<?xml version="1.0" encoding="UTF-8"?><edgarSubmission xmlns="http://www.sec.gov/edgar/schedule13D" xmlns:com="http://www.sec.gov/edgar/common">
  <headerData>
    <submissionType>SCHEDULE 13D/A</submissionType>
    <previousAccessionNumber>0001104659-24-005645</previousAccessionNumber>
    <filerInfo>
      <filer>
        <filerCredentials>
          <!-- Field: Pseudo-Tag; ID: Name; Data: Nantahala Capital Management, LLC -->
          <cik>0001472322</cik>
          <ccc>XXXXXXXX</ccc>
        </filerCredentials>
      </filer>
      <liveTestFlag>LIVE</liveTestFlag>



    </filerInfo>
  </headerData>
  <formData>
    <coverPageHeader>
      <amendmentNo>2</amendmentNo>
      <securitiesClassTitle>Common Stock, par value $0.001 per share</securitiesClassTitle>
      <dateOfEvent>03/31/2025</dateOfEvent>
      <previouslyFiledFlag>false</previouslyFiledFlag>
      <issuerInfo>
        <issuerCIK>0001427925</issuerCIK>
        <issuerCUSIP>00444T209</issuerCUSIP>
        <issuerName>TALPHERA, INC.</issuerName>
        <address>
          <com:street1>1850 Gateway Drive</com:street1>
          <com:street2>Suite 175</com:street2>
          <com:city>San Mateo</com:city>
          <com:stateOrCountry>CA</com:stateOrCountry>
          <com:zipCode>94404</com:zipCode>
        </address>
      </issuerInfo>
      <authorizedPersons>
        <notificationInfo>
          <personName>Taki Vasilakis</personName>
          <personPhoneNum>(203) 308-4440</personPhoneNum>
          <personAddress>
            <com:street1>130 Main St. 2nd Floor</com:street1>
            <com:city>New Canaan</com:city>
            <com:stateOrCountry>CT</com:stateOrCountry>
            <com:zipCode>06840</com:zipCode>
          </personAddress>
        </notificationInfo>
      </authorizedPersons>
    </coverPageHeader>
    <reportingPersons>
      <reportingPersonInfo>
        <reportingPersonCIK>0001472322</reportingPersonCIK>
        <reportingPersonNoCIK>N</reportingPersonNoCIK>
        <reportingPersonName>Nantahala Capital Management, LLC</reportingPersonName>
        <fundType>AF</fundType>
        <legalProceedings>N</legalProceedings>
        <citizenshipOrOrganization>MA</citizenshipOrOrganization>
        <soleVotingPower>0.00</soleVotingPower>
        <sharedVotingPower>1992519.00</sharedVotingPower>
        <soleDispositivePower>0.00</soleDispositivePower>
        <sharedDispositivePower>1992519.00</sharedDispositivePower>
        <aggregateAmountOwned>1992519.00</aggregateAmountOwned>
        <isAggregateExcludeShares>N</isAggregateExcludeShares>
        <percentOfClass>11.7</percentOfClass>
        <typeOfReportingPerson>IA</typeOfReportingPerson>
        <typeOfReportingPerson>OO</typeOfReportingPerson>
      </reportingPersonInfo>
      <reportingPersonInfo>
        <reportingPersonCIK>0001775952</reportingPersonCIK>
        <reportingPersonNoCIK>N</reportingPersonNoCIK>
        <reportingPersonName>Wilmot B. Harkey</reportingPersonName>
        <fundType>AF</fundType>
        <legalProceedings>N</legalProceedings>
        <citizenshipOrOrganization>X1</citizenshipOrOrganization>
        <soleVotingPower>0.00</soleVotingPower>
        <sharedVotingPower>1992519.00</sharedVotingPower>
        <soleDispositivePower>0.00</soleDispositivePower>
        <sharedDispositivePower>1992519.00</sharedDispositivePower>
        <aggregateAmountOwned>1992519.00</aggregateAmountOwned>
        <isAggregateExcludeShares>N</isAggregateExcludeShares>
        <percentOfClass>11.7</percentOfClass>
        <typeOfReportingPerson>IN</typeOfReportingPerson>
        <typeOfReportingPerson>HC</typeOfReportingPerson>
      </reportingPersonInfo>
      <reportingPersonInfo>
        <reportingPersonCIK>0001775831</reportingPersonCIK>
        <reportingPersonNoCIK>N</reportingPersonNoCIK>
        <reportingPersonName>Daniel Mack</reportingPersonName>
        <fundType>AF</fundType>
        <legalProceedings>N</legalProceedings>
        <citizenshipOrOrganization>X1</citizenshipOrOrganization>
        <soleVotingPower>0.00</soleVotingPower>
        <sharedVotingPower>1992519.00</sharedVotingPower>
        <soleDispositivePower>0.00</soleDispositivePower>
        <sharedDispositivePower>1992519.00</sharedDispositivePower>
        <aggregateAmountOwned>1992519.00</aggregateAmountOwned>
        <isAggregateExcludeShares>N</isAggregateExcludeShares>
        <percentOfClass>11.7</percentOfClass>
        <typeOfReportingPerson>IN</typeOfReportingPerson>
        <typeOfReportingPerson>HC</typeOfReportingPerson>
      </reportingPersonInfo>
    </reportingPersons>
    <items1To7>
      <item1>
        <securityTitle>Common Stock, par value $0.001 per share</securityTitle>
        <issuerName>TALPHERA, INC.</issuerName>
        <issuerPrincipalAddress>
          <com:street1>1850 Gateway Drive</com:street1>
          <com:street2>Suite 175</com:street2>
          <com:city>San Mateo</com:city>
          <com:stateOrCountry>CA</com:stateOrCountry>
          <com:zipCode>94404</com:zipCode>
        </issuerPrincipalAddress>
        <commentText>This filing is Amendment No. 2 ("Amendment No. 2") to the Schedule 13D filed with the Securities and Exchange Commission on behalf of Nantahala Capital Management, LLC, a Massachusetts limited liability company ("Nantahala"), Mr. Wilmot B. Harkey and Mr. Daniel Mack, the principals of Nantahala, on January 23, 2024 (the "Original Schedule 13D"), with respect to the Common Stock, par value $0.001 per share (the "Common Stock"), of Talphera, Inc. (the "Issuer"), as previously amended on April 2, 2025. Nantahala and Messrs. Harkey and Mack are referred to herein as the "Reporting Persons."

This Amendment No. 2 is filed solely for the purpose of attaching Exhibit 99.9. Except as specifically provided herein, this Amendment No. 2 does not modify any of the information reported in the Original Schedule 13D as previously amended, which, as amended further hereby, is referred to as the "Schedule 13D."

The Reporting Persons have jointly filed this Schedule 13D pursuant to Rule 13d-1(k)(1).</commentText>
      </item1>
      <item7>
        <filedExhibits>Item 7 is hereby amended by the addition of the following exhibits:

Exhibit 99.9 Securities Purchase Agreement, dated January 31, 2025, by and among the Issuer and entities affiliated with Nantahala Management, LLC</filedExhibits>
      </item7>
    </items1To7>
    <signatureInfo>
      <signaturePerson>
        <signatureReportingPerson>Nantahala Capital Management, LLC</signatureReportingPerson>
        <signatureDetails>
          <signature>/s/ Taki Vasilakis</signature>
          <title>Taki Vasilakis / Chief Compliance Officer</title>
          <date>04/03/2025</date>
        </signatureDetails>
      </signaturePerson>
      <signaturePerson>
        <signatureReportingPerson>Wilmot B. Harkey</signatureReportingPerson>
        <signatureDetails>
          <signature>/s/ Wilmot B. Harkey</signature>
          <title>Wilmot B. Harkey / Manager</title>
          <date>04/03/2025</date>
        </signatureDetails>
      </signaturePerson>
      <signaturePerson>
        <signatureReportingPerson>Daniel Mack</signatureReportingPerson>
        <signatureDetails>
          <signature>/s/ Daniel Mack</signature>
          <title>Daniel Mack / Manager</title>
          <date>04/03/2025</date>
        </signatureDetails>
      </signaturePerson>
    </signatureInfo>
  </formData>

</edgarSubmission>
