the following for both the homocystinuria and arginase 1 deficiency programs (which was being developed in collaboration with a
European licensing partner): maintaining manufacturing rights and capabilities, the orderly wind down of existing clinical trials to allow another party to continue research and development, the collection and storage of patient data, the
documentation of technical aspects of the legacy assets, and the retention of key staff and consultants to conduct these activities. These activities were conducted before and continued after the acquisition of Spyre on June 22, 2023. At the
time of the Spyre acquisition, the Company had nine employees. Following the Spyre acquisition, this number increased to 14 employees (as of June 30, 2023). While perhaps not dispositive, we would note that the Adopting Release (addressing the
rationale of why shell companies should not need Form S-8 eligibility) states that shell companies “do not operate businesses and, hence, rarely have employees.” In contrast, the Company had an
annual payroll of approximately $2.3 million at the time of the Spyre acquisition.

 For the three and six months ended June 30, 2023, the
Company’s operating expenses associated with these operating activities (i.e., research and development expenses, plus general and administrative expenses) totaled approximately $29.4 million and $48.5 million, respectively.2 In light of these operating activities and corresponding expenses, we would respectfully submit that the Company’s operations at all times through the acquisition of Spyre were substantial and
anything but “nominal”, as required under Rule 405 in order for the Company to be deemed a shell company. Since the acquisition of Spyre, the Company has further ramped up its operations and had 18 employees as of September 30, 2023.

 Before considering the second prong of the shell company test (i.e., no/nominal assets), we would note that the prongs are conjunctive, such that both
prongs must be met in order for a company to be deemed a shell company. Accordingly, we would respectfully submit that solely on the basis of its operations through the closing of the Spyre acquisition (and since that time), the Company should not
be deemed to be a shell company. However, we would submit that the Company also fails the asset test for shell company status, as described below.

No or nominal assets

 As of March 31, 2023
and June 30, 2023, the Company had total assets (excluding cash, cash equivalents, marketable securities and restricted cash) of approximately $12.7 million and $6.9 million, respectively. While the Adopting Release declined to adopt
a bright-line test for what constitutes “nominal” assets, the foregoing asset values are not “nominal.”

2
 In the period ended June 30, 2023, the Company recorded a separate IPR&D expense of approximately
$130 million relating to the Spyre acquisition, which was accounted for as an asset purchase under GAAP.

 3

 U.S. Securities and Exchange Commission

October 26, 2023

 Moreover, we would note that the book value of the Company’s assets reflected on the balance sheet do
not reflect the fair value of the Company’s drug development programs, which had been expensed as incurred as in-process research and development in accordance with GAAP.3 Under generally accepted accounting principles, expenses incurred in the development of pre-revenue assets are expensed as incurred (as reflected in the
Company’s accumulated deficit of $661 million as of June 30, 2023). Accordingly, the fair value of the Company’s non-cash assets was substantially higher than the $6.9 million
reflected on the Company’s June 30, 2023 balance sheet. This is reflected by the Company’s divestiture in July 2023 of one of the Company’s two clinical-stage legacy assets for an upfront payment of $15 million and up to
$100 million of contingent consideration.

 Taking into account this post-closing sale, it is clear that the Company had more than nominal assets at
closing, both based on book value and fair value.

 Other Considerations

In discussing the traits of shell companies and the need for regulation of shell companies, the Proposing Release identified a number of other factors that are
often present in entities that are deemed to be shell companies. We have copied these below with an analysis of how such factors relate to the Company and its business combination with Spyre:

 Shell Company Trait

 Analysis

No or nominal assets and operations

 As discussed above, Aeglea had substantial operations and assets at all times through (and after) the Spyre acquisition. Since inception, the
Company has incurred a cumulative deficit of $661 million, including approximately $20.1 million in operational expenses in the three months ended June 30, 2023 (i.e., the period in which the business combination with Spyre was
completed). At the time of consummation of the Spyre acquisition, the Company had nine full-time employees and an annual payroll of approximately $2.3 million.

Also, as noted above, Aeglea had non-cash assets with a book value of $6.9 million as of June 30, 2023 and
additional assets with a greater value on a fair-value basis (as reflected in the subsequent sale of one such asset for $15 million of upfront consideration, with a potential $100 million of contingent consideration).

3
 We acknowledge that the Adopting Release contemplates measuring assets based on GAAP (i.e., book value and not
fair value). However, the Staff’s September 29, 2023 comment letter raises considerations that we believe to be outside of the parameters of Rule 405. Accordingly, we thought it would be helpful to provide a fuller picture of other non-cash assets held by the Company that are not recorded on the balance sheet for GAAP purposes.

 4

 U.S. Securities and Exchange Commission

October 26, 2023

Small trading market

 Aeglea has traded on Nasdaq since 2016 (with substantive trading volume during that time), while shell companies typically trade on the OTC
market. We would note that Nasdaq does not permit the initial listing or continued listing of shell companies (other than companies that initially list as a SPAC, which does not apply in the Company’s case).

Shell company promoters issue large amounts of securities to themselves or designated nominees

 Aeglea has operated as a Nasdaq-listed biotechnology company since 2016. Accordingly, there are no “promoters” for Aeglea. While
Rule 405 has a broad definition of what constitutes a “promoter,” the definition focuses on persons (and their affiliates) who are engaged in the founding or organizing of a company. In the case of Aeglea, it was founded as a
limited liability company in 2013 and converted to the current corporate entity in 2015.

From the time of its IPO through the Spyre acquisition, there have been no issuances to directors, officers or employees outside of stockholder-approved equity
compensation plans (or inducement grants, as permitted by Nasdaq rules) since 2016.4 At the time of the Spyre acquisition, new equity awards were approved for the directors and officers, but such
awards are subject to stockholder approval at a meeting expected to be held in November 2023.

 The shell company acquires a private business that the promoters claim has high growth potential

Aeglea does believe that the Spyre assets have high growth potential. However, as noted above, there are no “promoters” with respect to Aeglea.

Inadequate information is available to investors regarding the post-transaction company

 Following the acquisition of Spyre, Aeglea has provided information regarding Spyre’s business, operations and risks. This information
was provided in Aeglea’s Current Report on Form 8-K filed on June 23, 2023, Quarterly Report on Form 10-Q for the quarter ended June 30, 2023, preliminary
proxy statement on Schedule 14-A (filed August 8, 2023) and in the Registration Statement.

We also note that Aeglea is deemed to be the accounting acquirer of Spyre for GAAP purposes. Accordingly, Aeglea’s historical financial statements will
continue to be the financial statements for the combined business on a going-forward basis. With respect to Spyre’s historical financial statements, the Office of Chief Accountant granted a request for relief from the requirement to provide
historical financial statements and instead accepted an audited Statement of Assets Acquired and Liabilities Assumed, prepared on the basis of the purchase price of the Spyre assets and not its historical carrying value.

4
 We note that the Staff’s comment refers to former affiliates of Spyre (not Aeglea), while the focus
of the Staff’s inquiry in the prior two comment letters related to the assets and operations of Aeglea, as the potential shell entity. With respect to shares issued to the selling stockholders listed in the Registration Statement who were also
former affiliates of Spyre, those selling stockholders invested an aggregate sum of approximately $75 million in the concurrent June 2023 PIPE offering consummated by Aeglea. Accordingly, we would submit that such a significant investment
(which has now been subject to market risk for approximately four months) does not align with the market abuses that the shell rules seek to deter, nor does it align with the view that such parties are acting as underwriters.

 5

 U.S. Securities and Exchange Commission

October 26, 2023

Promoters “pump” up the price of the stock to investors through unduly positive press releases on the company and its prospects, exaggerated tout sheets, or fraudulent messages on the Internet

 As noted above, there are no “promoters” in the context of the Spyre acquisition, nor has the Staff alleged any inappropriate
messages intended to “pump” up the stock price. The Company believes that its disclosures have, at all times, been measured and appropriate. While the stock price has reacted positively to the Spyre acquisition, we note that this is also
in the context of a $210 million PIPE that was completed simultaneously with the business combination. We do not believe that this type of catalyst (i.e., a substantive acquisition, coupled with a large financing supported by many well-regarded
investment funds) is the type of promotional hype that the shell rules were intended to address.

Promoters “dump” their stock in the company by selling it at the artificially high prices their promotional activities have created, halt those activities and move on, allowing the price of the stock to sink in value in
th

United States securities and exchange commission logo
October 24, 2023
Cameron Turtle, DPhil
Chief Operating Officer
Aeglea BioTherapeutics, Inc.
221 Crescent Street
Building 23, Suite 105
Waltham, MA 02453
Re:Aeglea BioTherapeutics, Inc.
Preliminary Proxy Statement on Schedule 14A
Filed August 8, 2023
File No. 001-37722
Dear Cameron Turtle:
            We have completed our review of your filing. 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.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden C. Berns

United States securities and exchange commission logo
October 20, 2023
Jonathan D. Alspaugh
President and Chief Financial Officer
Aeglea BioTherapeutics, Inc.
221 Crescent Street
Building 17, Suite 102B
Waltham, MA 02453
Re:Aeglea BioTherapeutics, Inc.
Amendment No. 1 to Registration Statement on Form S-1
Filed October 10, 2023
File No. 333-273769
Dear Jonathan D. Alspaugh:
            We have reviewed your amended registration statement and have the following
comments.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies to your facts and circumstances
or do not believe an amendment is appropriate, please tell us why in your response.
            After reviewing any amendment to your registration statement and the information you
provide in response to this letter, we may have additional comments. Unless we note otherwise,
any references to prior comments are to comments in our September 29, 2023 letter.
Amendment No. 1 to Form S-3 on Form S-1
General
1.We note the representation in Section 2.4 of the Agreement and Plan of Merger, filed on
June 23, 2023 as exhibit 2.1 to Aeglea’s Form 8-K, that Spyre’s holders were required to
consent to the merger.  We further note your Form S-1 seeks to registers the resale of
securities issued and issuable to Spyre’s security holders as consideration for the merger.
 Please revise to identify all former affiliates of Spyre reselling pursuant to this Form S-1
as underwriters and fix a selling price for the duration of their offering.  See Securities Act
Rule 145(c).
2.Please revise to remove all incorporation by reference from the Form S-1 and file a
complete prospectus with your amendment.  See General Instruction VII.D.1.b to Form S-

 FirstName LastNameJonathan D. Alspaugh
 Comapany NameAeglea BioTherapeutics, Inc.
 October 20, 2023 Page 2
 FirstName LastName
Jonathan D. Alspaugh
Aeglea BioTherapeutics, Inc.
October 20, 2023
Page 2
1.
            Please contact Dillon Hagius at 202-551-7967 or Laura Crotty at 202-551-7614 with any
other questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden C. Berns

CORRESP
1
filename1.htm

CORRESP

 October 6, 2023

CONFIDENTIAL SUBMISSION VIA EDGAR

 U.S. Securities and
Exchange Commission

 Division of Corporation Finance

 Office
of Life Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

 Attn: Dillon Hagius and Joe McCann

Re:
 Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-3

Filed on August 7, 2023

File No. 333-273769

Dear Dillon Hagius and Joe McCann:

 On behalf
of Aeglea BioTherapeutics, Inc. (the “Company”), this letter responds to the comments of the staff of the Securities and Exchange Commission (the “SEC”) Division of Corporation Finance (the “Staff”) contained in your
letter, dated September 29, 2023 (the “Comment Letter”), regarding the above-referenced Registration Statement on Form S-3 (the “Registration Statement”), filed on August 7, 2023.
The Staff’s comment is set forth below, followed by the Company’s response. For ease of reference, the heading and numbered paragraph below correspond to the heading and numbered comment in the Comment Letter. The Company’s response
is set forth in ordinary type beneath the Staff comment, which is set out in bold type.

 General

1.
 We note your response to comment 1 from our letter dated August 28, 2023. Based on the totality of the
transactions, including the entry into the CVR agreement and disposition of the legacy assets, as well as the termination of the legacy employees and executives, we are unable to concur with your analysis. Please amend your registration statement to
register the offering on Form S-1.

 We have complied with your request and have amended the
Registration Statement to file on Form S-1. However, in doing so, we respectfully reiterate our view that the Company has not, at any time, been a “shell company,” as defined in Rule 501 of the
Securities Act of 1933 or Rule 12b-2 under the Securities Exchange Act of 1934 (the “1934 Act”). As we discussed with the Staff, at all times while the Company has had a class of securities
registered under the 1934 Act, the Company has maintained substantive operations and material assets (in addition to the Company’s cash and cash equivalents).1

***

1
 With respect to the Company having “no or nominal operations” under the shell company test, we would
note that the Company’s aggregate R&D and G&A expense in the three and six months ended June 30, 2023 was $29.4 million and $48.5 million, respectively. With respect to the “no or nominal assets” test, we would
note that after the acquisition of Spyre Therapeutics on June 22, 2023, the Company sold a legacy drug development program related to internally developed IPR&D with no book value on July 27, 2023 for $15 million upfront and
potential milestone payments of up to $100 million. See the Company’s Current Report on Form 8-K filed on July 27, 2023 for additional details.

 U.S. Securities and Exchange Commission

October 6, 2023

 If you have any questions regarding the response set forth above, please do not hesitate to
call me at (415) 393-4631 or Ryan Murr at (415) 393-8373.

Sincerely,

/s/ Branden C. Berns

Branden C. Berns

cc:
 Cameron Turtle, Aeglea BioTherapeutics, Inc.

Scott Burrows, Aeglea BioTherapeutics, Inc.

Heidy King-Jones, Aeglea BioTherapeutics, Inc.

Jonathan Campbell, Aeglea BioTherapeutics, Inc.

Ryan A. Murr, Gibson, Dunn & Crutcher LLP

Melanie E. Neary, Gibson, Dunn & Crutcher LLP

 2

CORRESP
1
filename1.htm

CORRESP

 October 6, 2023

CONFIDENTIAL SUBMISSION VIA EDGAR

 U.S. Securities and
Exchange Commission

 Division of Corporation Finance

 Office
of Life Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

 Attn: Dillon Hagius and Joe McCann

Re:
 Aeglea BioTherapeutics, Inc.

 
 Preliminary Proxy Statement on Schedule 14A

 
 Filed on August 8, 2023

 
 File No. 001-37722

Dear Dillon Hagius and Joe McCann:

 On behalf
of Aeglea BioTherapeutics, Inc. (the “Company”), this letter responds to the oral comments of the staff of the Division of Corporation Finance of the Securities and Exchange Commission (the “Staff”) provided to the Company on
August 28, 2023 regarding the above-referenced Preliminary Proxy Statement on Schedule 14A (the “Proxy Statement”), filed on August 8, 2023. The Staff’s comments are set forth below, followed by the Company’s responses.
For ease of reference, the headings and numbered paragraphs below correspond to the Staff’s oral comments. The Company’s responses are set forth in ordinary type below the Staff’s comments, which are set forth in bold type. Page
numbers referenced in the Company’s responses refer to page numbers in Amendment No. 1 to the Company’s Preliminary Proxy Statement on Schedule 14A (the “Amendment”).

General

1.
 Please include a section in the Proxy Statement that describes the tax consequences of the Spyre acquisition
and the issuance of the contingent value rights to the Company’s stockholders.

 In response to the Staff’s comment, the
Company has added disclosure on pages 14-16 of the Amendment to provide additional discussion with respect to the material U.S. federal tax considerations of the Spyre acquisition and the issuance of the
contingent value rights to the Company’s stockholders.

 U.S. Securities and Exchange Commission

October 6, 2023

2.
 Please provide a written response as to why the disclosures required by Items
401-404 of Regulation S-K were excluded from the Proxy Statement.

In response to the Staff’s comment, the Company respectively submits the following:

•

 Items 401 and 404 of Regulation S-K (“Items 401 and
404”): The disclosures required by Items 401 and 404 were excluded from the Proxy Statement in compliance with Item 7 of Schedule 14A as the Company is not undertaking any action with respect to the election of directors at the Special
Meeting of Stockholders.

•

 Item 402 of Regulation S-K: In response to the Staff’s
comment, the Company has added disclosure on pages 102-113 of the Amendment under the new heading “Executive Compensation.”

•

 Item 403 of Regulation S-K (“Item 403”): The disclosures
required by Item 403 are included under the heading “Principal Stockholders” on page 113 of the Proxy Statement.

3.
 Please provide additional disclosure with respect to the Company’s plans for the allocation of the
proceeds from the PIPE transaction and the Company’s cash on hand, similar to the disclosures required for an initial public offering pursuant to Item 504 of Regulation S-K.

In response to the Staff’s comment, the Company has added disclosure on pages 60 and 61 of the Amendment to provide additional discussion on its use of
proceeds from the PIPE transaction and the Company’s cash on hand.

 If you have any questions regarding the Amendment or the response set forth
above, please do not hesitate to call me at (415) 393-4631.

Sincerely,

/s/ Branden C. Berns

Branden C. Berns

cc:
 Cameron Turtle, Aeglea BioTherapeutics, Inc.

 
 Scott Burrows, Aeglea BioTherapeutics, Inc.

 
 Heidy King-Jones, Aeglea BioTherapeutics, Inc.

 
 Jonathan Campbell, Aeglea BioTherapeutics, Inc.

 
 Ryan A. Murr, Gibson, Dunn & Crutcher LLP

 
 Melanie E. Neary, Gibson, Dunn & Crutcher LLP

 2

United States securities and exchange commission logo
September 29, 2023
Jonathan D. Alspaugh
President and Chief Financial Officer
Aeglea BioTherapeutics, Inc.
221 Crescent Street
Building 17, Suite 102B
Waltham, MA 02453
Re:Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Response dated September 8, 2023
File No. 333-273769
Dear Jonathan D. Alspaugh:
            We have limited our review of your registration statement to those issues we have
addressed in our comment.
            Please respond to this letter by amending your registration statement and providing the
requested information.  If you do not believe our comment applies to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.
            After reviewing any amendment to your registration statement and the information you
provide in response to this comment, we may have additional comments.
Registration Statement on Form S-3
General
1.We note your response to comment 1 from our letter dated August 28, 2023. Based on the
totality of the transactions, including the entry into the CVR agreement and disposition of
the legacy assets, as well as the termination of the legacy employees and executives, we
are unable to concur with your analysis. Please amend your registration statement to
register the offering on Form S-1.

 FirstName LastNameJonathan D. Alspaugh
 Comapany NameAeglea BioTherapeutics, Inc.
 September 29, 2023 Page 2
 FirstName LastName
Jonathan D. Alspaugh
Aeglea BioTherapeutics, Inc.
September 29, 2023
Page 2
            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.
            Refer to Rules 460 and 461 regarding requests for acceleration.  Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Dillon Hagius at 202-551-7967 or Joe McCann at 202-551-6262 with any
other questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Branden C. Berns

CORRESP
1
filename1.htm

CORRESP

 September 8, 2023

CONFIDENTIAL SUBMISSION VIA EDGAR

 U.S. Securities and
Exchange Commission

 Division of Corporation Finance

 Office
of Life Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

 Attn: Dillon Hagius and Joe McCann

Re:
 Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-3

Filed on August 7, 2023

File No. 333-273769

Dear Dillon Hagius and Joe McCann:

 On behalf of
Aeglea BioTherapeutics, Inc. (the “Company”), this letter responds to the comments of the staff of the Securities and Exchange Commission (the “SEC”) Division of Corporation Finance (the “Staff”) contained in your
letter, dated August 28, 2023 (the “Comment Letter”), regarding the above-referenced Registration Statement on Form S-3 (the “Registration Statement”), filed on August 7, 2023.
The Staff’s comment is set forth below, followed by the Company’s response. For ease of reference, the heading and numbered paragraph below correspond to the heading and numbered comment in the Comment Letter. The Company’s response
is set forth in ordinary type beneath the Staff comment, which is set out in bold type.

 General

1.
 Based on your public filings, we note that Aeglea recently acquired Spyre Therapeutics, Inc. and distributed
to Aeglea stockholders of record a non-transferrable contingent value right (“CVR”) relating to the disposition or monetization of Aeglea’s legacy business assets. We further note that your Form
S-3 does not provide (or incorporate by reference to) material information relating to your newly-acquired/current business operations. Given these circumstances, please tell us your basis for registering this
transaction on Form S-3. See Use of Form S-8, Form 8-K, and Form 20-F by Shell Companies,
Release No. 33-8587 (July 15, 2005) at n. 32 as reiterated in Special Purpose Acquisition Companies, Shell Companies, and Projections, Release No. 33-11048
(March 30, 2022) at n. 239 and accompanying text.

 Abu Dhabi • Beijing
• Brussels • Century City • Dallas • Denver • Dubai • Frankfurt • Hong Kong • Houston • London • Los Angeles

Munich • New York • Orange County • Palo Alto • Paris • San Francisco • Singapore • Washington, D.C.

 U.S. Securities and Exchange Commission

September 8, 2023

 In response to the Staff’s comment, the Company does not believe that the Spyre acquisition was an
acquisition of a business and is in the process of requesting a pre-clearance from the Office of the Chief Accountant, Division of Corporation Finance. Notwithstanding, the Company respectfully submits that it
has not been and is not a shell company. A shell company, as defined in Rule 12b-2 under the Securities Exchange Act of 1934 (the “Exchange Act”), is a company that has no or nominal operations and
either no or nominal assets consisting of cash and cash equivalence or assets consisting of any amount of cash and cash equivalence and nominal other assets.

Prior to the acquisition of Spyre Therapeutics, Inc. (“Spyre”), the Company was a clinical-stage biotechnology company focused on redefining the
potential of human enzyme therapeutics to benefit people with rare metabolic diseases with limited treatment options. As the Company states in its preliminary proxy statement on Schedule 14A filed with the SEC, following a review of its interim
results announced in April 2023 from its Phase 1/2 clinical trial of pegtarviliase for the treatment of classical homocystinuria, it began a process of exploring strategic alternatives, including possible business combinations and/or a divestiture
of its clinical programs. Concurrent with the process to explore strategic alternatives, the Company continued to invest resources in its clinical programs in a way that would preserve the future value of the legacy assets, including the maintaining
of manufacturing reservations for drug substance, the orderly wind down of existing clinical trials to allow a future investor to continue research and development, the collection and storage of remaining patient data, the documentation of all
technical aspects of the legacy assets, and the retention of key staff and consultants to conduct these activities. These activities were being conducted prior to the acquisition of Spyre and continued after the acquisition closed.

At the time of the acquisition of Spyre on June 22, 2023, because the Company had not yet materially divested its legacy business assets, the Company
entered into a CVR agreement with its legacy stockholders in order to distribute proceeds from the sale of such assets following the closing of the acquisition. The Company respectfully submits that it did not enter into any agreement to materially
dispose of legacy business assets until it entered into an asset purchase agreement with Immedica Pharma AB on July 27, 2023. As the Company states in the Registration Statement, following its acquisition of Spyre the Company significantly
reshaped its business into a preclinical stage biotechnology company focused on developing next generation therapeutics for patients living with inflammatory bowel disease. Notwithstanding its recent strategic pivot from pursuing treatments for
homocystinuria to pursuing treatments for inflammatory bowel disease, the Company has always been operating its business with a focus on developing therapeutics for human indications.

Based on the above facts, we do not believe that the Company is a shell company as defined in the Exchange Act nor was it a shell company at any relevant time
for determining its eligibility to register its securities on Form S-3.

 2

 U.S. Securities and Exchange Commission

September 8, 2023

 If you have any questions regarding the response set forth above, please do not hesitate to
call me at (415) 393-4631.

Sincerely,

/s/ Branden C. Berns

Branden C. Berns

cc:
 Cameron Turtle, Aeglea BioTherapeutics, Inc.

Scott Burrows, Aeglea BioTherapeutics, Inc.

Heidy King-Jones, Aeglea BioTherapeutics, Inc.

Jonathan Campbell, Aeglea BioTherapeutics, Inc.

Ryan A. Murr, Gibson, Dunn & Crutcher LLP

Melanie E. Neary, Gibson, Dunn & Crutcher LLP

 3

United States securities and exchange commission logo
August 28, 2023
Jonathan D. Alspaugh
President and Chief Financial Officer
Aeglea BioTherapeutics, Inc.
221 Crescent Street
Building 17, Suite 102B
Waltham, MA 02453
Re:Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Filed August 7, 2023
File No. 333-273769
Dear Jonathan D. Alspaugh:
            We have limited our review of your registration statement to those issues we have
addressed in our comment.  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 amending your registration statement and providing the
requested information.  If you do not believe our comment applies to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.
            After reviewing any amendment to your registration statement and the information you
provide in response to the comment, we may have additional comments.
Registration Statement on Form S-3
General
1.Based on your public filings, we note that Aeglea recently acquired Spyre Therapeutics,
Inc. and distributed to Aeglea stockholders of record a non-transferrable contingent value
right (“CVR”) relating to the disposition or monetization of Aeglea’s legacy business
assets. We further note that your Form S-3 does not provide (or incorporate by reference
to) material information relating to your newly-acquired/current business operations.
Given these circumstances, please tell us your basis for registering this transaction on
Form S-3. See Use of Form S-8, Form 8-K, and Form 20-F by Shell Companies, Release
No. 33-8587 (July 15, 2005) at n. 32 as reiterated in Special Purpose Acquisition
Companies, Shell Companies, and Projections, Release No. 33-11048 (March 30, 2022) at

 FirstName LastNameJonathan D. Alspaugh
 Comapany NameAeglea BioTherapeutics, Inc.
 August 28, 2023 Page 2
 FirstName LastName
Jonathan D. Alspaugh
Aeglea BioTherapeutics, Inc.
August 28, 2023
Page 2
n. 239 and accompanying text.
            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.
            Refer to Rules 460 and 461 regarding requests for acceleration.  Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Dillon Hagius at (202) 551-7967 or Joe McCann at (202) 551-6262 with
any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
1
filename1.htm

CORRESP

 AEGLEA BIOTHERAPEUTICS, INC.

805 Las Cimas Parkway

 Suite 100

 Austin, TX 78746

June 4, 2021

 United States Securities and
Exchange Commission

 Division of Corporation Finance

 100 F
Street, N.E.

 Washington, DC 20549

Attention:

 Alan Campbell

 Office of Life
Sciences

        Re:

 Aeglea BioTherapeutics, Inc.

 Registration
Statement on Form S-3

 Filed May 28, 2021

File No. 333-256614

 Via EDGAR - Acceleration Request

            Requested Date:

June 8, 2021

            Requested Time:

4:00 p.m. Eastern Time

 Ladies and Gentlemen:

Aeglea BioTherapeutics, Inc. (the “Registrant”) hereby requests that the Securities and Exchange Commission (the
“Commission”) take appropriate action to make the above-captioned Registration Statement on Form S-3 effective at the “Requested Date” and “Requested Time” set forth
above or as soon thereafter as practicable.

 The Registrant hereby authorizes Robert A. Freedman or Ryan Mitteness, both of whom are
attorneys with the Registrant’s outside legal counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

Sincerely,

AEGLEA BIOTHERAPEUTICS, INC.

By:

/s/ Anthony Quinn

Anthony Quinn

Chief Executive Officer

cc:
 Robert A. Freedman, Esq.

Ryan Mitteness, Esq.

Fenwick & West LLP

United States securities and exchange commission logo
June 4, 2021
Anthony Quinn, M.B Ch.B, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
805 Las Cimas Parkway
Suite 100
Austin, TX 78746
Re:Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Filed May 28, 2021
File No. 333-256614
Dear Dr. Quinn:
            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 Alan Campbell at 202-551-4224 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Ryan Mitteness, Esq.

CORRESP
1
filename1.htm

agle-corresp.htm

AEGLEA BIOTHERAPEUTICS, Inc.

805 Las Cimas Parkway

Suite 100

Austin, TX 78746

July 10, 2020

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, DC 20549

Attention:Jeffrey Gabor

Office of Life Sciences

Re:Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-3

Filed July 6, 2020

File No. 333-239706

Via EDGAR - Acceleration Request

Requested Date:July 14, 2020

Requested Time:4:00 p.m. Eastern Time

Ladies and Gentlemen:

Aeglea BioTherapeutics, Inc. (the “Registrant”) hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to make the above-captioned Registration Statement on Form S-3 effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable.

The Registrant hereby authorizes Robert A. Freedman or Ryan Mitteness, both of whom are attorneys with the Registrant’s outside legal counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

Sincerely,

Aeglea BioTherapeutics, Inc.

By:  /s/ Charles N. York II

Charles N. York II
Chief Financial Officer

cc:

Anthony G. Quinn, Chief Executive Officer

Aeglea BioTherapeutics, Inc.

Robert A. Freedman, Esq.

Ryan Mitteness, Esq.

Fenwick & West LLP

United States securities and exchange commission logo
July 9, 2020
Anthony G. Quinn, M.B Ch.B, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
805 Las Cimas Parkway
Suite 100
Austin, TX 78746
Re:Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Filed July 6, 2020
File No. 333-239706
Dear Dr. Quinn:
            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 Jeffrey Gabor at 202-551-2544 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Ryan Mitteness, Esq.

CORRESP
1
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Acceleration Request

 AEGLEA BIOTHERAPEUTICS, INC.

901 S. MoPac Expressway

 Barton
Oaks Plaza One, Suite 250

 Austin, TX 78746

February 11, 2019

 United States Securities
and Exchange Commission

 Division of Corporation Finance

 100
F Street, N.E.

 Washington, DC 20549

Attention:
 Suzanne Hayes

 Assistant Director

 Office of Healthcare and Insurance

Re:
 Aeglea BioTherapeutics, Inc.

 Registration Statement on Form S-3

 Filed December 21, 2018

 File No. 333-228967

Via EDGAR - Acceleration Request

Requested Date:             February 13, 2019

Requested Time:            4:00 p.m. Eastern Time

Ladies and Gentlemen:

 Aeglea BioTherapeutics,
Inc. (the “Registrant”) hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to make the above-captioned Registration Statement on Form S-3 effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable.

The Registrant hereby authorizes Robert A. Freedman or Amanda Rose, both of whom are attorneys with the Registrant’s outside legal
counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

 Sincerely,

AEGLEA BIOTHERAPEUTICS, INC.

By:

/s/ Charles N. York II

Charles N. York II

Chief Financial Officer

cc:
 Anthony G. Quinn, Chief Executive Officer

 Aeglea BioTherapeutics, Inc.

 Robert A. Freedman, Esq.

 Amanda Rose, Esq.

 Fenwick & West LLP

February 4, 2019
Anthony G. Quinn, M.B Ch.B, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway
Barton Oaks Plaza One
Suite 250
Austin, TX 78746
Re:Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Filed December 21, 2018
File No. 333-228967
Dear Dr. Quinn:
            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 Irene Paik at 202-551-6553 with any questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Robert A. Freedman, Esq. - Fenwick & West LLP

CORRESP
1
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CORRESP

 AEGLEA BIOTHERAPEUTICS, INC.

901 S. MoPac Expressway

 Barton
Oaks Plaza One, Suite 250

 Austin, TX 78746

May 25, 2017

 United States Securities and
Exchange Commission

 Division of Corporation Finance

 100 F
Street, N.E.

 Washington, DC 20549

Attention:
Suzanne Hayes

Assistant Director

Office of Healthcare and Insurance

Re:
Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-3

Filed May 1, 2017

File No. 333-217573

 Via EDGAR - Acceleration Request

Requested Date:
May 30, 2017

Requested Time:
4:30 p.m. Eastern Time

 Ladies and Gentlemen:

Aeglea BioTherapeutics, Inc. (the “Registrant”) hereby requests that the Securities and Exchange Commission (the
“Commission”) take appropriate action to make the above-captioned Registration Statement on Form S-3 effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as
practicable.

 The Registrant hereby authorizes Robert A. Freedman or Effie Toshav, both of whom are attorneys with the Registrant’s
outside legal counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

Sincerely,

AEGLEA BIOTHERAPEUTICS, INC.

By:

 /s/ Charles N. York II

Charles N. York II

Chief Financial Officer

cc:
David G. Lowe, Chief Executive Officer

Aeglea BioTherapeutics, Inc.

Robert A. Freedman, Esq.

Effie Toshav, Esq.

Fenwick & West LLP

May 17, 2017
David Lowe
President and Chief Executive OfficerAeglea BioTherapeutics, Inc.901 S. MoPac ExpresswayBarton Oaks Plaza One, Suite 250Austin, TX 78746
Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3Response Dated May 12, 2017File No. 333-217573Re:
Dear Mr. Lowe:
        We have reviewed your May 12, 2017 response to our comment letter and have the
following comment.  In some of our comments, we may ask you to provide us with informationso we may better understand your disclosure.
        Please respond to this letter by amending your registration statement and providing the
requested information.  If you do not believe our comment applies to your facts andcircumstances or do not believe an amendment is appropriate, please tell us why in yourresponse.
        After reviewing any amendment to your registration statement and the information you
provide in response to the comment we may have additional comments.
Registration Statement on Form S-3
Cover Page
We acknowledge your response to prior comment 1, and your statement that there were
10,140,561 shares that were held by non-affiliates of the company on March 20, 2017.  However, we note that you stated in your Form 10-K that as of June 30, 2016, the market
value of your shares held by non-affiliates was approximately $24.6 million, based on the
per share price of $4.86, which indicates that there were approximately 5 million sharesthat were held by non-affiliates at that time.  We have not noted substantial changes inyour number of shares outstanding or a decrease in the holdings of your other significantshareholders since June 2016.  Accordingly, please explain how you1.

David Lowe
Aeglea BioTherapeutics, Inc.
2 PageMay 17, 2017
have changed your calculation of the market value of your non-affiliate shares and why.
        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 ofaction by the staff.
        Refer to Rules 460 and 461 regarding requests for acceleration.  Please allow adequate
time for us to review any amendment prior to the requested effective date of the registrationstatement.
        Please contact Dorrie Yale at 202-551-8776 or Erin Jaskot, Special Counsel, at 202-551-
3442 with any questions.
Division of Corporation Finance
Office of Healthcare & Insurance

CORRESP
1
filename1.htm

CORRESP

 May 18, 2017

U.S. Securities and Exchange Commission

 100 F Street, N.E.

Washington, D.C. 20549

 Attention:

 Dorrie Yale

 Erin Jaskot

Re:

Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-3

Filed May 1, 2017

File No. 333-217573

 Ladies and Gentlemen:

We are submitting this letter on behalf of Aeglea BioTherapeutics, Inc. (the “Company”) in response to additional
comments from the staff (the “Staff”) of the Securities and Exchange Commission (“Commission”) received by electronic mail on May 17, 2017 relating to the Company’s Registration Statement on
Form S-3 (File No. 333-217573) (the “Registration Statement”) filed with the Commission on May 1, 2017 (the
“Letter”). The numbered paragraphs below correspond to the numbered comments in the Letter and the Staff’s comment is presented in bold italics.

Registration Statement on Form S-3

Cover Page

1.
We acknowledge your response to prior comment 1, and your statement that there were 10,140,561 shares that were held by non-affiliates of the company on March 20, 2017.
However, we note that you stated in your Form 10-K that as of June 30, 2016, the market value of your shares held by non-affiliates was approximately
$24.6 million, based on the per share price of $4.86, which indicates that there were approximately 5 million shares that were held by non-affiliates at that time. We have not noted substantial
changes in your number of shares outstanding or a decrease in the holdings of your other significant shareholders since June 2016. Accordingly, please explain how you have changed your calculation of the market value of your non-affiliate shares and why.

 The Company informs the Staff that its calculation
of the aggregate market value of shares held by non-affiliates as of May 1, 2017, the date of filing the Registration Statement, differs from the calculation performed as of June 30, 2016 because
each of Novartis Bioventures Ltd., OrbiMed Private Investments V, LP and Jennison Global Healthcare Master Fund (each, an “Other 10% Holder” and collectively, the “Other 10% Holders”),
who were each previously considered an “affiliate” of the Company prior to the Company’s initial public offering (“IPO”) on April 6, 2016, were no longer considered an affiliate of the
Company on May 1, 2017.

 U.S. Securities and Exchange Commission

May 18, 2017

  Page
 2

 As described in the
Company’s response letter dated May 12, 2017 previously filed with the Commission (the “May 12 Letter”), the Other 10% Holders are not currently in a “control” relationship
with the Registrant. However, the Company believes that the facts and circumstances indicated that the Other 10% Holders were in a “control” relationship prior to the Company’s IPO in April 2016. Pursuant to a Voting Agreement dated
March 10, 2015 (the “Voting Agreement”) between the Company and certain of its stockholders, which terminated in connection with the IPO, Novartis Bioventures Ltd. (“Novartis”)
was entitled to designate one member of the Company’s board of directors and Novartis’s designee, Dr. Henry Skinner, served on the Company’s board until his resignation immediately prior to the effective date of the IPO
in April 2016. None of the Other 10% Holders at any time had the right to appoint a representative as an officer of the Company and only Novartis had the right to designate a director of the Company. Pursuant to a management rights letter dated
March 10, 2015 (the “MRL”) between the Company and Jennison Global Healthcare Master Fund (“Jennison”), which also terminated in connection with the IPO, Jennison was entitled to
consult with and advise management on significant business issues, including operating plans, at regularly scheduled meetings prior to the IPO. In addition, pursuant to the Company’s Restated Certificate of Incorporation in effect prior to the
IPO, holders of the Company’s Series B Preferred Stock enjoyed a variety of protective rights and provisions affecting the management of the Company. For instance, the consent of 62% of the outstanding shares of the Company’s Series B
Preferred Stock was required in order for the Company to, among others, sell, license or lease any intellectual property rights, authorize any merger or acquisition, declare or pay any dividends, incur indebtedness in excess of $250,000, appoint or
remove the Chief Executive Officer, and make certain changes to the Company’s capital structure. As such, the Other 10% Holders, together with Lilly Ventures Fund I, LLC, who collectively held approximately 65% of the Company’s Series B
Preferred Stock, had the power to control a variety of corporate actions.

 Immediately following the IPO, due to the termination of the
Voting Agreement and the MRL, the resignation of Dr. Skinner from the Company’s board of directors, the conversion of the Company’s Series B Preferred Stock into common stock, and the amendment of the Company’s certificate of
incorporation to remove all protective provisions, the Other 10% Holders no longer had contractual rights that led to a “control” relationship with the Company. In considering the affiliate status of stockholders as of June 30, 2016,
the Company considered the very recent control and active participation in corporate matters by the Other 10% Holders and the three-month cooling period for affiliates under the Securities Act.1
As a result, the Company continued to consider the Other 10% Holders as affiliates as of June 30, 2016.

1
See Rule 144(b)(1)(i) (“any person who is not an affiliate . . . and has not been an affiliate during the preceding three months”).

 2

 U.S. Securities and Exchange Commission

May 18, 2017

  Page
 3

 More than a year has
now passed since the IPO and the Company now does not view the Other 10% Holders as affiliates because of the demonstrated continuous passive nature of their investments. As described in the May 12 Letter:

•

None of the Other 10% Holders, directly or indirectly through intermediaries or otherwise, controls the Company.

•

None of the Other 10% Holders possesses the power, directly or indirectly, to designate or unilaterally elect directors of the Company, nor do their respective representatives serve as an officer or director of the
Company.

•

None of the Other 10% Holders, nor any of their respective representatives, has the ability, by contract or otherwise, to affect the management or policies of the Company.

•

Each Other 10% Holder in its respective Schedule 13G certified that its shares of the Company’s common stock were not acquired and are not held for the purpose of or with the effect of changing or influencing the
control of the Company and were not acquired in connection with or as a participant in any transaction having such purpose or effect.

•

Other factors that commonly indicate a controlling relationship also are absent — there are no familial, debtor-creditor or other business relationships between the Company or any of its directors or officers and
any Other 10% Holder.

 In addition, the Other 10% Holders are unaffiliated with each other and act independently with
respect to shareholder voting matters.

 Accordingly, given the now long-term lack of any control relationship between any of the Other 10%
Holders and the Company as of May 2017, the Company has concluded that none of the Other 10% Holders is an affiliate of the Company.

Should the Staff have any additional questions or comments regarding the foregoing, please do not hesitate to contact me at (650) 335-7292.

 Sincerely,

FENWICK & WEST LLP

/s/ Robert A. Freedman

Robert A. Freedman

cc:
David G. Lowe, Aeglea BioTherapeutics, Inc.

 3

CORRESP
1
filename1.htm

Correspondence

 May 12, 2017

U.S. Securities and Exchange Commission

 100 F Street, N.E.

Washington, D.C. 20549

Attention:
Dorrie Yale

 Erin Jaskot

Re:
Aeglea BioTherapeutics, Inc.

 Registration Statement on Form S-3

Filed May 1, 2017

File No. 333-217573

 Ladies and
Gentlemen:

 We are submitting this letter on behalf of Aeglea BioTherapeutics, Inc. (the “Company”) in response to
comments from the staff (the “Staff”) of the Securities and Exchange Commission (“Commission”) received by electronic mail on May 10, 2017 relating to the Company’s Registration Statement on
Form S-3 (File No. 333-217573) (the “Registration Statement”) filed with the Commission on May 1, 2017 (the “Letter”). The numbered paragraphs below correspond to the numbered comments in the
Letter and the Staff’s comment is presented in bold italics.

 Registration Statement on Form S-3

Cover Page

1.
It appears that you are relying on General Instruction I.B.6 of Form S-3. If true, please revise your sales agreement prospectus cover page to disclose the calculation of the aggregate market value of your
outstanding voting and nonvoting common equity and the amount of all securities offered pursuant to General Instruction I.B.6 during the prior 12 calendar month period that ends on, and includes, the date of the prospectus. Refer to Instruction 7 to
General Instruction I.B.6. Otherwise, please provide us your analysis demonstrating your eligibility to use Form S-3.

The Company respectfully advises the Staff that it is eligible to register securities on the Registration Statement pursuant to General
Instruction I.B.1 because the aggregate market value of its voting and non-voting common equity held by non-affiliates exceeded $75,000,000 as of a date within 60 days prior to the date of filing the Registration Statement. Specifically, on
March 20, 2017, (a) the closing price of the Company’s common stock on the NASDAQ Global Market was $8.03 per share, and (b) the Company had 13,452,260 shares of common stock outstanding, of which (i) 10,140,561 shares were
held by non-affiliates of the Company, and (ii) 3,311,699 shares were held by affiliates of the Company,

 U.S. Securities and Exchange Commission

May 12, 2017

  Page
 2

 consisting of the Company’s
directors, executive officers, and Lilly Ventures Fund I, LLC (“Lilly Ventures”). As such, the aggregate market value of the Company’s voting and non-voting common equity held by non-affiliates was $81,428,705 on
March 20, 2017.

 The term “affiliate” is defined in Rule 405 (“Rule 405”) under the
Securities Act of 1933, as amended (the “Securities Act”), as a “person that directly, or indirectly through one or more intermediaries, controls, is controlled by, or is under common control with,” an issuer. The
term “control” is defined in Rule 405 under the Securities Act as “the possession, direct or indirect, of the power to direct or cause the direction of the management and policies of a person, whether through the ownership of voting
securities, by contract, or otherwise.” The Staff has consistently taken the position that the determination of “control” status is dependent in large part on the facts and circumstances involved and, therefore, has declined to state
definitively what circumstances will result in a person being deemed to be in “control” of an issuer. While the Company recognizes that, as a rule of thumb, more than 10% ownership has become an informal benchmark at which control should
be evaluated, such ownership, standing alone, is not dispositive.

 The Company has determined that, other than its directors and executive
officers, Lilly Ventures is the only “affiliate” of the Company, as that term is defined in Rule 405. Lilly Ventures is the largest stockholder of the Company, holding approximately 19.1% of the Company’s common stock, and Armen
Shanafelt, a director of the Company, is the general partner of the management company of Lilly Ventures. As such, Lilly Ventures can be deemed to be an affiliate of the Company by virtue of its stock ownership as well as Dr. Shanafelt’s
service on the Company’s board of directors as a representative of Lilly Ventures. To the Company’s knowledge, the only other stockholders owning 10% or more of the Company’s common stock are Novartis Bioventures Ltd., OrbiMed Private
Investments V, LP and Jennison Global Healthcare Master Fund (each, an “Other 10% Holder” and collectively, the “Other 10% Holders”). However, the Company does not consider any of these Other 10%
Holders to be an affiliate of the Company because of the passive nature of their investments:

•

None of the Other 10% Holders, directly or indirectly through intermediaries or otherwise, controls the Company.

•

None of the Other 10% Holders possesses the power, directly or indirectly, to designate or unilaterally elect directors of the Company, nor do their respective representatives serve as an officer or director of the
Company.

•

None of the Other 10% Holders, nor any of their respective representatives, has the ability, by contract or otherwise, to affect the management or policies of the Company.

•

Each Other 10% Holder in its respective Schedule 13G certified that its shares of the Company’s common stock were not acquired and are not held for the purpose of or with the effect of changing or influencing the
control of the Company and were not acquired in connection with or as a participant in any transaction having such purpose or effect.

•

Other factors that commonly indicate a controlling relationship also are absent — there are no familial, debtor-creditor or other business relationships between the Company or any of its directors or officers and
any Other 10% Holder.

 Accordingly, given the lack of any control relationship between any of the Other 10% Holders and the
Company, the Company has concluded that none of the Other 10% Holders is an affiliate of the Company. We note, additionally, the recommendation of Commissioner Steven M.H. Wallman’s Advisory Committee on Capital Formation and Regulatory
Processes that affiliates of a reporting issuer be limited to its chief executive officer, inside directors, 10% holders with rights to designate a director and 20% holders.

 2

 U.S. Securities and Exchange Commission

May 12, 2017

  Page
 3

 Should the Staff
have any additional questions or comments regarding the foregoing, please do not hesitate to contact me at (650) 335-7292.

Sincerely,

FENWICK & WEST LLP

/s/ Robert A. Freedman

Robert A. Freedman

cc:
David G. Lowe, Aeglea BioTherapeutics, Inc.

 3

May 10, 2017
David Lowe
President and Chief Executive Officer
Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway
Barton Oaks Plaza One, Suite 250
Austin, TX 78746
Aeglea BioTherapeutics, Inc.
Registration Statement on Form S-3
Filed May 1, 2017
File No. 333-217573Re:
Dear Dr. Lowe:
        We have limited our review of your registration statement to those issues we have
addressed in our 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 amending your registration statement and providing the
requested information.  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 any amendment to your registration statement and the information you
provide in response to these comments, we may have additional comments.
Registration Statement on Form S-3
Cover Page
It appears that you are relying on General Instruction I.B.6 of Form S-3.  If true, please
revise your sales agreement prospectus cover page to disclose the calculation of the
aggregate market value of your outstanding voting and nonvoting common equity and the
amount of all securities offered pursuant to General Instruction I.B.6 during the prior 12
calendar month period that ends on, and includes, the date of the prospectus.  Refer to
Instruction 7 to General Instruction I.B.6.  Otherwise, please provide us your analysis
demonstrating your eligibility to use Form S-3.
 1.

David Lowe
Aeglea BioTherapeutics, Inc.
2 PageMay 10, 2017
        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.
        Refer to Rules 460 and 461 regarding requests for acceleration.  Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
              Please contact Dorrie Yale at 202-551-8776 or Erin Jaskot, Special Counsel, at 202-
551-3442 with any questions.
Division of Corporation Finance
Office of Healthcare & Insurance
cc: Robert A. Freedman

CORRESP
1
filename1.htm

CORRESP

 UBS Securities LLC

299 Park Avenue

 New York, New York 10171

BMO Capital Markets Corp.

 3 Times Square, 26th Floor

New York, New York 10036

 Wells Fargo Securities, LLC

375 Park Avenue, 4th Floor

New York, New York 10152

 April 4, 2016

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Attn:   Suzanne
Hayes

 Mary Beth Breslin

Christina Thomas

 Keira Nakada

 Joel Parker

Re:
Aeglea BioTherapeutics, Inc.

   Registration Statement on Form S-1

  Registration File No. 333-205001

Ladies and Gentlemen:

 In accordance with Rule
461 under the Securities Act of 1933, as amended (the “Act”), we, as representatives of the several underwriters, hereby join in the request of Aeglea BioTherapeutics, Inc. (the “Company”) for acceleration of the
effective date of the above-named Registration Statement so that it becomes effective at 4:00 PM, Washington, D.C. time, on April 6, 2016, or as soon thereafter as practicable, or at such other time as the Company or its outside counsel,
Fenwick & West LLP, request by telephone that such Registration Statement be declared effective.

 Pursuant to Rule 460 under the
Act, we, as representatives of the several underwriters, wish to advise you that we have effected the following distribution of the Company’s Preliminary Prospectus dated March 28, 2016:

(i)
Dates of distribution: March 28, 2016 through the date hereof

(ii)
Number of prospective underwriters to which the preliminary prospectus was furnished: 4

(iii)
Number of prospectuses furnished to investors: approximately 4,243

(iv)
Number of prospectuses distributed to others, including the Company, the Company’s counsel, independent accountants, and underwriters’ counsel: approximately 80.

We, the undersigned, as representatives of the several underwriters, have complied and will comply, and we have been informed by the
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.

Very truly yours,

 UBS SECURITIES LLC

 BMO CAPITAL
MARKETS CORP.

 WELLS FARGO SECURITIES, LLC

Acting severally on behalf of themselves and the

 several
Underwriters

By:

UBS SECURITIES LLC

By:

   /s/ Lee Schechter

Name:

Lee Schechter

Title:

Executive Director

By:

   /s/ Matt Schainker

Name:

Matt Schainker

Title:

Director

By:

BMO CAPITAL MARKETS CORP.

By:

   /s/ Steven Tuch

Name:

Steven Tuch

Title:

Managing Director

By:

WELLS FARGO SECURITIES, LLC

By:

   /s/ David Herman

Name:

David Herman

Title:

Director

CORRESP
1
filename1.htm

CORRESP

 AEGLEA BIOTHERAPEUTICS, INC.

901 S. MoPac Expressway

 Barton Oaks Plaza One

Suite 250

 Austin, TX 78746

April 4, 2016

 VIA EDGAR

United States Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, N.E.

 Washington, DC 20549

Attention:

 Suzanne Hayes

 Mary Beth Breslin

Christina Thomas

 Keira Nakada

Joel Parker

Re:

Aeglea BioTherapeutics, Inc. Form S-1 Registration Statement on Form S-1 (File No. 333-205001) initially filed June 16, 2015, as amended, and corresponding Registration Statement on
Form 8-A (File No. 001-37722) filed March 28, 2016.

 Ladies and Gentlemen:

Requested Date: April 6, 2016

Requested Time: 4:00 PM Eastern Time

 Ladies and
Gentlemen:

 Aeglea BioTherapeutics, Inc. (the “Registrant”) hereby requests that the Securities and Exchange
Commission (the “Commission”) take appropriate action to declare the above-captioned Registration Statements on Form S-1 and Form 8-A effective at the “Requested
Date” and “Requested Time” set forth above or as soon thereafter as practicable.

 The Registrant hereby authorizes Robert
A. Freedman or Niki Fang, both of whom are attorneys with the Registrant’s outside legal counsel, Fenwick & West LLP, to orally modify or withdraw this request for acceleration.

The Registrant hereby acknowledges that:

•

should the Commission or the staff of the Commission (the “Staff”), acting pursuant to delegated authority, declare the filing effective, it does not foreclose the Commission from taking any
action with respect to the filing;

•

the action of the Commission or the Staff, acting pursuant to delegated authority, in declaring the filing effective, does not relieve the Registrant from its full responsibility for the adequacy and accuracy of the
disclosure in the filing; and

•

the Registrant may not assert Staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

 The Registrant requests that it be notified of such effectiveness by a telephone call to Mr.
Freedman at (650) 335-7292, or in his absence, Ms. Fang at (650) 335-7252.

 Sincerely,

AEGLEA BIOTHERAPEUTICS, INC.

 By:

 /s/ David G. Lowe

 David G. Lowe, Ph.D.

 President and Chief Executive Officer

cc:
    Robert A. Freedman, Esq.

     Niki Fang, Esq.

    Fenwick & West LLP

Mail Stop 4720
March 29, 2016

David G. Lowe, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway
Barton Oaks Plaza One
Suite 250
Austin, TX 78746

Re: Aeglea BioTherapeutics, Inc.
Amendment No. 4 to Registration Statement on
Form S -1
Filed March 28, 2016
  File No. 333-205001

Dear Dr. Lowe :

We have reviewed your amended registration statement  and have the following comment.

Please respond to this letter by amending your registration statement and providing the
requested information .  If you do not believe our comment applies to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.

After reviewi ng any amendment to your registration statement and the information you
provide in response to this comment , we may have  additional comments.

Notes to Consolidated Financial Statements
6.  Convertible Preferred Shares/Stock
Conversion, page F -18

1.  Throughout your prospectus, you assume the automatic conversion of all outstanding
 shares of your convertible preferred stock into shares of common stock immediately
 prior to the completion of this offering.  Since your offering does not appear to fulfil l
 the conditions of the automatic conversion herein, please tell us your basis for
 assuming the automatic conversion.

We urge all persons who are responsible for the accuracy and adequacy of the disclosure
in the filing to be certain that the filing inc ludes the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.   Since the company and its management are in

David G. Lowe, Ph.D.
Aeglea Bi oTherapeutics, Inc.
March 29, 2016
Page 2

 possession of all facts relating to a company’s disclosure, they are responsible for the accuracy
and adequacy of  the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
of the pending regist ration statement, please provide  a written statement from the company
acknowledging that:

 should the Commiss ion or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission from taking any action with respect
to the filing;

 the action of the Commission or the staff, acting pursuant to delegated author ity, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

 the company may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Please refer to Rules 460 and 461 regarding reque sts for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securitie s Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to review any amendment prior to the requested effectiv e date of the
registration statement.

You may contact Keira Nakada at (202) 551 -3659 or Joel Parker at 202 -551-3651  if you
have questions regarding comments on the financial statements and related matters.  Please
contact Christina Thomas at (202) 55 1-3577, Mary Beth Breslin at (202) 551 -3625 or me at
(202) 551 -3675 with any other questions.

Sincerely,

 /s/ Mary Beth Breslin for

 Suzanne Hayes
Assistant Director
Office of Healthcare and Insurance
cc: Robert A. Freedman
 Fenwick & West LLP

CORRESP
1
filename1.htm

CORRESP

 March 29, 2016

ROBERT A. FREEDMAN

 EMAIL RFREEDMAN@FENWICK.COM

Direct Dial (650) 335-7292

 VIA EDGAR AND OVERNIGHT DELIVERY

U.S. Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, NE

 Washington, DC 20549

Attention:

Suzanne Hayes, Assistant Director

 Mary Beth Breslin

 Christina Thomas

Keira Nakada

Joel Parker

Re:

Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-1

File No. 333-205001

 Ladies and Gentlemen:

On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), we are transmitting this letter in response to the comments
received from the staff of the Securities and Exchange Commission (“Staff”) contained in the Staff’s letter dated March 29, 2016, relating to the above referenced Registration Statement on Form S-1 (the
“Registration Statement”). The numbered paragraphs below correspond to the numbered comments in that letter and the Staff’s comment is presented in bold italics. For the convenience of the Staff, we are also sending, by
overnight courier, copies of this letter addressing the comments in the Staff’s letter.

*    *    *    *    *

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 March 29, 2016

Page 2

 Notes to Consolidated Financial Statements

6. Convertible Preferred Shares/Stock

Conversion, page F-18

1.
Throughout your prospectus, you assume the automatic conversion of all outstanding shares of your convertible preferred stock into shares of common stock immediately prior to the completion of this offering. Since
your offering does not appear to fulfill the conditions of the automatic conversion herein, please tell us your basis for assuming the automatic conversion.

The Company respectfully advises the Staff that as disclosed in “Note 16 to the Consolidated Financial Statements – Subsequent
Events” on page F-32 of the Registration Statement, the Company filed a restated certificate of incorporation with the Secretary of State of Delaware on March 28, 2016 to effect a 10.5-to-1 reverse stock split. This restated certificate also
amended the provision with respect to the automatic conversion of the Company’s preferred stock to provide that all of the outstanding convertible preferred stock will automatically convert into common stock in connection with the completion of
an offering pursuant to this Registration Statement, irrespective of the conditions of automatic conversion that were required as of the date of the Company’s consolidated financial statements included in the Registration Statement.

*    *    *    *    *

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 March 29, 2016

Page 3

 Should the Staff have additional questions or comments regarding the foregoing, please do not
hesitate to contact me at (650) 335-7292 or, in my absence, Niki Fang at (650) 335-7252.

 Sincerely,

 /s/ Robert A. Freedman

 Robert A. Freedman

cc:
Via E-mail

David G. Lowe

Aeglea BioTherapeutics, Inc.

Effie Toshav, Esq.

Niki Fang, Esq.

Melissa V. Frayer, Esq.

Fenwick & West LLP

Bruce K. Dallas, Esq.

Davis Polk & Wardwell LLP

CORRESP
1
filename1.htm

CORRESP

 March 24, 2016

ROBERT A. FREEDMAN

 EMAIL RFREEDMAN@FENWICK.COM

Direct Dial (650) 335-7292

 VIA EDGAR AND OVERNIGHT DELIVERY

U.S. Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, NE

 Washington, DC 20549

Attention:

Jeffrey P. Reidler, Assistant Director

Daniel Greenspan

Tara Keating Brooks

Keira Nakada

Joel Parker

Re:

Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-1

File No. 333-205001

 Ladies and Gentlemen:

On behalf of Aeglea BioTherapeutics, Inc. (the “Company”), we are transmitting this letter in response to the comments
received from the staff of the Securities and Exchange Commission (“Staff”) contained in the Staff’s letter dated March 24, 2016, relating to the above referenced Registration Statement on Form S-1. The numbered
paragraphs below correspond to the numbered comments in that letter and the Staff’s comment is presented in bold italics. Proposed revisions to the disclosures in the Registration Statement addressing the Staff’s comments are attached as
Exhibit A to this letter and are proposed to be included in the preliminary prospectus. For the convenience of the Staff, we are also sending, by overnight courier, copies of this letter and Exhibit A to show changes addressing
the comments in the Staff’s letter.

 *  *  *  *  *

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 March 24, 2016

 Page
 2

 Risk Factors

“We have only very recently initiated enrollment…,” page 18

1.
We note your disclosure that you have observed serious adverse events, including death, in some of the patients in your ongoing Phase 1 clinical trial. Here, or in an appropriate section of your document, please
expand your disclosure to list all serious adverse events reported to date and the number of patients who have reported such events, or provide us with an analysis as to why expanded disclosure here or elsewhere would not be material.

 In response to the Staff’s comment, the Company has revised the disclosure on pages 19 to list the
serious adverse events reported to date and the number of patients who have reported such events.

 Business

Our Development Programs

 AEB1102,
page 80

2.
We note the following statement on page 81: “In addition, in the first 11 patients in our Phase 1 dose escalation trial in patients with advanced solid tumors, we have observed a temporary reduction in blood
arginine levels.” However, we note your disclosure throughout the registration statement that only “seven patients in total” have been treated in your Phase 1 clinical trial. Please correct any typographical error or explain the
reason for the inconsistency.

 In response to the Staff’s comment, the Company has revised the disclosure on
page 84 to correct the typographical error.

 Executive and Director Compensation

Summary Compensation Table, page 115

3.
We note your statement in footnote (4) to the Summary Compensation Table explaining that: “Mr. Hebel performed consulting services for us prior to joining the company as an executive employee in May 2015.
Compensation reflected in the table above includes only compensation paid during the period of employment as an executive officer.” However, in footnote (5) to the same table you state that the amount under “All Other Compensation”
includes Mr. Hebel’s “…pre-employment consulting fees of $71,369…” If it is not accurate, please remove footnote (4).

In response to the Staff’s comment, the Company has revised the disclosure on page 118 to remove footnote (4).

The Company appreciates the Staff’s willingness to accommodate the Company and respectfully requests that the Staff review Exhibit
A in advance of the filing of the preliminary prospectus.

 *  *  *  *  *

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 March 24, 2016

 Page
 3

 Should the Staff have additional questions or comments regarding the foregoing, please do not
hesitate to contact me at (650) 335-7292 or, in my absence, Niki Fang at (650) 335-7252.

Sincerely,

 /s/ Robert A. Freedman

Robert A. Freedman

 cc:

 Via E-mail

 David G. Lowe

 Aeglea BioTherapeutics, Inc.

 Effie Toshav, Esq.

 Niki Fang, Esq.

 Melissa V. Frayer, Esq.

 Fenwick & West LLP

 Bruce K. Dallas, Esq.

 Davis Polk & Wardwell LLP

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 March 24, 2016

 Page
 4

 Exhibit A

 We have only very recently initiated enrollment in our Phase 1 clinical trial for the treatment of solid tumors for
AEB1102 and treated our first two cohorts of seven patients total. We have not dosed any of our other product candidates in humans. Our planned clinical trials may reveal significant adverse events, toxicities or other side effects not seen in our
nonclinical studies and may result in a safety profile that could inhibit regulatory approval or market acceptance of any of our product candidates.

In order to obtain marketing approval for any of our product candidates, we must demonstrate the safety and efficacy of the product candidate for the
relevant clinical indication or indications through nonclinical studies and clinical trials as well as additional supporting data. If our product candidates are associated with undesirable side effects in nonclinical studies or clinical trials or
have characteristics that are unexpected, we may need to interrupt, delay or abandon their development or limit development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less
severe or more acceptable from a risk-benefit perspective.

 We have only very recently initiated enrollment for our clinical trial for AEB1102 for
the treatment of solid tumors and treated our first two cohorts of seven patients total. Given the nature of the patient population enrolled in this trial, we expect to andWe have observed serious adverse events in
some of these patients, including death. Six serious adverse events were reported in a total of four patients. These included hypercalcemia, bacteremia, pericardial effusion, respiratory failure and worsening of the patients’ underlying
cancer, none of which were assessed as trial therapy-related. All patients recovered except for one who died after discontinuing the trial due to worsening of the underlying cancer.However, To date, we do not consider any
of these serious adverse events to be drug-related and are proceeding with the dosing schedule. We have not dosed any of our other product candidates in humans. Subjects in our ongoing and planned clinical trials may suffer significant serious
adverse events, including those that are drug-related, or other side effects not observed in our nonclinical studies, including, but not limited to, immune responses, organ toxicities such as liver, heart or kidney or other tolerability issues.

Testing in animals, such as our primate studies in AEB1102, may not uncover all side effects in humans or any observed side effects in animals may be
more severe in humans. For example, it is possible that patients’ immune systems may recognize our engineered human enzymes as foreign and trigger an immune response. This risk is heightened in patients who lack the target enzyme, as is the
case with patients with Arginase I deficiency we will be treating in our planned Phase 1 dose escalation and Phase 2 trials for this IEM. In addition, our product candidates such as AEB1102 break down target amino acids such as arginine, thereby
releasing metabolites such as ornithine into the bloodstream. Some patients may be sensitive to these metabolites, increasing the risk of an adverse reaction due to treatment, which risk may not be able to be mitigated through dosing. Finally,
although our engineered human enzyme product candidates such as AEB1102 are engineered from the human genome, AEB1102 is produced in E. coli. This manufacturing process could lead AEB1102 to be more likely to trigger an immune response than
we expect.

 To the extent significant adverse events or other side effects are observed in any of our clinical trials, we may have difficulty
recruiting patients to the clinical trial, patients may drop out of our trial, or we may be required to abandon the trial or our development efforts of that product candidate altogether. Some potential therapeutics developed in the biotechnology
industry that initially showed therapeutic promise in early-stage studies have later been found to cause side effects that prevented their further development. Even if the side effects do not preclude the drug from obtaining or maintaining marketing
approval, undesirable side effects may inhibit market acceptance of the approved product due to its tolerability versus other therapies. Any of these developments could materially harm our business, financial condition and prospects.

 19

solid tumors. In October 2015, we initiated enrollment and have since treated our first two cohorts of seven patients total in a Phase 1 dose escalation trial in patients with advanced solid
tumors. We have an effective IND and plan to initiate a Phase 1 dose escalation trial in patients with hematological malignancies after investigating the optimal biological dose in solid tumors in the first half of 2016. We plan to initiate
expansion arms in solid tumors and an additional Phase 1 trial in combination with the standard of care in one or more solid tumor types in 2017. If we see evidence of anti-tumor activity in the expansion phase, we plan to meet with regulatory
authorities to discuss expedited regulatory strategies. In June 2015, we submitted an IND for AEB1102 for Arginase I deficiency. Following discussion with the FDA, we withdrew our submitted IND in order to comply with new draft guidance issued by
the FDA on nonclinical assessment of enzyme replacement therapies. In October 2015, we met with the FDA and the MHRA in the United Kingdom regarding our planned clinical and regulatory path for AEB1102 in Arginase I deficiency. Based on these
discussions, we submitted a revised IND, which became effective in January 2016, and plan to submit a CTA to the EMA and initiate clinical trials in patients with Arginase I deficiency in 2016 in the United States and in the first half of 2017 in
Europe.

 We believe our lead compound offers the following advantages:

n

Market opportunities in both IEM and oncology.    We believe that AEB1102 can be applied to address both the rare IEM Arginase I deficiency, as well as solid tumors and hematological
malignancies that depend on arginine for growth and survival.

n

Well-understood mechanism of action.    Arginase I has been investigated extensively in both scientific and clinical research as a method for degrading arginine, a naturally occurring amino
acid that is one of the building blocks of proteins and is a contributor to cell proliferation and survival. AEB1102 has demonstrated the ability to reduce blood arginine levels in our nonclinical studies. In addition, in the first
11two cohorts of seven patients total in our Phase 1 dose escalation trial in patients with advanced solid tumors, we have observed a temporary reduction in blood arginine levels.

n

Proof of mechanism.    The target of AEB1102, the amino acid arginine, is easily measured and detected in the blood to enable selection of the optimal dose and schedule.

n

Clinical precedent for our approach in oncology.    Third-party clinical trials with a microbial arginine degrading enzyme have yielded positive results in acute myelogenous leukemia,
metastatic melanoma, hepatocellular carcinoma and pleural mesothelioma. These clinical trials highlight the potential of targeting the metabolic dependence of some cancers on arginine as an attractive approach for cancer treatment.

n

Improved activity and stability.    AEB1102 has increased catalytic activity and serum stability compared to native human Arginase I, due to the substitution of the native manganese cofactor
with cobalt. A cofactor is a non-protein chemical compound required for an enzyme’s biological activity. Pegylation further improves the half-life in vivo. These improvements have provided increased potency in both our in vitro
and in vivo models.

n

Potential of lower risk of immunogenicity.    The AEB1102 amino acid sequence is engineered from the native human amino acid sequence. As such, we believe that patients’ immune systems
are less likely to recognize this therapeutic candidate as a foreign molecule and mount an immune response as compared to microbial enzymes.

n

Manufacturing.    We have entered into a strategic partnership with an experienced manufacturer and have agreements with other manufacturers in the field of biologic drugs. We have produced
AEB1102 in E. coli for our planned clinical trials.

n

Intellectual property.    We have an issued composition of matter patent covering AEB1102 that expires in 2030, with the potential for patent-term extension. Intellectual property rights to
AEB1102 were assigned to us on an exclusive and royalty-free basis.

 84

 EXECUTIVE AND DIRECTOR COMPENSATION

The following tables and accompanying narrative disclosure set forth information about the compensation provided to our Chief Executive Officer and
President, Dr. David G. Lowe; our Vice President, Product Development, Henry L. Hebel; and our Vice President, Research, Dr. Scott W. Rowlinson during the year ended December 31, 2015.

We refer to Dr. Lowe, Mr. Hebel and Dr. Rowlinson in this section as our “Named Executive Officers.”

Summary Compensation Table

 The following table presents
summary information regarding the total compensation for services rendered in all capacities that was awarded to, earned by and paid to our Named Executive Officers during the years ended December 31, 2014 and December 31, 2015.

 Name and Principal Position

Fiscal
Year

Salary
($)

Bonus
($)(1)

Equity
Awards
($)(2)

All Other
Compensation
($)

Total
($)

 David G. Lowe, Ph.D.

2015

382,500

66,900

522,016

14,255(3)

985,671

 Chief Executive Officer

2014

375,000

111,563

295,964

15,614(3)

798,141

 Henry L. Hebel(4)

2015

144,000

28,800

207,281

78,961(45)

459,042

 Vice President, Product Development

 Scott W. Rowlinson, Ph.D.

2015

249,538

49,800

118,789

14,851(3)

432,978

 Vice President, Research

2014

203,968

40,794

34,312

15,518(3)

294,592

(1)
Discretionary cash bonuses earned in 2015 and paid in 2016, based in part on achievement of specified milestones and performance objectives. Amounts for 2014 represent discretionary cash bonuses earned in 2014, and paid
in 2015, based in part on achievement of specified milestones and performance objectives.

(2)
The amounts reported in this column represent the aggregate grant date fair value of the awards granted to our Named Executive Officers during the years ended December 31, 2014 and 2015, as computed in accordance
with Accounting Standards Codification Topic 718. The assumptions used in calculating the grant date fair value of the awards reported in the Equity Awards column are set forth in Note 9 to our consolidated financial statements. Note that the
amounts reported in this column reflect the aggregate accounting cost for these awards, and do not necessarily correspond to the actual economic value that may be received by the Named Executive Officers from the awards.

(3)
Represents a health insurance premium paid by us in the applicable period on behalf of each of our Named Executive Officers.

(4)
Mr. Hebel performed consulting services for us prior to joining the company as an executive employee in May 2015. Compensation reflected in the table above includes only compensation paid during the period of
employment as an executive officer.

(45)
Represents (i) pre-employment consulting fees of $71,369 and (ii) a health insurance premium paid by us in the applicable period for on behalf of Mr

March 24 , 2016

David G. Lowe, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway
Barton Oaks Plaza One
Suite 250
Austin, TX 78746

Re: Aeglea BioTherapeutics, Inc.
Amendment No. 3 to Registration Statement on
Form S -1
Filed March 14, 2016
  File No. 333 -205001

Dear Dr. Lowe:

We have reviewed your amended 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 amending your registration statement and providing the
requested information.   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 any amendment to your registration statement and the information you
provide in response to these comments, we may have additional comments .

Risk Factors

“We have only very recently initiated enrollment…,” page 18

1. We note your disclosure that you have observed serious adverse events, including death,
in some of the patients in your ongoing Phase 1 clinical trial.  Here , or in an appropria te
section of your document, please  expand your disclosure to list all serious adverse events
reported to date and the number of patients who have reported such events, or provide us
with an analysis as to why expanded disclosure here or elsewhere would no t be material.

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
March 24, 2016
Page 2

Business

Our Development Programs

AEB1102, page 80

2. We note the following statement on page 81: “In addition, in the first 11 patients in our
Phase 1 dose escalation trial in patients with advanced solid tumors, we have observed a
temp orary reduction in blood arginine levels.”  However, we note your disclosure
throughout the registration statement that only “seven patients in total” have been treated
in your Phase 1 clinical trial.  Please correct any typographical error or explain the reason
for the inconsistency.

Executive and Director Compensation

Summary Compensation Table, page 115

3. We note your statement in footnote (4) to the Summary Compensation Table explaining
that: “Mr. Hebel  performed consulting services for us prior to joining the company as an
executive employee in May 2015.  Compensation reflected in the table above includes
only compensation paid during the period of employment as an executive officer.”
However, in footn ote (5) to the same table you state that the amount under “All Other
Compensation” includes Mr. Hebel’s “…pre -employment consulting fees of $71,369…”
If it is not accurate, please remove footnote (4).

We urge all persons who are responsible for the acc uracy and adequacy of the disclosure
in the filing to be certain that the filing includes the information the Securities Act of 1933 and
all applicable Securities Act rules require.   Since the company and its management are in
possession of all facts relat ing to a company’s disclosure, they are responsible for the accuracy
and adequacy of the disclosures they have made.

Notwithstanding our comments, in the event you request acceleration of the effective date
of the pending registration statement, please provide a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not foreclose the Commission from taking any action with respect
to the fili ng;

 the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
March 24, 2016
Page 3

  the c ompany may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.

Please refer to Rules 460 and 461 regarding request s for acceleration.  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of 1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the
registration statement.

Please contact Chr istina Thomas at (202) 551 -3577 or  Mary Beth Breslin at (202) 551 -
3625 or me at (202) 551 -3675 with any questions.

Sincerely,

 /s/ Mary Beth Breslin for

 Suzanne Hayes
Assistant Director
Office of Healthcare and Insurance

cc: Robert A. Freedman
 Fenwick & West LLP

CORRESP
1
filename1.htm

CORRESP

March 22, 2016

ROBERT A. FREEDMAN

 EMAIL RFREEDMAN@FENWICK.COM

Direct Dial (650) 335-7292

CERTAIN PORTIONS OF THIS LETTER AS FILED VIA EDGAR HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE COMMISSION. CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED FOR THE OMITTED PORTIONS, WHICH HAVE BEEN REPLACED WITH THE FOLLOWING PLACEHOLDER: “[*].”

 VIA EDGAR
AND OVERNIGHT DELIVERY

 Securities and Exchange Commission

Division of Corporation Finance

 100 F Street, NE

Washington, DC 20549

 Attention:

 Jeffrey P. Riedler, Assistant Director

 Daniel Greenspan

 Tara Keating Brooks

 Keira Nakada

 Joel Parker

             Re:

 Aeglea BioTherapeutics, Inc.

 Registration Statement on Form S-1

File No. 333-205001

 Ladies and Gentlemen:

 On
behalf of Aeglea BioTherapeutics, Inc. (the “Company”), and in connection with a supplemental letter dated June 24, 2015 (the “Prior Letter”) that the Company submitted in response to comments from the
staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) contained in your letter dated June 3, 2015 (the “Initial Comment Letter”), relating to the
above-referenced Registration Statement on Form S-1 (the “Registration Statement”), we submit this supplemental letter to further address comment 7 of the Initial Comment Letter concerning valuation considerations related to
the Company’s recent equity awards and to assist the Staff in its review of the Registration Statement. For the convenience of the Staff, we are providing to the Staff by overnight delivery copies of this letter.

Because of the commercially sensitive nature of information contained herein, this submission is accompanied by the Company’s request for confidential
treatment of selected portions of this letter pursuant to Rule 83 of the Commission’s Rules on Information and Requests, 17 C.F.R. § 200.83 and the Freedom of Information Act.

 CONFIDENTIAL TREATMENT REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -1

 Securities and Exchange Commission

Division of Corporation Finance

 March 22, 2016

Page 2

 The Company advises the Staff that the Company currently anticipates that it will include an expected price
range in its preliminary prospectus (the “Preliminary Prospectus”) for the proposed initial public offering (the “IPO”) that will be between $[*] and $[*] per share before effecting a proposed reverse
stock split (the “Preliminary Price Range”). The Company anticipates effecting the reverse stock split in connection with its IPO pursuant to a future amendment of the Company’s certificate of incorporation that will be
filed with the Secretary of State of the State of Delaware prior to filing the Preliminary Prospectus with the Commission. The share numbers and stock prices set forth in this letter do not reflect the anticipated reverse stock split. The Company
also notes that the actual price range included in the Preliminary Prospectus (the “Bona Fide Price Range”) is expected to fall within the Preliminary Price Range and will be narrowed in advance of such inclusion such that it
will not vary more than $2.00 from the low end to the high end. The Preliminary Price Range has been determined based, in part, upon current market conditions, recent public offerings of other comparable companies and input received from the lead
underwriters of the proposed offering, including discussions that took place on March 16, 2016 between senior management of the Company and representatives of UBS Securities LLC, BMO Capital Markets Corp. and Wells Fargo Securities, LLC, the lead
underwriters.

 As stated in the Prior Letter, prior to June 19, 2015, the Company had not held formal discussions with the underwriters regarding a price
range for the IPO. On March 16, 2016, the Company held its most recent discussions with the lead underwriters regarding a preliminary price range for the IPO. The Preliminary Price Range does not take into account the current lack of liquidity for
the Company’s common stock and assumes a successful initial public offering as of today’s date with no weighting attributed to any other outcome for the Company’s business, such as remaining a privately held company.

We supplementally advise the Staff that, as described on pages 70-71 of the Registration Statement, the Board of Directors of the Company (the
“Board”) has determined the fair value of the Company’s common stock at the time of the replacement awards and option grants by considering a number of objective and subjective factors, including the Company’s stage
of development, progress on its research and development efforts, completing the sale and issuance of Series B convertible preferred stock, the rights preferences and privileges of its convertible preferred shares relative to those of its common
stock, the lack of marketability of its common stock, and general and industry-specific economic outlooks. The Board also considered the status of the Company’s progress towards an IPO and valuations of the Company’s common stock by a
third-party valuation firm. The Board, as applicable, also determined that the assumptions and inputs used in connection with such valuations reflected the Board’s and management’s best estimate of the business condition, prospects and
operating and financial performance of the Company at each valuation date.

 The Company completed an equity financing on March 10, 2015 in which it
sold shares of its Series B convertible preferred stock at a price of $0.85 per share for an aggregate purchase price of $44.0 million (the “Series B Financing”). The Series B Financing included sales to new investors
exceeding 50% of the aggregate purchase price. In addition, shares of the Company’s convertible preferred stock have rights, preferences and privileges senior to shares of the Company’s common stock, specifically, the right to receive
dividends prior to any dividends declared or paid on any shares of the Company’s common stock, the right to receive proceeds upon a deemed liquidation event in preference to shares of common stock, anti-dilution protections, and certain
protective provisions that require the approval of shares of preferred stock for specific corporate actions.

 *Confidential material
redacted

 CONFIDENTIAL TREATMENT REQUESTED BY AEGLEA
BIOTHERAPEUTICS, INC.

 AEGLEA -2

 Securities and Exchange Commission

Division of Corporation Finance

 March 22, 2016

Page 3

 The third-party valuation reports were prepared based on a hybrid approach of the probability-weighted
expected return method (“PWERM”) and the option pricing method. Further, the third-party valuation report as of March 15, 2015 was also based on a backsolve method considering the Company’s Series B Financing on March
10, 2015. The Board used these valuation reports as one of the objective factors along with other subjective factors it considered in determining the fair value of the Company’s common stock.

On March 10, 2015, the Company converted outstanding Common B shares into restricted stock and options to purchase shares of common stock upon the
Company’s conversion from a Delaware LLC to a Delaware corporation (“March Replacement Awards”). The following table summarizes the converted and granted awards of the Company in 2015:

 Award Date

 Shares Underlying

 Valuation Date

Fair Value of
Common Stock/
Exercise Price of
Option

Discount for
Lack of
Marketability

Aggregate
Grant Date
Fair Value
(thousands)

 March 10, 2015

(March Replacement Awards)

2,659,973 (restricted shares) 1,054,747 (options)

March 15, 2015 (the “March Valuation Report”)

$
0.33

24.1
%

$
1,226

April 1, 2015

4,161,261 (options)

March Valuation Report

$
0.33

24.1
%

$
1,011

April 22, 2015

327,089 (options)

April 20, 2015 (the “April Valuation Report”)

$
0.48

20.0
%

$
118

May 28, 2015

686,193 (options)

May 25, 2015 (the “May Valuation Report”)

$
0.59

17.0
%

$
296

June 15, 2015

538,241 (options)

June 15, 2015 (the “June Valuation Report”)

$
1.22

9.1
%

$
548

 Following a delay in the anticipated IPO timeline due to market conditions, on February 25, 2016, the Company obtained a
third-party valuation report as of February 1, 2016, prepared based on a hybrid approach of PWERM and the option pricing method. The third-party valuation report indicated an increased discount for lack of marketability of 22.2% as compared to
the 9.1% discount for lack of marketability in the June Valuation Report, due in part to market conditions in early 2016. Subsequently, the Company granted options to new hires. The following table summarizes the granted awards of the
Company in 2016:

 Award Date

Shares
Underlying

 Valuation Date

Fair Value of
Common Stock/
Exercise Price
of Option

Discount for
Lack of
Marketability

Aggregate
Grant Date
Fair Value
(thousands)

 February 26, 2016

636,426

February 1, 2016 (the “February Valuation Report”)

$
0.52

22.2
%

$
240

 March 18, 2016

250,000

February Valuation Report

$
0.52

22.2
%

$
93

 CONFIDENTIAL TREATMENT REQUESTED BY
AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -3

 Securities and Exchange Commission

Division of Corporation Finance

 March 22, 2016

Page 4

 We are supplementally providing the Staff the following discussion regarding the significant factors
contributing to the difference between the estimated initial public offering price and the determined fair value of the Company’s common stock. The Company believes the difference between the fair value of its common stock on March 10, 2015,
April 1, 2015, April 22, 2015, May 28, 2015, June 15, 2015, February 26, 2016, March 18, 2016 and the current preliminary price range estimated by the Company is the result of the following factors:

•

the Preliminary Price Range necessarily assumes that the IPO has occurred and a public market for the Company’s common stock has been created, and therefore excludes any marketability or liquidity discount for the
Company’s common stock, which was appropriately taken into account in the Board’s determinations of fair value in March, April, May and June 2015, as well as in February and March 2016. The difference in the lack of marketability between
the March Valuation Report, the April Valuation Report, the May Valuation Report and the June Valuation Report took into account, among other factors, the decreased time to and increased likelihood of consummating an IPO in the near term as
reflected by the Company holding its IPO organizational meeting in April 2015, confidentially submitting its Registration Statement in May, and continuing its IPO preparations, which resulted in a higher initial public offering probability in each
of the March, April, May and June Valuation Reports;

•

Subsequently, the February Valuation Report took into account a much lower public offering probability indicating an increased discount for lack of marketability of 22.2% as compared to the 9.1% discount for lack of
marketability in the June Valuation Report. This was due in part to worsening market conditions in the fall of 2015 and the less robust IPO market in early 2016. For example, on June 24, 2015, the date of the Prior Letter, the high on the
NASDAQ Biotechnology Index was 3956.25, while as of February 1, 2016, the high on the NASDAQ Biotechnology Index was 2810.11, representing a decline of approximately 29%. In addition, the stock prices of public biotechnology companies were
highly volatile throughout the fourth quarter of 2015, with increasing volatility in January 2016. These conditions caused many companies to halt or delay their plans for an IPO or to price below their anticipated price range. As a result
of these factors, the February Valuation Report included a much lower weighting of the probability of an IPO in 2016;

•

differences in the valuation methodologies, assumptions and inputs used by the underwriters in their valuation analysis discussed with the Company, which do not take into account the current lack of liquidity for the
Company’s common stock and assume a successful IPO as of today’s date with no weighting attributed to any other outcome for the Company’s business, such as remaining a privately held company, compared to the valuation methodologies,
assumptions and inputs used in the valuations considered by the Board, which was based on the valuation methodologies mentioned above for each of the Valuation Reports (each as described on pages 71-73 of the Registration Statement);

•

differences in comparable companies in the life sciences and oncology markets discussed between the Company and the underwriters as compared to the prior analysis applied and comparable companies used by the Board;

 CONFIDENTIAL TREATMENT REQUESTED BY AEGLEA
BIOTHERAPEUTICS, INC.

 AEGLEA -4

 Securities and Exchange Commission

Division of Corporation Finance

 March 22, 2016

Page 5

•

the Company’s consideration of various objective and subjective factors in the previous fair value determinations, as described above, that were not applicable to the current preliminary price range; and

•

advancements in the Company’s development of its product candidates, in particular, the effectiveness of its Investigational New Drug Application with the United States Food and Drug Administration in March 2016
for AEB1102 for the treatment of patients with hematological malignancies.

 The Company expects to include the Bona Fide Price Range in an
amendment to the Registration Statement that would shortly precede the commencement of the Company’s public marketing process, which it anticipates could commence as soon as March 28, 2016. Such Bona Fide Price Range could differ from the
Preliminary Price Range based on then-current market conditions, continuing discussions with the lead underwriters and further business developments impacting the Company. We are providing this information to you supplementally to facilitate your
review process.

 The Company supplementally advises the Staff that, in the Preliminary Prospectus, it will include the following disclosure (with the
blanks to be filled with post-reverse stock split amounts):

 “We determined, after consultation with the underwriters, that our
initial public offering price range will be $            to $            per share. As of the dates of the March 10, 2015, April
1, 2015, April 22, 2015, May 28, 2015, June 15, 2015, February 26, 2016 and March 18, 2016 conversions and stock option grants, our board of directors had determined the fair value of our common stock to be
$                per share (for the March 10, 2015 conversion and for the April 1, 2015 grants),
$                per share (for the April 22, 2015 grants), $                per share
(for the May 28, 2015 grants), $                per share (for the June 15, 2015 grants), and
$                per share (for the February 26, 2016 and March 18, 2016 grants). The determination was based upon the objective and subjective factors described
above. We believe the difference between the fair value of our common stock for the March 10, 2015 conversion and for the April 1, April 22, May 28, June 15, 2015, February 26, 2016 and March 18, 2016 grants, in each case as determined by our board
of directors, and the initial offering price range is a result of the following factors:

•

the price range necessarily assumes that the initial public offering has occurred and a public market for our common stock has been created, and therefore excludes any marketability or liquidity discount for our common
stock, including those related to worsening market conditions in the fall of 2015 and early 2016, which was appropriately taken into account in our board of directors’ fair value determinations;

•

differences in the valuation methodologies, assumptions and inputs used by the underwriters in their valuation analysis discussed with our management, which assume a successful initial public offering with no weighting
attributed to any other outcome, compared to t

CORRESP
1
filename1.htm

CORRESP

 June 24, 2015

ROBERT A. FREEDMAN

 EMAIL RFREEDMAN@FENWICK.COM

Direct Dial (650) 335-7292

 CERTAIN PORTIONS OF THIS LETTER AS FILED VIA EDGAR HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE COMMISSION. CONFIDENTIAL
TREATMENT HAS BEEN REQUESTED FOR THE OMITTED PORTIONS, WHICH HAVE BEEN REPLACED WITH THE FOLLOWING PLACEHOLDER: “[*].”

 VIA EDGAR AND
OVERNIGHT DELIVERY

 Securities and Exchange Commission

Division of Corporation Finance

 100 F Street, NE

Washington, DC 20549

Attention:

Jeffrey P. Riedler, Assistant Director

 Daniel Greenspan

 Tara Keating Brooks

Keira Nakada

 Joel Parker

Re:

 Aeglea BioTherapeutics, Inc.

Registration Statement on Form S-1

 File
No. 333-205001

 Ladies and Gentlemen:

 On
behalf of Aeglea BioTherapeutics, Inc. (the “Company”), and in connection with the submission of a letter dated June 16, 2015 in response to comments from the staff (the “Staff”) of the Securities
and Exchange Commission (the “Commission”) contained in your letter dated June 3, 2015 (the “Initial Comment Letter”), relating to the above-referenced Registration Statement on Form S-1(the
“Registration Statement”), we submit this supplemental letter to further address comment 7 of the Initial Comment Letter concerning valuation considerations related to the Company’s recent equity awards and to assist the
Staff in its review of the Registration Statement. For the convenience of the Staff, we are providing to the Staff by overnight delivery copies of this letter.

Because of the commercially sensitive nature of information contained herein, this submission is accompanied by the Company’s request for confidential
treatment of selected portions of this letter pursuant to Rule 83 of the Commission’s Rules on Information and Requests, 17 C.F.R. § 200.83 and the Freedom of Information Act.

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -1

 Securities and Exchange Commission

Division of Corporation Finance

 June 24, 2015

 Page
 2

 The Company advises the Staff that the Company currently anticipates that it will include an expected price
range in its preliminary prospectus (the “Preliminary Prospectus”) for the proposed initial public offering (the “IPO”) that will be between $[*] and $[*] per share before effecting a proposed reverse
stock split (the “Preliminary Price Range”). The Company anticipates effecting the reverse stock split in connection with its IPO pursuant to a future amendment of the Company’s certificate of incorporation that will be
filed with the Secretary of State of the State of Delaware prior to filing the Preliminary Prospectus with the Commission. The share numbers and stock prices set forth in this letter do not reflect the anticipated reverse stock split. The Company
also notes that the actual price range included in the Preliminary Prospectus (the “Bona Fide Price Range”) is expected to fall within the Preliminary Price Range and will be narrowed in advance of such inclusion such that it
will not vary more than $2.00 from the low end to the high end. The Preliminary Price Range has been determined based, in part, upon current market conditions, recent public offerings of other comparable companies and input received from the lead
underwriters of the proposed offering, including discussions that took place on June 19, 2015 between senior management of the Company and representatives of Cowen and Company, LLC, UBS Securities LLC and BMO Capital Markets Corp., the lead
underwriters.

 Prior to June 19, 2015, the Company had not held formal discussions with the underwriters regarding a price range for the IPO. The
Preliminary Price Range does not take into account the current lack of liquidity for the Company’s common stock and assumes a successful initial public offering as of today’s date with no weighting attributed to any other outcome for the
Company’s business, such as remaining a privately held company.

 We supplementally advise the Staff that, as described on pages 69-70 of the
Registration Statement, the Board has determined the fair value of the Company’s common stock at the time of the replacement awards and option grants by considering a number of objective and subjective factors, including the Company’s
stage of development, progress on its research and development efforts, completing the sale and issuance of Series B convertible preferred stock, the rights preferences and privileges of its convertible preferred shares relative to those of its
common stock, the lack of marketability of its common stock, and general and industry-specific economic outlooks. The Board also considered the status of the Company’s progress towards an IPO and valuations of the Company’s common
stock by a third-party valuation firm. The Board, as applicable, also determined that the assumptions and inputs used in connection with such valuations reflected the Board’s and management’s best estimate of the business condition,
prospects and operating and financial performance of the Company at each valuation date.

 The Company completed an equity financing on March 10, 2015
in which it sold shares of its Series B convertible preferred stock at a price of $0.85 per share for an aggregate purchase price of $44.0 million (the “Series B Financing”). The Series B Financing included sales to new
investors exceeding 50% of the aggregate purchase price. In addition, shares of the Company’s convertible preferred stock have rights, preferences and privileges senior to shares of the Company’s common stock, specifically, the right to
receive dividends prior to any dividends declared or paid on any shares of the Company’s common stock, the right to receive proceeds upon a deemed liquidation event in preference to shares of common stock, anti-dilution protections, and certain
protective provisions that require the approval of shares of preferred stock for specific corporate actions.

 The third-party valuation reports were
prepared based on a hybrid approach of the probability-weighted expected return method (PWERM) and the option pricing method. Further, the third-party valuation report as of March 15, 2015 was also based on a backsolve method considering the
Company’s Series B Financing on March 10, 2015. The Board used these valuation reports as one of the objective factors along with other subjective factors it considered in determining the fair value of the Company’s common stock.

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -2

 Securities and Exchange Commission

Division of Corporation Finance

 June 24, 2015

 Page
 3

 On March 10, 2015, the Company converted outstanding Common B shares into restricted stock and options
to purchase shares of common stock upon the Company’s conversion from a Delaware LLC to a Delaware corporation ( “March Replacement Awards”). The following table summarizes the converted and granted awards of the Company
in 2015:

Award Date (1)

Shares Underlying

Valuation Date

Fair Value
of Common
Stock/
Exercise
Price of
Option

Discount for
Lack of
Marketability

 Aggregate
Grant
Date
Fair Value

 (thousands)

 March 10, 2015
(March Replacement Awards)

 2,659,973 (restricted shares) 1,054,747 (options)

 March 15, 2015 (the “March Valuation
Report”)

$
0.33

24.1
%

$
1,226

 April 1,
2015

 4,161,261 (options)

$
0.33

24.1
%

$
1,011

 April 22,
2015

 327,089 (options)

 April 20, 2015 (the “April Valuation Report”)

$
0.48

20.0
%

$
118

 May 28,
2015

 686,193 (options)

 May 25, 2015 (the “May Valuation Report”)

$
0.59

17.0
%

$
296

 June 15,
2015

 538,241 (options)

 June 15, 2015 (the “June Valuation Report”)

$
1.22

9.1
%

$
548

(1)
There were no significant grants awarded in the second half of 2014.

 We are supplementally providing the
Staff the following discussion regarding the significant factors contributing to the difference between the estimated initial public offering price and the determined fair value of the Company’s common stock. The Company believes the difference
between the fair value of its common stock on March 10, 2015, April 1, 2015, April 22, 2015, May 28, 2015, June 15, 2015 and the current preliminary price range estimated by the Company is the result of
the following factors:

•

the recent improvement in major stock market indices, with the NASDAQ Composite Index, NASDAQ Biotechnology Index and the Dow Jones Industrial average having increased approximately 5.8%, 11.0% and 2.1%, respectively
since March 15, 2015 and approximately 2.5%, 5.4% and 1.8%, respectively, since June 15, 2015;

•

 the Preliminary Price Range necessarily assumes that the IPO has occurred and a public market for the Company’s common stock has been created,
and therefore excludes any marketability or liquidity discount for the Company’s common stock, which was appropriately taken into account in the Board’s determinations of fair value in March, April, May and June 2015. The difference in the
lack of marketability between the March Valuation Report, the April Valuation Report, the May Valuation

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -3

 Securities and Exchange Commission

Division of Corporation Finance

 June 24, 2015

 Page
 4

Report and the June Valuation Report (collectively, the “Valuation Reports”) took into account, among other factors, the decreased time to and increased likelihood of
consummating an IPO in the near term as reflected by the Company holding its IPO organizational meeting in April 2015, confidentially submitting its Registration Statement in May, and continuing its IPO preparations, which resulted in a higher
initial public offering probability in each of the Valuation Reports;

•

differences in the valuation methodologies, assumptions and inputs used by the underwriters in their valuation analysis discussed with the Company, which do not take into account the current lack of liquidity for the
Company’s common stock and assume a successful IPO as of today’s date with no weighting attributed to any other outcome for the Company’s business, such as remaining a privately held company, compared to the valuation methodologies,
assumptions and inputs used in the valuations considered by the Board, which was based on the valuation methodologies mentioned above for each of the Valuation Reports (each as described on page 70 of the Registration Statement);

•

differences in comparable companies in the life sciences and oncology markets discussed between the Company and the underwriters as compared to the prior analysis applied and comparable companies used by the Board;

•

the Company’s consideration of various objective and subjective factors in the previous fair value determinations, as described above, that were not applicable to the current preliminary price range;

•

advancements in the Company’s development of its product candidates and, in particular, with respect to AEB1102 for the treatment of Arginase I deficiency, the submission and receipt of an Investigational New Drug
Application with the United States Food and Drug Administration on June 11, 2015; and

•

execution on June 15, 2015 of a Cancer Research Grant Contract with the Cancer Prevention Research Institute of Texas, not to exceed $19.8 million, for use in funding the development of potential cancer treatments.

 The Company expects to include the Bona Fide Price Range in an amendment to the Registration Statement that would shortly precede the
commencement of the Company’s public marketing process, which it anticipates could commence as soon as July 8, 2015. Such Bona Fide Price Range could differ from the Preliminary Price Range based on then-current market conditions,
continuing discussions with the lead underwriters and further business developments impacting the Company. We are providing this information to you supplementally to facilitate your review process.

The Company supplementally advises the Staff that, in the Preliminary Prospectus, it will include the following disclosure (with the blanks to be filled with
post-reverse stock split amounts):

 “We determined, after consultation with the underwriters, that our initial public offering price
range will be $         to $         per share. As of the dates of the March 10, 2015, April 1, 2015, April 22, 2015, May 28, 2015 and
June 15, 2015 conversions and stock option grants, our board of directors had determined the fair value of our common stock to be $         per share (for the March 10, 2015 conversion and for the
April 1,

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -4

 Securities and Exchange Commission

Division of Corporation Finance

 June 24, 2015

 Page
 5

2015 grants), $         per share (for the April 22, 2015 grants), $         per share (for the May 28,
2015 grants) and $         per share (for the June 15, 2015 grants). The determination was based upon the objective and subjective factors described above. We believe the difference between the fair
value of our common stock for the March 10, 2015 conversion and for the April 1, April 22, May 28 and June 15, 2015 grants, in each case as determined by our board of directors, and the initial offering price range
is a result of the following factors:

•

the price range necessarily assumes that the initial public offering has occurred and a public market for our common stock has been created, and therefore excludes any marketability or liquidity discount for our common
stock, which was appropriately taken into account in our board of directors’ fair value determinations;

•

differences in the valuation methodologies, assumptions and inputs used by the underwriters in their valuation analysis discussed with our management, which assume a successful initial public offering with no weighting
attributed to any other outcome, compared to the valuation methodologies, assumptions and inputs used in the valuations considered by our board of directors;

•

differences in comparable companies in the life sciences and oncology markets discussed between us and the underwriters as compared to the more narrow prior analysis applied and comparable companies used by our board of
directors;

•

advancements in the development of our product candidates and, in particular, with respect to AEB1102 for the treatment of Arginase I deficiency, the submission and receipt of our Investigational New Drug Application
with the FDA in June 2015; and

•

execution in June 2015 of a Cancer Research Grant Contract with the Cancer Prevention Research Institute of Texas, not to exceed $19.8 million, for use in funding the development of potential cancer treatments.”

 *********

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -5

 Securities and Exchange Commission

Division of Corporation Finance

 June 24, 2015

 Page
 6

 Should the Staff have questions or comments regarding the foregoing, please do not hesitate to contact the
undersigned at (650) 335-7292.

Sincerely,

/s/ Robert A. Freedman

Robert A. Freedman

 cc:

 David G. Lowe,
Ph.D., Chief Executive Officer

 Aeglea BioTherapeutics, Inc.

Effie Toshav, Esq.

 Niki Fang, Esq.

Melissa V. Frayer, Esq.

 Fenwick & West LLP

Bruce K. Dallas, Esq.

 Davis Polk & Wardwell LLP

 *Confidential material redacted

 CONFIDENTIAL TREATMENT
REQUESTED BY AEGLEA BIOTHERAPEUTICS, INC.

 AEGLEA -6

June 3 , 2015

David G. Lowe, Ph.D.
Chief Executive Officer
Aeglea BioTherapeutics, Inc.
901 S. MoPac Expressway
Barton Oaks Plaza One
Suite 250
Austin, TX 78746

Re: Aeglea BioTherapeutics, Inc.
Draft Registration Statement on Form S-1
Submitted May 6, 2015
  CIK No. 0001636282

Dear Dr. Lowe :

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.

Prospectus Summary

1. Please clarify the meaning of any significant scientific or technical terms the first time
they are used in your prospectus in order to ensure that lay readers will understand the
disclosure.  For example,  pleas e define each  of the following at their first use:

 arginine ;
 cysteine/cystine ;
 microbial ;
 methionine;
 metabolite;

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
June 3, 2015
Page 2

  immunogenicity ;
 xenograft ;
 immunogenic ;
 moieties ;
 pharmacodynamic  marker ;
 native manganese cofactor ;
 pegylation ;
 orphan drug designation; and
 urea cycle disorders

2. We refer to your product pipeline table on page s 2 and 77 .  Please revise your product
candidate pipeline table to add  “solid tumors” in the therapeutic category for AEB1102.
In addition, p lease revise your table to identify the target amino acid for AEB4104.  The
product pipeline table is intended to provide information about actua l products. Unless a
therapeutic category  and a compound have been identified, the product appears  too
preliminary for inclusion in the table. Accordingly, please identify the target amino acid
for AEB4101 in the table or alternately, eliminate this product candidate from the table.

Risks Affecting Us , page 5

3. Please expand your list of bullet p oint risks to include:

 risks related to t he novelty  associated with your engineered human enzyme
product candidates for your potential cancer indications , which could result in
heightened regulatory scrutiny, delays in clinical development, or delays in your
ability to achiev e regulatory approval or commercialization of your product
candidates ; and

 the availability of patients to enroll in your planned Phase  1/2 proof -of-concept
clinical trial  of AEB1102  for the treatment of Arginase I deficiency.

Risk Factors, page 11

4. We note that  certain of your risk factors are substantially repetitive including:

 the last risk factors on page 13 and 15 ;
 the last risk factors on page 20 and 21 ;
 the first full risk factor on page 25 and the first risk factor on page 11 and the last
risk factor on page 25 ; and
 the first full risk factor on page 30 and the second risk factor on page 32 .

Please revise you r disclosure in the above referenced ex amples to provide a single  risk
factor.

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
June 3, 2015
Page 3

5. We refer to your disclosure on page 125, “ Choice of Forum .”  Please add a risk factor
describing the disadvantages to stock holders  attendant to the exclusive forum provision
contained in your proposed amended and restated certificate of incorporation.

If we fail to comply with environmental, health and safety laws…, page 36

6. Please state in this risk factor whether the company currently maintains insurance with
sufficient coverage to protect against the liability risks di scussed and whether, to your
knowledge, this coverage is consistent with industry norms.

Valuation of Equity Instruments, page 69

7. We may have additional comments on your accounting for equity issuances including
stock compensation and beneficial conversion features. Once you have an estimated
offering price, please provide us an analysis explaining the reasons for the differences
between recent valuations of your common stock leading up to the IPO and the estimated
offering price.

Business , page 71

8. Please revise you r Intellectual Property disclosure on page 85, to the extent not otherwise
disclosed,  to discuss any right s of your founding scientists in your intellectual property.

Background on inborn errors of metabolism, page 73

9. We note your illustration on the top on page 74.  Please expand your disclosure to
provide, through a legend or other explanatory narrative, a brief guide in layman’s terms
to the images as they relate to Arginase I and the reduction in arginine levels in the ur ea
cycle .

AEB1102, page 77

10. We note that an integral part of your development programs involves the precise
identification of patients who are best suited for amino acid depletion therapy.  Please
advise us what, if any, re gulatory approvals of concomitant genetic and biomarker
diagnostic tests will be necessary in order to advance your product to commercialization.
We may have further comments based on your response.

11. We refer to your first bullet point on page 78.  Please revise your disclosure to explain
how the development of AEB1102 in two indications provides you with a capital
efficient product development strategy.  In that regard, we note the planned indications
for AEB1102 require separate clinical trials  for different indications with separate INDs
developed under potentially different regulatory pathways.  In the alternative, please

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
June 3, 2015
Page 4

 remove the statement.

AEB1102 clinical development in Arginase I deficiency, page 81

12. Please explain the FDA ’s preference for alternative endpoints in connection with  your
intended Phase 1/2 proof -of-concept trial and any concern s the FDA expressed  about the
appropriateness of your proposed endpoint (s).

13.  We refer to your disclosure on the top of page 82.  Please briefly explain the meaning
and significance o f the terms “ clinically meaningful benefit ” and “statistically
significant ” as they relate to your planned clinical trials.

Clinical development plan for AEB1102 in  oncology , page 83

14. Please revise your disclosure to include the anticipated  number of patients in your
planned Phase 1 clinical trial.

Intellectual Property, page 85

15. We note your disclosure in this section regarding your patent portfolio. Please revise your
disclosure on  page 86 for your material patents and patent applications to include whether
each of the patents or patent applications are owned or licensed (if licensed, please
identify the licensor  and the term of the license ).  Please also state whether you believe
your owned or licensed patents will provide sufficient protection for your lead product
candidates.

Licensing , page 86

16. Please revise your disclosure for each agreement to include the duration and the
aggregate amounts paid or received to date under each  agreement which may include up -
front , execution payments or license fees received or paid.  In addition, please file each
agreement as exhibits to your Form S -1 pursuant to Item 601  of Regulation S -K.

Sponsored Research Agreement, page 87

17. Please revise your disclosure to discuss  the material terms of the agreement including:

 nature and scope of each party’s intellectual property rights in the sponsored
research ;
 each parties’ rights and obligations ;
 duration and t ermination provisions ;
 material  payment provisions , which may include u p-front or execution payments ;
 milestones, royalty rates or revenue sharing; and
 aggregate a mounts paid or received to date.

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
June 3, 2015
Page 5

Manufacturing, page 88

18. We refer to your disclosure regarding your third -party suppliers and manufacturers. We
also note your last risk factor on page 26, citing your dependence on these third parties to
manufacture your product candidates for nonclinical and for your future planned clinical
testing.   In that regard , please expand your disclosure to provide the material terms of
each of your agreements with KBI Biopharma, Inc. and Lyophili zation Services of New
England Inc., including each party’s material rights and obligations, duration, minimum
purchase obligations , termination provisions and any material  payment provisions. In
addition, please disclose whether you believe you have suffi cient supplies of AEB110 2
for your planned Phase 1  and Phase 1/2  studies.  In accordance with Item 601 of
Regulation S -K, please file each of the agreements  as exhibits  to your Form S -1.
Alternatively, please provide an analysis as to why the company is not substantially
dependent upon these agreements.

19. We refer to your d isclosure in note 11 on page F -22.   Please revise your prospectus to
provide the material terms of your agreement with your contract research organization ,
including the identity of the contracting party, each party’s material ri ghts and
obligations, duration , termination provisions and any material  payment provisions  and/or
stock issuances.   In addition, please file the agreement as an exhibit in accordance with
Item 601 of Regulation S -K.

Consulting Agreement with Ann M. Lowe, M.D .., page 116
Consu lting Agreement with George Georgiou, Ph.D .., page 116

20. Please revise your prospectus to disclose whether  Dr. Lowe or Dr. Georgiou  entered into
a nondisclosure and as signment of invention agreement.

Assignment of Intellectual Property from George Georgiou, Ph.D. ., page 117

21. Please revise your prospectus to disclose the nature and scope of the material assets
purchased from GMA.  In addition, please disclose the nature, rights and scope of the
intellectual property acquired from GMA including a desc ription of the material patents
or patent applications.  In addition,  please file a copy of the Assignment of Intellectual
Property as an exhibit in accordance with Item 601 of Regulation S -K.

Description of Capital Stock, page 121

22. We note that all of th e outstanding convertible preferred stock will automatically convert
into common shares  in the event that you receive gross proceeds in this offering of at
least $70,000,000 with a per share price of at least $2.55.  Please advise us of the material
risks to investors, if any, should the preferred stock not automatically convert .

David G. Lowe, Ph.D.
Aeglea BioTherapeutics, Inc.
June 3, 2015
Page 6

 Other Comments

23. Please submit all exhibits as soon as practicable. We may have further comments upon
examination of these exhibits.

24. Please confirm that the graphics included in your registration statement are the only
graphics you will use in your prospectus.  If those are not the only graphics, please
provide any additional graph ics prior to their use for our review.

25. 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.

You may contact Keira Nakada at (202) 551 -3659 or Joel Parker at 202 -551-3651 if you
have questions regarding comments on the financial statements an d related matters.  Please
contact Tara Keating Brooks at (202) 551 -8336, Daniel Greenspan at 202 -551-3623 or me at
(202) 551 -3715 with any other questions.

       Sincerely,

       /s/ Daniel Greenspan for

Jeffrey P. Riedler
Assistant Director

cc:  Via E -mail
 Robert Freedman
 Fenwick & West LLP