<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0609</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-04-27</periodOfReport>

    <notSubjectToSection16>1</notSubjectToSection16>

    <issuer>
        <issuerCik>0001678660</issuerCik>
        <issuerName>Prelude Therapeutics Inc</issuerName>
        <issuerTradingSymbol>PRLD</issuerTradingSymbol>
        <issuerForeignTradingSymbol></issuerForeignTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001346824</rptOwnerCik>
            <rptOwnerName>RA CAPITAL MANAGEMENT, L.P.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>200 BERKELEY STREET, 18TH FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>false</isDirector>
            <isOfficer>false</isOfficer>
            <isTenPercentOwner>true</isTenPercentOwner>
            <isOther>false</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001315082</rptOwnerCik>
            <rptOwnerName>RA Capital Healthcare Fund LP</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>C/O RA CAPITAL MANAGEMENT, L.P.</rptOwnerStreet1>
            <rptOwnerStreet2>200 BERKELEY STREET, 18TH FLOOR</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001384859</rptOwnerCik>
            <rptOwnerName>Kolchinsky Peter</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>C/O RA CAPITAL MANAGEMENT, L.P.</rptOwnerStreet1>
            <rptOwnerStreet2>200 BERKELEY STREET, 18TH FLOOR</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001619841</rptOwnerCik>
            <rptOwnerName>Shah Rajeev M.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>false</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>C/O RA CAPITAL MANAGEMENT, L.P.</rptOwnerStreet1>
            <rptOwnerStreet2>200 BERKELEY STREET, 18TH FLOOR</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>0</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2026-04-27</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F1"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>1407000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <footnoteId id="F1"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>6475882</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnotes</value>
                    <footnoteId id="F2"/>
                    <footnoteId id="F3"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Pre-Funded Warrants (Right to Buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>0.0001</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2026-04-27</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>J</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
                <footnoteId id="F1"/>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>1407000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <footnoteId id="F1"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F4"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F4"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>1407000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>1407000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnotes</value>
                    <footnoteId id="F2"/>
                    <footnoteId id="F3"/>
                </natureOfOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">On April 27, 2026, RA Capital Healthcare Fund, L.P. (the &quot;Fund&quot;) entered into an Exchange Agreement with the Issuer pursuant to which the Fund exchanged, for no additional consideration, 1,407,000 shares of the Issuer's Common Stock for a pre-funded warrant exercisable for up to 1,407,000 shares of the Issuer's Common Stock at an exercise price of $0.0001 per share (the &quot;Pre-Funded Warrant&quot;).</footnote>
        <footnote id="F2">Held directly by the Fund.</footnote>
        <footnote id="F3">RA Capital Management, L.P. (the &quot;Adviser&quot;) is the investment manager for the Fund. The general partner of the Adviser is RA Capital Management GP, LLC (the &quot;Adviser GP&quot;), of which Dr. Peter Kolchinsky and Mr. Rajeev Shah are the managing members. Each of
the Adviser, the Adviser GP, the Fund, Dr. Kolchinsky and Mr. Shah disclaims beneficial ownership of any of the reported securities, except to the extent of its or his respective pecuniary interest therein.</footnote>
        <footnote id="F4">The Pre-Funded Warrant has no expiration date and is exercisable immediately. Notwithstanding the foregoing, the Fund shall not be entitled to exercise the Pre-Funded Warrant to the extent that it would cause the aggregate number of shares of Common Stock beneficially owned by the Fund, together with its Attribution Parties (as defined in the Pre-Funded Warrant), to exceed 9.99% of the total number of issued and outstanding shares of Common Stock of the Issuer following such exercise.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Peter Kolchinsky, Manager of RA Capital Management, L.P.</signatureName>
        <signatureDate>2026-04-28</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Peter Kolchinsky, Manager of RA Capital Healthcare Fund GP, LLC the General Partner of RA Capital Healthcare Fund, L.P.</signatureName>
        <signatureDate>2026-04-28</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Peter Kolchinsky, individually</signatureName>
        <signatureDate>2026-04-28</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Rajeev Shah, individually</signatureName>
        <signatureDate>2026-04-28</signatureDate>
    </ownerSignature>
</ownershipDocument>