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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>As filed with the Securities and Exchange Commission on February&nbsp;29, 2024 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B>Registration No.&nbsp;333- </B></P> <P STYLE="font-size:4pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>UNITED STATES </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>SECURITIES
AND EXCHANGE COMMISSION </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B>WASHINGTON, DC 20549 </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
<P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>FORM <FONT
STYLE="white-space:nowrap">S-8</FONT> </B></P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>REGISTRATION STATEMENT </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>UNDER </I></B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>THE
SECURITIES ACT OF 1933 </I></B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>SPYRE THERAPEUTICS, INC. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(Exact name of registrant as specified in its charter) </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
<P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="top" ALIGN="center"><B>Delaware</B></TD>
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<TD VALIGN="top" ALIGN="center"><B><FONT STYLE="white-space:nowrap">46-4312787</FONT></B></TD></TR>
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<TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(State or Other Jurisdiction of</B></P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Incorporation or Organization)</B></P></TD>
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<TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(I.R.S. Employer</B></P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Identification No.)</B></P></TD></TR>
</TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>221 Crescent Street </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Building 23 </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Suite 105
</B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Waltham, Massachusetts 02453 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(617) <FONT STYLE="white-space:nowrap">651-5940</FONT> </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Address of Principal Executive Offices, Zip Code) </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Spyre Therapeutics, Inc. 2016 Equity Incentive Plan, As Amended and Restated </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, As Amended and Restated </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Full title of the plans) </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Heidy King-Jones </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Chief
Legal Officer and Corporate Secretary </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Spyre Therapeutics, Inc. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>221 Crescent Street </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Building 23 </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Suite 105
</B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Waltham, Massachusetts 02453 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Name, address, including zip code, and telephone number, including area code, of agent for service) </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><I>Copy to: </I></B></P> <P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Ryan
Murr </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Branden Berns </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Gibson, Dunn&nbsp;&amp; Crutcher LLP </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>One Embarcadero Center, Suite 3000 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>San Francisco, CA 94111 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(415) <FONT STYLE="white-space:nowrap">393-8373</FONT> </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
<P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Indicate by check mark whether
the registrant is a large accelerated filer, an accelerated filer, a <FONT STYLE="white-space:nowrap">non-accelerated</FONT> filer, a smaller reporting company or an emerging growth company. See the definitions of &#147;large accelerated
filer,&#148; &#147;accelerated filer&#148;, &#147;smaller reporting company&#148; and &#147;emerging growth company&#148; in Rule <FONT STYLE="white-space:nowrap">12b-2</FONT> of the Exchange Act. </P>
<P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="bottom">Large&nbsp;accelerated&nbsp;filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom">Accelerated&nbsp;filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD></TR>
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<TD VALIGN="bottom">Non-accelerated filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9746;</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom">Smaller&nbsp;reporting&nbsp;company</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9746;</TD></TR>
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<TD VALIGN="bottom">&nbsp;</TD>
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<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom">Emerging&nbsp;growth&nbsp;company</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD></TR>
</TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">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&nbsp;7(a)(2)(B) of the Securities Act.&#8194;&#9744; </P> <P STYLE="font-size:10pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>EXPLANATORY NOTE </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> is being filed by Spyre Therapeutics, Inc. (f/k/a Aeglea
BioTherapeutics, Inc.) (the &#147;<B><I>Registrant</I></B>&#148;) pursuant to General Instruction E to Form <FONT STYLE="white-space:nowrap">S-8,</FONT> 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 (&#147;<B><I>Common Stock</I></B>&#148;), issuable under the Registrant&#146;s Equity Incentive Plan (as amended and restated, the &#147;<B><I>2016 Plan</I></B>&#148;) and (ii) 360,571 shares of Common
Stock, issuable under the Registrant&#146;s 2016 Employee Stock Purchase Plan (as amended and restated, the &#147;<B><I>ESPP</I></B>&#148;), pursuant to the provisions of those plans providing for an automatic increase in the number of shares
reserved for issuance under such plans. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The information contained in the Registrant&#146;s registration statements on Form <FONT
STYLE="white-space:nowrap">S-8</FONT> filed with the Securities and Exchange Commission (&#147;<B><I>SEC</I></B>&#148;) on </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">April&nbsp;7,
2016 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312516532563/d173440ds8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-210633</FONT></A>), March&nbsp;
23, 2017 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459017005140/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-216903</FONT></A>), March&nbsp;
13, 2018 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459018005405/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-223614</FONT></A>), March&nbsp;
7, 2019 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459019006831/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-230137</FONT></A>), February&nbsp;
24, 2020 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459020005895/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-236584</FONT></A>), March&nbsp;
18, 2021 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459021014024/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-254430</FONT></A>), March&nbsp;
8, 2022 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000156459022008998/agle-s8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-263357</FONT></A>), March&nbsp;
2, 2023 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312523057310/d472327ds8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-270208</FONT></A>), and December&nbsp;
22, 2023 (Registration No.<A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312523302201/d593177ds8.htm"><FONT STYLE="white-space:nowrap">&nbsp;333-276256</FONT></A>), together with all exhibits filed therewith or incorporated therein by
reference, are hereby incorporated by reference pursuant to General Instruction E to Form <FONT STYLE="white-space:nowrap">S-8,</FONT> 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. </P> <P STYLE="margin-top:24pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>PART I </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="2%" VALIGN="top" ALIGN="left"><B>Item</B></TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><B>1. Plan Information</B>. </P></TD></TR></TABLE>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The documents containing the information required by Part I of Form <FONT STYLE="white-space:nowrap">S-8</FONT> (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 &#147;<B><I>Securities Act</I></B>&#148;). 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&nbsp;10(a) of the Securities Act. </P>
<P STYLE="margin-top:24pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>PART II </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>INFORMATION
REQUIRED IN THE REGISTRATION STATEMENT </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="10%" VALIGN="top" ALIGN="left"><B>Item&#8201;8.</B></TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left"><B>Exhibits. </B></P></TD></TR></TABLE> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="bottom" NOWRAP ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman; " ALIGN="center"><B>Exhibit<BR>Number</B></P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom" NOWRAP ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman; " ALIGN="center"><B>Exhibit Description</B></P></TD></TR>


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<TD VALIGN="top" NOWRAP>&#8199;4.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312523283693/d610145dex31.htm">Amended and Restated Certificate of Incorporation of the Company, effective as of November<U></U>&nbsp;
28, 2023 (incorporated by reference to Exhibit 3.1 to the Registrant&#146;s Current Report on Form <FONT STYLE="white-space:nowrap">8-K</FONT> filed on November<U></U>&nbsp;28, 2023).</A></TD></TR>
<TR STYLE="font-size:1pt">
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<TD VALIGN="top" NOWRAP>&#8199;4.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312524023462/d732838dex31.htm">Amended and Restated Bylaws of the Company, effective as of February<U></U>&nbsp;
1, 2024 (incorporated by reference to Exhibit 3.1 to the Registrant&#146;s Current Report on Form <FONT STYLE="white-space:nowrap">8-K</FONT> filed on February<U></U>&nbsp;5, 2024). </A></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;5.1*</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d516790dex51.htm">Opinion of Gibson, Dunn&nbsp;&amp; Crutcher LLP </A></TD></TR>
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<TD VALIGN="top" NOWRAP>23.1*</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d516790dex231.htm">Consent of PricewaterhouseCoopers LLP, independent registered public accounting firm </A></TD></TR>
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<TD VALIGN="top" NOWRAP>23.2*</TD>
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<TD VALIGN="top"><A HREF="d516790dex51.htm">Consent of Gibson, Dunn&nbsp;&amp; Crutcher LLP (included in Exhibit 5.1) </A></TD></TR>
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<TD VALIGN="top" NOWRAP>24.1*</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="#sig">Power of Attorney (included on the signature page of this Registration Statement) </A></TD></TR>
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<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
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<TD VALIGN="top" NOWRAP>99.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000119312523302201/d593177dex991.htm">Spyre Therapeutics, Inc. 2016 Equity Incentive Plan, As Amended and Restated Effective November<U></U>&nbsp;
21, 2023 (incorporated by reference to Exhibit&nbsp;99.1 to the Registrant&#146;s Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> filed on December<U></U>&nbsp;22, 2023).</A></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" NOWRAP>99.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1636282/000163628224000005/ex104_spyre-2016employeest.htm">Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, as amended by the First Amendment on January&nbsp;
31, 2024 (incorporated by reference to Exhibit&nbsp;10.4 to the Registrant&#146;s Annual Report on Form <FONT STYLE="white-space:nowrap">10-K</FONT> filed on February&nbsp;29, 2024).</A></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" NOWRAP>107</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d516790dexfilingfees.htm">Filing Fee Table </A></TD></TR>
</TABLE> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">*</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Filed herewith. </P></TD></TR></TABLE>
</DIV></Center>


<p style="margin-top:1em; margin-bottom:0em; page-break-before:always"> </p>
<HR SIZE="3" style="COLOR:#999999" WIDTH="100%" ALIGN="CENTER">


<Center><DIV STYLE="width:8.5in" align="left">
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>SIGNATURES </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">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 <FONT STYLE="white-space:nowrap">S-8</FONT> 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<SUP
STYLE="font-size:75%; vertical-align:top">th</SUP> day of February, 2024. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><DIV ALIGN="right">
<TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="40%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">


<TR>

<TD WIDTH="12%"></TD>

<TD VALIGN="bottom" WIDTH="1%"></TD>
<TD WIDTH="87%"></TD></TR>


<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" COLSPAN="3"><B>SPYRE THERAPEUTICS, INC.</B></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">By:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:1pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Cameron Turtle, DPhil</P></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Name:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top">Cameron Turtle, DPhil</TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Title:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top">Chief Executive Officer</TD></TR>
</TABLE></DIV> <P STYLE="margin-top:24pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><A NAME="sig"></A>POWER OF ATTORNEY </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman"><B>KNOW ALL PERSONS BY THESE PRESENTS,</B>&nbsp;that each person whose signature appears below hereby constitutes and appoints
Dr.&nbsp;Cameron Turtle and Mr.&nbsp;Scott Burrows, jointly and severally, as his or her true and <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">lawful&nbsp;attorney-in-fact&nbsp;and</FONT></FONT> 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 <FONT STYLE="white-space:nowrap">Form&nbsp;S-8,&nbsp;and</FONT> to file the same, with all
exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">said&nbsp;attorney-in-fact&nbsp;and</FONT></FONT> 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 <FONT
STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">said&nbsp;attorney-in-fact&nbsp;and</FONT></FONT> agent, or his or her substitute, may lawfully do or cause to be done by virtue hereof. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">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. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
<TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">


<TR>

<TD WIDTH="35%"></TD>

<TD VALIGN="bottom" WIDTH="1%"></TD>
<TD WIDTH="32%"></TD>

<TD VALIGN="bottom" WIDTH="1%"></TD>
<TD WIDTH="31%"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
<TD VALIGN="bottom" NOWRAP> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman; ">Signature</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom" NOWRAP ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman; " ALIGN="center">Title</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom" NOWRAP ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; border-bottom:1.00pt solid #000000; display:table-cell; font-size:8pt; font-family:Times New Roman; " ALIGN="center">Date</P></TD></TR>


<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Cameron Turtle, DPhil</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Cameron Turtle, DPhil</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Chief Executive Officer and Director</P> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">(Principal
Executive Officer)</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Scott Burrows</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Scott Burrows</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Chief Financial Officer</P> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">(Principal Financial
Officer and Principal Accounting Officer)</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Russell J. Cox</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Russell J. Cox</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Chairman of the Board</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Jeffrey W. Albers</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Jeffrey W. Albers</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Peter Harwin</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Peter Harwin</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Michael Henderson, M.D.</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Michael Henderson, M.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Tomas Kiselak</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Tomas Kiselak</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Mark McKenna</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Mark McKenna</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Laurie Stelzer</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Laurie Stelzer</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">February&nbsp;29, 2024</TD></TR>
</TABLE>
</DIV></Center>

</BODY></HTML>
[{"type": "S-8", "sequence": "1", "filename": "d516790ds8.htm", "description": "S-8", "secsgml_size_bytes": 34710}]
{"company-data": {"conformed-name": "Spyre Therapeutics, Inc.", "cik": "0001636282", "assigned-sic": "2834", "organization-name": "03 Life Sciences", "irs-number": "464312787", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-277542", "film-number": "24704947"}, "business-address": {"street1": "221 CRESCENT STREET", "street2": "BUILDING 23, SUITE 105", "city": "WALTHAM", "state": "MA", "zip": "02453", "phone": "6176515940"}, "mail-address": {"street1": "221 CRESCENT STREET", "street2": "BUILDING 23, SUITE 105", "city": "WALTHAM", "state": "MA", "zip": "02453"}, "former-company": {"former-conformed-name": "Aeglea BioTherapeutics, Inc.", "date-changed": "20150311"}}
S-8
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)
Delaware
46-4312787
(State or Other Jurisdiction of
Incorporation or Organization)
(I.R.S. Employer
Identification No.)
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.
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
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
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
Amended and Restated Certificate of Incorporation of the Company, effective as of November
28, 2023 (incorporated by reference to Exhibit 3.1 to the Registrant's Current Report on Form
8-K
filed on November
28, 2023).
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. 2016 Equity Incentive Plan, As Amended and Restated Effective November
21, 2023 (incorporated by reference to Exhibit 99.1 to the Registrant's Registration Statement on Form
S-8
filed on December
22, 2023).
99.2
Spyre Therapeutics, Inc. 2016 Employee Stock Purchase Plan, as amended by the First Amendment on January 
31, 2024 (incorporated by reference to Exhibit 10.4 to the Registrant's Annual Report on Form
10-K
filed on February 29, 2024).
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 29
th
day of February, 2024.
SPYRE THERAPEUTICS, INC.
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
Cameron Turtle, DPhil
Chief Executive Officer and Director
(Principal
Executive Officer)
February 29, 2024
/s/ Scott Burrows
Scott Burrows
Chief Financial Officer
(Principal Financial
Officer and Principal Accounting Officer)
February 29, 2024
/s/ Russell J. Cox
Russell J. Cox
Chairman of the Board
February 29, 2024
/s/ Jeffrey W. Albers
Jeffrey W. Albers
Director
February 29, 2024
/s/ Peter Harwin
Peter Harwin
Director
February 29, 2024
/s/ Michael Henderson, M.D.
Michael Henderson, M.D.
Director
February 29, 2024
/s/ Tomas Kiselak
Tomas Kiselak
Director
February 29, 2024
/s/ Mark McKenna
Mark McKenna
Director
February 29, 2024
/s/ Laurie Stelzer
Laurie Stelzer
Director
February 29, 2024