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

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2020-05-07</periodOfReport>

    <noSecuritiesOwned>0</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001797336</issuerCik>
        <issuerName>Ayala Pharmaceuticals, Inc.</issuerName>
        <issuerTradingSymbol>AYLA</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001385115</rptOwnerCik>
            <rptOwnerName>Maimon Yossi</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>OPPENHEIMER 4</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>REHOVOT</rptOwnerCity>
            <rptOwnerState>L3</rptOwnerState>
            <rptOwnerZipCode>7670104</rptOwnerZipCode>
            <rptOwnerStateDescription>ISRAEL</rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>1</isOfficer>
            <isTenPercentOwner>0</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle>CFO</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <derivativeTable>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>5.16</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F1"/>
            </exerciseDate>
            <expirationDate>
                <value>2029-03-15</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>70500</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
        <derivativeHolding>
            <securityTitle>
                <value>Stock Option</value>
            </securityTitle>
            <conversionOrExercisePrice>
                <value>6.50</value>
            </conversionOrExercisePrice>
            <exerciseDate>
                <footnoteId id="F2"/>
            </exerciseDate>
            <expirationDate>
                <value>2029-12-24</value>
            </expirationDate>
            <underlyingSecurity>
                <underlyingSecurityTitle>
                    <value>Common Stock</value>
                </underlyingSecurityTitle>
                <underlyingSecurityShares>
                    <value>9460</value>
                </underlyingSecurityShares>
            </underlyingSecurity>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                </directOrIndirectOwnership>
            </ownershipNature>
        </derivativeHolding>
    </derivativeTable>

    <footnotes>
        <footnote id="F1">The option vests and becomes exercisable as to 25% on March 15, 2020 and as to the remainder of the shares in 12 equal quarterly installments thereafter.</footnote>
        <footnote id="F2">The option vests and becomes exercisable in 16 equal quarterly installments beginning on December 24, 2019.</footnote>
    </footnotes>

    <remarks>Exhibit 24 - Power of Attorney.</remarks>

    <ownerSignature>
        <signatureName>/s/ Roni Mamluk, Ph.D., Attorney-in-Fact for Yossi Maimon, CPA, MBA</signatureName>
        <signatureDate>2020-05-07</signatureDate>
    </ownerSignature>
</ownershipDocument>
