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

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2025-12-17</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>2025-12-17</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>D</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionTotalValue>
                    <value>9000000</value>
                </transactionTotalValue>
                <transactionPricePerShare>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2025-11-06</value>
            </exerciseDate>
            <expirationDate>
                <value>2027-11-06</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>261309</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>0</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeTransaction>
        <derivativeTransaction>
            <securityTitle>
                <value>Senior Secured Convertible Note</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>29.73</value>
            </conversionOrExercisePrice>
            <transactionDate>
                <value>2025-12-17</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>A</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionTotalValue>
                    <value>9000000</value>
                </transactionTotalValue>
                <transactionPricePerShare>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <exerciseDate>
                <value>2025-11-06</value>
            </exerciseDate>
            <expirationDate>
                <value>2027-11-06</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>302724</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <postTransactionAmounts>
                <valueOwnedFollowingTransaction>
                    <value>9000000</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                </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 Convertible Note includes a beneficial ownership limitation of 49.9% with respect to the reporting person.</footnote>
        <footnote id="F2">On December 17, 2025, at the annual meeting of the Issuer's shareholders, the Issuer's shareholders approved the waiver of the limit on the number of shares of Common Stock that may be issued to the holders of the Convertible Notes pursuant to the rules of the NYSE American LLC, which requires shareholder approval before issuing common stock (or securities convertible into or exercisable for common stock) in a private placement that constitutes 20% or more of the Issuer's pre-transaction outstanding common stock.  As a result, the conversion price of the Convertible Note was reduced from $34.442 per share to $29.73 per share.  The reduction in the conversion price is reported above as the cancellation of a Convertible Note and the acquisition of a new Convertible Note.</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>2025-12-19</signatureDate>
    </ownerSignature>
</ownershipDocument>
