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

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2025-11-06</periodOfReport>

    <issuer>
        <issuerCik>0001919246</issuerCik>
        <issuerName>Pelthos Therapeutics Inc.</issuerName>
        <issuerTradingSymbol>PTHS</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0000886163</rptOwnerCik>
            <rptOwnerName>LIGAND PHARMACEUTICALS INC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>555 HERITAGE DRIVE, SUITE 200</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>JUPITER</rptOwnerCity>
            <rptOwnerState>FL</rptOwnerState>
            <rptOwnerZipCode>33458</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>true</isDirector>
            <isOfficer>false</isOfficer>
            <isTenPercentOwner>true</isTenPercentOwner>
            <isOther>false</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <derivativeTable>
        <derivativeTransaction>
            <securityTitle>
                <value>Senior Secured Convertible Note</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>34.442</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2025-11-06</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionTotalValue>
                    <value>9000000</value>
                </transactionTotalValue>
                <transactionPricePerShare>
                    <value>9000000</value>
                    <footnoteId id="F1"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <footnoteId id="F1"/>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>261309</value>
                    <footnoteId id="F1"/>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <valueOwnedFollowingTransaction>
                    <value>9000000</value>
                    <footnoteId id="F1"/>
                </valueOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeTransaction>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">On November 6, 2025, Pelthos Therapeutics Inc. (the &quot;Issuer&quot;) entered into a Securities Purchase Agreement with the reporting person and certain other investors, pursuant to which the Issuer issued a senior secured convertible note (the &quot;Convertible Note&quot;) in the aggregate principal amount of $9 million to the reporting person on November 6, 2025. The Convertible Note may be converted into Common Stock at a conversion price of $34.442 per share. The Note includes a beneficial ownership limitation of 49.9% with respect to the reporting person.</footnote>
    </footnotes>

    <remarks>The reporting person may be deemed to be a director by deputization by virtue of the fact that each of Todd Davis, Chief Executive Officer of the reporting person, and Richard Baxter, Senior Vice President of Investment Operations of the reporting person, serves on the board of directors of the Issuer.</remarks>

    <ownerSignature>
        <signatureName>/s/ Octavio Espinoza, Chief Financial Officer of Ligand Pharmaceuticals Incorporated</signatureName>
        <signatureDate>2025-11-10</signatureDate>
    </ownerSignature>
</ownershipDocument>
