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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 January&nbsp;11, 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;&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:6pt;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:6pt; 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:8pt; 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:6pt;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:6pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>REGULUS&nbsp;THERAPEUTICS&nbsp;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: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></TABLE>
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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>
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<TD VALIGN="bottom" 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:10pt; font-family:Times New Roman" ALIGN="center"><B>2022 Employee Stock Purchase Plan </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2021 Inducement Plan </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Full titles of the plans) </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>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>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="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:8pt; 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:6pt;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:6pt; 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"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">Large&nbsp;Accelerated&nbsp;filer</P></TD>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">&#9744;</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">Accelerated&nbsp;filer</P></TD>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">&#9744;</P></TD></TR>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman"><FONT STYLE="white-space:nowrap">Non-accelerated</FONT> filer</P></TD>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">&#9746;</P></TD>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">Smaller&nbsp;reporting&nbsp;company</P></TD>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">&#9746;</P></TD></TR>
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<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">Emerging&nbsp;growth&nbsp;company</P></TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">&#9744;</P></TD>
<TD VALIGN="bottom">&nbsp;&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: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>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 plans 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 2019 EIP under Registration Statements on Form <FONT
STYLE="white-space:nowrap">S-8</FONT> filed with the Securities and Exchange Commission (the &#147;Commission&#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<U></U>&nbsp;22, 2020</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-236020),</FONT> <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312521028843/d47076ds8.htm">February<U></U>&nbsp;4, 2021</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-252733)</FONT> and <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312522006938/d277572ds8.htm">January<U></U>&nbsp;12, 2022</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;333-262112).</FONT> 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: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 2022 ESPP under a Registration Statement on <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8</FONT> filed with Commission on <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312522218711/d374898ds8.htm">August<U></U>&nbsp;11, 2022</A> (File
<FONT STYLE="white-space:nowrap">No.&nbsp;333-266800).</FONT> Pursuant to General Instruction&nbsp;E to <FONT STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> this Registration Statement hereby incorporates by reference the contents of the
Registration Statements referenced above. </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 2021
Inducement Plan under a Registration Statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8</FONT> filed with Commission on <A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312521342440/d254055ds8.htm">November<U></U>&nbsp;29,
2021</A> (File <FONT STYLE="white-space:nowrap">No.&nbsp;333-261402).</FONT> Pursuant to General Instruction&nbsp;E to <FONT STYLE="white-space:nowrap">Form&nbsp;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="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/1505512/000162828022005771/rgls-20211231.htm"><FONT STYLE="white-space:nowrap">Form&nbsp;10-K</FONT></A>&nbsp;for the year ended December&nbsp;31, 2021, filed with
the SEC on March&nbsp;11, 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 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, 2021 from the registrant&#146;s definitive proxy statement on&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000119312522121451/d345768ddef14a.htm">Schedule 14A</A>&nbsp;relating to its 2022 annual meeting of stockholders, filed with the SEC on April&nbsp;27, 2022; </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 registrant&#146;s Quarterly Reports on <FONT STYLE="white-space:nowrap">Form&nbsp;10-Q&nbsp;for</FONT> the
quarters ended March&nbsp;31, 2022, June&nbsp;30, 2022 and September&nbsp;30, 2022, filed with the SEC on&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000162828022014165/rgls-20220331.htm">May&nbsp;13, 2022</A>,&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/0001505512/000162828022022505/rgls-20220630.htm">August&nbsp;
11, 2022</A> and <A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000162828022029546/rgls-20220930.htm">November&nbsp;14, 2022</A>, respectively; </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 registrant&#146;s Current Reports on <FONT STYLE="white-space:nowrap">Form&nbsp;8-K,&nbsp;filed</FONT> with
the SEC on&nbsp;<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312522002665/d277160d8k.htm">January&nbsp;5, 2022</A>,&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312522172905/d274776d8k.htm">June&nbsp;13, 2022</A>,&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312522182810/d307766d8k.htm">June&nbsp;27, 2022</A>,&nbsp;
<A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312522194935/d346170d8k.htm">July&nbsp;
15, 2022</A>, <A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312522302280/d387116d8k.htm">December<U></U>&nbsp;
12, 2022</A> and <A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1505512/000119312523003434/d427040d8k.htm">January<U></U>&nbsp;6, 2023</A>; and </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 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, 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>
</DIV></Center>


<p style="margin-top:1em; margin-bottom:0em; page-break-before:always">
<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>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">


<TR>

<TD></TD>

<TD VALIGN="bottom" WIDTH="5%"></TD>
<TD WIDTH="92%"></TD></TR>
<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"><B>Exhibit<BR>Number</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>


<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;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><U></U>&nbsp;filed with the Commission 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;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><U></U>&nbsp;filed with the Commission 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;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;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;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><U></U>&nbsp;filed with the Commission 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;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> filed with the Commission 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;5.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609dex51.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>23.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609dex231.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="d382609dex51.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>24.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609ds8.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>99.1</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609dex991.htm">Regulus Therapeutics Inc. 2019 Equity Incentive Plan. </A></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" NOWRAP>99.2</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/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 Commission 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>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
Commission 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>99.4</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1505512/000162828022022505/exhibit101-regulusx2022emp.htm">2022 Employee Stock Purchase Plan (incorporated by referenced to Exhibit 10.1 to the Registrant&#146;s Quarterly Report on Form
 <FONT STYLE="white-space:nowrap">10-Q</FONT> (File No.<U></U><FONT STYLE="white-space:nowrap">&nbsp;001-35670),</FONT> filed with the Commission 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>99.5</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609dex995.htm">Regulus Therapeutics Inc. 2021 Inducement Plan, as amended, and Form of Stock Option Grant Notice, Form of Option Agreement and Notice of Exercise thereunder. </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>99.6</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"><A HREF="d382609dex996.htm">Form of Stock Option Grant Notice, Form of Option Agreement and Notice of Exercise under the Regulus Therapeutics Inc. 2021 Inducement Plan. </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="d382609dexfilingfees.htm">Filing Fee Table </A></TD></TR>
</TABLE>
</DIV></Center>


<p style="margin-top:1em; margin-bottom:0em; page-break-before:always">
<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 January&nbsp;11, 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">


<TR>

<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>REGULUS&nbsp;THERAPEUTICS&nbsp;INC.</B></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="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">President and 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 (including post-effective amendments), 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 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">


<TR>

<TD WIDTH="38%"></TD>

<TD VALIGN="bottom"></TD>
<TD WIDTH="44%"></TD>

<TD VALIGN="bottom" WIDTH="1%"></TD>
<TD WIDTH="16%"></TD></TR>
<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>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;</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; font-size:10pt; font-family:Times New Roman" ALIGN="center">President, Chief Executive Officer</P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">and Member</P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center">of the Board of
Directors</P> <P STYLE="margin-top:0pt; margin-bottom:1pt; 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">January&nbsp;11, 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; font-size:10pt; font-family:Times New Roman" ALIGN="center">Chief Financial Officer</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><I>(Principal Financial Officer)</I></P></TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 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; font-size:10pt; font-family:Times New Roman" ALIGN="center">Controller</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; 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">January&nbsp;11, 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">Chairman of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></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/ 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">Member of the Board of Directors</TD>
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<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">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 2023</TD></TR>
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<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">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 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/ 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">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 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>
<TD VALIGN="top" ALIGN="center">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 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/ 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>
<TD VALIGN="top" ALIGN="center">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 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/ 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>
<TD VALIGN="top" ALIGN="center">Member of the Board of Directors</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top" NOWRAP ALIGN="center">January&nbsp;11, 2023</TD></TR>
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[{"type": "S-8", "sequence": "1", "filename": "d382609ds8.htm", "description": "S-8", "secsgml_size_bytes": 48761}]
{"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": "333-269184", "film-number": "23523763"}, "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 January 11, 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
REGULUS THERAPEUTICS INC.
(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
2022 Employee Stock Purchase Plan
2021 Inducement Plan
(Full titles of the plans)
Joseph P. Hagan
President and 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 plans are effective.
The Registrant previously registered shares of its Common Stock for issuance under the 2019 EIP under Registration Statements on Form
S-8
filed with the Securities and Exchange Commission (the "Commission") on
August
22, 2019
(File
No. 333-233414),
January
22, 2020
(File
No. 
333-236020),
February
4, 2021
(File
No. 
333-252733)
and
January
12, 2022
(File
No. 333-262112).
Pursuant to General Instruction E
to Form
S-8,
this Registration Statement hereby incorporates by reference the contents of the Registration Statements referenced above.
The Registrant previously registered shares of its Common Stock for issuance under the 2022 ESPP under a Registration Statement on
Form S-8
filed with Commission on
August
11, 2022
(File
No. 333-266800).
Pursuant to General Instruction E to
Form S-8,
this Registration Statement hereby incorporates by reference the contents of the
Registration Statements referenced above.
The Registrant previously registered shares of its Common Stock for issuance under the 2021
Inducement Plan under a Registration Statement on
Form S-8
filed with Commission on
November
29,
2021
(File
No. 333-261402).
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, 2021, filed with
the SEC on March 11, 2022;
•
the information specifically incorporated by reference into the registrant's Annual Report on Form
10-K
for the year ended December 31, 2021 from the registrant's definitive proxy statement on
Schedule 14A
relating to its 2022 annual meeting of stockholders, filed with the SEC on April 27, 2022;
•
the registrant's Quarterly Reports on
Form 10-Q for
the
quarters ended March 31, 2022, June 30, 2022 and September 30, 2022, filed with the SEC on
May 13, 2022
,
August 
11, 2022
and
November 14, 2022
, respectively;
•
the registrant's Current Reports on
Form 8-K, filed
with
the SEC on
January 5, 2022
,
June 13, 2022
,
June 27, 2022
,
July 
15, 2022
,
December
12, 2022
and
January
6, 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, 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,
filed with the Commission 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,
filed with the Commission 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,
filed with the Commission 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,
filed with the Commission 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.
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 Commission 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
Commission on August
22, 2019).
99.4
2022 Employee Stock Purchase Plan (incorporated by referenced to Exhibit 10.1 to the Registrant's Quarterly Report on Form
10-Q
(File No.
001-35670),
filed with the Commission on August
11, 2022).
99.5
Regulus Therapeutics Inc. 2021 Inducement Plan, as amended, and Form of Stock Option Grant Notice, Form of Option Agreement and Notice of Exercise thereunder.
99.6
Form of Stock Option Grant Notice, Form of Option Agreement and Notice of Exercise under the Regulus Therapeutics Inc. 2021 Inducement Plan.
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 January 11, 2023.
REGULUS THERAPEUTICS INC.
By:
/s/ Joseph P. Hagan
Joseph P. Hagan
President and 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 (including post-effective amendments), 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 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
President, Chief Executive Officer
and Member
of the Board of
Directors
(Principal Executive Officer)
January 11, 2023
/s/ Cris Calsada
Cris Calsada
Chief Financial Officer
(Principal Financial Officer)
January 11, 2023
/s/ Daniel Penksa
Daniel Penksa
Controller
(Principal Accounting Officer)
January 11, 2023
/s/ Stelios Papadopoulos
Stelios Papadopoulos, Ph.D.
Chairman of the Board of Directors
January 11, 2023
/s/ David Baltimore
David Baltimore, Ph.D.
Member of the Board of Directors
January 11, 2023
/s/ Kathryn J. Collier
Kathryn J. Collier
Member of the Board of Directors
January 11, 2023
/s/ Alice S. Huang
Alice S. Huang, Ph.D.
Member of the Board of Directors
January 11, 2023
/s/ Jake R. Nunn
Jake R. Nunn
Member of the Board of Directors
January 11, 2023
/s/ William H. Rastetter
William H. Rastetter, Ph.D.
Member of the Board of Directors
January 11, 2023
/s/ Hugh Rosen
Hugh Rosen, M.D., Ph.D.
Member of the Board of Directors
January 11, 2023
/s/ Pascale Witz
Pascale Witz
Member of the Board of Directors
January 11, 2023