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 <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>As filed with the Securities and Exchange Commission on February&nbsp;17, 2023 </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-&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</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:12pt; 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>
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<TD VALIGN="top" ALIGN="center"><B>(Zip Code)</B></TD></TR>
</TABLE> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>2013 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>2022 Inducement Stock 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"> <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>
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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">Accelerated 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></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&nbsp;filer</FONT></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>
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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">&#9744;</P></TD></TR>
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<TD VALIGN="bottom">&nbsp;</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">Emerging growth 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">&#9744;</P></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.&nbsp;&nbsp;&#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>STATEMENT OF INCORPORATION BY REFERENCE </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman">This Registration Statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8</FONT> is being filed to register (a)&nbsp;an additional 484,848 shares of
Common Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the &#147;Registrant&#148;) issuable under the Registrant&#146;s 2013 Employee Stock Purchase Plan (the &#147;ESPP&#148;) and (b)&nbsp;an additional 1,200,000 shares of
Common Stock issuable under the Registrant&#146;s 2022 Inducement Stock Incentive Plan, as amended (the &#147;Inducement Plan&#148; and, together with the ESPP, the &#147;Plans&#148;). Pursuant to General Instruction E to <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> except as otherwise set forth below, this Registration Statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8</FONT> incorporates by reference the contents of (i)&nbsp;the Registration Statement
on Form <FONT STYLE="white-space:nowrap">S-8,</FONT> 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 <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000110465914021876/a14-8440_1s8.htm">March&nbsp;21, 2014</A> relating to the ESPP,
(ii)&nbsp;the Registration Statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-210221,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312516505284/d147775ds8.htm">March&nbsp;15, 2016</A> relating to the ESPP, (iii)&nbsp;the Registration Statement on <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-229971,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312519057870/d714625ds8.htm">February&nbsp;28, 2019</A> relating to the ESPP, (iv)&nbsp;the Registration Statement on <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-237160,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312520072904/d887912ds8.htm">March&nbsp;13, 2020</A> relating to the ESPP, (v)&nbsp;the Registration Statement on <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-263075,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522057836/d316693ds8.htm">February&nbsp;28, 2022</A> relating to the Plans and (vi)&nbsp;the Registration Statement on <FONT
STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
333-265386,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522166718/d319784ds8.htm">June&nbsp;3, 2022</A> relating to the Inducement 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:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>INFORMATION REQUIRED IN THE REGISTRATION STATEMENT </B></P>
<P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Item&nbsp;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">Number</TD>
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<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">Description</P></TD></TR>


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<TD VALIGN="top" NOWRAP>4.1&nbsp;(1)</TD>
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<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312519215344/d760010dex31.htm">Restated Certificate of Incorporation of the Registrant, as amended </A></TD></TR>
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<TD VALIGN="top" NOWRAP>4.2&nbsp;(2)</TD>
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<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>5.1</TD>
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<TD VALIGN="top"><A HREF="d265868dex51.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>23.1</TD>
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<TD VALIGN="top"><A HREF="d265868dex51.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>23.2</TD>
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<TD VALIGN="top"><A HREF="d265868dex232.htm">Consent of Ernst&nbsp;&amp; Young LLP </A></TD></TR>
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<TD VALIGN="top" NOWRAP>24.1</TD>
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<TD VALIGN="top"><A HREF="#sig">Power of attorney (included on the signature pages of this registration statement) </A></TD></TR>
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<TD VALIGN="top" NOWRAP>99.1&nbsp;(3)</TD>
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<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000104746913009972/a2216956zex-10_6.htm">2013 Employee Stock Purchase Plan </A></TD></TR>
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<TD VALIGN="top" NOWRAP>99.2&nbsp;(4)</TD>
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<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000095017022002548/kpti-ex10_17.htm">2022 Inducement Stock Incentive Plan </A></TD></TR>
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<TD VALIGN="top" NOWRAP>99.3&nbsp;(5)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522166718/d319784dex993.htm">Amendment No.&nbsp;1 to the 2022 Inducement Stock Incentive Plan </A></TD></TR>
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<TD VALIGN="top" NOWRAP>99.4</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="d265868dex994.htm">Amendment No.&nbsp;2 to the 2022 Inducement Stock Incentive Plan </A></TD></TR>
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<TD VALIGN="top" NOWRAP>107</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"><A HREF="d265868dexfilingfees.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 Securities and Exchange Commission 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 Securities and Exchange Commission on August&nbsp;7, 2019 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">(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 Securities and Exchange Commission 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 Securities and Exchange Commission 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 Securities and Exchange Commission as Exhibit 10.6 to the Registrant&#146;s
Registration Statement on <FONT STYLE="white-space:nowrap">Form&nbsp;S-1,</FONT> as amended <FONT STYLE="white-space:nowrap">(File&nbsp;No.&nbsp;333-191584)</FONT> filed with the SEC on October&nbsp;28, 2013 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 Securities and Exchange Commission as Exhibit 10.17 to the Registrant&#146;s
Registration Statement on Form <FONT STYLE="white-space:nowrap">10-K</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;001-36167)</FONT> filed with the Securities and Exchange Commission on March&nbsp;1, 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">(5)</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 Securities and Exchange Commission as Exhibit 99.3 to the Registrant&#146;s
Registration Statement on Form <FONT STYLE="white-space:nowrap">S-8</FONT> (File <FONT STYLE="white-space:nowrap">No.&nbsp;001-265386)</FONT> filed with the Securities and Exchange Commission on June&nbsp;3, 2022 and incorporated herein by
reference. </P></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; 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 17<SUP STYLE="font-size:75%; vertical-align:top">th</SUP> day of February, 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="12%"></TD>

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


<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top" COLSPAN="3"><B>KARYOPHARM THERAPEUTICS INC.</B></TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="16"></TD>
<TD HEIGHT="16" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">By:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:1pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Richard Paulson</P></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Name:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top">Richard Paulson</TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top">Title:</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top">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 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="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">President and Chief Executive Officer and Director (principal executive officer)</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" ALIGN="center">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Michael 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" ALIGN="center">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ 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" ALIGN="center">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ 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" ALIGN="center">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ Peter Honig</P>
<P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:10pt; font-family:Times New Roman">Peter Honig, M.D., M.P.H.</P></TD>
<TD VALIGN="bottom">&nbsp;&nbsp;</TD>
<TD VALIGN="top">Director</TD>
<TD VALIGN="bottom">&nbsp;</TD>
<TD VALIGN="top" ALIGN="center">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ 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" ALIGN="center">February&nbsp;17, 2023</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">

<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: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">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ 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">February&nbsp;17, 2023</TD></TR>
<TR STYLE="font-size:1pt">
<TD HEIGHT="8"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD>
<TD HEIGHT="8" COLSPAN="2"></TD></TR>
<TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
<TD VALIGN="top"> <P STYLE="margin-top:0pt; margin-bottom:0pt; border-bottom:1px solid #000000; font-size:10pt; font-family:Times New Roman">/s/ 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">February&nbsp;17, 2023</TD></TR>
</TABLE>
</DIV></Center>

</BODY></HTML>
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{"company-data": {"conformed-name": "Karyopharm Therapeutics Inc.", "cik": "0001503802", "assigned-sic": "2834", "irs-number": "263931704", "state-of-incorporation": "DE", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-269845", "film-number": "23640429"}, "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 February 17, 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
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)
2013 Employee Stock Purchase Plan
2022 Inducement Stock 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.  ☐
STATEMENT OF INCORPORATION BY REFERENCE
This Registration Statement on
Form S-8
is being filed to register (a) an additional 484,848 shares of
Common Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the "Registrant") issuable under the Registrant's 2013 Employee Stock Purchase Plan (the "ESPP") and (b) an additional 1,200,000 shares of
Common Stock issuable under the Registrant's 2022 Inducement Stock Incentive Plan, as amended (the "Inducement Plan" and, together with the ESPP, the "Plans"). 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 Plans and (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 Inducement 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)
2013 Employee Stock Purchase Plan
99.2 (4)
2022 Inducement Stock Incentive Plan
99.3 (5)
Amendment No. 1 to the 2022 Inducement Stock Incentive Plan
99.4
Amendment No. 2 to the 2022 Inducement Stock Incentive Plan
107
Filing Fee Table
(1)
Previously filed with the Securities and Exchange Commission as Exhibit 3.1 to the Registrant's Quarterly
Report on Form
10-Q
(File
No. 001-36167)
filed with the Securities and Exchange Commission on August 7, 2019 and incorporated herein by reference.
(2)
Previously filed with the Securities and Exchange Commission as Exhibit 3.1 to the Registrant's Current
Report on Form
8-K
(File
No. 001-36167)
filed with the Securities and Exchange Commission on December 2, 2022 and incorporated herein by reference.
(3)
Previously filed with the Securities and Exchange Commission as Exhibit 10.6 to the Registrant's
Registration Statement on
Form S-1,
as amended
(File No. 333-191584)
filed with the SEC on October 28, 2013 and incorporated herein by reference.
(4)
Previously filed with the Securities and Exchange Commission as Exhibit 10.17 to the Registrant's
Registration Statement on Form
10-K
(File
No. 001-36167)
filed with the Securities and Exchange Commission on March 1, 2022 and incorporated herein by
reference.
(5)
Previously filed with the Securities and Exchange Commission as Exhibit 99.3 to the Registrant's
Registration Statement on Form
S-8
(File
No. 001-265386)
filed with the Securities and Exchange Commission on June 3, 2022 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 17
th
day of February, 2023.
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)
February 17, 2023
/s/ Michael Mason
Michael Mason
Executive Vice President, Chief Financial Officer and Treasurer (principal financial and accounting officer)
February 17, 2023
/s/ Garen G. Bohlin
Garen G. Bohlin
Director
February 17, 2023
/s/ Barry E. Greene
Barry E. Greene
Director
February 17, 2023
/s/ Peter Honig
Peter Honig, M.D., M.P.H.
Director
February 17, 2023
/s/ Mansoor Raza Mirza
Mansoor Raza Mirza, M.D.
Director
February 17, 2023
/s/ Christy J. Oliger
Christy J. Oliger
Director
February 17, 2023
/s/ Deepika R. Pakianathan
Deepika R. Pakianathan, Ph.D.
Director
February 17, 2023
/s/ Chen Schor
Chen Schor
Director
February 17, 2023