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

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2023-03-07</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001661998</issuerCik>
        <issuerName>Homology Medicines, Inc.</issuerName>
        <issuerTradingSymbol>FIXX</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001968554</rptOwnerCik>
            <rptOwnerName>Jordan Julie</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O HOMOLOGY MEDICINES, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>ONE PATRIOTS PARK</rptOwnerStreet2>
            <rptOwnerCity>BEDFORD</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>01730</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>Chief Medical Officer</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeHolding>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>2519</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeHolding>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Employee Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>6.53</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2031-06-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>65000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Employee Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>2.71</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <value>2032-02-24</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>56000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Employee Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>3.59</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F3"/>
            </exerciseDate>
            <expirationDate>
                <value>2032-03-02</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>9000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Employee Stock Option (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>1.60</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F4"/>
            </exerciseDate>
            <expirationDate>
                <value>2033-02-23</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>143000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Restricted Stock Units</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F6"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F5"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F6"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>350</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Restricted Stock Units</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F6"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F7"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F6"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>5360</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Restricted Stock Units</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F6"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F8"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F6"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>1340</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Restricted Stock Units</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <footnoteId id="F6"/>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F9"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F6"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>24000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">The option vests or has vested as to 25% of the underlying shares on May 3, 2022 and in 36 substantially equal monthly installments upon the Reporting Person's completion of each full month of service thereafter so that such option will become fully vested on May 3, 2025.</footnote>
        <footnote id="F2">The option vests in 48 substantially equal monthly installments upon the Reporting Person's completion of each full month of service following January 1, 2022 so that such option will become fully vested on January 1, 2026.</footnote>
        <footnote id="F3">The option vests in 48 substantially equal monthly installments upon the Reporting Person's completion of each full month of service following January 1, 2022 so that such option will become fully vested on January 1, 2026.</footnote>
        <footnote id="F4">The option vests in 48 substantially equal monthly installments upon the Reporting Person's completion of each full month of service following January 1, 2023 so that such option will become fully vested on January 1, 2027.</footnote>
        <footnote id="F5">The restricted stock units will vest and settle in full on August 2, 2023.</footnote>
        <footnote id="F6">Each restricted stock unit represents a contingent right to receive one share of Issuer common stock. The restricted stock units have no expiration date.</footnote>
        <footnote id="F7">The restricted stock units will vest and settle as to one half of the restricted stock units on each of January 1, 2024 and January 1, 2025.</footnote>
        <footnote id="F8">The restricted stock units will vest and settle as to one half of the restricted stock units on each of January 1, 2024 and January 1, 2025.</footnote>
        <footnote id="F9">The restricted stock units will vest and settle as to one third of the restricted stock units on each of the first three anniversaries of January 1, 2023 so that such RSUs will become fully vested on January 1, 2026.</footnote>
    </footnotes>

    <remarks>Exhibit 24 - Power of Attorney.</remarks>

    <ownerSignature>
        <signatureName>/s/ Paul Alloway, Attorney-in-Fact for Julie Jordan</signatureName>
        <signatureDate>2023-03-16</signatureDate>
    </ownerSignature>
</ownershipDocument>
