<?xml version="1.0" encoding="US-ASCII"?>
<!-- DFIN New ActiveDisclosure (SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date :2023-03-15T08:50:20.2092+00:00 -->
<!-- Copyright (c) 2023 Donnelly Financial Solutions, Inc. All Rights Reserved. -->
<xsd:schema targetNamespace="http://preludetx.com/20221231" attributeFormDefault="unqualified" elementFormDefault="qualified" xmlns:country="http://xbrl.sec.gov/country/2022" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:srt="http://fasb.org/srt/2022" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:us-gaap="http://fasb.org/us-gaap/2022" xmlns:dei="http://xbrl.sec.gov/dei/2022" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:prld="http://preludetx.com/20221231" xmlns:xlink="http://www.w3.org/1999/xlink">
  <xsd:import schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/instance"/>
  <xsd:import schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" namespace="http://www.xbrl.org/2003/linkbase"/>
  <xsd:import schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" namespace="http://xbrl.org/2005/xbrldt"/>
  <xsd:import schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd" namespace="http://xbrl.sec.gov/dei/2022"/>
  <xsd:import schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd" namespace="http://fasb.org/us-gaap/2022"/>
  <xsd:import schemaLocation="https://xbrl.sec.gov/country/2022/country-2022.xsd" namespace="http://xbrl.sec.gov/country/2022"/>
  <xsd:import schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/types.xsd" namespace="http://www.xbrl.org/dtr/type/2020-01-21"/>
  <xsd:import schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.xsd" namespace="http://fasb.org/srt/2022"/>
  <xsd:annotation>
    <xsd:appinfo>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prld-20221231_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:title="Labels link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prld-20221231_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:title="Presentation link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prld-20221231_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:title="Definition link" xlink:type="simple"/>
      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="prld-20221231_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:title="Calculation link" xlink:type="simple"/>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DocumentDocumentAndEntityInformation" id="Role_DocumentDocumentAndEntityInformation">
        <link:definition>100000 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_StatementBALANCESHEETS" id="Role_StatementBALANCESHEETS">
        <link:definition>100010 - Statement - BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_StatementBALANCESHEETSPARENTHETICAL" id="Role_StatementBALANCESHEETSPARENTHETICAL">
        <link:definition>100020 - Statement - BALANCE SHEETS (PARENTHETICAL)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_StatementSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" id="Role_StatementSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS">
        <link:definition>100030 - Statement - STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/StatementStatementsOfChangesInStockholdersEquity1" id="StatementStatementsOfChangesInStockholdersEquity1">
        <link:definition>100040 - Statement - STATEMENTS OF CHANGES IN STOCKHOLDERS' EQUITY</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/StatementStatementsOfChangesInStockholdersEquityParenthetical" id="StatementStatementsOfChangesInStockholdersEquityParenthetical">
        <link:definition>100050 - Statement - STATEMENTS OF CHANGES IN STOCKHOLDERS' EQUITY (PARENTHETICAL)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_StatementSTATEMENTSOFCASHFLOWS" id="Role_StatementSTATEMENTSOFCASHFLOWS">
        <link:definition>100060 - Statement - STATEMENTS OF CASH FLOWS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureNatureOfOperations" id="Role_DisclosureNatureOfOperations">
        <link:definition>100070 - Disclosure - Nature of Operations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureRisksAndLiquidity" id="Role_DisclosureRisksAndLiquidity">
        <link:definition>100080 - Disclosure - Risks and Liquidity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPolicies" id="Role_DisclosureSummaryOfSignificantAccountingPolicies">
        <link:definition>100090 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureMarketableSecurities" id="Role_DisclosureMarketableSecurities">
        <link:definition>100100 - Disclosure - Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureFairValueOfFinancialInstruments" id="Role_DisclosureFairValueOfFinancialInstruments">
        <link:definition>100110 - Disclosure - Fair Value of Financial Instruments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosurePropertyAndEquipment" id="Role_DisclosurePropertyAndEquipment">
        <link:definition>100120 - Disclosure - Property and Equipment</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureAccruedExpensesAndOtherCurrentLiabilities" id="Role_DisclosureAccruedExpensesAndOtherCurrentLiabilities">
        <link:definition>100130 - Disclosure - Accrued Expenses and Other Current Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureCommitments" id="Role_DisclosureCommitments">
        <link:definition>100140 - Disclosure - Commitments</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/DisclosureCommonStock" id="DisclosureCommonStock">
        <link:definition>100150 - Disclosure - Common Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensation" id="Role_DisclosureStockBasedCompensation">
        <link:definition>100160 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxes" id="Role_DisclosureIncomeTaxes">
        <link:definition>100170 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesPolicies" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesPolicies">
        <link:definition>100180 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesTables" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesTables">
        <link:definition>100190 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureMarketableSecuritiesTables" id="Role_DisclosureMarketableSecuritiesTables">
        <link:definition>100200 - Disclosure - Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureFairValueOfFinancialInstrumentsTables" id="Role_DisclosureFairValueOfFinancialInstrumentsTables">
        <link:definition>100210 - Disclosure - Fair Value of Financial Instruments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosurePropertyAndEquipmentTables" id="Role_DisclosurePropertyAndEquipmentTables">
        <link:definition>100220 - Disclosure - Property and Equipment (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureAccruedExpensesAndOtherCurrentLiabilitiesTables" id="Role_DisclosureAccruedExpensesAndOtherCurrentLiabilitiesTables">
        <link:definition>100230 - Disclosure - Accrued Expenses and Other Current Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureCommitmentsTables" id="Role_DisclosureCommitmentsTables">
        <link:definition>100240 - Disclosure - Commitments (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationTables" id="Role_DisclosureStockBasedCompensationTables">
        <link:definition>100250 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxesTables" id="Role_DisclosureIncomeTaxesTables">
        <link:definition>100260 - Disclosure - Income Taxes (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureRisksAndLiquidityAdditionalInformationDetails" id="Role_DisclosureRisksAndLiquidityAdditionalInformationDetails">
        <link:definition>100270 - Disclosure - Risks and Liquidity - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashAndCashEquivalentsAndRestrictedCashDetails" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfReconciliationOfCashAndCashEquivalentsAndRestrictedCashDetails">
        <link:definition>100280 - Disclosure - Summary of Significant Accounting Policies - Schedule of Reconciliation of Cash and Cash Equivalents and Restricted Cash (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesAdditionalInformationDetails">
        <link:definition>100290 - Disclosure - Summary of Significant Accounting Policies - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfPropertyPlantAndEquipmentUsefulLifeDetails" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfPropertyPlantAndEquipmentUsefulLifeDetails">
        <link:definition>100300 - Disclosure - Summary of Significant Accounting Policies - Schedule of Property Plant and Equipment Useful Life (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedWeightedAverageSharesOfCommonStockOutstandingDetails" id="Role_DisclosureSummaryOfSignificantAccountingPoliciesScheduleOfPotentiallyDilutiveSecuritiesExcludedFromComputationOfDilutedWeightedAverageSharesOfCommonStockOutstandingDetails">
        <link:definition>100310 - Disclosure - Summary of Significant Accounting Policies - Schedule of Potentially Dilutive Securities Excluded from Computation of Diluted Weighted-average Shares of Common Stock Outstanding (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureMarketableSecuritiesScheduleOfMarketableSecuritiesDetails" id="Role_DisclosureMarketableSecuritiesScheduleOfMarketableSecuritiesDetails">
        <link:definition>100320 - Disclosure - Marketable Securities - Schedule of Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureMarketableSecuritiesAdditionalInformationDetails" id="Role_DisclosureMarketableSecuritiesAdditionalInformationDetails">
        <link:definition>100330 - Disclosure - Marketable Securities - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureFairValueOfFinancialInstrumentsScheduleOfAssetsAndLiabilitiesMeasuredAtFairValueOnRecurringBasisDetails" id="Role_DisclosureFairValueOfFinancialInstrumentsScheduleOfAssetsAndLiabilitiesMeasuredAtFairValueOnRecurringBasisDetails">
        <link:definition>100340 - Disclosure - Fair Value of Financial Instruments - Schedule of Assets and Liabilities Measured at Fair Value on Recurring Basis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosurePropertyAndEquipmentScheduleOfPropertyAndEquipmentDetails" id="Role_DisclosurePropertyAndEquipmentScheduleOfPropertyAndEquipmentDetails">
        <link:definition>100350 - Disclosure - Property and Equipment - Schedule of Property and Equipment (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureAccruedExpensesAndOtherCurrentLiabilitiesSummaryOfAccruedExpensesAndOtherCurrentLiabilitiesDetails" id="Role_DisclosureAccruedExpensesAndOtherCurrentLiabilitiesSummaryOfAccruedExpensesAndOtherCurrentLiabilitiesDetails">
        <link:definition>100360 - Disclosure - Accrued Expenses and Other Current Liabilities - Summary of Accrued Expenses and Other Current Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureCommitmentsAdditionalInformationDetails" id="Role_DisclosureCommitmentsAdditionalInformationDetails">
        <link:definition>100370 - Disclosure - Commitments - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureCommitmentsScheduleOfFutureMinimumLeasePaymentsUnderLeaseDetails" id="Role_DisclosureCommitmentsScheduleOfFutureMinimumLeasePaymentsUnderLeaseDetails">
        <link:definition>100380 - Disclosure - Commitments - Schedule of Future Minimum Lease Payments Under Lease (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/DisclosureCommonStockAdditionalInformationDetails" id="DisclosureCommonStockAdditionalInformationDetails">
        <link:definition>100390 - Disclosure - Common Stock - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationAdditionalInformationDetails" id="Role_DisclosureStockBasedCompensationAdditionalInformationDetails">
        <link:definition>100400 - Disclosure - Stock-Based Compensation - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureCommitmentsScheduleOfFutureMinimumLeasePaymentsUnderLeaseDetails2" id="Role_DisclosureCommitmentsScheduleOfFutureMinimumLeasePaymentsUnderLeaseDetails2">
        <link:definition>100410 - Disclosure - Commitments - Schedule of Future Minimum Lease Payments Under Lease (Details) 2</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationScheduleOfStockBasedCompensationExpenseRecordedInStatementsOfOperationsDetails" id="Role_DisclosureStockBasedCompensationScheduleOfStockBasedCompensationExpenseRecordedInStatementsOfOperationsDetails">
        <link:definition>100420 - Disclosure - Stock-Based Compensation - Schedule of Stock-Based Compensation Expense Recorded in Statements of Operations (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationSummaryOfStockOptionActivityDetails" id="Role_DisclosureStockBasedCompensationSummaryOfStockOptionActivityDetails">
        <link:definition>100430 - Disclosure - Stock-Based Compensation - Summary of Stock Option Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationSummaryOfInformationAboutStockOptionsOutstandingDetails" id="Role_DisclosureStockBasedCompensationSummaryOfInformationAboutStockOptionsOutstandingDetails">
        <link:definition>100440 - Disclosure - Stock-Based Compensation - Summary of Information about Stock Options Outstanding (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationScheduleOfFairValueOfEachOptionEstimatedOnDateOfGrantUsingWeightedAverageAssumptionsDetails" id="Role_DisclosureStockBasedCompensationScheduleOfFairValueOfEachOptionEstimatedOnDateOfGrantUsingWeightedAverageAssumptionsDetails">
        <link:definition>100450 - Disclosure - Stock-Based Compensation - Schedule of Fair Value of Each Option Estimated on Date of Grant Using Weighted Average Assumptions (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationSummaryOfActivityRelatedToRSAStockBasedPaymentAwardsDetails" id="Role_DisclosureStockBasedCompensationSummaryOfActivityRelatedToRSAStockBasedPaymentAwardsDetails">
        <link:definition>100460 - Disclosure - Stock-Based Compensation - Summary of Activity related to RSA Stock-Based Payment Awards (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureStockBasedCompensationSummaryOfActivityRelatedToRSUStockBasedPaymentAwardsDetails" id="Role_DisclosureStockBasedCompensationSummaryOfActivityRelatedToRSUStockBasedPaymentAwardsDetails">
        <link:definition>100470 - Disclosure - Stock-Based Compensation - Summary of Activity related to RSU Stock-Based Payment Awards (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxesScheduleOfDeferredTaxAssetsAndLiabilitiesDetails" id="Role_DisclosureIncomeTaxesScheduleOfDeferredTaxAssetsAndLiabilitiesDetails">
        <link:definition>100480 - Disclosure - Income Taxes - Schedule of Deferred Tax Assets and Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxesAdditionalInformationDetails" id="Role_DisclosureIncomeTaxesAdditionalInformationDetails">
        <link:definition>100490 - Disclosure - Income Taxes - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxesScheduleOfReconciliationOfFederalIncomeTaxRateToEffectiveTaxRateDetails" id="Role_DisclosureIncomeTaxesScheduleOfReconciliationOfFederalIncomeTaxRateToEffectiveTaxRateDetails">
        <link:definition>100500 - Disclosure - Income Taxes - Schedule of Reconciliation of the Federal Income tax Rate to Effective Tax Rate (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://preludetx.com/20221231/taxonomy/role/Role_DisclosureIncomeTaxesScheduleOfFederalAndStateNetOperatingLossesAndResearchTaxCreditsDetails" id="Role_DisclosureIncomeTaxesScheduleOfFederalAndStateNetOperatingLossesAndResearchTaxCreditsDetails">
        <link:definition>100510 - Disclosure - Income Taxes - Schedule of Federal and State Net Operating Losses and Research Tax Credits (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xsd:appinfo>
  </xsd:annotation>
  <xsd:element id="prld_DocumentDocumentAndEntityInformationAbstract" name="DocumentDocumentAndEntityInformationAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_RisksAndLiquidityAbstract" name="RisksAndLiquidityAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" 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_AdditionalGrantForDevelopmentOfLabSpace" name="AdditionalGrantForDevelopmentOfLabSpace" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_AggregateEstimatedRentPaymentsDueOverInitialTerm" name="AggregateEstimatedRentPaymentsDueOverInitialTerm" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_AreaOfLeasePremises" name="AreaOfLeasePremises" type="dtr-types:areaItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false"/>
  <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_DeferredTaxAssetsInResearchAndDevelopmentCapitalization" name="DeferredTaxAssetsInResearchAndDevelopmentCapitalization" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_DeferredTaxAssetsTaxDeferredExpenseLeaseLiabilities" name="DeferredTaxAssetsTaxDeferredExpenseLeaseLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_DeferredTaxLiabilitiesDepreciation" name="DeferredTaxLiabilitiesDepreciation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_DeferredTaxLiabilitiesRightOfUseAssets" name="DeferredTaxLiabilitiesRightOfUseAssets" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <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_EstimatedAmountOfPaymentOverAgreementTermInThreeEqualInstallments" name="EstimatedAmountOfPaymentOverAgreementTermInThreeEqualInstallments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_EstimatedNumberOfYearResearchCollaborationAgreement" name="EstimatedNumberOfYearResearchCollaborationAgreement" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_GracePeriodForPotentialRefund" name="GracePeriodForPotentialRefund" type="xbrli:durationItemType" 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_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_LeaseCommencementDate" name="LeaseCommencementDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_NonCancellableLeasePeriod" name="NonCancellableLeasePeriod" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_NumberOfEqualInstalments" name="NumberOfEqualInstalments" type="xbrli:integerItemType" 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_OfferingCostsInAccountsPayable" name="OfferingCostsInAccountsPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_OfferingCostsInAccruedExpenses" name="OfferingCostsInAccruedExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <xsd:element id="prld_OffsetAccruedExpenseAndOtherCurrentLiabilitiesToEliminateDeferredRent" name="OffsetAccruedExpenseAndOtherCurrentLiabilitiesToEliminateDeferredRent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_OperatingLeaseEstimatedIncrementalBorrowingRatePercent" name="OperatingLeaseEstimatedIncrementalBorrowingRatePercent" type="dtr-types:percentItemType" 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_PaymentsOfOfferingCosts" name="PaymentsOfOfferingCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit"/>
  <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_PotentialRefundReceivableFromAgreement" name="PotentialRefundReceivableFromAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_ReceivedCashForSatisfyingPerformanceBenchmarkMeasurement" name="ReceivedCashForSatisfyingPerformanceBenchmarkMeasurement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <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_ResearchTerm" name="ResearchTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <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_TaxCreditCarryforwardExpirationYear" name="TaxCreditCarryforwardExpirationYear" type="xbrli:gYearItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_TaxpayersRequiredPeriodToCapitalizeAndAmortizeResearchDevelopmentExpense" name="TaxpayersRequiredPeriodToCapitalizeAndAmortizeResearchDevelopmentExpense" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_TemporaryEquityStockConvertedDuringPeriodShares" name="TemporaryEquityStockConvertedDuringPeriodShares" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_TemporaryEquityStockConvertedDuringPeriodValue" name="TemporaryEquityStockConvertedDuringPeriodValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit"/>
  <xsd:element id="prld_TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" name="TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <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_IncomeTaxDisclosureLineItems" name="IncomeTaxDisclosureLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <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_DarwinHealthIncMember" name="DarwinHealthIncMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_DelawareMember" name="DelawareMember" 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_FollowOnOfferingMember" name="FollowOnOfferingMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_OperatingLeaseExpiringDecember2022Member" name="OperatingLeaseExpiringDecember2022Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_OperatingLeaseExpiringDecember2023Member" name="OperatingLeaseExpiringDecember2023Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_OperatingLeaseUntilDecember312023Member" name="OperatingLeaseUntilDecember312023Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_SeriesAConvertiblePreferredStockMember" name="SeriesAConvertiblePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_SeriesBConvertiblePreferredStockMember" name="SeriesBConvertiblePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_SeriesCConvertiblePreferredStockMember" name="SeriesCConvertiblePreferredStockMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true"/>
  <xsd:element id="prld_ShortTermLeaseMember" name="ShortTermLeaseMember" 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_TwoThousandTwentyEmployeeStockPurchasePlanMember" name="TwoThousandTwentyEmployeeStockPurchasePlanMember" 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_IncomeTaxDisclosureTable" name="IncomeTaxDisclosureTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" 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_PropertyPlantAndEquipmentUsefulLifeTableTextBlock" name="PropertyPlantAndEquipmentUsefulLifeTableTextBlock" 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:element id="prld_ScheduleOfFederalStateAndLocalNetOperatingLossesAndResearchTaxCreditsTableTextBlock" name="ScheduleOfFederalStateAndLocalNetOperatingLossesAndResearchTaxCreditsTableTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
  <xsd:element id="prld_TaxCreditPolicyTextBlock" name="TaxCreditPolicyTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false"/>
</xsd:schema>
