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

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-02-02</periodOfReport>

    <issuer>
        <issuerCik>0001680581</issuerCik>
        <issuerName>Fulcrum Therapeutics, Inc.</issuerName>
        <issuerTradingSymbol>FULC</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001714982</rptOwnerCik>
            <rptOwnerName>Oltmans Curtis Gale</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O FULCRUM THERAPEUTICS, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>26 LANDSDOWNE STREET</rptOwnerStreet2>
            <rptOwnerCity>CAMBRIDGE</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02139</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>false</isDirector>
            <isOfficer>true</isOfficer>
            <isTenPercentOwner>false</isTenPercentOwner>
            <isOther>false</isOther>
            <officerTitle>Chief Legal Officer</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Stock Option (right to buy)</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>10.72</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2026-02-02</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>170000</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>0.00</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2036-02-01</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>170000</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>170000</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">This option was granted on February 2, 2026 and is scheduled to vest in equal quarterly installments over four years beginning on the vesting commencement date of January 1, 2026, subject to the reporting person's continued service on each such vesting date.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ Curt Oltmans</signatureName>
        <signatureDate>2026-02-04</signatureDate>
    </ownerSignature>
</ownershipDocument>
