<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2020-08-18</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001802665</issuerCik>
        <issuerName>Harmony Biosciences Holdings, Inc.</issuerName>
        <issuerTradingSymbol>HRMY</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001821186</rptOwnerCik>
            <rptOwnerName>Valor IV Pharma Holdings, LLC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O VALOR EQUITY PARTNERS</rptOwnerStreet1>
            <rptOwnerStreet2>875 NORTH MICHIGAN AVENUE, SUITE 3214</rptOwnerStreet2>
            <rptOwnerCity>CHICAGO</rptOwnerCity>
            <rptOwnerState>IL</rptOwnerState>
            <rptOwnerZipCode>60611</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001495158</rptOwnerCik>
            <rptOwnerName>Gracias Antonio J.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O VALOR EQUITY PARTNERS</rptOwnerStreet1>
            <rptOwnerStreet2>875 NORTH MICHIGAN AVENUE, SUITE 3214</rptOwnerStreet2>
            <rptOwnerCity>CHICAGO</rptOwnerCity>
            <rptOwnerState>IL</rptOwnerState>
            <rptOwnerZipCode>60611</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001821210</rptOwnerCik>
            <rptOwnerName>Sabater Juan A.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O VALOR EQUITY PARTNERS</rptOwnerStreet1>
            <rptOwnerStreet2>875 NORTH MICHIGAN AVENUE, SUITE 3214</rptOwnerStreet2>
            <rptOwnerCity>CHICAGO</rptOwnerCity>
            <rptOwnerState>IL</rptOwnerState>
            <rptOwnerZipCode>60611</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>845336</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F1"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F2"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F2"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>9129640</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F1"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Series C Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F3"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F3"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F3"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>217527</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F1"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">Antonio Gracias is the Chief Executive Officer of Valor Management L.P. (&quot;Valor Management&quot;) and Juan A. Sabater is the President of Valor Management. Valor Management is the managing member of Valor Equity Capital IV LLC, which is the general partner of Valor Equity Associates IV L.P., which, in turn, is the general partner of each of Valor Equity Partners IV L.P., Valor Equity Partners IV-A L.P. and Valor Equity Partners IV-B L.P. (collectively, the &quot;Valor Funds&quot;). The Valor Funds are the sole members of the Valor IV Pharma Holdings, LLC (&quot;Valor&quot;). As such, Messers. Gracias and Sabater may be deemed to beneficially own the shares held by Valor. Each of Messers. Gracias and Sabater disclaims beneficial ownership over the shares described herein except to the extent of their pecuniary interest therein.</footnote>
        <footnote id="F2">The Series A Preferred Stock is convertible into Common Stock on a 8.215-for-1 basis into the number of shares of Common Stock as shown in Column 3 at the holder's election and automatically upon the closing of the Issuer's initial public offering without payment or further consideration. These shares have no expiration date.</footnote>
        <footnote id="F3">The Series C Preferred Stock is convertible into Common Stock on a 8.215-for-1 basis into the number of shares of Common Stock as shown in Column 3 at the holder's election and automatically upon the closing of the Issuer's initial public offering without payment or further consideration. These shares have no expiration date.</footnote>
    </footnotes>

    <remarks>Exhibit 24.1 - Power of Attorney for Valor IV Pharma Holdings, LLC.
Exhibit 24.2 - Power of Attorney for Antonio Gracias.
Exhibit 24.3 - Power of Attorney for Juan A. Sabater.</remarks>

    <ownerSignature>
        <signatureName>Valor Management L.P., By: /s/ Stephanie Wisdo,  Attorney-in-fact for Antonio Gracias, Chief Executive Officer</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Equity Capital IV LLC, By: Valor Management L.P., its managing member, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias, Chief Executive Officer</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Equity Associates IV L.P., By: Valor Equity Capital IV LLC, its general partner, By: Valor Management L.P., its managing member, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias, Chief Executive Officer</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Equity Partners IV L.P., By: Valor Equity Associates IV L.P., its general partner, By: Valor Equity Capital IV LLC, its general partner, By: Valor Management L.P., its managing member, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Equity Partners IV-A L.P.,By: Valor Equity Associates IV L.P., its general partner, By: Valor Equity Capital IV LLC, its general partner, By: Valor Management L.P., its managing member, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Equity Partners IV-B L.P., By: Valor Equity Associates IV L.P., its general partner, By: Valor Equity Capital IV LLC, its general partner, By: Valor Management L.P., its managing member, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Valor Pharma Holdings, LLC By Valor Equity Associates IV L.P. general partner of its sole members By Valor Equity Capital IV LLC, its general partner By Valor Management L.P. its managing member By /s/ Stephanie Wisdo Attorney-in-fact for Antonio Gracias</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Antonio Gracias, By: /s/ Stephanie Wisdo, Attorney-in-fact for Antonio Gracias</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Juan A. Sabater, By: /s/ Stephanie Wisdo, Attorney-in-fact for Juan A. Sabater</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>
</ownershipDocument>
