SYRE Spyre Therapeutics Inc

As filed with the Securities and Exchange Commission on February 29, 2024

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM S-8

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

SPYRE THERAPEUTICS, INC.

(Exact name of registrant as specified in its charter)

221 Crescent Street

Building 23

Suite 105

Waltham, Massachusetts 02453

(617) 651-5940

(Address of Principal Executive Offices, Zip Code)

Spyre Therapeutics, Inc. 2016 Equity Incentive Plan, As Amended and Restated

Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, As Amended and Restated

(Full title of the plans)

Heidy King-Jones

Chief Legal Officer and Corporate Secretary

Spyre Therapeutics, Inc.

221 Crescent Street

Building 23

Suite 105

Waltham, Massachusetts 02453

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copy to:

Ryan Murr

Branden Berns

Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 3000

San Francisco, CA 94111

(415) 393-8373

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer”, “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

EXPLANATORY NOTE

This Registration Statement on Form S-8 is being filed by Spyre Therapeutics, Inc. (f/k/a Aeglea BioTherapeutics, Inc.) (the “Registrant”) pursuant to General Instruction E to Form S-8, under the Securities Act of 1933, as amended, to register an additional (i) 3,023,650 shares of common stock, par value $0.0001 per share (“Common Stock”), issuable under the Registrant’s Equity Incentive Plan (as amended and restated, the “2016 Plan”) and (ii) 360,571 shares of Common Stock, issuable under the Registrant’s 2016 Employee Stock Purchase Plan (as amended and restated, the “ESPP”), pursuant to the provisions of those plans providing for an automatic increase in the number of shares reserved for issuance under such plans.

The information contained in the Registrant’s registration statements on Form S-8 filed with the Securities and Exchange Commission (“SEC”) on

April 7, 2016 (Registration No. 333-210633), March  23, 2017 (Registration No. 333-216903), March  13, 2018 (Registration No. 333-223614), March  7, 2019 (Registration No. 333-230137), February  24, 2020 (Registration No. 333-236584), March  18, 2021 (Registration No. 333-254430), March  8, 2022 (Registration No. 333-263357), March  2, 2023 (Registration No. 333-270208), and December  22, 2023 (Registration No. 333-276256), together with all exhibits filed therewith or incorporated therein by reference, are hereby incorporated by reference pursuant to General Instruction E to Form S-8, and the shares of Common Stock registered hereunder are in addition to the shares of Common Stock registered on such registration statements with respect to the 2016 Plan and the ESPP.

PART I

INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS

The documents containing the information required by Part I of Form S-8 (plan information and registrant information and employee plan annual information) will be sent or given to employees as specified by Rule 428(b)(1) of the Securities Act of 1933, as amended (the “Securities Act”). Such documents need not be filed with the SEC either as part of this Registration Statement or as prospectuses or prospectus supplements pursuant to Rule 424 of the Securities Act. These documents and the documents incorporated by reference in this Registration Statement pursuant to Item 3 of Part II, taken together, constitute a prospectus that meets the requirements of Section 10(a) of the Securities Act.

PART II

INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

SIGNATURES

Pursuant to the requirements of the Securities Act, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in Waltham, Massachusetts, on this 29^th day of February, 2024.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below hereby constitutes and appoints Dr. Cameron Turtle and Mr. Scott Burrows, jointly and severally, as his or her true and lawful attorney-in-fact and agent with full power of substitution, for him or her in any and all capacities, to sign any and all amendments (including post-effective amendments) to this Registration Statement on Form S-8, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully for all intents and purposes as he might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent, or his or her substitute, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act, this Registration Statement has been signed by the following persons in the capacities and on the date indicated.

Exhibit 5.1

February 29, 2024

Spyre Therapeutics, Inc.

221 Crescent Street, Building 23, Suite 105

Waltham, MA 02453

Registration Statement on Form S-8

Ladies and Gentlemen:

We have examined the Registration Statement on Form S-8 (f/k/a Aeglea BioTherapeutics, Inc.) (the “Registration Statement”), of Spyre Therapeutics, Inc., a Delaware corporation (the “Company”) to be filed with the Securities and Exchange Commission (the “Commission”) pursuant to the Securities Act of 1933, as amended (the “Securities Act”), in connection with the offering by the Company of (i) up 3,023,650 shares of the Company’s common stock, par value $0.0001 per share (the “Common Stock”), issuable to eligible individuals under the Spyre Therapeutics, Inc. 2016 Equity Incentive Plan (as amended and restated, the “2016 Plan”) and (ii) up to 360,571 shares of Common Stock issuable to eligible individuals under the Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan (as amended and restated, the “ESPP” and together with the 2016 Plan, the “Plans”).

We have examined the Plans and the originals, or photostatic or certified copies, of such records of the Company and certificates of officers of the Company and of public officials and such other documents as we have deemed relevant and necessary as the basis for the opinions set forth below. We have also made such other investigations as we have deemed relevant and necessary or appropriate in connection with the opinion hereinafter set forth. In our examination, we have assumed the genuineness of all signatures, the legal capacity and competency of all natural persons, the authenticity of all documents submitted to us as originals and the conformity to original documents of all documents submitted to us as copies. We have also assumed that there are no agreements or understandings between or among the Company and any participants in the Plans that would expand, modify or otherwise affect the terms of the Plans or the respective rights or obligations of the participants thereunder. Finally, we have assumed the accuracy of all other information provided to us by the Company during the course of our investigations, on which we have relied in issuing the opinion expressed below.

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.

Spyre Therapeutics, Inc.

February 29, 2024

Page 2

Based upon the foregoing examination and in reliance thereon, and subject to the assumptions stated and in reliance on statements of fact contained in the documents that we have examined, we are of the opinion that the shares of Common Stock issuable under the Plans, when issued and sold in accordance with the terms of the Plans and against payment therefor, and when the Registration Statement has become effective under the Securities Act, will be validly issued, fully paid and non-assessable.

We render no opinion herein as to matters involving the laws of any jurisdiction other than the Delaware General Corporation Law (the “DGCL”). We are not admitted to practice in the State of Delaware; however, we are generally familiar with the DGCL as currently in effect and have made such inquiries as we consider necessary to render the opinions above. This opinion is limited to the effect of the current state of the law of the DGCL and the facts as they currently exist. We assume no obligation to revise or supplement this opinion in the event of future changes in such law or the interpretations thereof or such facts.

We consent to the filing of this opinion as an exhibit to the Registration Statement. In giving this consent, we do not thereby admit that we are within the category of persons whose consent is required under Section 7 of the Securities Act or the Rules and Regulations of the Commission.

Very truly yours,

/s/ Gibson, Dunn & Crutcher, LLP

Gibson, Dunn & Crutcher, LLP

Exhibit 23.1

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We hereby consent to the incorporation by reference in this Registration Statement on Form S-8 of Spyre Therapeutics, Inc. of our report dated February 29, 2024 relating to the financial statements, which appears in Spyre Therapeutics, Inc. Annual Report on Form 10-K for the year ended December 31, 2023.

/s/ PricewaterhouseCoopers LLP

Austin, Texas

February 29, 2024

Exhibit 107

Calculation of Filing Fee Tables

FORM S-8

(Form Type)

Spyre Therapeutics, Inc.

(Exact Name of Registrant as Specified in its Charter)

Table 1: Newly Registered Securities