<?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>0001602402</rptOwnerCik>
            <rptOwnerName>Nielsen Jack</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O HARMONY BIOSCIENCES, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>630 W. GERMANTOWN PIKE, SUITE 215</rptOwnerStreet2>
            <rptOwnerCity>PLYMOUTH MEETING</rptOwnerCity>
            <rptOwnerState>PA</rptOwnerState>
            <rptOwnerZipCode>19462</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F1"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F1"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>3208764</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Vivo Capital Fund VIII, L.P.</value>
                    <footnoteId id="F2"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Series A Preferred Stock</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F1"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F1"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>443091</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Vivo Capital Surplus Fund VIII, L.P.</value>
                    <footnoteId id="F2"/>
                </natureOfOwnership>
            </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>183358</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Vivo Capital Fund VIII, L.P.</value>
                    <footnoteId id="F2"/>
                </natureOfOwnership>
            </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>25319</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>By Vivo Capital Surplus Fund VIII, L.P.</value>
                    <footnoteId id="F2"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">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="F2">The management company of the holder is Vivo Capital LLC, of which the Reporting Person is a voting member. The Reporting Person may be deemed to share voting and dispositive power over these shares with four (4) other voting members. The Reporting Person disclaims beneficial ownership over such shares except to the extent of his pecuniary interest therein, and the inclusion of these shares in this report shall not be deemed an admission of beneficial ownership of the reported shares for purposes of Section 16 or for any other purposes.</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 - Power of Attorney.</remarks>

    <ownerSignature>
        <signatureName>/s/ Stephanie Wisdo, Attorney-in-fact for Jack Bech Nielsen</signatureName>
        <signatureDate>2020-08-18</signatureDate>
    </ownerSignature>
</ownershipDocument>
