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<!-- DFIN New ActiveDisclosure (SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2023-05-08T07:45:49.3651+00:00 -->
<!-- Copyright (c) 2023 Donnelly Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="prld_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainNetOfTax" name="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainNetOfTax" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossNetOfTax" name="AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossNetOfTax" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_BeneficialOwnershipPercentage" name="BeneficialOwnershipPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_CommonStockAdditionalCapitalSharesReservedForFutureIssuance" name="CommonStockAdditionalCapitalSharesReservedForFutureIssuance" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <xsd:element id="prld_DisbursementIncurredCostsForLabSpace" name="DisbursementIncurredCostsForLabSpace" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_EligibleEmployeesContributionPercentage" name="EligibleEmployeesContributionPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_GrantForDevelopmentOfLabSpace" name="GrantForDevelopmentOfLabSpace" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_IncreaseDecreaseInLongTermPrepaidExpenseAndOtherLongTermAssets" name="IncreaseDecreaseInLongTermPrepaidExpenseAndOtherLongTermAssets" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_IncreaseDecreaseInOperatingLeaseLiabilities" name="IncreaseDecreaseInOperatingLeaseLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_InitialTermOfLease" name="InitialTermOfLease" type="xbrli:durationItemType" 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_NumberOfLeaseExtensions" name="NumberOfLeaseExtensions" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_ParticipantsAccrueRightsToPurchaseMaximumCommonStockAmount" name="ParticipantsAccrueRightsToPurchaseMaximumCommonStockAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_PercentageOfSharesOutstandingUsedToCalculateAnnualIncreaseInNumberOfSharesThatCanBeIssued" name="PercentageOfSharesOutstandingUsedToCalculateAnnualIncreaseInNumberOfSharesThatCanBeIssued" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_ReimbursementsForDevelopmentOfLabSpace" name="ReimbursementsForDevelopmentOfLabSpace" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_ReimbursementsForDevelopmentOfLabSpaceExpirationYear" name="ReimbursementsForDevelopmentOfLabSpaceExpirationYear" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_ReimbursementsForDevelopmentOfLabSpacePeriod" name="ReimbursementsForDevelopmentOfLabSpacePeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_RentExpense" name="RentExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_StockIssuedDuringPeriodSharesStockOptionsExercisedAndVestingOfRestrictedStockUnits" name="StockIssuedDuringPeriodSharesStockOptionsExercisedAndVestingOfRestrictedStockUnits" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_StockIssuedDuringPeriodValueStockOptionsExercisedAndVestingOfRestrictedStockUnits" name="StockIssuedDuringPeriodValueStockOptionsExercisedAndVestingOfRestrictedStockUnits" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_UnrealizedGainLossOnMarketableSecurities" name="UnrealizedGainLossOnMarketableSecurities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_LeaseLiabilityLineItems" name="LeaseLiabilityLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" 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_ChestnutRunLeaseMember" name="ChestnutRunLeaseMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_ExercisePriceRangeFourMember" name="ExercisePriceRangeFourMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_ExercisePriceRangeOneMember" name="ExercisePriceRangeOneMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_ExercisePriceRangeThreeMember" name="ExercisePriceRangeThreeMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_ExercisePriceRangeTwoMember" name="ExercisePriceRangeTwoMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_OperatingLeaseUntilDecember302023Member" name="OperatingLeaseUntilDecember302023Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_OperatingLeaseUntilJune302023Member" name="OperatingLeaseUntilJune302023Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_SiliconValleyBankMember" name="SiliconValleyBankMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_TwoThousandTwentyEmployeesStockPurchasePlanMember" name="TwoThousandTwentyEmployeesStockPurchasePlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_TwoThousandTwentyEquityIncentivePlanMember" name="TwoThousandTwentyEquityIncentivePlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_VotingCommonStockMember" name="VotingCommonStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_LeaseLiabilityTable" name="LeaseLiabilityTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" 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_AccruedExpensesAndOtherCurrentLiabilitiesTextBlock" name="AccruedExpensesAndOtherCurrentLiabilitiesTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_EmergingGrowthCompanyStatusPolicyTextBlock" name="EmergingGrowthCompanyStatusPolicyTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_RisksAndLiquidityTextBlock" name="RisksAndLiquidityTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" name="ScheduleOfAccruedExpensesAndOtherCurrentLiabilitiesTableTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
</xsd:schema>
