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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 May&nbsp;30, 2024 </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="right"><B>Registration <FONT STYLE="white-space:nowrap">No.&nbsp;333-&#8195;&#8195;&#8195;</FONT> </B></P>
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<P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&nbsp;</P> <P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>UNITED STATES </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>SECURITIES AND EXCHANGE COMMISSION </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B>Washington, D.C. 20549 </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
<P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>FORM <FONT
STYLE="white-space:nowrap">S-8</FONT> </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>REGISTRATION STATEMENT </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>UNDER </I></B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>THE
SECURITIES ACT OF 1933 </I></B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>Karyopharm Therapeutics Inc. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(Exact name of registrant as specified in its charter) </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
<P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="top" ALIGN="center"><B>Delaware</B></TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" ALIGN="center"><B><FONT STYLE="white-space:nowrap">26-3931704</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>85 Wells Avenue, 2nd Floor</B></P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Newton, MA</B></P></TD>
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<TD VALIGN="bottom" ALIGN="center"><B>02459</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="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Amended&nbsp;&amp; Restated 2013 Employee Stock Purchase Plan, as amended </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2022 Equity Incentive Plan, as amended </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:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Richard Paulson </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>Karyopharm Therapeutics Inc. </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>85 Wells Avenue, 2nd Floor </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>Newton, MA 02459 </B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Name
and address of agent for service) </B></P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>(617) <FONT STYLE="white-space:nowrap">658-0600</FONT> </B></P>
<P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(Telephone number, including area code, of agent for service) </B></P>
<P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a <FONT STYLE="white-space:nowrap">non-accelerated</FONT>
filer, a smaller reporting company, or an emerging growth company. See the definitions of &#147;large accelerated filer,&#148; &#147;accelerated filer,&#148; &#147;smaller reporting company,&#148; and &#147;emerging growth company&#148; in Rule <FONT
STYLE="white-space:nowrap">12b-2</FONT> of the Exchange Act. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="bottom">Large&nbsp;accelerated&nbsp;filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom">Accelerated&nbsp;filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9746;</TD></TR>
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<TD VALIGN="bottom"><FONT STYLE="white-space:nowrap">Non-accelerated</FONT> filer</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="bottom">Smaller&nbsp;reporting&nbsp;company</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD></TR>
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<TD VALIGN="bottom">&nbsp;</TD>
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<TD VALIGN="bottom">Emerging growth company</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="bottom">&#9744;</TD></TR>
</TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period
for complying with any new or revised financial accounting standards provided pursuant to Section&nbsp;7(a)(2)(B) of the Securities Act.&#8194;&#9744; </P> <P STYLE="font-size:10pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>EXPLANATORY NOTE </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">This Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> is being filed to register (a)&nbsp;an additional 5,000,000 shares of Common
Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the &#147;Registrant&#148;) issuable under the Registrant&#146;s Amended&nbsp;&amp; Restated 2013 Employee Stock Purchase Plan, as amended (the &#147;ESPP&#148;) and (b)&nbsp;an
additional 6,000,000 shares of Common Stock issuable under the Registrant&#146;s 2022 Equity Incentive Plan, as amended (the &#147;2022 Plan&#148;). Pursuant to General Instruction E to Form <FONT STYLE="white-space:nowrap">S-8,</FONT> except as
otherwise set forth below, this Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> incorporates by reference the contents of (i)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000110465914021876/a14-8440_1s8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-194746,</FONT> filed
by the Registrant with the Securities and Exchange Commission (the &#147;SEC&#148;) on March&nbsp;21, 2014 relating to the ESPP, (ii)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312516505284/d147775ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-210221,</FONT> filed by
the Registrant with the SEC on March&nbsp;15, 2016 relating to the ESPP, (iii)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312519057870/d714625ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-229971,</FONT> filed by
the Registrant with the SEC on February&nbsp;28, 2019 relating to the ESPP, (iv)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312520072904/d887912ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-237160,</FONT> filed by
the Registrant with the SEC on March&nbsp;13, 2020 relating to the ESPP, (v)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522057836/d316693ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-263075,</FONT> filed by
the Registrant with the SEC on February&nbsp;28, 2022 relating to the ESPP, (vi)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522166718/d319784ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-265386,</FONT> filed by
the Registrant with the SEC on June&nbsp;3, 2022 relating to the 2022 Plan, (vii)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312523041597/d265868ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-269845,</FONT> filed by
the Registrant with the SEC on February&nbsp;17, 2023, relating to the ESPP and (viii)&nbsp;
the Registration Statement on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312523201207/d712199ds8.htm">Form <FONT STYLE="white-space:nowrap">S-8</FONT></A>, File <FONT STYLE="white-space:nowrap">No.&nbsp;333-273593,</FONT> filed by
the Registrant with the SEC on August&nbsp;2, 2023, relating to the ESPP and the 2022 Plan. </P>
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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>PART II </B></P>
<P STYLE="margin-top:6pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>INFORMATION REQUIRED IN THE REGISTRATION STATEMENT </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Item&#8201;8. Exhibits. </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
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<TD VALIGN="bottom" ALIGN="center"><B>Number</B></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>Description</B></P></TD></TR>


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<TD VALIGN="top" NOWRAP>&#8199;&#8199;4.1&nbsp;(1)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000095017023036780/kpti-ex3_1.htm">Restated Certificate of Incorporation of the Registrant, as amended </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;&#8199;4.2&nbsp;(2)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522297530/d423713dex31.htm">Third Amended and Restated <FONT STYLE="white-space:nowrap">By-Laws</FONT> of the Registrant </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;&#8199;5.1</TD>
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<TD VALIGN="top"><A HREF="d843249dex51.htm">Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;23.1</TD>
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<TD VALIGN="top"><A HREF="d843249dex51.htm">Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1) </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;23.2</TD>
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<TD VALIGN="top"><A HREF="d843249dex232.htm">Consent of Ernst&nbsp;&amp; Young LLP </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;24.1</TD>
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<TD VALIGN="top"><A HREF="d843249ds8.htm#sig">Power of attorney (included on the signature pages of this registration statement) </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;99.1&nbsp;(3)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1503802/000095017024045717/kpti-20240417.htm#appendix_b">Amended&nbsp;&amp; Restated 2013 Employee Stock Purchase Plan, as amended </A></TD></TR>
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<TD VALIGN="top" NOWRAP>&#8199;99.2&nbsp;(4)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/../../../ix?doc=/Archives/edgar/data/1503802/000095017024045717/kpti-20240417.htm#appendix_a">2022 Equity Incentive Plan, as amended</A></TD></TR>
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<TD VALIGN="top" NOWRAP>107</TD>
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<TD VALIGN="top"><A HREF="d843249dexfilingfees.htm">Filing Fee Table </A></TD></TR>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">(1)</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Previously filed with the SEC as Exhibit 3.1 to the Registrant&#146;s Quarterly Report on Form <FONT
STYLE="white-space:nowrap">10-Q</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;001-36167)</FONT> filed with the SEC on August&nbsp;2, 2023 and incorporated herein by reference. </P></TD></TR></TABLE>
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<TD WIDTH="4%" VALIGN="top" ALIGN="left">(2)</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Previously filed with the SEC as Exhibit 3.1 to the Registrant&#146;s Current Report on Form <FONT
STYLE="white-space:nowrap">8-K</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;001-36167)</FONT> filed with the SEC on December&nbsp;2, 2022 and incorporated herein by reference. </P></TD></TR></TABLE>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">(3)</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Previously filed with the SEC as Appendix B to the Registrant&#146;s Definitive Proxy Statement on Schedule 14A
(File <FONT STYLE="white-space:nowrap">No.&nbsp;001-36167)</FONT> filed with the SEC on April&nbsp;19, 2024 and incorporated herein by reference. </P></TD></TR></TABLE>
<TABLE STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" BORDER="0" CELLPADDING="0" CELLSPACING="0" WIDTH="100%">
<TR style = "page-break-inside:avoid">
<TD WIDTH="4%" VALIGN="top" ALIGN="left">(4)</TD>
<TD ALIGN="left" VALIGN="top"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman; " ALIGN="left">Previously filed with the SEC as Appendix A to the Registrant&#146;s Definitive Proxy Statement on Schedule 14A
(File <FONT STYLE="white-space:nowrap">No.&nbsp;001-36167)</FONT> filed with the SEC on April&nbsp;19, 2024 and incorporated herein by reference. </P></TD></TR></TABLE>
</DIV></Center>


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


<Center><DIV STYLE="width:8.5in" align="left">
 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B><A NAME="sig"></A>SIGNATURES </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the
requirements for filing on Form <FONT STYLE="white-space:nowrap">S-8</FONT> and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Newton, Commonwealth of
Massachusetts, on this 30<SUP STYLE="font-size:75%; vertical-align:top">th</SUP> day of May, 2024. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><DIV ALIGN="right">
<TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="40%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">


<TR>

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

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


<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" COLSPAN="3"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman"><B>KARYOPHARM THERAPEUTICS INC.</B></P></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"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">By:</P></TD>
<TD VALIGN="bottom" STYLE=" BORDER-BOTTOM:1px solid #000000">&nbsp;</TD>
<TD VALIGN="bottom" STYLE="BORDER-BOTTOM:1px solid #000000"> <P STYLE=" margin-top:0pt ; margin-bottom:0pt; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">/s/ Richard Paulson</P></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<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">Name:</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">Richard Paulson</P></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<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">Title:</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">President and Chief Executive Officer</P></TD></TR>
</TABLE></DIV>
</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>POWER OF ATTORNEY AND SIGNATURES </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">We, the undersigned officers and directors of Karyopharm Therapeutics Inc., hereby severally constitute and appoint Richard Paulson, Michael Mason and Michael
Mano, and each of them singly, our true and lawful attorneys with full power to them, and each of them singly, to sign for us and in our names in the capacities indicated below, the registration statement on Form
<FONT STYLE="white-space:nowrap">S-8</FONT> filed herewith and any and all subsequent amendments to said registration statement, and generally to do all such things in our names and on our behalf in our capacities as officers and directors to enable
Karyopharm Therapeutics Inc. to comply with the provisions of the Securities Act of 1933, as amended, and all requirements of the Securities and Exchange Commission, hereby ratifying and confirming our signatures as they may be signed by our said
attorneys, or any of them, to said registration statement and any and all amendments thereto. </P> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">Pursuant to the requirements of the Securities Act of 1933,
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">/s/ Richard Paulson</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Richard Paulson</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">President and Chief Executive Officer and Director</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">(principal executive officer)</P></TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Michael Mason</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Michael Mason</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Executive Vice President, Chief Financial Officer and Treasurer (principal financial and accounting officer)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Garen G. Bohlin</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Garen G. Bohlin</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Barry E. Greene</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Barry E. Greene</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Mansoor Raza Mirza</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Mansoor Raza Mirza, M.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Christy J. Oliger</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Christy J. Oliger</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Deepika R. Pakianathan</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Deepika R. Pakianathan, Ph.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Chen Schor</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Chen Schor</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Zhen Su</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Zhen Su, M.D.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" NOWRAP>May&nbsp;30, 2024</TD></TR>
</TABLE>
</DIV></Center>

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{"company-data": {"conformed-name": "Karyopharm Therapeutics Inc.", "cik": "0001503802", "assigned-sic": "2834", "organization-name": "03 Life Sciences", "irs-number": "263931704", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-279823", "film-number": "241005226"}, "business-address": {"street1": "85 WELLS AVENUE", "street2": "SECOND FLOOR", "city": "NEWTON", "state": "MA", "zip": "02459", "phone": "617-658-0600"}, "mail-address": {"street1": "85 WELLS AVENUE", "street2": "SECOND FLOOR", "city": "NEWTON", "state": "MA", "zip": "02459"}}
S-8
As filed with the Securities and Exchange Commission on May 30, 2024
Registration
No. 333-
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
S-8
REGISTRATION STATEMENT
UNDER
THE
SECURITIES ACT OF 1933
Karyopharm Therapeutics Inc.
(Exact name of registrant as specified in its charter)
Delaware
26-3931704
(State or other jurisdiction of
incorporation or organization)
(I.R.S. Employer
Identification No.)
85 Wells Avenue, 2nd Floor
Newton, MA
02459
(Address of Principal Executive Offices)
(Zip Code)
Amended & Restated 2013 Employee Stock Purchase Plan, as amended
2022 Equity Incentive Plan, as amended
(Full title of the plan)
Richard Paulson
President and Chief Executive Officer
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459
(Name
and address of agent for service)
(617)
658-0600
(Telephone number, including area code, of agent for service)
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a
non-accelerated
filer, a smaller reporting company, or an emerging growth company. See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company," and "emerging growth company" in Rule
12b-2
of the Exchange Act.
Large accelerated filer
☐
Accelerated filer
☒
Non-accelerated
filer
☐
Smaller reporting company
☐
Emerging growth company
☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period
for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐
EXPLANATORY NOTE
This Registration Statement on Form
S-8
is being filed to register (a) an additional 5,000,000 shares of Common
Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the "Registrant") issuable under the Registrant's Amended & Restated 2013 Employee Stock Purchase Plan, as amended (the "ESPP") and (b) an
additional 6,000,000 shares of Common Stock issuable under the Registrant's 2022 Equity Incentive Plan, as amended (the "2022 Plan"). Pursuant to General Instruction E to Form
S-8,
except as
otherwise set forth below, this Registration Statement on Form
S-8
incorporates by reference the contents of (i) 
the Registration Statement on
Form
S-8
, File
No. 333-194746,
filed
by the Registrant with the Securities and Exchange Commission (the "SEC") on March 21, 2014 relating to the ESPP, (ii) 
the Registration Statement on
Form
S-8
, File
No. 333-210221,
filed by
the Registrant with the SEC on March 15, 2016 relating to the ESPP, (iii) 
the Registration Statement on
Form
S-8
, File
No. 333-229971,
filed by
the Registrant with the SEC on February 28, 2019 relating to the ESPP, (iv) 
the Registration Statement on
Form
S-8
, File
No. 333-237160,
filed by
the Registrant with the SEC on March 13, 2020 relating to the ESPP, (v) 
the Registration Statement on
Form
S-8
, File
No. 333-263075,
filed by
the Registrant with the SEC on February 28, 2022 relating to the ESPP, (vi) 
the Registration Statement on
Form
S-8
, File
No. 333-265386,
filed by
the Registrant with the SEC on June 3, 2022 relating to the 2022 Plan, (vii) 
the Registration Statement on
Form
S-8
, File
No. 333-269845,
filed by
the Registrant with the SEC on February 17, 2023, relating to the ESPP and (viii) 
the Registration Statement on
Form
S-8
, File
No. 333-273593,
filed by
the Registrant with the SEC on August 2, 2023, relating to the ESPP and the 2022 Plan.
PART II
INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
Item 8. Exhibits.
Number
Description
4.1 (1)
Restated Certificate of Incorporation of the Registrant, as amended
4.2 (2)
Third Amended and Restated
By-Laws
of the Registrant
5.1
Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant
23.1
Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1)
23.2
Consent of Ernst & Young LLP
24.1
Power of attorney (included on the signature pages of this registration statement)
99.1 (3)
Amended & Restated 2013 Employee Stock Purchase Plan, as amended
99.2 (4)
2022 Equity Incentive Plan, as amended
107
Filing Fee Table
(1)
Previously filed with the SEC as Exhibit 3.1 to the Registrant's Quarterly Report on Form
10-Q
(File
No. 001-36167)
filed with the SEC on August 2, 2023 and incorporated herein by reference.
(2)
Previously filed with the SEC as Exhibit 3.1 to the Registrant's Current Report on Form
8-K
(File
No. 001-36167)
filed with the SEC on December 2, 2022 and incorporated herein by reference.
(3)
Previously filed with the SEC as Appendix B to the Registrant's Definitive Proxy Statement on Schedule 14A
(File
No. 001-36167)
filed with the SEC on April 19, 2024 and incorporated herein by reference.
(4)
Previously filed with the SEC as Appendix A to the Registrant's Definitive Proxy Statement on Schedule 14A
(File
No. 001-36167)
filed with the SEC on April 19, 2024 and incorporated herein by reference.
SIGNATURES
Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it has reasonable grounds to believe that it meets all of the
requirements for filing on Form
S-8
and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Newton, Commonwealth of
Massachusetts, on this 30
th
day of May, 2024.
KARYOPHARM THERAPEUTICS INC.
By:
/s/ Richard Paulson
Name:
Richard Paulson
Title:
President and Chief Executive Officer
POWER OF ATTORNEY AND SIGNATURES
We, the undersigned officers and directors of Karyopharm Therapeutics Inc., hereby severally constitute and appoint Richard Paulson, Michael Mason and Michael
Mano, and each of them singly, our true and lawful attorneys with full power to them, and each of them singly, to sign for us and in our names in the capacities indicated below, the registration statement on Form
S-8
filed herewith and any and all subsequent amendments to said registration statement, and generally to do all such things in our names and on our behalf in our capacities as officers and directors to enable
Karyopharm Therapeutics Inc. to comply with the provisions of the Securities Act of 1933, as amended, and all requirements of the Securities and Exchange Commission, hereby ratifying and confirming our signatures as they may be signed by our said
attorneys, or any of them, to said registration statement and any and all amendments thereto.
Pursuant to the requirements of the Securities Act of 1933,
this registration statement has been signed by the following persons in the capacities and on the dates indicated.
Signature
Title
Date
/s/ Richard Paulson
Richard Paulson
President and Chief Executive Officer and Director
(principal executive officer)
May 30, 2024
/s/ Michael Mason
Michael Mason
Executive Vice President, Chief Financial Officer and Treasurer (principal financial and accounting officer)
May 30, 2024
/s/ Garen G. Bohlin
Garen G. Bohlin
Director
May 30, 2024
/s/ Barry E. Greene
Barry E. Greene
Director
May 30, 2024
/s/ Mansoor Raza Mirza
Mansoor Raza Mirza, M.D.
Director
May 30, 2024
/s/ Christy J. Oliger
Christy J. Oliger
Director
May 30, 2024
/s/ Deepika R. Pakianathan
Deepika R. Pakianathan, Ph.D.
Director
May 30, 2024
/s/ Chen Schor
Chen Schor
Director
May 30, 2024
/s/ Zhen Su
Zhen Su, M.D.
Director
May 30, 2024