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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 June&nbsp;29, 2023 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B><FONT STYLE="white-space:nowrap">Registration&nbsp;No.&nbsp;333-&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
</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:8pt;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:8pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B><FONT
STYLE="white-space:nowrap">FORM&nbsp;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:8pt;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:8pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>R<SMALL>EGULUS</SMALL>&nbsp;T<SMALL>HERAPEUTICS</SMALL>&nbsp;I<SMALL>NC</SMALL>. </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:8pt;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:8pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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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">26-4738379</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>
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<TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>4224 Campus Point Court, Suite 210</B></P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>San Diego, CA</B></P></TD>
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<TD VALIGN="bottom" ALIGN="center"><B>92121</B></TD></TR>
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<TD VALIGN="top" ALIGN="center"><B>(Address of Principal Executive Offices)</B></TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" ALIGN="center"><B>(Zip Code)</B></TD></TR>
</TABLE> <P STYLE="margin-top:8pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2019 Equity 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 plan) </B></P>
<P STYLE="margin-top:8pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Joseph P. Hagan </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Chief
Executive Officer </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Regulus Therapeutics Inc. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>4224 Campus Point Court, Suite 210 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>San Diego, CA 92121 </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><FONT
STYLE="white-space:nowrap">(858)&nbsp;202-6300</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:8pt;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:8pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><I>Copies to: </I></B></P> <P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Thomas
A. Coll, Esq. </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Asa M. Henin, Esq. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Cooley LLP </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>10265 Science
Center Drive </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>San Diego, California 92121 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><FONT STYLE="white-space:nowrap">Tel:&nbsp;(858)&nbsp;550-6000</FONT> </B></P>
<P STYLE="font-size:8pt;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:8pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer,
<FONT STYLE="white-space:nowrap">a&nbsp;non-accelerated&nbsp;filer,</FONT> 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 <FONT STYLE="white-space:nowrap">Rule&nbsp;12b-2&nbsp;of</FONT> the Exchange Act. </P> <P STYLE="font-size:8pt;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">Emerging&nbsp;growth&nbsp;company</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
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<TD VALIGN="bottom">&nbsp;</TD>
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</TABLE> <P STYLE="margin-top:8pt; 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.&nbsp;&nbsp;&#9744; </P> <P STYLE="font-size:8pt;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>REGISTRATION OF ADDITIONAL SHARES </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>PURSUANT TO GENERAL INSTRUCTION E </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">This Registration Statement is being filed for the purpose of increasing the number of securities of the same class as other securities for
which Registration Statements of the registrant on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8</FONT> relating to the same employee benefit plan are effective. </P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">The registrant previously registered shares of its Common Stock for issuance under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan
under Registration Statements on Form <FONT STYLE="white-space:nowrap">S-8</FONT> filed with the Securities and Exchange Commission (the &#147;SEC&#148;) on <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312519226942/d797111ds8.htm">August
<U></U>&nbsp;22, 2019</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;333-233414),</FONT> <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312520012118/d866891ds8.htm">January&nbsp;22, 2020</A> (File No.&nbsp;
333-236020), <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312521028843/d47076ds8.htm">February&nbsp;4, 2021</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-252733),</FONT> <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312522006938/d277572ds8.htm">January&nbsp;12, 2022</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-262112)</FONT> and <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523006485/d382609ds8.htm">January 11, 2023</A> (File No.&nbsp;333-269184). Pursuant to General Instruction E to Form <FONT STYLE="white-space:nowrap">S-8,</FONT>
this Registration Statement hereby incorporates by reference the contents of the Registration Statements referenced above. </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:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Item&nbsp;3. Incorporation of Documents by Reference </B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">The following documents filed by the registrant with the SEC are incorporated by reference into this registration statement: </P>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
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<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">the registrant&#146;s Annual Report on&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000162828023009061/rgls-20221231.htm"><FONT STYLE="white-space:nowrap">Form&nbsp;10-K</FONT></A>&nbsp;for the year ended December&nbsp;31, 2022, filed with
the SEC on March&nbsp;23, 2023; </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">the information specifically incorporated by reference into the registrant&#146;s Annual Report on Form <FONT
STYLE="white-space:nowrap">10-K</FONT> for the year ended December&nbsp;31, 2022 from the registrant&#146;s definitive proxy statement on&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523126912/d504496ddef14a.htm">Schedule 14A</A>&nbsp;relating to its 2023 annual meeting of stockholders, filed with the SEC on April&nbsp;28, 2022; </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">the registrant&#146;s Quarterly Report on <FONT STYLE="white-space:nowrap">Form&nbsp;10-Q&nbsp;for</FONT> the
quarterly period ended March&nbsp;31, 2023, filed with the SEC on&nbsp;<A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000162828023017587/rgls-20230331.htm">May&nbsp;11, 2023</A>; </P></TD></TR></TABLE>
<P STYLE="font-size:6pt;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="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">the registrant&#146;s Current Reports on <FONT STYLE="white-space:nowrap">Form&nbsp;8-K,&nbsp;filed</FONT> with
the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312523003434/d427040d8k.htm">January&nbsp;
6, 2023</A>, <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523100519/d464217d8k.htm">April&nbsp;
13, 2023</A>, <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523165267/d513663d8k.htm">June 12, 2023</A> and <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523166837/d285651d8k.htm">June<U></U>&nbsp;14, 2023</A>;
and </P></TD></TR></TABLE> <P STYLE="font-size:6pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TR style = "page-break-inside:avoid">
<TD WIDTH="5%">&nbsp;</TD>
<TD WIDTH="3%" VALIGN="top" ALIGN="left">&#149;</TD>
<TD WIDTH="1%" VALIGN="top">&nbsp;</TD>
<TD ALIGN="left" VALIGN="top"> <P ALIGN="left" STYLE=" margin-top:0pt ; margin-bottom:0pt; font-family:Times New Roman; font-size:10pt">the description of the registrant&#146;s common stock contained in the registrant&#146;s registration statement
on&nbsp;<A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312512406616/d415918d8a12b.htm">Form <FONT STYLE="white-space:nowrap">8-A</FONT></A>, filed with the SEC on September&nbsp;27, 2012, including any amendments or reports filed for
the purpose of updating such description. </P></TD></TR></TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">All reports and other documents filed by the registrant pursuant to Section&nbsp;13(a),
13(c), 14 or 15(d) of the Securities Exchange Act of 1934, as amended, other than Current Reports furnished under Item 2.02 or Item 7.01 of <FONT STYLE="white-space:nowrap">Form&nbsp;8-K&nbsp;and</FONT> exhibits furnished on such form that relate to
such items and other portions of documents that are furnished but not filed or are otherwise not incorporated into registration statements pursuant to the applicable rules promulgated by the SEC, after the date of this registration statement and
prior to the filing of a post-effective amendment which indicates that all securities offered hereby have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference herein and to be a part of
this registration statement from the date of filing such reports and documents. Any statement contained in a document incorporated or deemed to be incorporated herein by reference shall be deemed to be modified or superseded for purposes of this
registration statement to the extent that a statement herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes that statement. Any such statement so modified or
superseded shall not constitute a part of this registration statement, except as so modified or superseded. </P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>EXHIBIT INDEX </B></P>
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<TD VALIGN="top" NOWRAP>&nbsp;&nbsp;&nbsp;&nbsp;4.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000162828016018315/ex-3120160630.htm">Amended and Restated Certificate of Incorporation of the registrant (incorporated by reference to Exhibit 3.1 to the registrant&#146;s Quarterly
 Report on<U></U>&nbsp;Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;10-Q</FONT> (File No. <FONT STYLE="white-space:nowrap">001-35670),</FONT><U></U>&nbsp;filed with the SEC on August<U></U>&nbsp;3, 2016).</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>&nbsp;&nbsp;&nbsp;&nbsp;4.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312518290991/d630756dex31.htm">Certificate of Amendment of Amended and Restated Certificate of Incorporation of the registrant (incorporated by reference to Exhibit 3.1 to the
 registrant&#146;s Current Report on<U></U>&nbsp;Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;8-K</FONT> (File No. <FONT STYLE="white-space:nowrap">001-35670),</FONT><U></U>&nbsp;filed with the SEC on October<U></U>&nbsp;2, 2018).</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>&nbsp;&nbsp;&nbsp;&nbsp;4.3</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312521192088/d169767dex31.htm">Certificate of Amendment of 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> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-35670),</FONT> filed with the SEC on June<U></U>&nbsp;16, 2021).</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>&nbsp;&nbsp;&nbsp;&nbsp;4.4</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312522182810/d307766dex31.htm">Certificate of Amendment of 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> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-35670),</FONT> filed with the SEC on June<U></U>&nbsp;27, 2022).</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>&nbsp;&nbsp;&nbsp;&nbsp;4.5</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312516616627/d203908dex31.htm">Amended and Restated Bylaws of the registrant (incorporated by reference to Exhibit<U></U>&nbsp;
3.1 to the registrant&#146;s Current Report on<U></U>&nbsp;Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;8-K</FONT> (File No. <FONT STYLE="white-space:nowrap">001-35670),</FONT><U></U>&nbsp;filed with the SEC on June<U></U>&nbsp;8,
2016).</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>&nbsp;&nbsp;&nbsp;&nbsp;4.6</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000162828022022505/ex-42x20220630.htm">Form of Common Stock Certificate of the registrant (incorporated by reference to Exhibit<U></U>&nbsp;
4.2 to the registrant&#146;s Quarterly Report on<U></U>&nbsp;Form<U></U><FONT STYLE="white-space:nowrap">&nbsp;10-Q</FONT> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-35670),</FONT> filed with the SEC on August<U></U>&nbsp;11,
2022).</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>&nbsp;&nbsp;&nbsp;&nbsp;5.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d477380dex51.htm">Opinion of Cooley 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>&nbsp;&nbsp;23.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d477380dex231.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>&nbsp;&nbsp;23.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d477380dex51.htm">Consent of Cooley LLP. Reference is made to Exhibit&nbsp;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>&nbsp;&nbsp;24.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d477380ds8.htm#sig">Power of Attorney. Reference is made to the signature page hereto. </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>&nbsp;&nbsp;99.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312523166837/d285651dex991.htm">Regulus Therapeutics Inc. 2019 Equity Incentive Plan, as amended (incorporated by reference to Exhibit 99.1 to the registrant&#146;s current
 report on Form <FONT STYLE="white-space:nowrap">8-K</FONT> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-35670),</FONT> filed with the SEC on June<U></U>&nbsp;14, 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>&nbsp;&nbsp;99.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312519226942/d797111dex992.htm">Form of Stock Option Grant Notice and Option Agreement under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan (incorporated by reference
 to Exhibit 99.2 to the registrant&#146;s Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File<U></U>&nbsp;No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-233414),</FONT> filed with the SEC on August<U></U>&nbsp;22,
2019)</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>&nbsp;&nbsp;99.3</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312519226942/d797111dex993.htm">Form of Restricted Stock Unit Grant Notice and Restricted Stock Unit Agreement under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan
 (incorporated by reference to Exhibit 99.3 to the registrant&#146;s Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File<U></U>&nbsp;No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;333-233414),</FONT> filed with the SEC
on August<U></U>&nbsp;22, 2019).</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="d477380dexfilingfees.htm">Filing Fee Table </A></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, as amended, the registrant certifies that it has reasonable grounds to believe
that it meets all of the requirements for filing <FONT STYLE="white-space:nowrap">on&nbsp;Form&nbsp;S-8&nbsp;and</FONT> has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City
of San Diego, State of California, on June&nbsp;29, 2023. </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">


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<TD WIDTH="7%"></TD>

<TD VALIGN="bottom" WIDTH="1%"></TD>
<TD WIDTH="92%"></TD></TR>


<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" COLSPAN="3"><B>R<SMALL>EGULUS</SMALL>&nbsp;T<SMALL>HERAPEUTICS</SMALL>&nbsp;I<SMALL>NC</SMALL>.</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="bottom">By:</TD>
<TD VALIGN="bottom" STYLE=" BORDER-BOTTOM:1px solid #000000">&nbsp;</TD>
<TD VALIGN="bottom" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Joseph P. Hagan</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">Joseph P. Hagan</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">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>POWER OF ATTORNEY </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; text-indent:4%; font-size:10pt; font-family:Times New Roman">KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Joseph P. Hagan 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 and in his or her name, place or stead, in any and all capacities, to
sign any and all amendments to this Registration Statement, and 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 to all intents and
purposes as he or she 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 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 of 1933, as amended, this Registration Statement
has been signed by the following persons in the capacities and on the dates 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" 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>Signature</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;&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" ALIGN="center">/s/ Joseph P. Hagan</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Joseph P. Hagan</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 Executive Officer and Member of the Board of Directors</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;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Preston S. Klassen</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Preston S. Klassen, M.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 and Member of the Board of Directors</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Cris Calsada</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Cris Calsada</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:1pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman" ALIGN="center"><I>(Principal Financial Officer)</I></P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Daniel Penksa</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Daniel Penksa</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">Controller</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;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Stelios Papadopoulos</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Stelios Papadopoulos, 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 of the Board of Directors</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ David Baltimore</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">David Baltimore, 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">Member of the Board of Directors</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Kathryn J. Collier</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Kathryn J. Collier</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">Member of the Board of Directors</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</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" ALIGN="center">/s/ Alice S. Huang</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Alice S. Huang, 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">Member of the Board of Directors</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</TD></TR></TABLE>
</DIV></Center>


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<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman" ALIGN="center">/s/ Jake R. Nunn</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Jake R. Nunn</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">Member of the Board of Directors</P></TD>
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<TD VALIGN="top" NOWRAP ALIGN="center">June&nbsp;29, 2023</TD></TR>
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<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman" ALIGN="center">/s/ William H. Rastetter</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">William H. Rastetter, Ph.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
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<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman" ALIGN="center">/s/ Hugh Rosen</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Hugh Rosen, M.D., Ph.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
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<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman" ALIGN="center">/s/ Pascale Witz</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">Pascale Witz</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
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{"company-data": {"conformed-name": "Regulus Therapeutics Inc.", "cik": "0001505512", "assigned-sic": "2834", "irs-number": "264738379", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-273027", "film-number": "231058164"}, "business-address": {"street1": "4224 CAMPUS POINT COURT", "street2": "SUITE 210", "city": "SAN DIEGO", "state": "CA", "zip": "92121", "phone": "858-202-6300"}, "mail-address": {"street1": "4224 CAMPUS POINT COURT", "street2": "SUITE 210", "city": "SAN DIEGO", "state": "CA", "zip": "92121"}}
S-8
As filed with the Securities and Exchange Commission on June 29, 2023
Registration No. 333-
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM S-8
REGISTRATION STATEMENT
UNDER
THE
SECURITIES ACT OF 1933
R
EGULUS
T
HERAPEUTICS
I
NC
.
(Exact name of registrant as specified in its charter)
Delaware
26-4738379
(State or other jurisdiction of
incorporation or organization)
(I.R.S. Employer
Identification No.)
4224 Campus Point Court, Suite 210
San Diego, CA
92121
(Address of Principal Executive Offices)
(Zip Code)
2019 Equity Incentive Plan
(Full title of the plan)
Joseph P. Hagan
Chief
Executive Officer
Regulus Therapeutics Inc.
4224 Campus Point Court, Suite 210
San Diego, CA 92121
(858) 202-6300
(Name, address, including zip code, and telephone number, including area code,
of agent for service)
Copies to:
Thomas
A. Coll, Esq.
Asa M. Henin, Esq.
Cooley LLP
10265 Science
Center Drive
San Diego, California 92121
Tel: (858) 550-6000
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer,
a non-accelerated filer,
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.  ☐
REGISTRATION OF ADDITIONAL SHARES
PURSUANT TO GENERAL INSTRUCTION E
This Registration Statement is being filed for the purpose of increasing the number of securities of the same class as other securities for
which Registration Statements of the registrant on
Form S-8
relating to the same employee benefit plan are effective.
The registrant previously registered shares of its Common Stock for issuance under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan
under Registration Statements on Form
S-8
filed with the Securities and Exchange Commission (the "SEC") on
August
22, 2019
(File
No. 333-233414),
January 22, 2020
(File No. 
333-236020),
February 4, 2021
(File
No. 
333-252733),
January 12, 2022
(File
No. 
333-262112)
and
January 11, 2023
(File No. 333-269184). Pursuant to General Instruction E to Form
S-8,
this Registration Statement hereby incorporates by reference the contents of the Registration Statements referenced above.
PART II
Item 3. Incorporation of Documents by Reference
The following documents filed by the registrant with the SEC are incorporated by reference into this registration statement:
•
the registrant's Annual Report on
Form 10-K
for the year ended December 31, 2022, filed with
the SEC on March 23, 2023;
•
the information specifically incorporated by reference into the registrant's Annual Report on Form
10-K
for the year ended December 31, 2022 from the registrant's definitive proxy statement on
Schedule 14A
relating to its 2023 annual meeting of stockholders, filed with the SEC on April 28, 2022;
•
the registrant's Quarterly Report on
Form 10-Q for
the
quarterly period ended March 31, 2023, filed with the SEC on
May 11, 2023
;
•
the registrant's Current Reports on
Form 8-K, filed
with
the SEC on
January 
6, 2023
,
April 
13, 2023
,
June 12, 2023
and
June
14, 2023
;
and
•
the description of the registrant's common stock contained in the registrant's registration statement
on
Form
8-A
, filed with the SEC on September 27, 2012, including any amendments or reports filed for
the purpose of updating such description.
All reports and other documents filed by the registrant pursuant to Section 13(a),
13(c), 14 or 15(d) of the Securities Exchange Act of 1934, as amended, other than Current Reports furnished under Item 2.02 or Item 7.01 of
Form 8-K and
exhibits furnished on such form that relate to
such items and other portions of documents that are furnished but not filed or are otherwise not incorporated into registration statements pursuant to the applicable rules promulgated by the SEC, after the date of this registration statement and
prior to the filing of a post-effective amendment which indicates that all securities offered hereby have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference herein and to be a part of
this registration statement from the date of filing such reports and documents. Any statement contained in a document incorporated or deemed to be incorporated herein by reference shall be deemed to be modified or superseded for purposes of this
registration statement to the extent that a statement herein or in any other subsequently filed document which also is or is deemed to be incorporated by reference herein modifies or supersedes that statement. Any such statement so modified or
superseded shall not constitute a part of this registration statement, except as so modified or superseded.
EXHIBIT INDEX
Exhibit
Number
Description
4.1
Amended and Restated Certificate of Incorporation of the registrant (incorporated by reference to Exhibit 3.1 to the registrant's Quarterly
 Report on
Form
10-Q
(File No.
001-35670),
filed with the SEC on August
3, 2016).
4.2
Certificate of Amendment of 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
(File No.
001-35670),
filed with the SEC on October
2, 2018).
4.3
Certificate of Amendment of 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
(File No.
001-35670),
filed with the SEC on June
16, 2021).
4.4
Certificate of Amendment of 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
(File No.
001-35670),
filed with the SEC on June
27, 2022).
4.5
Amended and Restated Bylaws of the registrant (incorporated by reference to Exhibit
3.1 to the registrant's Current Report on
Form
8-K
(File No.
001-35670),
filed with the SEC on June
8,
2016).
4.6
Form of Common Stock Certificate of the registrant (incorporated by reference to Exhibit
4.2 to the registrant's Quarterly Report on
Form
10-Q
(File No.
001-35670),
filed with the SEC on August
11,
2022).
5.1
Opinion of Cooley LLP.
23.1
Consent of Independent Registered Public Accounting Firm.
23.2
Consent of Cooley LLP. Reference is made to Exhibit 5.1.
24.1
Power of Attorney. Reference is made to the signature page hereto.
99.1
Regulus Therapeutics Inc. 2019 Equity Incentive Plan, as amended (incorporated by reference to Exhibit 99.1 to the registrant's current
 report on Form
8-K
(File No.
001-35670),
filed with the SEC on June
14, 2023).
99.2
Form of Stock Option Grant Notice and Option Agreement under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan (incorporated by reference
 to Exhibit 99.2 to the registrant's Registration Statement on Form
S-8
(File
No.
333-233414),
filed with the SEC on August
22,
2019)
.
99.3
Form of Restricted Stock Unit Grant Notice and Restricted Stock Unit Agreement under the Regulus Therapeutics Inc. 2019 Equity Incentive Plan
 (incorporated by reference to Exhibit 99.3 to the registrant's Registration Statement on Form
S-8
(File
No.
333-233414),
filed with the SEC
on August
22, 2019).
107
Filing Fee Table
SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, as amended, 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 San Diego, State of California, on June 29, 2023.
R
EGULUS
T
HERAPEUTICS
I
NC
.
By:
/s/ Joseph P. Hagan
Joseph P. Hagan
Chief Executive Officer
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Joseph P. Hagan as his or her true
and
lawful attorney-in-fact and
agent, with full power of substitution, for him or her and in his or her name, place or stead, in any and all capacities, to
sign any and all amendments to this Registration Statement, 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 to all intents and
purposes as he or she might or could do in person, hereby ratifying and confirming all that
said attorney-in-fact and
agent or his substitute 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 dates indicated.
Signature
Title
Date
/s/ Joseph P. Hagan
Joseph P. Hagan
Chief Executive Officer and Member of the Board of Directors
(Principal Executive Officer)
June 29, 2023
/s/ Preston S. Klassen
Preston S. Klassen, M.D.
President and Member of the Board of Directors
June 29, 2023
/s/ Cris Calsada
Cris Calsada
Chief Financial Officer
(Principal Financial Officer)
June 29, 2023
/s/ Daniel Penksa
Daniel Penksa
Controller
(Principal Accounting Officer)
June 29, 2023
/s/ Stelios Papadopoulos
Stelios Papadopoulos, Ph.D.
Chairman of the Board of Directors
June 29, 2023
/s/ David Baltimore
David Baltimore, Ph.D.
Member of the Board of Directors
June 29, 2023
/s/ Kathryn J. Collier
Kathryn J. Collier
Member of the Board of Directors
June 29, 2023
/s/ Alice S. Huang
Alice S. Huang, Ph.D.
Member of the Board of Directors
June 29, 2023
/s/ Jake R. Nunn
Jake R. Nunn
Member of the Board of Directors
June 29, 2023
/s/ William H. Rastetter
William H. Rastetter, Ph.D.
Member of the Board of Directors
June 29, 2023
/s/ Hugh Rosen
Hugh Rosen, M.D., Ph.D.
Member of the Board of Directors
June 29, 2023
/s/ Pascale Witz
Pascale Witz
Member of the Board of Directors
June 29, 2023