<?xml version="1.0" encoding="us-ascii"?>
<!-- DFIN ActiveDisclosure(SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-11-09T14:16:30.6329091+00:00 -->
<!-- Version            : 5.0.1.513 -->
<!-- Package ID         : 13cb5bd658c340bcb68e6276f562bdc9 -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="prld_SeriesCConvertiblePreferredStockMember" name="SeriesCConvertiblePreferredStockMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_VotingCommonStockMember" name="VotingCommonStockMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" name="TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_TemporaryEquityConversionOfConvertiblePreferredStockIntoCommonStockShares" name="TemporaryEquityConversionOfConvertiblePreferredStockIntoCommonStockShares" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_TemporaryEquityConversionOfConvertiblePreferredStockIntoCommonStockValue" name="TemporaryEquityConversionOfConvertiblePreferredStockIntoCommonStockValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="prld_PaymentsOfOfferingCosts" name="PaymentsOfOfferingCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="prld_OfferingCostsInAccruedExpensesAndOtherCurrentLiabilities" name="OfferingCostsInAccruedExpensesAndOtherCurrentLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="prld_OfferingCostsInAccountsPayable" name="OfferingCostsInAccountsPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="prld_BackgroundAbstract" name="BackgroundAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_RisksAndLiquidityTextBlock" name="RisksAndLiquidityTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_RisksAndLiquidityAbstract" name="RisksAndLiquidityAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_AccruedExpensesAndOtherCurrentLiabilitiesTextBlock" name="AccruedExpensesAndOtherCurrentLiabilitiesTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" name="ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" type="nonnum:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_RisksAndLiquidityLineItems" name="RisksAndLiquidityLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_RisksAndLiquidityTable" name="RisksAndLiquidityTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_SummaryOfSignificantAccountingPoliciesLineItems" name="SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_SummaryOfSignificantAccountingPoliciesTable" name="SummaryOfSignificantAccountingPoliciesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_AccruedResearchAndDevelopmentLiabilitiesCurrent" name="AccruedResearchAndDevelopmentLiabilitiesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="prld_AccruedOfferingCostsCurrent" name="AccruedOfferingCostsCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="prld_AccruedProfessionalServicesAndOtherLiabilitiesCurrent" name="AccruedProfessionalServicesAndOtherLiabilitiesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="prld_TemporaryEquityPricePerShare" name="TemporaryEquityPricePerShare" type="num:perShareItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="prld_BeneficialOwnershipPercentage" name="BeneficialOwnershipPercentage" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_NumberOfEquityIncentivePlans" name="NumberOfEquityIncentivePlans" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_PercentageOfSharesOutstandingUsedToCalculateAnnualIncreaseInNumberOfSharesThatCanBeIssued" name="PercentageOfSharesOutstandingUsedToCalculateAnnualIncreaseInNumberOfSharesThatCanBeIssued" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_TwoThousandTwentyEquityIncentivePlanMember" name="TwoThousandTwentyEquityIncentivePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_TwoThousandTwentyEmployeeStockPurchasePlanMember" name="TwoThousandTwentyEmployeeStockPurchasePlanMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_ExercisePriceRangeOneMember" name="ExercisePriceRangeOneMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_ExercisePriceRangeTwoMember" name="ExercisePriceRangeTwoMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_ExercisePriceRangeThreeMember" name="ExercisePriceRangeThreeMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_AreaOfPremises" name="AreaOfPremises" type="num:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_LicenseTerm" name="LicenseTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_LicenseAgreementTermDescription" name="LicenseAgreementTermDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_SecondAmendedAndRestatedEntrepreneurClientLicenseAgreementMember" name="SecondAmendedAndRestatedEntrepreneurClientLicenseAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="prld_LicenseFee" name="LicenseFee" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="prld_LicenseRenewalTerm" name="LicenseRenewalTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_DescriptionOfLicenseRenewalOption" name="DescriptionOfLicenseRenewalOption" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_PercentageIncreaseInMonthlyRenewalLicenseFee" name="PercentageIncreaseInMonthlyRenewalLicenseFee" type="xbrli:pureItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="prld_MonthlyRenewalLicenseFeePayable" name="MonthlyRenewalLicenseFeePayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="prld_IncreaseInLicenseFeeUponExerciseOfRightOfFirstOffer" name="IncreaseInLicenseFeeUponExerciseOfRightOfFirstOffer" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="prld_OneTimePaymentMadeAsConsiderationForRightOfFirstOffer" name="OneTimePaymentMadeAsConsiderationForRightOfFirstOffer" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
</xsd:schema>
