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  <xs:element id="lxrx_ConsolidatedBalanceSheetsAbstract" abstract="true" name="ConsolidatedBalanceSheetsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_ConsolidatedStatementsOfOperationsAbstract" abstract="true" name="ConsolidatedStatementsOfOperationsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_ProceedsFromSeptember2021ATMOffering" abstract="false" name="ProceedsFromSeptember2021ATMOffering" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_SummaryOfSignificantAccountingPoliciesAbstract" abstract="true" name="SummaryOfSignificantAccountingPoliciesAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_FinalPaymentWithExtention" abstract="false" name="FinalPaymentWithExtention" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_AccruedInterestOnConvertible" abstract="false" name="AccruedInterestOnConvertible" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanD" abstract="false" name="TermLoanD" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_SanofiDisputedCosts" abstract="false" name="SanofiDisputedCosts" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_AccruedCompensationAndBenefitsCurrent" abstract="false" name="AccruedCompensationAndBenefitsCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_Netproductrevenue" abstract="false" name="Netproductrevenue" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_Sellinggeneralandadministrativeexpenses" abstract="false" name="Sellinggeneralandadministrativeexpenses" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ConvertibleDebtExchangeSeptemberSharePayment" abstract="false" name="ConvertibleDebtExchangeSeptemberSharePayment" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lxrx_ConvertibleDebtExchangeTotalPrincipalAmount" abstract="false" name="ConvertibleDebtExchangeTotalPrincipalAmount" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ProceedsFromJanuary2021ATMOffering" abstract="false" name="ProceedsFromJanuary2021ATMOffering" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_Stockbasedcompensationexpenseassociatedwithsellinggeneralandadministrativeexpense" abstract="false" name="Stockbasedcompensationexpenseassociatedwithsellinggeneralandadministrativeexpense" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_DebtObligationsAbstract" abstract="true" name="DebtObligationsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_AccruedLiabilitiesDomain" abstract="true" name="AccruedLiabilitiesDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="lxrx_TermLoanB" abstract="false" name="TermLoanB" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_AccruedLiabilitiesAxis" abstract="true" name="AccruedLiabilitiesAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_TermLoanABWarrant" abstract="false" name="TermLoanABWarrant" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateOfficersAndNonEmployeeDirectors" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateOfficersAndNonEmployeeDirectors" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_AccruedLiabilitiesTable" abstract="true" name="AccruedLiabilitiesTable" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_A2027OxfordPrincipalPayments" abstract="false" name="A2027OxfordPrincipalPayments" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_IpsenMilestonePayment" abstract="false" name="IpsenMilestonePayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanC" abstract="false" name="TermLoanC" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_OxfordLoanFacility" abstract="false" name="OxfordLoanFacility" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanADebtDiscount" abstract="false" name="TermLoanADebtDiscount" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ConsolidatedStatementsOfStockholdersEquityAbstract" abstract="true" name="ConsolidatedStatementsOfStockholdersEquityAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRateOfficersAndNonEmployeeDirectors" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRateOfficersAndNonEmployeeDirectors" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRateEmployees" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRateEmployees" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_IpsenMaximumSalesMilestones" abstract="false" name="IpsenMaximumSalesMilestones" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanCWarrant" abstract="false" name="TermLoanCWarrant" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_FutureConvertibleDebtExchangeShares" abstract="false" name="FutureConvertibleDebtExchangeShares" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lxrx_SharePriceInSeptember2021ATMOfferring" abstract="false" name="SharePriceInSeptember2021ATMOfferring" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanAWarrantExercisePrice" abstract="false" name="TermLoanAWarrantExercisePrice" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:perShareItemType"/>
  <xs:element id="lxrx_OxfordFacilityFee" abstract="false" name="OxfordFacilityFee" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedTermOfficersAndNonEmployeeDirectors" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedTermOfficersAndNonEmployeeDirectors" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="lxrx_FutureConvertibleDebtExchange" abstract="false" name="FutureConvertibleDebtExchange" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_SharePriceInNovember20ATMOffering" abstract="false" name="SharePriceInNovember20ATMOffering" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ConvDebtInstrumentInterestRateStatedPercentage" abstract="false" name="ConvDebtInstrumentInterestRateStatedPercentage" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_IpsenRevenueRecognized" abstract="false" name="IpsenRevenueRecognized" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedvolatilityrateEmployees" abstract="false" name="ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedvolatilityrateEmployees" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_LiabilitiesAssumedByTerSera" abstract="false" name="LiabilitiesAssumedByTerSera" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_TermLoanADebtIssuanceCosts" abstract="false" name="TermLoanADebtIssuanceCosts" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_FinalPaymentWithNoExtention" abstract="false" name="FinalPaymentWithNoExtention" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_Lxrx_sanofiInitialCashPayment" abstract="false" name="Lxrx_sanofiInitialCashPayment" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_ATMOfferingTotal" abstract="false" name="ATMOfferingTotal" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_CashAndCashEquivalentsAndInvestmentsAbstract" abstract="true" name="CashAndCashEquivalentsAndInvestmentsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_IpsenTotalPayments" abstract="false" name="IpsenTotalPayments" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_LexiconIncrementalBorrowingRate" abstract="false" name="LexiconIncrementalBorrowingRate" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="lxrx_RecentAccountingPronouncementsAbstract" abstract="true" name="RecentAccountingPronouncementsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="lxrx_SanofiRevenueRecognized" abstract="false" name="SanofiRevenueRecognized" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_SharesSoldInSeptember2021ATMOfferring" abstract="false" name="SharesSoldInSeptember2021ATMOfferring" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lxrx_SharePriceInJanuary2021ATMOffering" abstract="false" name="SharePriceInJanuary2021ATMOffering" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="lxrx_ConvertibleDebtExchange" abstract="false" name="ConvertibleDebtExchange" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="lxrx_PrincipalAmountOfConvertibleNotes" abstract="false" name="PrincipalAmountOfConvertibleNotes" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
</xs:schema>
