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<title>Document</title></head><body><div id="ie77655cf466e4e2ca2b77d7d413f6bca_1"></div><div style="min-height:45pt;width:100%"><div><font><br></font></div></div><div style="margin-top:6pt;text-align:center"><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:98.900%"></td><td style="width:0.1%"></td></tr><tr style="height:3pt"><td colspan="3" style="border-bottom:3pt double #000;padding:0 1pt"></td></tr></table></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">As filed with the Securities and Exchange Commission on November 7, 2024 </font></div><div style="text-align:right"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Registration No. 333- </font></div><div><font><br></font></div><div><font><br></font></div><div><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:18pt;font-weight:700;line-height:112%">UNITED STATES </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:18pt;font-weight:700;line-height:112%">SECURITIES AND EXCHANGE COMMISSION </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:12pt;font-weight:700;line-height:112%">WASHINGTON, DC 20549 </font></div><div><font><br></font></div><div><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:18pt;font-weight:700;line-height:112%">FORM S-8 </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:18pt;font-weight:700;line-height:112%">REGISTRATION STATEMENT </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:12pt;font-style:italic;font-weight:700;line-height:112%">UNDER </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:12pt;font-style:italic;font-weight:700;line-height:112%">THE SECURITIES ACT OF 1933 </font></div><div><font><br></font></div><div><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:24pt;font-weight:700;line-height:112%">SPYRE THERAPEUTICS, INC. </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">(Exact name of registrant as specified in its charter) </font></div><div style="margin-top:6pt;text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:120%">___________________________________________________________________________________________________</font><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:32.233%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:32.233%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:32.234%"></td><td style="width:0.1%"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:100%">Delaware</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:100%">46-4312787</font></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:7.5pt;font-weight:700;line-height:120%">(State or Other Jurisdiction<br>of Incorporation)</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:7.5pt;font-weight:700;line-height:120%">(IRS Employer<br>Identification No.)</font></td></tr><tr><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:120%">221 Crescent Street</font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:120%">Building 23</font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:120%">Suite 105</font></div></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:100%">Waltham, Massachusetts 02453 </font></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:7.5pt;font-weight:700;line-height:100%">(Address of Principal Executive Offices, Zip Code)</font></td><td colspan="3" style="padding:0 1pt"></td></tr></table></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Spyre Therapeutics, Inc. 2018 Equity Inducement Plan</font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:8pt;font-weight:700;line-height:112%">(Full title of the plans) </font></div><div style="text-align:center"><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Heidy King-Jones </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Chief Legal Officer and Corporate Secretary </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Spyre Therapeutics, Inc. </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">221 Crescent Street </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Building 23 </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Suite 105 </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Waltham, Massachusetts 02453 </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:8pt;font-weight:700;line-height:112%">(Name, address, including zip code, and telephone number, including area code, of agent for service) </font></div><div style="text-align:center"><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">Copy to&#58; </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Ryan Murr </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Branden Berns </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Gibson, Dunn &#38; Crutcher LLP </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">One Embarcadero Center, Suite 3000 </font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">San Francisco, CA 94111 </font></div><div style="margin-top:6pt;text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:120%">___________________________________________________________________________________________________</font></div><div style="text-align:center"><font><br></font></div><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">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 &#8220;large accelerated filer,&#8221; &#8220;accelerated filer&#8221;, &#8220;smaller reporting company&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act. </font></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:95.909%"><tr><td style="width:1.0%"></td><td style="width:25.914%"></td><td style="width:0.1%"></td><td style="width:0.1%"></td><td style="width:0.589%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:13.591%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:13.591%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:25.282%"></td><td style="width:0.1%"></td><td style="width:0.1%"></td><td style="width:1.537%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:13.596%"></td><td style="width:0.1%"></td></tr><tr style="height:15pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Large accelerated filer</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9744;</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Accelerated filer</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9744;</font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Non-accelerated filer</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9746;</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Smaller reporting company</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9746;</font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Emerging growth company</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9744;</font></div></td></tr></table></div><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">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.&#8194;</font><font style="color:#000000;font-family:'Arial',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#9744;</font><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:98.900%"></td><td style="width:0.1%"></td></tr><tr style="height:3pt"><td colspan="3" style="border-bottom:3pt double #000;padding:0 1pt"></td></tr></table></div><div style="height:45pt;position:relative;width:100%"><div style="bottom:0;position:absolute;width:100%"><div><font><br></font></div></div></div><div id="ie77655cf466e4e2ca2b77d7d413f6bca_7"></div><hr style="page-break-after:always"><div style="min-height:45pt;width:100%"><div><font><br></font></div></div><div><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">EXPLANATORY NOTE </font></div><div style="text-align:center"><font><br></font></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">On September 20, 2024, Spyre Therapeutics, Inc. (the &#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">Registrant</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;) amended the Registrant&#8217;s 2018 Equity Inducement Plan (as amended, the &#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">2018 Plan</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;) to provide for the issuance of an additional 1,000,000 shares (the &#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">Additional Shares</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;) of common stock, par value $0.0001 per share (&#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">Common Stock</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;), which may be granted by the Registrant to certain employees as a material inducement to their acceptance of employment with the Registrant in accordance with Nasdaq Listing Rule 5635(c)(4). These shares are in addition to the 6,044,000 shares of Common Stock previously authorized for issuance pursuant to the 2018 Plan.</font></div><div style="text-indent:24.5pt"><font><br></font></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">This Registration Statement on Form S-8 is being filed by the Registrant pursuant to General Instruction E to Form S-8, under the Securities Act of 1933, as amended, to register the Additional Shares to be issued pursuant to the 2018 Plan.</font></div><div style="text-indent:24.5pt"><font><br></font></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">The information contained in the Registrant&#8217;s registration statements on Form S-8 filed with the Securities and Exchange Commission (&#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">SEC</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;) on March 13, 2018 (Registration No.333-223614) 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 2018 Plan. </font></div><div style="height:45pt;position:relative;width:100%"><div style="bottom:0;position:absolute;width:100%"><div><font><br></font></div></div></div><div id="ie77655cf466e4e2ca2b77d7d413f6bca_118"></div><hr style="page-break-after:always"><div style="min-height:45pt;width:100%"><div><font><br></font></div></div><div><font><br></font></div><div id="ie77655cf466e4e2ca2b77d7d413f6bca_10"></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">PART I </font></div><div style="text-align:center"><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS </font></div><div style="text-align:center"><font><br></font></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:33.636%"><tr><td style="width:1.0%"></td><td style="width:93.945%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:3.855%"></td><td style="width:0.1%"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Item 1. Plan Information</font></td><td colspan="3" style="padding:0 1pt"></td></tr></table></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">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 &#8220;</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-style:italic;font-weight:700;line-height:112%">Securities Act</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#8221;). 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. </font></div><div style="text-indent:24.5pt"><font><br></font></div><div id="ie77655cf466e4e2ca2b77d7d413f6bca_107"></div><div style="text-align:center"><font><br></font></div><div style="-sec-extract:summary;text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">PART II </font></div><div style="text-align:center"><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">INFORMATION REQUIRED IN THE REGISTRATION STATEMENT </font></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:32.424%"><tr><td style="width:1.0%"></td><td style="width:53.572%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:44.228%"></td><td style="width:0.1%"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Item&#8201;8. Exhibits</font></td><td colspan="3" style="padding:0 1pt"></td></tr></table></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:12.990%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:12.990%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:70.720%"></td><td style="width:0.1%"></td></tr><tr style="height:15pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Exhibit Number</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:center;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">Exhibit Description</font></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">4.1</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%"><a href="https://www.sec.gov/Archives/edgar/data/1636282/000119312524138893/d839821dex32.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:none">Second Amended and Restated Certificate of Incorporation of the Company, effective as of May 14, 2024 (incorporated by reference to Exhibit 3.2 to the Registrant&#8217;s Current Report on Form 8-K filed on May 15, 2024).</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">4.2</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%"><a href="https://www.sec.gov/Archives/edgar/data/1636282/000119312524023462/d732838dex31.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:none">Amended and Restated Bylaws of the Company, effective as of February 1, 2024 (incorporated by reference to Exhibit 3.1 to the Registrant&#8217;s Current Report on Form 8-K filed on February 5, 2024).</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">5.1*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="ex51-gibsonopinion.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Opinion of Gibson, Dunn &#38; Crutcher LLP</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">23.1*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="ex231pwcs-8consent.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">23.2*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="ex51-gibsonopinion.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Consent of Gibson, Dunn &#38; Crutcher LLP (included in Exhibit 5.1)</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">24.1*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="#ie77655cf466e4e2ca2b77d7d413f6bca_13" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Power of Attorney (included on the signature page of this Registration Statement)</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">99.1*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="ex9912018equityinducementp.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment, Fourth Amendment and Fifth Amendment thereto.</a></font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">107*</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline"><a href="ex107feetablespyredraft102.htm" style="-sec-extract:exhibit;color:#0000ff;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%;text-decoration:underline">Filing Fee Table</a></font></div></td></tr></table></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:18.787%"><tr><td style="width:1.0%"></td><td style="width:23.900%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:73.900%"></td><td style="width:0.1%"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">*</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Filed herewith.</font></td></tr></table></div><div style="height:45pt;position:relative;width:100%"><div style="bottom:0;position:absolute;width:100%"><div><font><br></font></div></div></div><div id="ie77655cf466e4e2ca2b77d7d413f6bca_13"></div><hr style="page-break-after:always"><div style="min-height:45pt;width:100%"><div><font><br></font></div></div><div style="margin-top:12pt;text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:120%">SIGNATURES</font></div><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">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 7</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:6.47pt;font-weight:400;line-height:112%;position:relative;top:-3.48pt;vertical-align:baseline">th</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%"> day of November, 2024. </font></div><div style="margin-top:12pt"><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:4.472%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:43.779%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:2.966%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:43.779%"></td><td style="width:0.1%"></td><td style="width:0.1%"></td><td style="width:0.404%"></td><td style="width:0.1%"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:114%">SPYRE THERAPEUTICS, INC.</font></div></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">Date&#58;</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div style="margin-top:6pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:120%">November 7, 2024</font></div></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">By&#58; </font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#47;s&#47; Cameron Turtle, DPhil</font></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:114%">&#160;</font></td><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:120%">Name&#58; Cameron Turtle, DPhil<br>Title&#58;  Chief Executive Officer</font></td><td colspan="3" style="padding:0 1pt"></td></tr></table></div><div style="text-align:center"><font><br></font></div><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">POWER OF ATTORNEY </font></div><div style="text-align:center"><font><br></font></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:700;line-height:112%">KNOW ALL PERSONS BY THESE PRESENTS,</font><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%"> 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. </font></div><div style="text-indent:24.5pt"><font><br></font></div><div style="text-indent:24.5pt"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">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. </font></div><div><table style="border-collapse:collapse;display:inline-table;margin-bottom:5pt;vertical-align:text-bottom;width:100.000%"><tr><td style="width:1.0%"></td><td style="width:24.354%"></td><td style="width:0.1%"></td><td style="width:0.1%"></td><td style="width:0.406%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:51.627%"></td><td style="width:0.1%"></td><td style="width:0.1%"></td><td style="width:1.466%"></td><td style="width:0.1%"></td><td style="width:1.0%"></td><td style="width:18.447%"></td><td style="width:0.1%"></td></tr><tr style="height:15pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:8pt;font-weight:400;line-height:112%">Signature</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:8pt;font-weight:400;line-height:112%">Title</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div style="text-align:center"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:8pt;font-weight:400;line-height:112%">Date</font></div></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Cameron Turtle, DPhil</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Chief Executive Officer and Director</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Cameron Turtle, DPhil</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">(Principal Executive Officer)</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Scott Burrows</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Chief Financial Officer</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Scott Burrows</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">(Principal Financial Officer and Principal Accounting Officer)</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Jeffrey W. Albers</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Chairman of the Board</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Jeffrey W. Albers</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Peter Harwin</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Director</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Peter Harwin</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Michael Henderson, M.D.</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Director</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Michael Henderson, M.D.</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Tomas Kiselak</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Director</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Tomas Kiselak</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Mark McKenna</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Director</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Mark McKenna</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; Sandra Milligan</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Director</font></div></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">November 7, 2024</font></div></td></tr><tr><td colspan="3" style="border-top:1pt solid #000;padding:2px 1pt;text-align:left;vertical-align:top"><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">Sandra Milligan</font></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td><td colspan="3" style="padding:0 1pt"></td></tr><tr style="height:6pt"><td colspan="3" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td><td colspan="6" style="padding:0 1pt"></td></tr><tr><td colspan="3" style="padding:2px 1pt;text-align:left;vertical-align:top"><div><font style="color:#000000;font-family:'Times New Roman',sans-serif;font-size:10pt;font-weight:400;line-height:112%">&#47;s&#47; 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Document
As filed with the Securities and Exchange Commission on November 7, 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)
___________________________________________________________________________________________________
Delaware
46-4312787
(State or Other Jurisdiction
of Incorporation)
(IRS Employer
Identification No.)
221 Crescent Street
Building 23
Suite 105
Waltham, Massachusetts 02453
(Address of Principal Executive Offices, Zip Code)
Spyre Therapeutics, Inc. 2018 Equity Inducement Plan
(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
___________________________________________________________________________________________________
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.
Large accelerated filer
☐
Accelerated filer
☐
Non-accelerated filer
☒
Smaller reporting company
☒
Emerging growth company
☐
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
On September 20, 2024, Spyre Therapeutics, Inc. (the "
Registrant
") amended the Registrant's 2018 Equity Inducement Plan (as amended, the "
2018 Plan
") to provide for the issuance of an additional 1,000,000 shares (the "
Additional Shares
") of common stock, par value $0.0001 per share ("
Common Stock
"), which may be granted by the Registrant to certain employees as a material inducement to their acceptance of employment with the Registrant in accordance with Nasdaq Listing Rule 5635(c)(4). These shares are in addition to the 6,044,000 shares of Common Stock previously authorized for issuance pursuant to the 2018 Plan.
This Registration Statement on Form S-8 is being filed by the Registrant pursuant to General Instruction E to Form S-8, under the Securities Act of 1933, as amended, to register the Additional Shares to be issued pursuant to the 2018 Plan.
The information contained in the Registrant's registration statements on Form S-8 filed with the Securities and Exchange Commission ("
SEC
") on March 13, 2018 (Registration No.333-223614) 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 2018 Plan.
PART I
INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS
Item 1. Plan Information
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
Item 8. Exhibits
Exhibit Number
Exhibit Description
4.1
Second Amended and Restated Certificate of Incorporation of the Company, effective as of May 14, 2024 (incorporated by reference to Exhibit 3.2 to the Registrant's Current Report on Form 8-K filed on May 15, 2024).
4.2
Amended and Restated Bylaws of the Company, effective as of February 1, 2024 (incorporated by reference to Exhibit 3.1 to the Registrant's Current Report on Form 8-K filed on February 5, 2024).
5.1*
Opinion of Gibson, Dunn & Crutcher LLP
23.1*
Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm
23.2*
Consent of Gibson, Dunn & Crutcher LLP (included in Exhibit 5.1)
24.1*
Power of Attorney (included on the signature page of this Registration Statement)
99.1*
Spyre Therapeutics, Inc. 2018 Equity Inducement Plan and the First Amendment, Second Amendment, Third Amendment, Fourth Amendment and Fifth Amendment thereto.
107*
Filing Fee Table
*
Filed herewith.
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 7
th
day of November, 2024.
SPYRE THERAPEUTICS, INC.
Date:
November 7, 2024
By:
/s/ Cameron Turtle, DPhil
Name: Cameron Turtle, DPhil
Title:  Chief Executive Officer
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.
Signature
Title
Date
/s/ Cameron Turtle, DPhil
Chief Executive Officer and Director
November 7, 2024
Cameron Turtle, DPhil
(Principal Executive Officer)
/s/ Scott Burrows
Chief Financial Officer
November 7, 2024
Scott Burrows
(Principal Financial Officer and Principal Accounting Officer)
/s/ Jeffrey W. Albers
Chairman of the Board
November 7, 2024
Jeffrey W. Albers
/s/ Peter Harwin
Director
November 7, 2024
Peter Harwin
/s/ Michael Henderson, M.D.
Director
November 7, 2024
Michael Henderson, M.D.
/s/ Tomas Kiselak
Director
November 7, 2024
Tomas Kiselak
/s/ Mark McKenna
Director
November 7, 2024
Mark McKenna
/s/ Sandra Milligan
Director
November 7, 2024
Sandra Milligan
/s/ Laurie Stelzer
Director
November 7, 2024
Laurie Stelzer