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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 November 5, 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;&#8195;</FONT> </B></P>
  <P STYLE="font-size:4pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P> <P STYLE="line-height:1.0pt;margin-top:0pt;margin-bottom:0pt;border-bottom:1px solid #000000">&nbsp;</P>
  <P STYLE="line-height:3.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000">&nbsp;</P> <P STYLE="margin-top:4pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>UNITED STATES </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>SECURITIES AND EXCHANGE COMMISSION </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B>Washington, D.C. 20549 </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center>
  <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center> <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>FORM <FONT
  STYLE="white-space:nowrap">S-8</FONT></B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:18pt; font-family:Times New Roman" ALIGN="center"><B>REGISTRATION STATEMENT </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>UNDER </I></B></P> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:12pt; font-family:Times New Roman" ALIGN="center"><B><I>THE
  SECURITIES ACT OF 1933 </I></B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P><center> <P STYLE="line-height:6.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1.00pt solid #000000;width:21%">&nbsp;</P></center>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:24pt; font-family:Times New Roman" ALIGN="center"><B>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>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:8pt" ALIGN="center">
  
  
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  <TD VALIGN="top" ALIGN="center"><B>Delaware</B></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"><B><FONT STYLE="white-space:nowrap">26-3931704</FONT></B></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(State or other jurisdiction of</B></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>incorporation or organization)</B></P></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"> <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>(I.R.S. Employer</B></P>
  <P STYLE="margin-top:0pt; margin-bottom:1pt; font-size:8pt; font-family:Times New Roman" ALIGN="center"><B>Identification No.)</B></P></TD></TR>
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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>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom" ALIGN="center"><B>02459</B></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:8pt">
  <TD VALIGN="top" ALIGN="center"><B>(Address of Principal Executive Offices)</B></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center"><B>(Zip Code)</B></TD></TR>
  </TABLE> <P STYLE="margin-top:12pt; 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>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">
  
  
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  <TD VALIGN="bottom">Large&nbsp;accelerated&nbsp;filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9744;</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom">Accelerated filer</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#9746;</TD></TR>
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  <TD VALIGN="bottom"><FONT STYLE="white-space:nowrap">Non-accelerated&nbsp;filer</FONT></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">&#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 HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD>
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  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <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>
  <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>
  </DIV></Center>
  
  
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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 an additional 1,000,000 shares of Common
  Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the &#147;Registrant&#148;) issuable under the Registrant&#146;s 2022 Inducement Stock Incentive Plan, as amended (the &#147;Plan&#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 <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<U></U>&nbsp;28, 2022</A> relating to the Plan, (ii)&nbsp;the Registration Statement on <FONT
  STYLE="white-space:nowrap">Form&nbsp;S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
  333-265386,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522166718/d319784ds8.htm">June<U></U>&nbsp;3, 2022</A> relating to the Plan, and (iii)&nbsp;the Registration Statement on Form
  <FONT STYLE="white-space:nowrap">S-8,</FONT> File <FONT STYLE="white-space:nowrap">No.&nbsp;
  333-269845,</FONT> filed by the Registrant with the SEC on <A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312523041597/d265868ds8.htm">February<U></U>&nbsp;17, 2023</A> relating to the Plan. </P>
  </DIV></Center>
  
  
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   <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>PART II </B></P>
  <P STYLE="margin-top:0pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman" ALIGN="center"><B>INFORMATION REQUIRED IN THE REGISTRATION STATEMENT </B></P>
  <P STYLE="margin-top:12pt; margin-bottom:0pt; font-size:10pt; font-family:Times New Roman"><B>Item&#8201;8. Exhibits. </B></P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="100%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt" ALIGN="center">
  
  
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  <TD VALIGN="bottom" ALIGN="center">Number</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">Description</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 HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>&#8199;&#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>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004dex51.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>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004dex51.htm">Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1) </A></TD></TR>
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  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>&#8199;23.2</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004dex232.htm">Consent of Ernst&nbsp;&amp; Young LLP </A></TD></TR>
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  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>&#8199;24.1</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004ds8.htm#sig">Power of attorney (included on the signature pages of this registration statement) </A></TD></TR>
  <TR STYLE="font-size:1pt">
  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>&#8199;99.1&nbsp;(3)</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <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 HEIGHT="8" COLSPAN="2"></TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top" NOWRAP>&#8199;99.2&nbsp;(4)</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000119312522166718/d319784dex993.htm">Amendment No.<U></U>&nbsp;1 to the 2022 Inducement Stock 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>&#8199;99.3&nbsp;(5)</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="http://www.sec.gov/Archives/edgar/data/1503802/000095017023003129/kpti-ex10_20.htm">Amendment No.<U></U>&nbsp;2 to the 2022 Inducement Stock 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>&#8199;99.4</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004dex994.htm">Amendment No.&nbsp;3 to the 2022 Inducement Stock Incentive Plan </A></TD></TR>
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  <TD HEIGHT="8"></TD>
  <TD HEIGHT="8" COLSPAN="2"></TD></TR>
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  <TD VALIGN="top" NOWRAP>107</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"><A HREF="d855004dexfilingfees.htm">Filing Fee Table </A></TD></TR>
  </TABLE> <P STYLE="line-height:8.0pt;margin-top:0pt;margin-bottom:2pt;border-bottom:1px solid #000000;width:11%">&nbsp;</P>
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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;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 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 10.17 to the Registrant&#146;s Annual
  Report 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">(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 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;333-265386)</FONT> filed with the Securities and Exchange Commission on June&nbsp;3, 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 10.20 to the Registrant&#146;s Annual
  Report 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 February&nbsp;17, 2023 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 5<SUP STYLE="font-size:75%; vertical-align:top">th</SUP> day of November, 2024. </P> <P STYLE="font-size:12pt;margin-top:0pt;margin-bottom:0pt">&nbsp;</P>
  <TABLE CELLSPACING="0" CELLPADDING="0" WIDTH="40%" BORDER="0" STYLE="BORDER-COLLAPSE:COLLAPSE; font-family:Times New Roman; font-size:10pt">
  
  
  <TR>
  
  <TD WIDTH="13%"></TD>
  
  <TD VALIGN="bottom" WIDTH="1%"></TD>
  <TD WIDTH="86%"></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="bottom">By:</TD>
  <TD VALIGN="bottom" STYLE=" BORDER-BOTTOM:1px solid #000000">&nbsp;</TD>
  <TD VALIGN="bottom" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Richard Paulson</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom">Name:</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">Richard Paulson</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="bottom">Title:</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom">President and Chief Executive Officer</TD></TR>
  </TABLE> <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 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" 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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Richard Paulson</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2"> <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" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Richard Paulson</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Michael Mason</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Executive Vice President, Chief Financial Officer and Treasurer (principal financial and accounting officer)</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Michael Mason</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Garen G. Bohlin</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Director</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Garen G. Bohlin</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Barry E. Green</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Director</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Barry E. Green</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Mansoor Raza Mirza</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Director</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Mansoor Raza Mirza, M.D.</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Christy J. Oliger</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Director</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Christy J. Oliger</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Deepika R. Pakianathan</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2">Director</TD>
  <TD VALIGN="bottom" ROWSPAN="2">&nbsp;</TD>
  <TD VALIGN="top" ROWSPAN="2" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Deepika R. Pakianathan, Ph.D.</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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Chen Schor</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">November 5, 2024</TD></TR>
  <TR STYLE="page-break-inside:avoid ; font-family:Times New Roman; font-size:10pt">
  <TD VALIGN="top">Chen Schor</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top"></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" STYLE="BORDER-BOTTOM:1px solid #000000">/s/ Zhen Su</TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="top">Director</TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="top" ALIGN="center">November 5, 2024</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; margin-left:1.00em; text-indent:-1.00em; font-size:10pt; font-family:Times New Roman">Zhen Su, M.D., M.B.A.</P></TD>
  <TD VALIGN="bottom">&nbsp;&nbsp;</TD>
  <TD VALIGN="bottom"></TD>
  <TD VALIGN="bottom">&nbsp;</TD>
  <TD VALIGN="bottom"></TD></TR>
  </TABLE>
  </DIV></Center>
  
  </BODY></HTML>
metadata_documents: [{"type": "S-8", "sequence": "1", "filename": "d855004ds8.htm", "description": "S-8", "secsgml_size_bytes": 32489}]
metadata_filer: {"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": "333-282994", "film-number": "241425709"}, "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"}}
text: S-8
  As filed with the Securities and Exchange Commission on November 5, 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)
  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 an additional 1,000,000 shares of Common
  Stock, $0.0001 par value per share, of Karyopharm Therapeutics Inc. (the "Registrant") issuable under the Registrant's 2022 Inducement Stock Incentive Plan, as amended (the "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. 
  333-263075,
  filed by the Registrant with the SEC on
  February
  28, 2022
  relating to the Plan, (ii) 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 Plan, and (iii) 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 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)
  2022 Inducement Stock Incentive Plan
  99.2 (4)
  Amendment No.
  1 to the 2022 Inducement Stock Incentive Plan
  99.3 (5)
  Amendment No.
  2 to the 2022 Inducement Stock Incentive Plan
  99.4
  Amendment No. 3 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 2, 2023 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 10.17 to the Registrant's Annual
  Report on Form
  10-K
  (File
  No. 001-36167)
  filed with the Securities and Exchange Commission on March 1, 2022 and incorporated herein by reference.
  (4)
  Previously filed with the Securities and Exchange Commission as Exhibit 99.3 to the Registrant's
  Registration Statement on Form
  S-8
  (File
  No. 333-265386)
  filed with the Securities and Exchange Commission on June 3, 2022 and incorporated herein by
  reference.
  (5)
  Previously filed with the Securities and Exchange Commission as Exhibit 10.20 to the Registrant's Annual
  Report on Form
  10-K
  (File
  No. 001-36167)
  filed with the Securities and Exchange Commission on February 17, 2023 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 5
  th
  day of November, 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 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
  President and Chief Executive Officer and Director
  (principal executive officer)
  November 5, 2024
  Richard Paulson
  /s/ Michael Mason
  Executive Vice President, Chief Financial Officer and Treasurer (principal financial and accounting officer)
  November 5, 2024
  Michael Mason
  /s/ Garen G. Bohlin
  Director
  November 5, 2024
  Garen G. Bohlin
  /s/ Barry E. Green
  Director
  November 5, 2024
  Barry E. Green
  /s/ Mansoor Raza Mirza
  Director
  November 5, 2024
  Mansoor Raza Mirza, M.D.
  /s/ Christy J. Oliger
  Director
  November 5, 2024
  Christy J. Oliger
  /s/ Deepika R. Pakianathan
  Director
  November 5, 2024
  Deepika R. Pakianathan, Ph.D.
  /s/ Chen Schor
  Director
  November 5, 2024
  Chen Schor
  /s/ Zhen Su
  Director
  November 5, 2024
  Zhen Su, M.D., M.B.A.