Spyre Therapeutics Inc

As filed with the Securities and Exchange Commission on April 18, 2024

Registration No. 333-

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

(Exact name of registrant as specified in its charter)

221 Crescent Street

Building 23, Suite 105

Waltham,

MA

(617)

651-5940

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Heidy King-Jones

Chief Legal Officer and Corporate Secretary

221 Crescent Street

Building 23, Suite 105

Waltham,

MA

(617)

651-5940

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

Copies to:

Ryan A. Murr

Branden C. Berns

Melanie E. Neary

Gibson, Dunn & Crutcher LLP

One Embarcadero Center, Suite 2600

San Francisco, CA 94111

(415)

393-8373

Approximate date of commencement of proposed sale to the public

: From time to time after the effective date of this Registration Statement.

If any of the securities being registered on this form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box. ☒

If this form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

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. ☐

Pursuant to Rule 429 under the Securities Act of 1933,

as amended,

the prospectus included in this

r

s

tatement is a combined prospectus and also relates to the securities previously registered under the Registrant’s Registration Statement on Form S-1 (File No. 333-2

)

and Registration Statement on Form S-1 (File No. 333-276251)

. Accordingly, this

r

s

tatement, which is a new registration statement, also constitutes Post-Effective Amendment No.

to Registration Statement No. 333-2

73769 and Post-Effective Amendment No. 1 to Registration Statement No. 333-276251

, which post-effective amendment

s

shall hereafter become effective concurrently with the effectiveness of this

r

s

tatement in accordance with Section 8(c) of the Securities Act of 1933

, as amended (the “Securities Act”)

.

The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment that specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act, or until this registration statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

EXPLANATORY NOTE

Spyre Therapeutics, Inc., a Delaware corporation, initially filed with the Securities and

Exchange

Commission (the “SEC”) a Registration Statement on Form

(File

No. 333-273769)

on November 15, 2023, which was declared effective on November 20, 2023 (as subsequently amended, the “November 2023 Prior Registration Statement”), and a Registration Statement on Form

(File

No. 333-276251)

on March 26, 2024, which was declared effective on April 1, 2024 (the “April 2024 Prior Registration Statement” and together with the November 2023 Prior Registration Statement, the “Prior Registration Statements”). The Prior Registration Statements collectively registered the resale of up to (i) 24,809,064 shares of Common Stock (as defined below) and (ii) 6,000,000 shares of Common Stock issuable upon the conversion of 150,000 shares of Series B Preferred Stock (as defined below). A total of (i) 22,496,402 shares of Common Stock and (ii) 6,000,000 shares of Common Stock issuable upon the conversion of 150,000 shares of Series B Preferred Stock registered for resale under the Previous Registration Statements remain unsold.

Pursuant to Rule 429 under the Securities Act, the prospectus included in this registration statement is a combined prospectus and also relates to all the securities registered for resale and remaining unsold under the Prior Registration Statements. Accordingly, this registration statement, which is a new registration statement also constitutes Post-Effective Amendment No. 4 to the November 2023 Prior Registration Statement and Post-Effective Amendment No. 1 to the April 2024 Prior Registration Statement and is being filed to register the resale of up to an additional 4,865,000 shares of Common Stock issuable upon the conversion of 121,625 shares of Series B Preferred Stock that were purchased by certain Selling Stockholders in the March 2024 PIPE (as such terms are defined below). Such post-effective amendments shall hereafter become effective concurrently with the effectiveness of this registration statement in accordance with Section 8(c) of the Securities Act.

Accordingly, this registration statement (i) carries forward from the Prior Registration Statements all the securities registered in the Prior Registration Statements remaining unsold and (ii) registers the resale of up to an additional 4,865,000 shares of Common Stock issuable upon the conversion of 121,625 shares of Series B Preferred Stock.

The information in this prospectus is not complete and may be changed. The selling stockholders named in this prospectus may not sell these securities until the registration statement filed with the Securities and Exchange Commission (the “SEC”) is effective. This prospectus is not an offer to sell these securities, and it is not soliciting an offer to buy these securities, in any jurisdiction where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED APRIL 18, 2024

PRELIMINARY PROSPECTUS

33,361,402 Shares

Common Stock

Offered by the Selling Stockholders

This prospectus relates to the proposed resale or other disposition by the selling stockholders identified herein (the “Selling Stockholders”) of up to (i) 8,864 shares (the “Merger Common Shares”) of our Common Stock, (ii) 248,560 shares of Common Stock (the “Merger Conversion Shares”) that were issued upon the conversion of 6,214 shares (“Merger Preferred Shares”) of our Series A Preferred Stock, par value $0.0001 per share (the “Series A Preferred Stock”), (iii) 16,239,000 shares of Common Stock (the “June 2023 Private Placement Conversion Shares”) that were issued upon the conversion of 405,975 shares (the “June 2023 Private Placement Preferred Shares”) of Series A Preferred Stock, (iv) 5,999,978 shares (the “December 2023 Private Placement Common Shares”) of our common stock, par value $0.0001 per share (“Common Stock”), (v) 6,000,000 shares of Common Stock (the “December 2023 Private Placement Conversion Shares”) issuable upon the conversion of 150,000 shares (the “December 2023 Private Placement Preferred Shares”) of Series B preferred stock, par value $0.0001 (the “Series B Preferred Stock”), and (vi) 4,865,000 shares (the “March 2024 Private Placement Conversion Shares”) of Common Stock issuable upon the conversion of 121,625 shares (the “March 2024 Private Placement Preferred Shares”) of Series B Preferred Stock. Subject to receiving the requisite stockholder approval and certain beneficial ownership limitations set by each preferred stockholder, each share of Series B Preferred Stock will automatically convert upon the requisite stockholder approval into an aggregate of 40 shares of Common Stock. The shares of Common Stock registered by this prospectus are referred to herein as the “Resale Shares.”

The Merger Common Shares and Merger Preferred Shares were issued and sold to our former stockholders in connection with the Asset Acquisition (as defined below), which closed on June 22, 2023. The June 2023 Private Placement Preferred Shares were issued and sold to in a private placement (the “June 2023 PIPE” and, together with the Asset Acquisition, the “June 2023 Transactions”), which closed on June 26, 2023. The December 2023 Private Placement Preferred Shares and December 2023 Private Placement Common Shares were issued and sold to accredited investors in a private placement (the “December 2023 PIPE”), which closed on December 11, 2023. The March 2024 Private Placement Preferred Shares were issued and sold to accredited investors in a private placement (the “March 2024 PIPE”), which closed on March 20, 2024. We are not selling any Resale Shares under this prospectus and will not receive any of the proceeds from the sale or other disposition of Resale Shares by the Selling Stockholders.

The Selling Stockholders may sell the Resale Shares on any national securities exchange or quotation service on which the securities may be listed or quoted at the time of sale, on theover-the-counter market, in one or more transactions otherwise than on these exchanges or systems, such as privately negotiated transactions, or using a combination of these methods, and at fixed prices, at prevailing market prices at the time of the sale, at varying prices determined at the time of sale, or at negotiated prices. See the disclosure under the heading “Plan of Distribution” elsewhere in this prospectus for more information about how the Selling Stockholders may sell or otherwise dispose of their Resale Shares hereunder.

The Selling Stockholders may sell any, all or none of the securities offered by this prospectus and we do not know when or in what amount the Selling Stockholders may sell their Resale Shares hereunder following the effective date of the registration statement of which this prospectus forms a part.

You should carefully read this prospectus and any applicable prospectus supplement before you invest in any of the securities being offered.

Our Common Stock is traded on The Nasdaq Global Select Market under the symbol “SYRE.” On April 17, 2024, the last reported sale price for our Common Stock was $34.31 per share.

An investment in our securities involves a high degree of risk. You should carefully consider the information under the heading “Risk Factors” beginning on page 12 of this prospectus and any applicable prospectus supplement.

We are a “smaller reporting company” as defined by Rule 12b-2 of the Exchange Act and are subject to reduced public company reporting requirements.

Neither the SEC nor any state securities commission has approved or disapproved of these securities or determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date of this prospectus is , 2024