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    <div style="text-align: center; font-weight: bold;">As filed with the Securities and Exchange Commission on July 30, 2021</div>
    <div style="text-align: right; font-weight: bold;">Registration Statement No. 333-</div>
    <div style="text-align: right; font-weight: bold;"> <br>
    </div>
    <div style="text-align: right; font-weight: bold;">
      <hr align="center" style="border: none; border-bottom: 1px solid black; border-top: 4px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;">
      <div style="text-align: left; font-weight: normal;">
        <div style="text-align: center; font-weight: bold; font-size: 14pt;">UNITED STATES</div>
        <font style="font-size: 14pt;"> </font>
        <div style="text-align: center; font-weight: bold; font-size: 14pt;">SECURITIES AND EXCHANGE COMMISSION</div>
        <div style="text-align: center; font-weight: bold; font-size: 12pt;">Washington, D.C. 20549</div>
        <div style="text-align: center; font-weight: bold;"> <br>
        </div>
        <div>
          <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000; text-align: center;"> </div>
        <div> <br>
        </div>
        <div style="text-align: center; font-weight: bold; font-size: 18pt;">FORM S-8</div>
        <div style="text-align: center; font-variant: small-caps; font-weight: bold;">REGISTRATION STATEMENT UNDER THE</div>
        <div style="text-align: center; font-variant: small-caps; font-weight: bold;">SECURITIES ACT OF 1933</div>
        <div style="text-align: center; font-variant: small-caps; font-weight: bold;"> <br>
        </div>
        <div>
          <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000; text-align: center;"> </div>
        <div><br>
        </div>
        <div style="text-align: center; font-weight: bold; font-size: 24pt;">CYCLERION THERAPEUTICS, INC.</div>
        <div style="text-align: center; font-weight: bold;">(Exact name of registrant as specified in its charter)</div>
        <div style="text-align: center;"><a name="z_Hlk75871649"></a><br>
          <div>
            <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000;"> </div>
          <div><br>
          </div>
        </div>
        <table cellspacing="0" cellpadding="0" border="0" id="ze04013e154004907a631d7b8827c58dc" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center; font-weight: bold;">Massachusetts</div>
              </td>
              <td style="width: 2%; vertical-align: top;">&#160;</td>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center; font-weight: bold;">83-1895370</div>
              </td>
            </tr>
            <tr>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center;">(State or other jurisdiction of incorporation or organization)</div>
              </td>
              <td style="width: 2%; vertical-align: top;">&#160;</td>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center;">(I.R.S. Employer Identification No.)</div>
              </td>
            </tr>
            <tr>
              <td style="width: 49%; vertical-align: top;">&#160;</td>
              <td style="width: 2%; vertical-align: top;">&#160;</td>
              <td style="width: 49%; vertical-align: top;">&#160;</td>
            </tr>
            <tr>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center; font-weight: bold;">245 First Street, 18th Floor</div>
                <div style="text-align: center; font-weight: bold;">Cambridge, Massachusetts</div>
              </td>
              <td style="width: 2%; vertical-align: top;">&#160;</td>
              <td style="width: 49%; vertical-align: bottom;">
                <div style="text-align: center; font-weight: bold;">02142</div>
              </td>
            </tr>
            <tr>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center;">(Address of Principal Executive Offices)</div>
              </td>
              <td style="width: 2%; vertical-align: top;">&#160;</td>
              <td style="width: 49%; vertical-align: top;">
                <div style="text-align: center;">(Zip Code)</div>
              </td>
            </tr>

        </table>
        <div><br>
          <div>
            <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000; text-align: center;"> </div>
          <div><br>
          </div>
        </div>
        <div style="text-align: center; font-weight: bold;">Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan</div>
        <div style="text-align: center; font-weight: bold;">Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan</div>
        <div style="text-align: center;">(Full title of the plan)</div>
        <div><br>
          <div>
            <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000; text-align: center;"> </div>
          <div><br>
          </div>
        </div>
        <div style="text-align: center; font-weight: bold;">Anjeza Gjino</div>
        <div style="text-align: center; font-weight: bold;">245 First Street, 18th Floor</div>
        <div style="text-align: center; font-weight: bold;">Cambridge, Massachusetts 02142</div>
        <div style="text-align: center;">(Name and address of agent for service)</div>
        <div style="text-align: center; font-weight: bold;">(857) 327-8778</div>
        <div style="text-align: center;">(Telephone number, including area code, of agent for service)</div>
        <div><br>
          <div>
            <hr noshade="noshade" align="center" style="background-color: #000000; border-bottom: medium none; border-left: medium none; border-right: medium none; border-top: medium none; margin: 0px auto; height: 2px; width: 20%; color: #000000; text-align: center;"> </div>
          <div><br>
          </div>
        </div>
        <div style="text-align: center; font-weight: bold;">Please send copies of all communications to:</div>
        <div><br>
        </div>
        <div style="text-align: center; font-weight: bold;">Gary J. Simon, Esq.</div>
        <div style="text-align: center; font-weight: bold;">Hughes Hubbard &amp; Reed LLP</div>
        <div style="text-align: center; font-weight: bold;">One Battery Park Plaza</div>
        <div style="text-align: center; font-weight: bold;">New York, NY 10004</div>
        <div><br>
        </div>
        <div>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 &#8220;large accelerated filer,&#8221;
          &#8220;accelerated filer,&#8221; &#8220;smaller reporting company&#8221; and &#8220;emerging growth company&#8221; in Rule 12b-2 of the Exchange Act.</div>
        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" border="0" id="z560bb033995645feae1e65852ad9c35c" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 24.77%; vertical-align: top;">
                <div>Large accelerated filer &#9744;</div>
              </td>
              <td style="width: 20.18%; vertical-align: top;">
                <div>Accelerated filer &#9744;</div>
              </td>
              <td style="width: 25.69%; vertical-align: top;">
                <div>Non-accelerated filer &#9746;</div>
              </td>
              <td style="width: 29.36%; vertical-align: top;">
                <div>Smaller reporting company &#9746;</div>
              </td>
            </tr>
            <tr>
              <td style="width: 24.77%; vertical-align: top;">&#160;</td>
              <td style="width: 20.18%; vertical-align: top;">&#160;</td>
              <td style="width: 25.69%; vertical-align: top;">&#160;</td>
              <td style="width: 29.36%; vertical-align: top;">
                <div>Emerging growth company &#9746;</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div>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. &#9744;</div>
        <div> <br>
        </div>
        <div style="text-align: center; font-weight: bold;">CALCULATION OF REGISTRATION FEE</div>
        <table cellspacing="0" cellpadding="0" style="font-family: 'Times New Roman'; font-size: 10pt; text-align: left; color: #000000; width: 100%;" id="z1a8cd38f2e6b4c8fac3f6889b484c966" class="cfttable">

            <tr>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="2">&#160;</td>
              <td valign="bottom" nowrap="nowrap" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="2">&#160;</td>
              <td valign="bottom" nowrap="nowrap" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="2">&#160;</td>
              <td valign="bottom" nowrap="nowrap" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="2">&#160;</td>
              <td valign="bottom" nowrap="nowrap" rowspan="1" style="vertical-align: bottom; border-bottom: 4px double rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
            </tr>
            <tr>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center; font-weight: bold;">Title of securities</div>
                <div style="text-align: center; font-weight: bold;">to be registered</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;">Amount to be registered(1)</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;">Proposed</div>
                <div style="text-align: center; font-weight: bold;">maximum</div>
                <div style="text-align: center; font-weight: bold;">offering price</div>
                <div style="text-align: center; font-weight: bold;">per share(2)</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;">Proposed maximum</div>
                <div style="text-align: center; font-weight: bold;">aggregate</div>
                <div style="text-align: center; font-weight: bold;">offering price(2)</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);" colspan="2">
                <div style="text-align: center; font-weight: bold;">Amount of</div>
                <div style="text-align: center; font-weight: bold;">registration fee</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; padding-bottom: 2px;" colspan="1" class="cftfncell">&#160;</td>
            </tr>
            <tr>
              <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">Common Stock</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>1,996,991</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; background-color: rgb(204, 238, 255); border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">
                <div>(3)</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>3.34</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>6,669,949.94</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>727.69</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; padding-bottom: 2px; background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
            </tr>
            <tr>
              <td valign="bottom" style="vertical-align: bottom; width: 52%; border-bottom: 2px solid rgb(0, 0, 0);">
                <div style="text-align: center;">Common Stock</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftcurrcell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftnumcell">
                <div>499,248</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">
                <div>(4)</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftnumcell">
                <div>3.34</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftnumcell">
                <div>1,667,488.32</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 2px solid rgb(0, 0, 0);" colspan="1" class="cftnumcell">
                <div>181.92</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; padding-bottom: 2px;" colspan="1" class="cftfncell">&#160;</td>
            </tr>
            <tr>
              <td valign="bottom" style="vertical-align: bottom; width: 52%; background-color: rgb(204, 238, 255); border-bottom: 4px double rgb(0, 0, 0);">
                <div style="text-align: center;">TOTAL</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>2,496,239</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">&#160;</td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftcurrcell">
                <div>$</div>
              </td>
              <td valign="bottom" style="vertical-align: bottom; text-align: right; width: 9%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftnumcell">
                <div>8,337,438.26</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
              <td valign="bottom" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftguttercell">&#160;</td>
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                <div>$</div>
              </td>
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                <div>909.61</div>
              </td>
              <td valign="bottom" nowrap="nowrap" style="vertical-align: bottom; width: 1%; border-bottom: 4px double rgb(0, 0, 0); background-color: rgb(204, 238, 255);" colspan="1" class="cftfncell">&#160;</td>
            </tr>

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        <div> <br>
        </div>
        <table cellspacing="0" cellpadding="0" id="ze0755900e6914d408ff60530333f0c34" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 18pt; vertical-align: top;">(1)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Pursuant to Rule 416(a) under the Securities Act of 1933, as amended (the &#8220;Securities Act&#8221;), this Registration Statement also covers such additional shares of Common Stock as may be issued to prevent dilution resulting from stock
                  splits, stock dividends and similar transactions.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zedb12c8485874123880e01a49633207e" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 18pt; vertical-align: top;">(2)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Pursuant to Rules 457(c) and 457(h)(1) under the Securities Act, the proposed maximum offering price per share and the maximum aggregate offering price for the shares have been calculated solely for the purpose of computing the
                  registration fee on the basis of the average high and low prices of the Common Stock trading on a &#8220;when issued&#8221; basis as reported by the Nasdaq Global Select Market, which were $3.50 and $3.17, respectively on July 27, 2021.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z0d92ae150c9243f6a4d31b04cac93d06" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 18pt; vertical-align: top;">(3)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Represents additional shares of Common Stock authorized for issuance under the Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z77dc1a13eed745df83e8d84e1d11db62" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 18pt; vertical-align: top;">(4)</td>
              <td style="width: auto; vertical-align: top;">
                <div>Represents additional shares of Common Stock authorized for issuance under the Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <div>
          <hr align="center" style="border: none; border-bottom: 4px solid black; border-top: 1px solid black; height: 10px; color: #ffffff; background-color: #ffffff; text-align: center; margin-left: auto; margin-right: auto;"> </div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageBreak" style="page-break-after:always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-align: center; font-weight: bold;">REGISTRATION OF ADDITIONAL SECURITIES</div>
        <div style="text-align: center; font-weight: bold;">INCORPORATION OF EARLIER REGISTRATION STATEMENT BY REFERENCE</div>
        <div>&#160;</div>
        <div>This Registration Statement (the &#8220;Registration Statement&#8221;) is being filed by Cyclerion Therapeutics, Inc. (the &#8220;Company&#8221;) to register &#8220;Additional Shares&#8221;, consisting of an additional 1,996,991 shares of Common Stock of the Company issuable
          under the Company&#8217;s 2019 Equity Incentive Plan (the &#8220;2019 Incentive Plan&#8221;) and an additional 499,248 shares of Common Stock of the Company issuable under the Company&#8217;s 2019 Employee Stock Purchase Plan (the &#8220;2019 ESPP&#8221; and together with the 2019
          Incentive Plan, the &#8220;Plans&#8221;). The Additional Shares are in addition to the Common Stock previously registered for issuance in respect of the Plans on the Company&#8217;s Registration Statement on Form S-8 (File No. 333-230615), filed with the
          Securities and Exchange Commission (the &#8220;SEC&#8221;) on <a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465919018720/a19-7436_1s8.htm">March 29, 2019</a><u>,</u> and the Company&#8217;s Registration Statement on Form S-8 (File No.
          333-248957), filed with the SEC on <a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465920107118/tm2031264-1_s8.htm">September 22, 2020</a> (the &#8220;Prior Registration Statements&#8221;).</div>
        <div>&#160;</div>
        <div>This Registration Statement relates to securities of the same class as that to which the Prior Registration Statements relate, and is submitted in accordance with General Instruction E to Form S-8 regarding registration of additional
          securities. Pursuant to such instruction, the contents of the Prior Registration Statements are incorporated by reference and made part of this Registration Statement, except to the extent otherwise updated or modified by this Registration
          Statement.</div>
        <div>&#160;</div>
        <div style="text-align: center; font-weight: bold;">PART II</div>
        <div style="text-align: center; font-weight: bold;">INFORMATION REQUIRED IN THE REGISTRATION STATEMENT</div>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="zec7447e05865406e99c3d764a5df528a" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54pt; vertical-align: top; font-weight: bold;">Item 3.</td>
              <td style="width: auto; vertical-align: top;">
                <div style="font-weight: bold;">Incorporation of Documents by Reference.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <div style="text-indent: 36pt;">The following documents filed by Cyclerion Therapeutics, Inc. (the &#8220;Registrant&#8221;) with the SEC are incorporated herein by reference (excluding any portions of such documents that have been &#8220;furnished&#8221; but not &#8220;filed&#8221;
          for purposes of the Securities Exchange Act of 1934, as amended (the &#8220;Exchange Act&#8221;)):</div>
        <div>&#160;</div>
        <div style="text-indent: 36pt; background-color: rgb(255, 255, 255); font-weight: normal; color: rgb(0, 0, 0); font-style: normal; font-variant: normal; text-transform: none;">(1)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Registrant&#8217;s Annual Report on Form 10-K for the year
          ended December 31, 2020, filed with the SEC on <a href="https://www.sec.gov/Archives/edgar/data/1755237/000156459021008434/cycn-10k_20201231.htm">February 25, 2021</a>;</div>
        <div>&#160;</div>
        <div style="text-indent: 36pt; background-color: rgb(255, 255, 255); font-weight: normal; color: rgb(0, 0, 0); font-style: normal; font-variant: normal; text-transform: none;">(2)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Registrant&#8217;s Quarterly Reports on Form 10-Q for the
          quarters ended March 31, 2021 and June 30, 2021, filed with the SEC on <a href="https://www.sec.gov/Archives/edgar/data/1755237/000156459021022522/cycn-10q_20210331.htm">April </a><a href="https://www.sec.gov/Archives/edgar/data/1755237/000156459021022522/cycn-10q_20210331.htm">30, 2021</a> and <a href="https://www.sec.gov/Archives/edgar/data/1755237/000156459021039205/cycn-10q_20210630.htm">July 29, 2021</a>,
          respectively;</div>
        <div>&#160;</div>
        <div style="text-indent: 36pt;">(3)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The Registrant&#8217;s Current Reports on Form 8-K filed with the SEC on <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121009117/brhc10021961_8k.htm">March 18, 2021</a>, <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121009236/brhc10022037_8ka.htm">March 19, 2021</a>, <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121014205/brhc10023576_8k.htm">April 26, 2021</a> (only with
          respect to Item 5.02 thereof), <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121015739/brhc10024036_8k.htm">May 4, 2021</a>, <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121019923/brhc10025496_8k.htm">June




            4, 2021</a> and <a href="https://www.sec.gov/Archives/edgar/data/1755237/000114036121022349/brhc10026259_8k.htm">June 25, 2021</a>; and</div>
        <div>&#160;</div>
        <div style="text-indent: 36pt;">(4)&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;&#160;The description of the Registrant&#8217;s Common Stock contained in the Information Statement filed with the SEC as Exhibit 99.1 to the Registrant&#8217;s <a href="https://www.sec.gov/Archives/edgar/data/1755237/000104746919000256/a2237521z10-12b.htm">Form 10</a> (File No. 001-38787), including any amendments or reports filed for the purpose of updating such description.</div>
        <div>&#160;</div>
        <div>All documents subsequently filed by the Registrant pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the filing of a post-effective amendment to this Registration Statement that indicates that all securities offered
          have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference herein from the date of filing of such documents. In no event, however, will any information that the Registrant discloses
          under Item 2.02 or 7.01 of any Current Report on Form 8-K that the Registrant may from time to time furnish to the SEC, or any other information that is not deemed &#8220;filed&#8221; with the SEC, be incorporated by reference into, or otherwise become part
          of, this Registration Statement.</div>
        <div>&#160;</div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageBreak" style="page-break-after:always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div></div>
        <div>Any statement contained herein or in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for the purposes of this Registration Statement to the extent that a statement contained
          herein or in any subsequently filed document that also is or is deemed to be incorporated by reference herein modifies or supersedes such earlier statement. Any statement so modified or superseded shall not be deemed, except as so modified or
          superseded, to constitute part of this Registration Statement.</div>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" id="z87523ab8442543ca9e5401e6b7135557" class="DSPFListTable" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; text-align: left; color: #000000;">

            <tr>
              <td style="width: 54pt; vertical-align: top; font-weight: bold;">Item 8.</td>
              <td style="width: auto; vertical-align: top;">
                <div style="font-weight: bold;">Exhibits.</div>
              </td>
            </tr>

        </table>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" border="0" id="z8ecbd2849bb147b78221ec4206a81af3" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 10%; vertical-align: middle; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: center; font-weight: bold;">Exhibit</div>
                  <div style="text-align: center; font-weight: bold;">Number</div>
                </div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
              <td style="width: 89%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="font-weight: bold;">Description</div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;"><a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465919018720/a19-7436_1ex4d1.htm">3.1</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 89%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div>Restated Articles of Organization of Cyclerion Therapeutics, Inc. (incorporated by reference to Exhibit 4.1 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top;">
                <div style="text-align: center;"><a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465919018720/a19-7436_1ex4d2.htm">3.2</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 89%; vertical-align: top;">
                <div>Amended and Restated Bylaws of Cyclerion Therapeutics, Inc. (incorporated by reference to Exhibit 4.2 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;"><a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465919018720/a19-7436_1ex4d3.htm">3.3</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 89%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div>Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan (incorporated by reference to Exhibit 4.3 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top;">
                <div style="text-align: center;"><a href="https://www.sec.gov/Archives/edgar/data/1755237/000110465919018720/a19-7436_1ex4d4.htm">3.4</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 89%; vertical-align: top;">
                <div>Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan (incorporated by reference to Exhibit 4.4 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;"><a href="brhc10027360_ex5-1.htm">5.1</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 89%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div>Opinion of Foley Hoag LLP (filed herewith)</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top;">
                <div style="text-align: center;"><a href="brhc10027360_ex23-1.htm">23.1</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 89%; vertical-align: top;">
                <div>Consent of Ernst &amp; Young, LLP (filed herewith)</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div style="text-align: center;"><a href="brhc10027360_ex5-1.htm">23.2</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; background-color: rgb(204, 238, 255);">&#160;</td>
              <td style="width: 89%; vertical-align: top; background-color: rgb(204, 238, 255);">
                <div>Consent of Foley Hoag LLP (included in the opinion filed as Exhibit 5.1).</div>
              </td>
            </tr>
            <tr>
              <td style="width: 10%; vertical-align: top;">
                <div style="text-align: center;"><a href="#POWEROFATTORNEY">24.1</a></div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 89%; vertical-align: top;">
                <div>Power of Attorney (included in the signature page to this Registration Statement)</div>
              </td>
            </tr>

        </table>
        <div> <br>
        </div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageBreak" style="page-break-after:always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div style="text-align: center; font-weight: bold;">SIGNATURES</div>
        <div> <br>
        </div>
        <div style="text-indent: 36pt;">Pursuant to the requirements of the Securities Act, 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 Cambridge, Massachusetts, on the 30th day of July, 2021.</div>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" border="0" id="zd82b564deeb042b0a1f2a67382598fef" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 50%; vertical-align: top;">&#160;</td>
              <td style="vertical-align: top;" colspan="3">
                <div style="font-weight: bold;">CYCLERION THERAPEUTICS, INC.</div>
              </td>
            </tr>
            <tr>
              <td rowspan="1" style="width: 50%; vertical-align: top;">&#160;</td>
              <td rowspan="1" style="vertical-align: top;" colspan="3">&#160;</td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;">&#160;</td>
              <td style="width: 3%; vertical-align: top;">
                <div>By:</div>
              </td>
              <td style="vertical-align: top; border-bottom: 2px solid black;" colspan="2">
                <div>/s/ Anjeza Gjino</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;">&#160;</td>
              <td style="width: 3%; vertical-align: top;">&#160;</td>
              <td style="width: 5%; vertical-align: top;">
                <div>Name:</div>
              </td>
              <td style="width: 42%; vertical-align: top;">
                <div>Anjeza Gjino</div>
              </td>
            </tr>
            <tr>
              <td style="width: 50%; vertical-align: top;">&#160;</td>
              <td style="width: 3%; vertical-align: top;">&#160;</td>
              <td style="width: 5%; vertical-align: top;">
                <div>Title:</div>
              </td>
              <td style="width: 42%; vertical-align: top;">
                <div>Chief Financial Officer</div>
              </td>
            </tr>

        </table>
        <div><br>
        </div>
        <div id="DSPFPageBreakArea" style="clear: both; margin-top: 10pt; margin-bottom: 10pt;">
          <div id="DSPFPageBreak" style="page-break-after:always;">
            <hr noshade="noshade" style="margin: 4px 0px; width: 100%; border-width: 0; height: 2px; color: #000000; background-color: #000000; clear: both;"></div>
        </div>
        <div></div>
        <div style="text-align: center; font-weight: bold;"><a name="POWEROFATTORNEY"><!--Anchor--></a>POWER OF ATTORNEY</div>
        <div> <br>
        </div>
        <div style="text-indent: 36pt;">KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Peter M. Hecht and Anjeza Gjino, jointly and severally, as their true and lawful attorney-in-fact and agent,
          with full power of substitution and re-substitution, for them and in their name, place and stead, in any and all capacities, to execute any or all amendments including any post-effective amendments and supplements to this Registration Statement
          on Form S-8 of Cyclerion Therapeutics, Inc., and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent full power and
          authority to do and perform each and every act and thing requisite and necessary to be done, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent,
          or his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.</div>
        <div>&#160;</div>
        <div style="text-indent: 36pt;">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:</div>
        <div>&#160;</div>
        <table cellspacing="0" cellpadding="0" border="0" id="za74b6528ea574d36a65e62e1cc598ada" style="font-family: 'Times New Roman'; font-size: 10pt; width: 100%; border-collapse: collapse; text-align: left; color: #000000;">

            <tr>
              <td style="width: 35%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: center; margin-right: 9pt; font-weight: bold;">Signature</div>
                </div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top; padding-bottom: 2px;">&#160;</td>
              <td style="width: 35%; vertical-align: top; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: center; margin-right: 9pt; margin-left: 4.5pt; font-weight: bold;">Title</div>
                </div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: bottom; padding-bottom: 2px;">&#160;</td>
              <td style="width: 27.62%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="text-align: center; font-weight: bold;">Date</div>
                </div>
              </td>
            </tr>
            <tr>
              <td style="width: 35%; vertical-align: bottom;">&#160;</td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 35%; vertical-align: top;">&#160;</td>
              <td colspan="1" style="width: 1%; vertical-align: bottom;">&#160;</td>
              <td style="width: 27.62%; vertical-align: bottom;">&#160;</td>
            </tr>
            <tr>
              <td style="width: 35%; vertical-align: bottom; border-bottom: 2px solid rgb(0, 0, 0);">
                <div>
                  <div style="margin-right: 9pt;">/s/ Peter M. Hecht</div>
                </div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: top;">&#160;</td>
              <td style="width: 35%; vertical-align: top;">
                <div style="margin-right: 9pt; margin-left: 4.5pt;">Chief Executive Officer (Principal Executive Officer)</div>
              </td>
              <td colspan="1" style="width: 1%; vertical-align: bottom;">&#160;</td>
              <td style="width: 27.62%; vertical-align: bottom;">
                <div style="text-align: center;">July 30, 2021</div>
              </td>
            </tr>
            <tr>
              <td style="width: 35%; vertical-align: top;">
                <div style="margin-right: 9pt;">Peter M. Hecht</div>
              </td>
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{"company-data": {"conformed-name": "Cyclerion Therapeutics, Inc.", "cik": "0001755237", "assigned-sic": "2834", "irs-number": "831895370", "state-of-incorporation": "MA", "fiscal-year-end": "1231"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-258316", "film-number": "211133006"}, "business-address": {"street1": "301 BINNEY STREET", "city": "CAMBRIDGE", "state": "MA", "zip": "02142", "phone": "617-621-7722"}, "mail-address": {"street1": "301 BINNEY STREET", "city": "CAMBRIDGE", "state": "MA", "zip": "02142"}}
As filed with the Securities and Exchange Commission on July 30, 2021
Registration Statement No. 333-
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM S-8
REGISTRATION STATEMENT UNDER THE
SECURITIES ACT OF 1933
CYCLERION THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Massachusetts
83-1895370
(State or other jurisdiction of incorporation or organization)
(I.R.S. Employer Identification No.)
245 First Street, 18th Floor
Cambridge, Massachusetts
02142
(Address of Principal Executive Offices)
(Zip Code)
Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan
Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan
(Full title of the plan)
Anjeza Gjino
245 First Street, 18th Floor
Cambridge, Massachusetts 02142
(Name and address of agent for service)
(857) 327-8778
(Telephone number, including area code, of agent for service)
Please send copies of all communications to:
Gary J. Simon, Esq.
Hughes Hubbard & Reed LLP
One Battery Park Plaza
New York, NY 10004
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. ☐
CALCULATION OF REGISTRATION FEE
Title of securities
to be registered
Amount to be registered(1)
Proposed
maximum
offering price
per share(2)
Proposed maximum
aggregate
offering price(2)
Amount of
registration fee
Common Stock
1,996,991
(3)
$
3.34
$
6,669,949.94
$
727.69
Common Stock
499,248
(4)
$
3.34
$
1,667,488.32
$
181.92
TOTAL
2,496,239
$
8,337,438.26
$
909.61
(1)
Pursuant to Rule 416(a) under the Securities Act of 1933, as amended (the "Securities Act"), this Registration Statement also covers such additional shares of Common Stock as may be issued to prevent dilution resulting from stock
                  splits, stock dividends and similar transactions.
(2)
Pursuant to Rules 457(c) and 457(h)(1) under the Securities Act, the proposed maximum offering price per share and the maximum aggregate offering price for the shares have been calculated solely for the purpose of computing the
                  registration fee on the basis of the average high and low prices of the Common Stock trading on a "when issued" basis as reported by the Nasdaq Global Select Market, which were $3.50 and $3.17, respectively on July 27, 2021.
(3)
Represents additional shares of Common Stock authorized for issuance under the Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan.
(4)
Represents additional shares of Common Stock authorized for issuance under the Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan.
REGISTRATION OF ADDITIONAL SECURITIES
INCORPORATION OF EARLIER REGISTRATION STATEMENT BY REFERENCE
This Registration Statement (the "Registration Statement") is being filed by Cyclerion Therapeutics, Inc. (the "Company") to register "Additional Shares", consisting of an additional 1,996,991 shares of Common Stock of the Company issuable
          under the Company's 2019 Equity Incentive Plan (the "2019 Incentive Plan") and an additional 499,248 shares of Common Stock of the Company issuable under the Company's 2019 Employee Stock Purchase Plan (the "2019 ESPP" and together with the 2019
          Incentive Plan, the "Plans"). The Additional Shares are in addition to the Common Stock previously registered for issuance in respect of the Plans on the Company's Registration Statement on Form S-8 (File No. 333-230615), filed with the
          Securities and Exchange Commission (the "SEC") on
March 29, 2019
,
and the Company's Registration Statement on Form S-8 (File No.
          333-248957), filed with the SEC on
September 22, 2020
(the "Prior Registration Statements").
This Registration Statement relates to securities of the same class as that to which the Prior Registration Statements relate, and is submitted in accordance with General Instruction E to Form S-8 regarding registration of additional
          securities. Pursuant to such instruction, the contents of the Prior Registration Statements are incorporated by reference and made part of this Registration Statement, except to the extent otherwise updated or modified by this Registration
          Statement.
PART II
INFORMATION REQUIRED IN THE REGISTRATION STATEMENT
Item 3.
Incorporation of Documents by Reference.
The following documents filed by Cyclerion Therapeutics, Inc. (the "Registrant") with the SEC are incorporated herein by reference (excluding any portions of such documents that have been "furnished" but not "filed"
          for purposes of the Securities Exchange Act of 1934, as amended (the "Exchange Act")):
(1)          The Registrant's Annual Report on Form 10-K for the year
          ended December 31, 2020, filed with the SEC on
February 25, 2021
;
(2)          The Registrant's Quarterly Reports on Form 10-Q for the
          quarters ended March 31, 2021 and June 30, 2021, filed with the SEC on
April
30, 2021
and
July 29, 2021
,
          respectively;
(3)          The Registrant's Current Reports on Form 8-K filed with the SEC on
March 18, 2021
,
March 19, 2021
,
April 26, 2021
(only with
          respect to Item 5.02 thereof),
May 4, 2021
,
June

            4, 2021
and
June 25, 2021
; and
(4)          The description of the Registrant's Common Stock contained in the Information Statement filed with the SEC as Exhibit 99.1 to the Registrant's
Form 10
(File No. 001-38787), including any amendments or reports filed for the purpose of updating such description.
All documents subsequently filed by the Registrant pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Exchange Act prior to the filing of a post-effective amendment to this Registration Statement that indicates that all securities offered
          have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference herein from the date of filing of such documents. In no event, however, will any information that the Registrant discloses
          under Item 2.02 or 7.01 of any Current Report on Form 8-K that the Registrant may from time to time furnish to the SEC, or any other information that is not deemed "filed" with the SEC, be incorporated by reference into, or otherwise become part
          of, this Registration Statement.
Any statement contained herein or in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for the purposes of this Registration Statement to the extent that a statement contained
          herein or in any subsequently filed document that also is or is deemed to be incorporated by reference herein modifies or supersedes such earlier statement. Any statement so modified or superseded shall not be deemed, except as so modified or
          superseded, to constitute part of this Registration Statement.
Item 8.
Exhibits.
Exhibit
Number
Description
3.1
Restated Articles of Organization of Cyclerion Therapeutics, Inc. (incorporated by reference to Exhibit 4.1 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).
3.2
Amended and Restated Bylaws of Cyclerion Therapeutics, Inc. (incorporated by reference to Exhibit 4.2 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).
3.3
Cyclerion Therapeutics, Inc. 2019 Employee Stock Purchase Plan (incorporated by reference to Exhibit 4.3 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).
3.4
Cyclerion Therapeutics, Inc. 2019 Equity Incentive Plan (incorporated by reference to Exhibit 4.4 to Registration Statement on Form S-8 filed on March 29, 2019) (File No. 333-230615).
5.1
Opinion of Foley Hoag LLP (filed herewith)
23.1
Consent of Ernst & Young, LLP (filed herewith)
23.2
Consent of Foley Hoag LLP (included in the opinion filed as Exhibit 5.1).
24.1
Power of Attorney (included in the signature page to this Registration Statement)
SIGNATURES
Pursuant to the requirements of the Securities Act, 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 Cambridge, Massachusetts, on the 30th day of July, 2021.
CYCLERION THERAPEUTICS, INC.
By:
/s/ Anjeza Gjino
Name:
Anjeza Gjino
Title:
Chief Financial Officer
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Peter M. Hecht and Anjeza Gjino, jointly and severally, as their true and lawful attorney-in-fact and agent,
          with full power of substitution and re-substitution, for them and in their name, place and stead, in any and all capacities, to execute any or all amendments including any post-effective amendments and supplements to this Registration Statement
          on Form S-8 of Cyclerion Therapeutics, Inc., and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent full power and
          authority to do and perform each and every act and thing requisite and necessary to be done, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorney-in-fact and agent,
          or his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.
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/ Peter M. Hecht
Chief Executive Officer (Principal Executive Officer)
July 30, 2021
Peter M. Hecht
/s/ Anjeza Gjino
Chief Financial Officer (Principal Financial Officer and Principal Accounting Officer)
July 30, 2021
Anjeza Gjino
/s/ Kevin Churchwell
Director
July 30, 2021
Kevin Churchwell
/s/ George Conrades
Director
July 30, 2021
George Conrades
/s/ Errol De Souza
Director
July 30, 2021
Errol De Souza
/s/ Marsha Fanucci
Director
July 30, 2021
Marsha Fanucci
/s/ Ole Isacson
Director
July 30, 2021
Ole Isacson
/s/ Stephanie Lovell
Director
July 30, 2021
Stephanie Lovell
/s/ Terrance McGuire
Director
July 30, 2021
Terrance McGuire
/s/ Michael Mendelsohn
Director
July 30, 2021
Michael Mendelsohn