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  <TITLE>S-8</TITLE>
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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 March&nbsp;27, 2025 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B>Registration <FONT STYLE="white-space:nowrap">No.&nbsp;333-&#8195;&#8195;&#8195;</FONT> </B></P>
  <P STYLE="font-size:4pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P> <P STYLE="line-height:1.0pt;margin-top:0pt;margin-bottom:0pt;border-bottom:1px solid #000000">&nbsp;</P>
  <P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&nbsp;</P> <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, D.C. 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:0pt; 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>SEPTERNA, 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>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:8pt" ALIGN="center">
  
  
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  <TD VALIGN="top" ALIGN="center"><B>Delaware</B></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"><B><FONT STYLE="white-space:nowrap">84-3891440</FONT></B></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <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>
  <TD VALIGN="bottom">&nbsp;</TD>
  <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>Septerna, Inc. </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>250 East Grand Avenue </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>South San Francisco, California 94080 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(650) <FONT STYLE="white-space:nowrap">338-3533</FONT> </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Address, including zip code and telephone number, including area code, of registrant&#146;s principal executive offices) </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Septerna, Inc. 2024 Stock Option and Incentive Plan </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>Jeffrey Finer, M.D., Ph.D. </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>President and Chief Executive Officer </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Septerna, Inc. </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>250 East
  Grand Avenue </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>South San Francisco, California 94080 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(650) <FONT STYLE="white-space:nowrap">338-3533</FONT> </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="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" ALIGN="center"><B><I>Copies to: </I></B></P>
  <P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Mitchell S. Bloom </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Deepa
  M. Rich </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Adam V. Johnson </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Goodwin Procter LLP </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>601
  Marshall Street </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Redwood City, California 94063 </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(650) <FONT STYLE="white-space:nowrap">752-3100</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 filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9744;</TD></TR>
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  <TD VALIGN="bottom"><FONT STYLE="white-space:nowrap">Non-accelerated&nbsp;filer</FONT></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 growth company</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9746;</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>
  <P STYLE="line-height:1.0pt;margin-top:0pt;margin-bottom:0pt;border-bottom:1px solid #000000">&nbsp;</P> <P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&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 <FONT STYLE="white-space:nowrap">on&nbsp;Form&nbsp;S-8&nbsp;(this</FONT> &#147;Registration Statement&#148;)
  is&nbsp;being filed for the purposes of registering&nbsp;an additional 2,221,125 shares of common stock, par value $0.001 per share (&#147;Common Stock&#148;), of Septerna, Inc. (the &#147;Registrant&#148;) to be issued under the Registrant&#146;s
  2024 Stock Option and Incentive Plan (the &#147;2024 Plan&#148;). </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The number of shares of Common Stock reserved and available for
  issuance under the 2024 Plan is subject to an automatic annual increase on each January&nbsp;1 by an amount equal to the lesser of: (i)&nbsp;five percent (5%) of the number of shares of Common Stock issued and outstanding on the immediately
  preceding December&nbsp;31, or (ii)&nbsp;such number of shares of Common Stock as determined by the Administrator (as defined in the 2024 Plan). Accordingly, on January&nbsp;1, 2025, the number of shares of Common Stock reserved and available for
  issuance under the 2024 Plan increased by 2,221,125 (the &#147;Additional Shares&#148;). This Registration Statement registers the Additional Shares. The Additional Shares are of the same class as other securities relating to the 2024 Plan for which
  the Registrant&#146;s Registration Statement <FONT STYLE="white-space:nowrap">on&nbsp;Form&nbsp;S-8</FONT> <FONT STYLE="white-space:nowrap">(File&nbsp;No.&nbsp;333-282837)&nbsp;filed</FONT> with the Securities and Exchange Commission (the
  &#147;Commission&#148;) on October&nbsp;25, 2024 is effective (the &#147;Prior Registration Statement&#148;). </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Pursuant to General
  Instruction E <FONT STYLE="white-space:nowrap">to&nbsp;Form&nbsp;S-8,&nbsp;the&nbsp;contents</FONT> of the Prior Registration Statement, except for &#147;Item 8. Exhibits&#148;, are hereby incorporated by reference, except to the extent
  supplemented, amended or superseded by the information set forth herein. Only those items <FONT STYLE="white-space:nowrap">of&nbsp;Form&nbsp;S-8&nbsp;containing&nbsp;new</FONT> information not contained in the Prior Registration Statement is
  presented herein. </P>
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   <P STYLE="margin-top:0pt; 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="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Item&#8201;8. Exhibits. </B></P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>EXHIBIT INDEX
  </B></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">
  
  
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  <TD VALIGN="bottom" NOWRAP ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"><B>Exhibit&nbsp;No.</B></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>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/1984086/000119312524245578/d851611dex31.htm">Amended and Restated Certificate of Incorporation of the Registrant (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 with the Commission on October<U></U>&nbsp;28, 2024 (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-42382)).</FONT><U>&nbsp;</U></A></TD></TR>
  <TR STYLE="font-size:1pt">
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  <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>&#8199;4.2</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1984086/000119312524245578/d851611dex32.htm">Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit 3.2 to the Registrant&#146;s Current Report on Form <FONT
  STYLE="white-space:nowrap">8-K,</FONT> filed with the Commission on October<U></U>&nbsp;28, 2024 (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-42382)).</FONT><U>&nbsp;</U></A></TD></TR>
  <TR STYLE="font-size:1pt">
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  <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>&#8199;4.3</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1984086/000119312524239994/d762905dex42.htm">Specimen Common Stock Certificate (incorporated by reference to Exhibit 4.2 to the Registrant&#146;s Registration Statement on Form <FONT
  STYLE="white-space:nowrap">S-1,</FONT> as amended, filed with the Commission on October<U></U>&nbsp;21, 2024 (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-282469)).</FONT><U>&nbsp;</U></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>&#8199;4.4&#134;</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1984086/000119312524231178/d762905dex41.htm">Amended and Restated Investors&#146; Rights Agreement, by and among the Registrant and certain of its stockholders, dated as of June<U></U>&nbsp;28,
   2023 (incorporated by reference to Exhibit 4.1 to the Registrant&#146;s Registration Statement on Form <FONT STYLE="white-space:nowrap">S-1,</FONT> as amended, filed with the Commission on October<U></U>&nbsp;2, 2024 (File No.<U></U><FONT
  STYLE="white-space:nowrap">&nbsp;333-282469)).</FONT><U>&nbsp;</U></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>&#8199;5.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d943795dex51.htm">Opinion of Goodwin Procter LLP. </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>23.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d943795dex231.htm">Consent of Independent Registered Public Accounting Firm. </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>23.2*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d943795dex51.htm">Consent of Goodwin Procter LLP (included in Exhibit 5.1). </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>24.1*</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d943795ds8.htm#sig">Power of Attorney (included on signature page). </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>99.1</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1984086/000119312524239994/d762905dex102.htm">Septerna, Inc. 2024 Stock Option and Incentive Plan and forms of award agreements thereunder (incorporated by reference to Exhibit 10.2 to the
  Registrant&#146;s Registration Statement on Form <FONT STYLE="white-space:nowrap">S-1,</FONT> as amended, filed with the Commission on October<U></U>&nbsp;21, 2024 (File
  No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-282469)).</FONT></A><U>&nbsp;</U></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="d943795dexfilingfees.htm">Filing Fee Table </A></TD></TR>
  </TABLE> <P STYLE="line-height:8.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000;width:11%">&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>
  <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">&#134;</TD>
  <TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Annexes, schedules and/or exhibits have been omitted pursuant to Item 601(a)(5) of Regulation <FONT
  STYLE="white-space:nowrap">S-K.</FONT> The Registrant agrees to furnish supplementally a copy of any omitted attachment to the Commission on a confidential basis upon request. </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><A NAME="sig"></A>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 of 1933, 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 the City of South San Francisco,
  California, on this 27th day of March, 2025. </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="7%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="12%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="79%"></TD></TR>
  
  
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" COLSPAN="5"><B>SEPTERNA, INC.</B></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="4"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom">By:</TD>
  <TD VALIGN="bottom" STYLE=" BORDER-BOTTOM:1px solid #000000">&nbsp;</TD>
  <TD VALIGN="bottom" COLSPAN="3" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Jeffrey Finer, M.D., Ph.D.</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">Name:</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">Jeffrey Finer, M.D., Ph.D.</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom" COLSPAN="3">Title: President, Chief Executive Officer and Director</TD></TR>
  </TABLE></DIV> <P STYLE="margin-top:24pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>POWER OF ATTORNEY AND SIGNATURES </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Each individual whose signature appears below hereby constitutes and appoints each of Jeffrey Finer, M.D., Ph.D. and Gil Labrucherie, CFA,
  J.D. as such person&#146;s true and lawful <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">attorney-in-fact</FONT></FONT> and agent with full power of substitution and resubstitution, for such person in such person&#146;s name,
  place and stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8,</FONT> and to file the same, with all exhibits thereto, and
  all documents in connection therewith, with the Securities and Exchange Commission granting unto each said <FONT STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">attorney-in-fact</FONT></FONT> and agent full power and authority to do and
  perform each and every act and thing requisite and necessary to be done in and about the premises, as fully to all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that any said <FONT
  STYLE="white-space:nowrap"><FONT STYLE="white-space:nowrap">attorney-in-fact</FONT></FONT> and agent, or any substitute or substitutes of any of them, 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 of 1933, as amended, this Registration Statement has been signed by the following persons
  in the capacities and on the date indicated. </P>
  </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">
  
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">
  
  
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  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="bottom" NOWRAP ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Name</B></P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Title</B></P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center" STYLE="border-bottom:1.00pt solid #000000"> <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Date</B></P></TD></TR>
  
  
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Jeffrey Finer, M.D., Ph.D.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Jeffrey Finer, M.D., Ph.D.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">President, Chief Executive Officer and Director</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">(<I>Principal Executive Officer</I>)</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Gil Labrucherie, CFA, J.D.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Gil Labrucherie, CFA, J.D.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Chief Financial Officer</P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">(<I>Principal Financial Officer and</I></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center"><I>Principal Accounting Officer</I>)</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Jeffrey Tong, Ph.D.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Jeffrey Tong, Ph.D.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Chairman and Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Abraham Bassan, M.S.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Abraham Bassan, M.S.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Bernard Coulie, M.D., Ph.D., M.B.A.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Bernard Coulie, M.D., Ph.D., M.B.A.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Alan Ezekowitz, M.D., D.Phil.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Alan Ezekowitz, M.D., D.Phil.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Shalini Sharp, M.B.A.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Shalini Sharp, M.B.A.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="16"></TD>
  <TD HEIGHT="16" COLSPAN="2"></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"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Jake Simson, Ph.D.</P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Jake Simson, Ph.D.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center">Director</P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" NOWRAP ALIGN="center">March&nbsp;27, 2025</TD></TR>
  </TABLE>
  </DIV></Center>
  
  </BODY></HTML>
metadata_documents: [{"type": "S-8", "sequence": "1", "filename": "d943795ds8.htm", "description": "S-8", "secsgml_size_bytes": 34833}]
metadata_filer: {"company-data": {"conformed-name": "Septerna, Inc.", "cik": "0001984086", "assigned-sic": "2834", "organization-name": "03 Life Sciences", "ein": "843891440", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-286152", "film-number": "25775527"}, "business-address": {"street1": "250 EAST GRAND AVENUE, SUITE 65", "city": "SOUTH SAN FRANCISCO", "state": "CA", "zip": "94080", "phone": "650-338-3533"}, "mail-address": {"street1": "250 EAST GRAND AVENUE, SUITE 65", "city": "SOUTH SAN FRANCISCO", "state": "CA", "zip": "94080"}}
text: S-8
  As filed with the Securities and Exchange Commission on March 27, 2025
  Registration
  No. 333-
  UNITED STATES
  SECURITIES AND EXCHANGE COMMISSION
  Washington, D.C. 20549
  FORM
  S-8
  REGISTRATION STATEMENT
  UNDER
  THE
  SECURITIES ACT OF 1933
  SEPTERNA, INC.
  (Exact
  name of registrant as specified in its charter)
  Delaware
  84-3891440
  (State or other jurisdiction of
  incorporation or organization)
  (I.R.S. Employer
  Identification No.)
  Septerna, Inc.
  250 East Grand Avenue
  South San Francisco, California 94080
  (650)
  338-3533
  (Address, including zip code and telephone number, including area code, of registrant's principal executive offices)
  Septerna, Inc. 2024 Stock Option and Incentive Plan
  (Full title of the plans)
  Jeffrey Finer, M.D., Ph.D.
  President and Chief Executive Officer
  Septerna, Inc.
  250 East
  Grand Avenue
  South San Francisco, California 94080
  (650)
  338-3533
  (Name, address, including zip code, and telephone number, including area code, of agent for service)
  Copies to:
  Mitchell S. Bloom
  Deepa
  M. Rich
  Adam V. Johnson
  Goodwin Procter LLP
  601
  Marshall Street
  Redwood City, California 94063
  (650)
  752-3100
  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 (this
  "Registration Statement")
  is being filed for the purposes of registering an additional 2,221,125 shares of common stock, par value $0.001 per share ("Common Stock"), of Septerna, Inc. (the "Registrant") to be issued under the Registrant's
  2024 Stock Option and Incentive Plan (the "2024 Plan").
  The number of shares of Common Stock reserved and available for
  issuance under the 2024 Plan is subject to an automatic annual increase on each January 1 by an amount equal to the lesser of: (i) five percent (5%) of the number of shares of Common Stock issued and outstanding on the immediately
  preceding December 31, or (ii) such number of shares of Common Stock as determined by the Administrator (as defined in the 2024 Plan). Accordingly, on January 1, 2025, the number of shares of Common Stock reserved and available for
  issuance under the 2024 Plan increased by 2,221,125 (the "Additional Shares"). This Registration Statement registers the Additional Shares. The Additional Shares are of the same class as other securities relating to the 2024 Plan for which
  the Registrant's Registration Statement
  on Form S-8
  (File No. 333-282837) filed
  with the Securities and Exchange Commission (the
  "Commission") on October 25, 2024 is effective (the "Prior Registration Statement").
  Pursuant to General
  Instruction E
  to Form S-8, the contents
  of the Prior Registration Statement, except for "Item 8. Exhibits", are hereby incorporated by reference, except to the extent
  supplemented, amended or superseded by the information set forth herein. Only those items
  of Form S-8 containing new
  information not contained in the Prior Registration Statement is
  presented herein.
  Part II
  INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
  Item 8. Exhibits.
  EXHIBIT INDEX
  Exhibit No.
  Description
  4.1
  Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.1 to the Registrant's Current
   Report on Form
  8-K,
  filed with the Commission on October
  28, 2024 (File No.
  001-42382)).
  4.2
  Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit 3.2 to the Registrant's Current Report on Form
  8-K,
  filed with the Commission on October
  28, 2024 (File No.
  001-42382)).
  4.3
  Specimen Common Stock Certificate (incorporated by reference to Exhibit 4.2 to the Registrant's Registration Statement on Form
  S-1,
  as amended, filed with the Commission on October
  21, 2024 (File No.
  333-282469)).
  4.4†
  Amended and Restated Investors' Rights Agreement, by and among the Registrant and certain of its stockholders, dated as of June
  28,
   2023 (incorporated by reference to Exhibit 4.1 to the Registrant's Registration Statement on Form
  S-1,
  as amended, filed with the Commission on October
  2, 2024 (File No.
  333-282469)).
  5.1*
  Opinion of Goodwin Procter LLP.
  23.1*
  Consent of Independent Registered Public Accounting Firm.
  23.2*
  Consent of Goodwin Procter LLP (included in Exhibit 5.1).
  24.1*
  Power of Attorney (included on signature page).
  99.1
  Septerna, Inc. 2024 Stock Option and Incentive Plan and forms of award agreements thereunder (incorporated by reference to Exhibit 10.2 to the
  Registrant's Registration Statement on Form
  S-1,
  as amended, filed with the Commission on October
  21, 2024 (File
  No.
  333-282469)).
  107*
  Filing Fee Table
  *
  Filed herewith.
  †
  Annexes, schedules and/or exhibits have been omitted pursuant to Item 601(a)(5) of Regulation
  S-K.
  The Registrant agrees to furnish supplementally a copy of any omitted attachment to the Commission on a confidential basis upon request.
  SIGNATURES
  Pursuant to the requirements of the Securities Act of 1933, 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 the City of South San Francisco,
  California, on this 27th day of March, 2025.
  SEPTERNA, INC.
  By:
  /s/ Jeffrey Finer, M.D., Ph.D.
  Name:
  Jeffrey Finer, M.D., Ph.D.
  Title: President, Chief Executive Officer and Director
  POWER OF ATTORNEY AND SIGNATURES
  Each individual whose signature appears below hereby constitutes and appoints each of Jeffrey Finer, M.D., Ph.D. and Gil Labrucherie, CFA,
  J.D. as such person's true and lawful
  attorney-in-fact
  and agent with full power of substitution and resubstitution, for such person in such person's name,
  place and stead, 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
  all documents in connection therewith, with the Securities and Exchange Commission granting unto each 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 and about the premises, as fully to all intents and purposes as such person might or could do in person, hereby ratifying and confirming all that any said
  attorney-in-fact
  and agent, or any substitute or substitutes of any of them, may lawfully do or cause to be done by virtue hereof.
  Pursuant to the requirements of the Securities Act of 1933, as amended, this Registration Statement has been signed by the following persons
  in the capacities and on the date indicated.
  Name
  Title
  Date
  /s/ Jeffrey Finer, M.D., Ph.D.
  Jeffrey Finer, M.D., Ph.D.
  President, Chief Executive Officer and Director
  (
  Principal Executive Officer
  )
  March 27, 2025
  /s/ Gil Labrucherie, CFA, J.D.
  Gil Labrucherie, CFA, J.D.
  Chief Financial Officer
  (
  Principal Financial Officer and
  Principal Accounting Officer
  )
  March 27, 2025
  /s/ Jeffrey Tong, Ph.D.
  Jeffrey Tong, Ph.D.
  Chairman and Director
  March 27, 2025
  /s/ Abraham Bassan, M.S.
  Abraham Bassan, M.S.
  Director
  March 27, 2025
  /s/ Bernard Coulie, M.D., Ph.D., M.B.A.
  Bernard Coulie, M.D., Ph.D., M.B.A.
  Director
  March 27, 2025
  /s/ Alan Ezekowitz, M.D., D.Phil.
  Alan Ezekowitz, M.D., D.Phil.
  Director
  March 27, 2025
  /s/ Shalini Sharp, M.B.A.
  Shalini Sharp, M.B.A.
  Director
  March 27, 2025
  /s/ Jake Simson, Ph.D.
  Jake Simson, Ph.D.
  Director
  March 27, 2025