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<!-- DFIN ActiveDisclosure(SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-03-05T16:18:05.9477032+00:00 -->
<!-- Version            : 5.0.1.321 -->
<!-- Package ID         : 977cfab0d97f40de8cf6b11d27c37586 -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="zfgn_PercentageOfPrincipalBalanceToBeSecuredInRestrictedCashAccount" name="PercentageOfPrincipalBalanceToBeSecuredInRestrictedCashAccount" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_DebtInstrumentRestrictiveCovenantsInvestmentInSubsidiaries" name="DebtInstrumentRestrictiveCovenantsInvestmentInSubsidiaries" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_LongTermNotesPayableBeforeAccretion" name="LongTermNotesPayableBeforeAccretion" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_PublicOfferingMember" name="PublicOfferingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_CowenAndCompanyLimitedLiabilityCompanyMember" name="CowenAndCompanyLimitedLiabilityCompanyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_AtTheMarketEquityOfferingProgramMember" name="AtTheMarketEquityOfferingProgramMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_AggregateGrossSalesProceedsUnderSalesAgreement" name="AggregateGrossSalesProceedsUnderSalesAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_PercentageOfCompensationForServicesEqualToGrossProceeds" name="PercentageOfCompensationForServicesEqualToGrossProceeds" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_SalesAgreementDescription" name="SalesAgreementDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_TwoThousandFourteenStockOptionAndIncentivePlanMember" name="TwoThousandFourteenStockOptionAndIncentivePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_TwoThousandAndFourteenEmployeeStockPurchasePlanMember" name="TwoThousandAndFourteenEmployeeStockPurchasePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_GrantsOutsideOfTwoThousandFourteenPlanMember" name="GrantsOutsideOfTwoThousandFourteenPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_NonemployeeMember" name="NonemployeeMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantTargetSharesPercentage" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantTargetSharesPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateGrantDateFairValue" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateGrantDateFairValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_FirstOfferingPeriodStartDate" name="FirstOfferingPeriodStartDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_FirstOfferingPeriodEndDate" name="FirstOfferingPeriodEndDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_SecondOfferingPeriodStartDate" name="SecondOfferingPeriodStartDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_SecondOfferingPeriodEndDate" name="SecondOfferingPeriodEndDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_NumeratorAbstract" name="NumeratorAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_DenominatorAbstract" name="DenominatorAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_EarningPerShareAbstract" name="EarningPerShareAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_AreaOfOfficeSpace" name="AreaOfOfficeSpace" type="num:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_LeaseCommencementDate" name="LeaseCommencementDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_BostonMember" name="BostonMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_ShigoCenterPlazaOwnersLLCMember" name="ShigoCenterPlazaOwnersLLCMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_AdditionalOfficeSpaceMember" name="AdditionalOfficeSpaceMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_OfficeSpaceLeaseMember" name="OfficeSpaceLeaseMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_AdditionalOfficeSpaceTwoMember" name="AdditionalOfficeSpaceTwoMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_UnrelatedThirdPartyMember" name="UnrelatedThirdPartyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_PreCommercializationMilestonesMember" name="PreCommercializationMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_ProductCommercializationMilestonesMember" name="ProductCommercializationMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_SubsequentLicensedProductMember" name="SubsequentLicensedProductMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_OperatingLeasesNumberOfOptionsToExtendLease" name="OperatingLeasesNumberOfOptionsToExtendLease" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_SubleaseAreaOfRealEstateProperty" name="SubleaseAreaOfRealEstateProperty" type="num:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="zfgn_SubleaseExpirationDate" name="SubleaseExpirationDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_OperatingLeasesFutureMinimumPaymentsDueInSixYears" name="OperatingLeasesFutureMinimumPaymentsDueInSixYears" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_CashPaidForAmountsIncludedInMeasurementOfLeaseLiabilitiesAbstract" name="CashPaidForAmountsIncludedInMeasurementOfLeaseLiabilitiesAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_RightOfUseAssetsObtainedInExchangeForLeaseObligationsAbstract" name="RightOfUseAssetsObtainedInExchangeForLeaseObligationsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_MilestonePaymentAmount" name="MilestonePaymentAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_LicensingFeesPerProductMaximum" name="LicensingFeesPerProductMaximum" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_MilestoneLiability" name="MilestoneLiability" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_IncomeTaxesDisclosureLineItems" name="IncomeTaxesDisclosureLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_IncomeTaxesDisclosureTable" name="IncomeTaxesDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_NoExpirationMember" name="NoExpirationMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilitiesNoncurrent" name="DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilitiesNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_DeferredTaxAssetsOtherNoncurrent" name="DeferredTaxAssetsOtherNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_DeferredTaxAssetsOperatingLeaseLiabilityNoncurrent" name="DeferredTaxAssetsOperatingLeaseLiabilityNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssetsNoncurrent" name="DeferredTaxLiabilitiesOperatingLeaseRightOfUseAssetsNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_ValuationAllowanceDeferredTaxAssetChangeInAmountDecrease" name="ValuationAllowanceDeferredTaxAssetChangeInAmountDecrease" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_ValuationAllowanceDeferredTaxAssetChangeInAmountIncrease" name="ValuationAllowanceDeferredTaxAssetChangeInAmountIncrease" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_NetOperatingLossCarryForwardExpirationYearBegin" name="NetOperatingLossCarryForwardExpirationYearBegin" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_TaxCreditCarryForwardExpirationYearStart" name="TaxCreditCarryForwardExpirationYearStart" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_OperatingLossCarryforwardsMinimumPercentageOfTaxableIncomeInTaxPeriod" name="OperatingLossCarryforwardsMinimumPercentageOfTaxableIncomeInTaxPeriod" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_DeferredTaxAssetsNetOfLiabilitiesBeforeValuationAllowance" name="DeferredTaxAssetsNetOfLiabilitiesBeforeValuationAllowance" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_Retirement401KPlanMember" name="Retirement401KPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_SIMPLEIRAPlanMember" name="SIMPLEIRAPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_EffectiveTaxIncentiveRateRelatedToResearchAndDevelopment" name="EffectiveTaxIncentiveRateRelatedToResearchAndDevelopment" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_TaxIncentiveResearchAndDevelopmentActivities" name="TaxIncentiveResearchAndDevelopmentActivities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="zfgn_PercentageReductionResearchAndDevelopmentCosts" name="PercentageReductionResearchAndDevelopmentCosts" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="zfgn_TaxIncentiveReceivable" name="TaxIncentiveReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="zfgn_ResearchAndDevelopmentTaxIncentiveLineItems" name="ResearchAndDevelopmentTaxIncentiveLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_ResearchAndDevelopmentExpensesTable" name="ResearchAndDevelopmentExpensesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="zfgn_NonCashMember" name="NonCashMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
</xsd:schema>
