<?xml version="1.0" encoding="us-ascii"?>
<!-- DFS ActiveDisclosure(SM) XBRL Schema Document - http://www.dfsco.com/financial-services/ -->
<!-- Creation Date      : 2019-03-14T21:09:06.6128203+00:00 -->
<!-- Version            : 3.3.6989.14284 -->
<!-- Package ID         : 2f20dd7522a24ea58e96fa5e90bc9e1d -->
<!-- Copyright (c) 2019 Donnelley Financial, LLC. All Rights Reserved. -->
<schema xmlns:nonnum="http://www.xbrl.org/dtr/type/non-numeric" xmlns:num="http://www.xbrl.org/dtr/type/numeric" xmlns:us-types="http://fasb.org/us-types/2018-01-31" xmlns:stpr="http://xbrl.sec.gov/stpr/2018-01-31" xmlns:srt-types="http://fasb.org/srt-types/2018-01-31" xmlns:zfgn="http://www.zafgen.com/20181231" xmlns:naics="http://xbrl.sec.gov/naics/2017-01-31" xmlns:invest="http://xbrl.sec.gov/invest/2013-01-31" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:srt="http://fasb.org/srt/2018-01-31" xmlns:us-gaap="http://fasb.org/us-gaap/2018-01-31" xmlns:dei="http://xbrl.sec.gov/dei/2018-01-31" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:country="http://xbrl.sec.gov/country/2017-01-31" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:currency="http://xbrl.sec.gov/currency/2017-01-31" xmlns:exch="http://xbrl.sec.gov/exch/2018-01-31" xmlns:sic="http://xbrl.sec.gov/sic/2011-01-31" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.zafgen.com/20181231" xmlns="http://www.w3.org/2001/XMLSchema">
  <import schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/instance" />
  <import schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/linkbase" />
  <import schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" namespace="http://xbrl.org/2005/xbrldt" />
  <import schemaLocation="https://xbrl.sec.gov/dei/2018/dei-2018-01-31.xsd" namespace="http://xbrl.sec.gov/dei/2018-01-31" />
  <import schemaLocation="http://xbrl.fasb.org/us-gaap/2018/elts/us-gaap-2018-01-31.xsd" namespace="http://fasb.org/us-gaap/2018-01-31" />
  <import schemaLocation="http://xbrl.fasb.org/srt/2018/elts/srt-2018-01-31.xsd" namespace="http://fasb.org/srt/2018-01-31" />
  <import schemaLocation="http://xbrl.fasb.org/us-gaap/2018/elts/us-types-2018-01-31.xsd" namespace="http://fasb.org/us-types/2018-01-31" />
  <import schemaLocation="http://www.xbrl.org/dtr/type/numeric-2009-12-16.xsd" namespace="http://www.xbrl.org/dtr/type/numeric" />
  <import schemaLocation="http://www.xbrl.org/dtr/type/nonNumeric-2009-12-16.xsd" namespace="http://www.xbrl.org/dtr/type/non-numeric" />
  <import schemaLocation="http://xbrl.fasb.org/srt/2018/elts/srt-types-2018-01-31.xsd" namespace="http://fasb.org/srt-types/2018-01-31" />
  <import schemaLocation="http://xbrl.sec.gov/country/2017/country-2017-01-31.xsd" namespace="http://xbrl.sec.gov/country/2017-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/currency/2017/currency-2017-01-31.xsd" namespace="http://xbrl.sec.gov/currency/2017-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/exch/2018/exch-2018-01-31.xsd" namespace="http://xbrl.sec.gov/exch/2018-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/invest/2013/invest-2013-01-31.xsd" namespace="http://xbrl.sec.gov/invest/2013-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/naics/2017/naics-2017-01-31.xsd" namespace="http://xbrl.sec.gov/naics/2017-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/sic/2011/sic-2011-01-31.xsd" namespace="http://xbrl.sec.gov/sic/2011-01-31" />
  <import schemaLocation="https://xbrl.sec.gov/stpr/2018/stpr-2018-01-31.xsd" namespace="http://xbrl.sec.gov/stpr/2018-01-31" />
  <annotation>
    <appinfo>
      <link:roleType id="TemplateLink" roleURI="http://www.zafgen.com/20181231/role/TemplateLink" xmlns:link="http://www.xbrl.org/2003/linkbase">
        <link:definition>00000 - Document - Template Link</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="zfgn-20181231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:title="Calculation Links, all" xlink:type="simple" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" />
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="zfgn-20181231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:title="Definition Links, all" xlink:type="simple" />
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="zfgn-20181231_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:title="Label Links, all" xlink:type="simple" />
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="zfgn-20181231_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:title="Presentation Links, all" xlink:type="simple" />
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DocumentDocumentAndEntityInformation" id="Role_DocumentDocumentAndEntityInformation">
        <link:definition>100000 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/StatementConsolidatedBalanceSheets" id="Role_StatementConsolidatedBalanceSheets">
        <link:definition>100010 - Statement - Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/StatementConsolidatedBalanceSheetsParenthetical" id="Role_StatementConsolidatedBalanceSheetsParenthetical">
        <link:definition>100020 - Statement - Consolidated Balance Sheets (Parenthetical)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/StatementConsolidatedStatementsOfOperationsAndComprehensiveLoss" id="Role_StatementConsolidatedStatementsOfOperationsAndComprehensiveLoss">
        <link:definition>100030 - Statement - Consolidated Statements of Operations and Comprehensive Loss</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/StatementConsolidatedStatementsOfChangesInStockholdersEquity" id="Role_StatementConsolidatedStatementsOfChangesInStockholdersEquity">
        <link:definition>100040 - Statement - Consolidated Statements of Changes in Stockholders&apos; Equity</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/StatementConsolidatedStatementsOfCashFlows" id="Role_StatementConsolidatedStatementsOfCashFlows">
        <link:definition>100050 - Statement - Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNatureOfBusinessAndBasisOfPresentation" id="Role_DisclosureNatureOfBusinessAndBasisOfPresentation">
        <link:definition>100060 - Disclosure - Nature of the Business and Basis of Presentation</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSummaryOfSignificantAccountingPolicies" id="Role_DisclosureSummaryOfSignificantAccountingPolicies">
        <link:definition>100070 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureFairValueMeasurementsAndMarketableSecurities" id="Role_DisclosureFairValueMeasurementsAndMarketableSecurities">
        <link:definition>100080 - Disclosure - Fair Value Measurements and Marketable Securities</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosurePropertyAndEquipmentNet" id="Role_DisclosurePropertyAndEquipmentNet">
        <link:definition>100090 - Disclosure - Property and Equipment, net</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureAccruedExpenses" id="Role_DisclosureAccruedExpenses">
        <link:definition>100100 - Disclosure - Accrued Expenses</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNotesPayable" id="Role_DisclosureNotesPayable">
        <link:definition>100110 - Disclosure - Notes Payable</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockholdersEquity" id="Role_DisclosureStockholdersEquity">
        <link:definition>100120 - Disclosure - Stockholders&apos; Equity</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwards" id="Role_DisclosureStockBasedAwards">
        <link:definition>100130 - Disclosure - Stock-Based Awards</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNetLossPerShare" id="Role_DisclosureNetLossPerShare">
        <link:definition>100140 - Disclosure - Net Loss Per Share</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureCommitmentsAndContingencies" id="Role_DisclosureCommitmentsAndContingencies">
        <link:definition>100150 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxes" id="Role_DisclosureIncomeTaxes">
        <link:definition>100160 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRetirementPlan" id="Role_DisclosureRetirementPlan">
        <link:definition>100170 - Disclosure - Retirement Plan</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureAustraliaResearchAndDevelopmentTaxIncentive" id="Role_DisclosureAustraliaResearchAndDevelopmentTaxIncentive">
        <link:definition>100180 - Disclosure - Australia Research and Development Tax Incentive</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRestructuring" id="Role_DisclosureRestructuring">
        <link:definition>100190 - Disclosure - Restructuring</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureQuarterlyFinancialDataUnaudited" id="Role_DisclosureQuarterlyFinancialDataUnaudited">
        <link:definition>100200 - Disclosure - Quarterly Financial Data (Unaudited)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSubsequentEvents" id="Role_DisclosureSubsequentEvents">
        <link:definition>100210 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesPolicies" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesPolicies">
        <link:definition>100220 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureFairValueMeasurementsAndMarketableSecuritiesTables" id="Role_DisclosureFairValueMeasurementsAndMarketableSecuritiesTables">
        <link:definition>100230 - Disclosure - Fair Value Measurements and Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosurePropertyAndEquipmentNetTables" id="Role_DisclosurePropertyAndEquipmentNetTables">
        <link:definition>100240 - Disclosure - Property and Equipment, net (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureAccruedExpensesTables" id="Role_DisclosureAccruedExpensesTables">
        <link:definition>100250 - Disclosure - Accrued Expenses (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNotesPayableTables" id="Role_DisclosureNotesPayableTables">
        <link:definition>100260 - Disclosure - Notes Payable (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwardsTables" id="Role_DisclosureStockBasedAwardsTables">
        <link:definition>100270 - Disclosure - Stock-Based Awards (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNetLossPerShareTables" id="Role_DisclosureNetLossPerShareTables">
        <link:definition>100280 - Disclosure - Net Loss Per Share (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureCommitmentsAndContingenciesTables" id="Role_DisclosureCommitmentsAndContingenciesTables">
        <link:definition>100290 - Disclosure - Commitments and Contingencies (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesTables" id="Role_DisclosureIncomeTaxesTables">
        <link:definition>100300 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRestructuringTables" id="Role_DisclosureRestructuringTables">
        <link:definition>100310 - Disclosure - Restructuring (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureQuarterlyFinancialDataUnauditedTables" id="Role_DisclosureQuarterlyFinancialDataUnauditedTables">
        <link:definition>100320 - Disclosure - Quarterly Financial Data (Unaudited) (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSubsequentEventsTables" id="Role_DisclosureSubsequentEventsTables">
        <link:definition>100330 - Disclosure - Subsequent Events (Tables)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNatureOfBusinessAndBasisOfPresentationAdditionalInformationDetail" id="Role_DisclosureNatureOfBusinessAndBasisOfPresentationAdditionalInformationDetail">
        <link:definition>100340 - Disclosure - Nature of the Business and Basis of Presentation - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetail" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetail">
        <link:definition>100350 - Disclosure - Summary of Significant Accounting Policies - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureFairValueMeasurementsAndMarketableSecuritiesSummaryOfCashEquivalentsAndMarketableSecuritiesDetail" id="Role_DisclosureFairValueMeasurementsAndMarketableSecuritiesSummaryOfCashEquivalentsAndMarketableSecuritiesDetail">
        <link:definition>100360 - Disclosure - Fair Value Measurements and Marketable Securities - Summary of Cash Equivalents and Marketable Securities (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureFairValueMeasurementsAndMarketableSecuritiesSummaryOfMarketableSecuritiesDetail" id="Role_DisclosureFairValueMeasurementsAndMarketableSecuritiesSummaryOfMarketableSecuritiesDetail">
        <link:definition>100370 - Disclosure - Fair Value Measurements and Marketable Securities - Summary of Marketable Securities (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosurePropertyAndEquipmentNetScheduleOfPropertyPlantAndEquipmentNetDetail" id="Role_DisclosurePropertyAndEquipmentNetScheduleOfPropertyPlantAndEquipmentNetDetail">
        <link:definition>100380 - Disclosure - Property and Equipment, Net - Schedule of Property Plant and Equipment Net (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosurePropertyAndEquipmentNetAdditionalInformationDetail" id="Role_DisclosurePropertyAndEquipmentNetAdditionalInformationDetail">
        <link:definition>100390 - Disclosure - Property and Equipment, net - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureAccruedExpensesScheduleOfAccruedExpensesDetail" id="Role_DisclosureAccruedExpensesScheduleOfAccruedExpensesDetail">
        <link:definition>100400 - Disclosure - Accrued Expenses - Schedule of Accrued Expenses (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNotesPayableAdditionalInformationDetail" id="Role_DisclosureNotesPayableAdditionalInformationDetail">
        <link:definition>100410 - Disclosure - Notes Payable - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNotesPayableScheduleOfNotesPayableDetail" id="Role_DisclosureNotesPayableScheduleOfNotesPayableDetail">
        <link:definition>100420 - Disclosure - Notes Payable - Schedule of Notes Payable (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNotesPayableScheduleOfEstimatedFuturePrincipalPaymentsDetail" id="Role_DisclosureNotesPayableScheduleOfEstimatedFuturePrincipalPaymentsDetail">
        <link:definition>100430 - Disclosure - Notes Payable - Schedule of Estimated Future Principal Payments (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockholdersEquityAdditionalInformationDetail" id="Role_DisclosureStockholdersEquityAdditionalInformationDetail">
        <link:definition>100440 - Disclosure - Stockholders&apos; Equity - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwardsAdditionalInformationDetail" id="Role_DisclosureStockBasedAwardsAdditionalInformationDetail">
        <link:definition>100450 - Disclosure - Stock-Based Awards - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwardsAssumptionsUsedToDetermineFairValueOfStockOptionsGrantedDetail" id="Role_DisclosureStockBasedAwardsAssumptionsUsedToDetermineFairValueOfStockOptionsGrantedDetail">
        <link:definition>100460 - Disclosure - Stock-Based Awards - Assumptions used to Determine Fair Value of Stock Options Granted (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwardsSummaryOfStockOptionActivityDetail" id="Role_DisclosureStockBasedAwardsSummaryOfStockOptionActivityDetail">
        <link:definition>100470 - Disclosure - Stock-Based Awards - Summary of Stock Option Activity (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureStockBasedAwardsSummaryOfStockBasedCompensationExpenseRelatedToStockOptionsAndRestrictedCommonStockDetail" id="Role_DisclosureStockBasedAwardsSummaryOfStockBasedCompensationExpenseRelatedToStockOptionsAndRestrictedCommonStockDetail">
        <link:definition>100480 - Disclosure - Stock-Based Awards - Summary of Stock-Based Compensation Expense Related To Stock Options And Restricted Common Stock (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNetLossPerShareComputationOfBasicAndDilutedEarningsPerShareDetail" id="Role_DisclosureNetLossPerShareComputationOfBasicAndDilutedEarningsPerShareDetail">
        <link:definition>100490 - Disclosure - Net Loss Per Share - Computation of Basic and Diluted Earnings Per Share (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureNetLossPerShareSummaryOfCommonStockEquivalentsOutstandingDetail" id="Role_DisclosureNetLossPerShareSummaryOfCommonStockEquivalentsOutstandingDetail">
        <link:definition>100500 - Disclosure - Net Loss Per Share - Summary of Common Stock Equivalents Outstanding (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureCommitmentsAndContingenciesAdditionalInformationDetail" id="Role_DisclosureCommitmentsAndContingenciesAdditionalInformationDetail">
        <link:definition>100510 - Disclosure - Commitments and Contingencies - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureCommitmentsAndContingenciesScheduleOfFutureMinimumLeasePaymentsForOperatingLeasesDetail" id="Role_DisclosureCommitmentsAndContingenciesScheduleOfFutureMinimumLeasePaymentsForOperatingLeasesDetail">
        <link:definition>100520 - Disclosure - Commitments and Contingencies - Schedule of Future Minimum Lease Payments for Operating Leases (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesAdditionalInformationDetail" id="Role_DisclosureIncomeTaxesAdditionalInformationDetail">
        <link:definition>100530 - Disclosure - Income Taxes - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesScheduleOfDomesticAndForeignComponentsOfLossBeforeIncomeTaxesDetail" id="Role_DisclosureIncomeTaxesScheduleOfDomesticAndForeignComponentsOfLossBeforeIncomeTaxesDetail">
        <link:definition>100540 - Disclosure - Income Taxes - Schedule of Domestic and Foreign Components of Loss Before Income Taxes (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesReconciliationOfFederalStatutoryIncomeTaxRateDetail" id="Role_DisclosureIncomeTaxesReconciliationOfFederalStatutoryIncomeTaxRateDetail">
        <link:definition>100550 - Disclosure - Income Taxes - Reconciliation of Federal Statutory Income Tax Rate (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesScheduleOfNetDeferredTaxAssetsDetail" id="Role_DisclosureIncomeTaxesScheduleOfNetDeferredTaxAssetsDetail">
        <link:definition>100560 - Disclosure - Income Taxes - Schedule of Net Deferred Tax Assets (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureIncomeTaxesSummaryOfChangesInValuationAllowanceForDeferredTaxAssetsDetail" id="Role_DisclosureIncomeTaxesSummaryOfChangesInValuationAllowanceForDeferredTaxAssetsDetail">
        <link:definition>100570 - Disclosure - Income Taxes - Summary of Changes in the Valuation Allowance for Deferred Tax Assets (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRetirementPlanAdditionalInformationDetail" id="Role_DisclosureRetirementPlanAdditionalInformationDetail">
        <link:definition>100580 - Disclosure - Retirement Plan - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureAustraliaResearchAndDevelopmentTaxIncentiveAdditionalInformationDetail" id="Role_DisclosureAustraliaResearchAndDevelopmentTaxIncentiveAdditionalInformationDetail">
        <link:definition>100590 - Disclosure - Australia Research and Development Tax Incentive - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRestructuringAdditionalInformationDetail" id="Role_DisclosureRestructuringAdditionalInformationDetail">
        <link:definition>100600 - Disclosure - Restructuring - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRestructuringSummaryOfRestructuringCostsByCategoryDetail" id="Role_DisclosureRestructuringSummaryOfRestructuringCostsByCategoryDetail">
        <link:definition>100610 - Disclosure - Restructuring - Summary of Restructuring Costs by Category (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureRestructuringSummaryOfRestructuringReserveDetail" id="Role_DisclosureRestructuringSummaryOfRestructuringReserveDetail">
        <link:definition>100620 - Disclosure - Restructuring - Summary of Restructuring Reserve (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureQuarterlyFinancialDataScheduleOfUnauditedConsolidatedFinancialStatementsDetail" id="Role_DisclosureQuarterlyFinancialDataScheduleOfUnauditedConsolidatedFinancialStatementsDetail">
        <link:definition>100630 - Disclosure - Quarterly Financial Data - Schedule of Unaudited Consolidated Financial Statements (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSubsequentEventsAdditionalInformationDetail" id="Role_DisclosureSubsequentEventsAdditionalInformationDetail">
        <link:definition>100640 - Disclosure - Subsequent Events - Additional Information (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.zafgen.com/20181231/taxonomy/role/DisclosureSubsequentEventsScheduleOfMonthlyBaseRentDetail" id="Role_DisclosureSubsequentEventsScheduleOfMonthlyBaseRentDetail">
        <link:definition>100650 - Disclosure - Subsequent Events - Schedule of Monthly Base Rent (Detail)</link:definition>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </appinfo>
  </annotation>
  <element id="zfgn_DocumentAndEntityInformationAbstract" name="DocumentAndEntityInformationAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_TaxIncentiveReceivableCurrent" name="TaxIncentiveReceivableCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_StockIssuedDuringPeriodSharesStockOptionsExercisedAndEmployeeStockPurchasePlans" name="StockIssuedDuringPeriodSharesStockOptionsExercisedAndEmployeeStockPurchasePlans" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_StockIssuedDuringPeriodValueStockOptionsExercisedAndEmployeeStockPurchasePlan" name="StockIssuedDuringPeriodValueStockOptionsExercisedAndEmployeeStockPurchasePlan" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_PremiumOnMarketableSecurities" name="PremiumOnMarketableSecurities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_IncreaseDecreaseInTaxIncentivesReceivable" name="IncreaseDecreaseInTaxIncentivesReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_DepositsForLeasedProperty" name="DepositsForLeasedProperty" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_PublicOfferingCostIncludedInAccountsPayable" name="PublicOfferingCostIncludedInAccountsPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_ResearchContractCostsAndAccrualsPolicyTextBlock" name="ResearchContractCostsAndAccrualsPolicyTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_ScheduleOfNotesPayableTableTextBlock" name="ScheduleOfNotesPayableTableTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TimeBasedVestingMember" name="TimeBasedVestingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_MarketBasedVestingConditionsMember" name="MarketBasedVestingConditionsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureLineItems" name="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTable" name="OrganizationConsolidationAndPresentationOfFinancialStatementsDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_TermLoanMember" name="TermLoanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_NetProceedsFromSaleOfSecurities" name="NetProceedsFromSaleOfSecurities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_SummaryOfSignificantAccountingPoliciesLineItems" name="SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_SummaryOfSignificantAccountingPoliciesTable" name="SummaryOfSignificantAccountingPoliciesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_EquipmentFurnitureAndFixturesAndOfficeEquipmentMember" name="EquipmentFurnitureAndFixturesAndOfficeEquipmentMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_LikelihoodPercentageMinimum" name="LikelihoodPercentageMinimum" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_PropertyPlantAndEquipmentCapitalizedInterestCostsAbstract" name="PropertyPlantAndEquipmentCapitalizedInterestCostsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_AccruedResearchAndDevelopmentExpenseCurrent" name="AccruedResearchAndDevelopmentExpenseCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_TwoThousandAndFourteenCreditFacilityMember" name="TwoThousandAndFourteenCreditFacilityMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_DebtInstrumentFeePercentage" name="DebtInstrumentFeePercentage" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_RestrictedCashAndInvestmentsAsPercentageOfOutstandingPrincipalAmount" name="RestrictedCashAndInvestmentsAsPercentageOfOutstandingPrincipalAmount" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_CashCashEquivalentsAndShortTermInvestmentsPercentage" name="CashCashEquivalentsAndShortTermInvestmentsPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <element id="zfgn_PercentageOfPrincipalBalanceToBeSecuredInRestrictedCashAccount" name="PercentageOfPrincipalBalanceToBeSecuredInRestrictedCashAccount" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_DebtInstrumentRestrictiveCovenantsInvestmentInSubsidiaries" name="DebtInstrumentRestrictiveCovenantsInvestmentInSubsidiaries" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_LineOfCreditFacilityDebtDefaultMinimumAmount" name="LineOfCreditFacilityDebtDefaultMinimumAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_LongTermNotesPayableBeforeAccretion" name="LongTermNotesPayableBeforeAccretion" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_PublicOfferingMember" name="PublicOfferingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_CowenAndCompanyLimitedLiabilityCompanyMember" name="CowenAndCompanyLimitedLiabilityCompanyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_AtTheMarketEquityOfferingProgramMember" name="AtTheMarketEquityOfferingProgramMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_AggregateGrossSalesProceedsUnderSalesAgreement" name="AggregateGrossSalesProceedsUnderSalesAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_PercentageOfCompensationForServicesEqualToGrossProceeds" name="PercentageOfCompensationForServicesEqualToGrossProceeds" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_SalesAgreementDescription" name="SalesAgreementDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TwoThousandFourteenStockOptionMember" name="TwoThousandFourteenStockOptionMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_GrantsOutsideOfTwoThousandFourteenPlanMember" name="GrantsOutsideOfTwoThousandFourteenPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_NonemployeeMember" name="NonemployeeMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_TwoThousandAndFourteenEmployeeStockPurchasePlanMember" name="TwoThousandAndFourteenEmployeeStockPurchasePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_TimeBasedOptionsMember" name="TimeBasedOptionsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_MarketBasedStockOptionsMember" name="MarketBasedStockOptionsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_ShareBasedCompensationArrangementByShareBasedPaymentAwardDateOfGrantedShareForfeited" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardDateOfGrantedShareForfeited" type="xbrli:gYearMonthItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_ConsecutivePeriodOfMinimumCommonStockPriceDuringEarningPeriodDescription" name="ConsecutivePeriodOfMinimumCommonStockPriceDuringEarningPeriodDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantTargetSharesPercentage" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantTargetSharesPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateGrantDateFairValue" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardAggregateGrantDateFairValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_FirstOfferingPeriodStartDate" name="FirstOfferingPeriodStartDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_FirstOfferingPeriodEndDate" name="FirstOfferingPeriodEndDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_SecondOfferingPeriodStartDate" name="SecondOfferingPeriodStartDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_SecondOfferingPeriodEndDate" name="SecondOfferingPeriodEndDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_NumeratorAbstract" name="NumeratorAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_DenominatorAbstract" name="DenominatorAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_EarningPerShareAbstract" name="EarningPerShareAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_OperatingLeasesNumberOfOptionsToExtendLease" name="OperatingLeasesNumberOfOptionsToExtendLease" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_SubleaseAreaOfRealEstateProperty" name="SubleaseAreaOfRealEstateProperty" type="num:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <element id="zfgn_SubleaseExpirationDate" name="SubleaseExpirationDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_OfficeSpaceLeaseMember" name="OfficeSpaceLeaseMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_AdditionalOfficeSpaceMember" name="AdditionalOfficeSpaceMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_AdditionalOfficeSpaceTwoMember" name="AdditionalOfficeSpaceTwoMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_UnrelatedThirdPartyMember" name="UnrelatedThirdPartyMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_PreCommercializationMilestonesMember" name="PreCommercializationMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_ProductCommercializationMilestonesMember" name="ProductCommercializationMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_SubsequentLicensedProductMember" name="SubsequentLicensedProductMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_DevelopmentBasedMilestonesMember" name="DevelopmentBasedMilestonesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_MilestonePaymentAmount" name="MilestonePaymentAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_LicensingFeesPerProductMaximum" name="LicensingFeesPerProductMaximum" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_MilestoneLiability" name="MilestoneLiability" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_IncomeTaxesDisclosureLineItems" name="IncomeTaxesDisclosureLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_IncomeTaxesDisclosureTable" name="IncomeTaxesDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_NoExpirationMember" name="NoExpirationMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_EffectiveIncomeTaxRateReconciliationOrphanDrugTaxCredits" name="EffectiveIncomeTaxRateReconciliationOrphanDrugTaxCredits" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilitiesNoncurrent" name="DeferredTaxAssetsTaxDeferredExpenseReservesAndAccrualsAccruedLiabilitiesNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_DeferredTaxAssetsOtherNoncurrent" name="DeferredTaxAssetsOtherNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_ValuationAllowanceDeferredTaxAssetChangeInAmountDecrease" name="ValuationAllowanceDeferredTaxAssetChangeInAmountDecrease" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_ValuationAllowanceDeferredTaxAssetChangeInAmountIncrease" name="ValuationAllowanceDeferredTaxAssetChangeInAmountIncrease" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_NetOperatingLossCarryForwardExpirationYearBegin" name="NetOperatingLossCarryForwardExpirationYearBegin" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TaxCreditCarryForwardExpirationYearStart" name="TaxCreditCarryForwardExpirationYearStart" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TaxCutsAndJobsActOf2017NetOperatingLossesCarryforwardMaximumPercentageOfTaxableIncome" name="TaxCutsAndJobsActOf2017NetOperatingLossesCarryforwardMaximumPercentageOfTaxableIncome" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TaxCutsAndJobsActOf2017ChangeInTaxRateIncomeTaxExpenseBenefit" name="TaxCutsAndJobsActOf2017ChangeInTaxRateIncomeTaxExpenseBenefit" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_TaxCutsAndJobsActOf2017IncompleteAccountingChangeInTaxRateDeferredTaxLiabilityProvisionalIncomeTaxBenefit" name="TaxCutsAndJobsActOf2017IncompleteAccountingChangeInTaxRateDeferredTaxLiabilityProvisionalIncomeTaxBenefit" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_Retirement401KPlanMember" name="Retirement401KPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_SIMPLEIRAPlanMember" name="SIMPLEIRAPlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_EffectiveTaxIncentiveRateRelatedToResearchAndDevelopment" name="EffectiveTaxIncentiveRateRelatedToResearchAndDevelopment" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TaxIncentiveResearchAndDevelopmentActivities" name="TaxIncentiveResearchAndDevelopmentActivities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_PercentageReductionResearchAndDevelopmentCosts" name="PercentageReductionResearchAndDevelopmentCosts" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_TaxIncentiveReceivable" name="TaxIncentiveReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <element id="zfgn_ResearchAndDevelopmentTaxIncentiveLineItems" name="ResearchAndDevelopmentTaxIncentiveLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_ResearchAndDevelopmentExpensesTable" name="ResearchAndDevelopmentExpensesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_NonCashMember" name="NonCashMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_OperatingLeaseCommencementDate" name="OperatingLeaseCommencementDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_AreaOfOfficeSpace" name="AreaOfOfficeSpace" type="num:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <element id="zfgn_BostonMember" name="BostonMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_ShigoCenterPlazaOwnersLLCMember" name="ShigoCenterPlazaOwnersLLCMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearOne" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearOne" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearTwo" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearTwo" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearThree" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearThree" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearFour" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearFour" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearFive" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearFive" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearSix" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearSix" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearSeven" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearSeven" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearEight" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearEight" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearNine" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearNine" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <element id="zfgn_OperatingLeasesRentExpenseMonthlyBaseRentDueInYearTen" name="OperatingLeasesRentExpenseMonthlyBaseRentDueInYearTen" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
</schema>
