<?xml version="1.0"?>
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    <schemaVersion>X0708</schemaVersion>

    <submissionType>D</submissionType>

    <testOrLive>LIVE</testOrLive>

    <primaryIssuer>
        <cik>0001724344</cik>
        <entityName>Entasis Therapeutics Holdings Inc.</entityName>
        <issuerAddress>
            <street1>35 Gatehouse Drive</street1>
            <city>Waltham</city>
            <stateOrCountry>MA</stateOrCountry>
            <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
            <zipCode>02451</zipCode>
        </issuerAddress>
        <issuerPhoneNumber>781-810-0120</issuerPhoneNumber>
        <jurisdictionOfInc>DELAWARE</jurisdictionOfInc>
        <issuerPreviousNameList>
            <value>None</value>
        </issuerPreviousNameList>
        <edgarPreviousNameList>
            <previousName>Entasis Therapeutics Ltd</previousName>
        </edgarPreviousNameList>
        <entityType>Corporation</entityType>
        <yearOfInc>
            <withinFiveYears>true</withinFiveYears>
            <value>2018</value>
        </yearOfInc>
    </primaryIssuer>

    <relatedPersonsList>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Manoussos</firstName>
                <lastName>Perros</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>David</firstName>
                <lastName>Meek</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Heather</firstName>
                <lastName>Behanna</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Heather</firstName>
                <lastName>Preston</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>David</firstName>
                <lastName>Hastings</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
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        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Howard</firstName>
                <lastName>Mayer</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Drive</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Director</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Michael</firstName>
                <lastName>Gutch</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Road</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
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        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>David</firstName>
                <lastName>Altarac</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Road</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
            </relatedPersonRelationshipList>
        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>John</firstName>
                <lastName>Mueller</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Road</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
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            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
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        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Ruben</firstName>
                <lastName>Tommasi</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Road</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
            </relatedPersonAddress>
            <relatedPersonRelationshipList>
                <relationship>Executive Officer</relationship>
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        </relatedPersonInfo>
        <relatedPersonInfo>
            <relatedPersonName>
                <firstName>Elizabeth</firstName>
                <lastName>Keiley</lastName>
            </relatedPersonName>
            <relatedPersonAddress>
                <street1>35 Gatehouse Road</street1>
                <city>Waltham</city>
                <stateOrCountry>MA</stateOrCountry>
                <stateOrCountryDescription>MASSACHUSETTS</stateOrCountryDescription>
                <zipCode>02451</zipCode>
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            <relatedPersonRelationshipList>
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        </relatedPersonInfo>
    </relatedPersonsList>

    <offeringData>
        <industryGroup>
            <industryGroupType>Biotechnology</industryGroupType>
        </industryGroup>
        <issuerSize>
            <revenueRange>Decline to Disclose</revenueRange>
        </issuerSize>
        <federalExemptionsExclusions>
            <item>06b</item>
        </federalExemptionsExclusions>
        <typeOfFiling>
            <newOrAmendment>
                <isAmendment>false</isAmendment>
            </newOrAmendment>
            <dateOfFirstSale>
                <value>2020-08-27</value>
            </dateOfFirstSale>
        </typeOfFiling>
        <durationOfOffering>
            <moreThanOneYear>false</moreThanOneYear>
        </durationOfOffering>
        <typesOfSecuritiesOffered>
            <isEquityType>true</isEquityType>
            <isOptionToAcquireType>true</isOptionToAcquireType>
        </typesOfSecuritiesOffered>
        <businessCombinationTransaction>
            <isBusinessCombinationTransaction>false</isBusinessCombinationTransaction>
            <clarificationOfResponse></clarificationOfResponse>
        </businessCombinationTransaction>
        <minimumInvestmentAccepted>0</minimumInvestmentAccepted>
        <salesCompensationList>
            <recipient>
                <recipientName>Cantor Fitzgerald &amp; Co.</recipientName>
                <recipientCRDNumber>134</recipientCRDNumber>
                <associatedBDName>None</associatedBDName>
                <associatedBDCRDNumber>None</associatedBDCRDNumber>
                <recipientAddress>
                    <street1>110 East 59th Street</street1>
                    <street2>4th Floor</street2>
                    <city>New York</city>
                    <stateOrCountry>NY</stateOrCountry>
                    <stateOrCountryDescription>NEW YORK</stateOrCountryDescription>
                    <zipCode>10022</zipCode>
                </recipientAddress>
                <statesOfSolicitationList>
                    <state>CA</state>
                    <description>CALIFORNIA</description>
                    <state>DE</state>
                    <description>DELAWARE</description>
                    <state>IL</state>
                    <description>ILLINOIS</description>
                    <state>MA</state>
                    <description>MASSACHUSETTS</description>
                    <state>NY</state>
                    <description>NEW YORK</description>
                    <state>NC</state>
                    <description>NORTH CAROLINA</description>
                </statesOfSolicitationList>
            </recipient>
            <recipient>
                <recipientName>A.G.P. / Alliance Global Partner</recipientName>
                <recipientCRDNumber>8361</recipientCRDNumber>
                <associatedBDName>None</associatedBDName>
                <associatedBDCRDNumber>None</associatedBDCRDNumber>
                <recipientAddress>
                    <street1>88 Post Road West</street1>
                    <street2>2nd Floor</street2>
                    <city>Westport</city>
                    <stateOrCountry>CT</stateOrCountry>
                    <stateOrCountryDescription>CONNECTICUT</stateOrCountryDescription>
                    <zipCode>06880</zipCode>
                </recipientAddress>
                <statesOfSolicitationList>
                    <state>CA</state>
                    <description>CALIFORNIA</description>
                    <state>DE</state>
                    <description>DELAWARE</description>
                    <state>IL</state>
                    <description>ILLINOIS</description>
                    <state>MA</state>
                    <description>MASSACHUSETTS</description>
                    <state>NY</state>
                    <description>NEW YORK</description>
                    <state>NC</state>
                    <description>NORTH CAROLINA</description>
                </statesOfSolicitationList>
            </recipient>
        </salesCompensationList>
        <offeringSalesAmounts>
            <totalOfferingAmount>24999999</totalOfferingAmount>
            <totalAmountSold>24999999</totalAmountSold>
            <totalRemaining>0</totalRemaining>
            <clarificationOfResponse></clarificationOfResponse>
        </offeringSalesAmounts>
        <investors>
            <hasNonAccreditedInvestors>false</hasNonAccreditedInvestors>
            <totalNumberAlreadyInvested>2</totalNumberAlreadyInvested>
        </investors>
        <salesCommissionsFindersFees>
            <salesCommissions>
                <dollarAmount>1312500</dollarAmount>
            </salesCommissions>
            <findersFees>
                <dollarAmount>0</dollarAmount>
            </findersFees>
            <clarificationOfResponse></clarificationOfResponse>
        </salesCommissionsFindersFees>
        <useOfProceeds>
            <grossProceedsUsed>
                <dollarAmount>0</dollarAmount>
            </grossProceedsUsed>
            <clarificationOfResponse></clarificationOfResponse>
        </useOfProceeds>
        <signatureBlock>
            <authorizedRepresentative>false</authorizedRepresentative>
            <signature>
                <issuerName>Entasis Therapeutics Holdings Inc.</issuerName>
                <signatureName>/s/ Elizabeth Keiley</signatureName>
                <nameOfSigner>Elizabeth Keiley</nameOfSigner>
                <signatureTitle>General Counsel</signatureTitle>
                <signatureDate>2020-09-10</signatureDate>
            </signature>
        </signatureBlock>
    </offeringData>
</edgarSubmission>
