<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:e94d99e8-c97f-4c8c-9760-53de3aa2c4a2,g:787d55e7-4309-4599-bf51-362bfd556ca3-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.biocryst.com/role/CondensedConsolidatedStatementsofStockholdersDeficit" xlink:type="simple" xlink:href="bcrx-20240930.xsd#CondensedConsolidatedStatementsofStockholdersDeficit"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/CondensedConsolidatedStatementsofStockholdersDeficit" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_de8a3dcc-6396-451c-ae7f-d3f533ec3b54" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_ccd622d7-8377-4293-8398-ba7518c10495" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_de8a3dcc-6396-451c-ae7f-d3f533ec3b54" xlink:to="loc_us-gaap_StatementTable_ccd622d7-8377-4293-8398-ba7518c10495" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_ae66ee17-707b-431b-814a-c970808ac883" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_ccd622d7-8377-4293-8398-ba7518c10495" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_ae66ee17-707b-431b-814a-c970808ac883" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_ae66ee17-707b-431b-814a-c970808ac883_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_ae66ee17-707b-431b-814a-c970808ac883" xlink:to="loc_us-gaap_EquityComponentDomain_ae66ee17-707b-431b-814a-c970808ac883_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_ae66ee17-707b-431b-814a-c970808ac883" xlink:to="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_cc05a0f5-e0e1-437a-8d82-24963ee6cbd3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:to="loc_us-gaap_CommonStockMember_cc05a0f5-e0e1-437a-8d82-24963ee6cbd3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_b71965aa-21c3-4e8f-ba2e-3d3b7dcac629" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_b71965aa-21c3-4e8f-ba2e-3d3b7dcac629" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_c726de96-a175-43d5-b4aa-dac9dd251ca0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_c726de96-a175-43d5-b4aa-dac9dd251ca0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_7a87bb82-9e58-460e-b55d-2b141b9754ab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_77280054-c9fd-4350-b570-9cfcfb17f626" xlink:to="loc_us-gaap_RetainedEarningsMember_7a87bb82-9e58-460e-b55d-2b141b9754ab" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_de8a3dcc-6396-451c-ae7f-d3f533ec3b54" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_5c2a133a-0314-4bf0-baae-419071c20a42" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_5c2a133a-0314-4bf0-baae-419071c20a42" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_3f8e600c-0f75-4d45-a047-d4fdd25de614" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockholdersEquity_3f8e600c-0f75-4d45-a047-d4fdd25de614" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_7c6867c3-4d9f-476f-9423-423ba737cdfa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_NetIncomeLoss_7c6867c3-4d9f-476f-9423-423ba737cdfa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_00a5bc55-f716-450a-a084-9c6140a8ad23" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParent_00a5bc55-f716-450a-a084-9c6140a8ad23" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_b4f42933-3748-40c2-b2f4-24cca71f6dd3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_b4f42933-3748-40c2-b2f4-24cca71f6dd3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_97820d24-92ab-4b66-88a1-ada8847550ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_97820d24-92ab-4b66-88a1-ada8847550ec" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_362a9d5b-f736-4f32-b626-cae59ee3fd95" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_362a9d5b-f736-4f32-b626-cae59ee3fd95" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_87e1e6c7-13a6-4911-b340-c4ea9db82f3f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_87e1e6c7-13a6-4911-b340-c4ea9db82f3f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_6958febf-248f-4a79-a319-ab5671a23a36" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_SharesPaidForTaxWithholdingForShareBasedCompensation_6958febf-248f-4a79-a319-ab5671a23a36" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_1ae71c86-e63d-470b-bce6-9fd3c572e748" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_AdjustmentsRelatedToTaxWithholdingForShareBasedCompensation_1ae71c86-e63d-470b-bce6-9fd3c572e748" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_922b74ab-4426-457f-9bf1-24c46768fa6e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_922b74ab-4426-457f-9bf1-24c46768fa6e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b9a4aa67-af6f-4a87-8bfb-a8ddc847adef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeStockPurchasePlan_b9a4aa67-af6f-4a87-8bfb-a8ddc847adef" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesIssuedForServices_2561f2c9-d4e4-42b8-9c8e-96c9707d23e7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesIssuedForServices"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesIssuedForServices_2561f2c9-d4e4-42b8-9c8e-96c9707d23e7" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueIssuedForServices_41945128-9b2b-406f-9fce-6fd0b6164142" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueIssuedForServices"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueIssuedForServices_41945128-9b2b-406f-9fce-6fd0b6164142" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_cc09c46d-0fea-483e-9405-270e5af3d562" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_36f77724-8586-48e2-9366-8bba6fbf4d60" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_cc09c46d-0fea-483e-9405-270e5af3d562" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_1f18accc-0b1e-4468-9566-7f74e9d91621" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_d8878f56-1c0a-4f0d-bf73-bf8b1a6d5b52" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#SignificantAccountingPoliciesandConcentrationsofRiskDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_440a4db7-93be-4c6b-abbe-53493827571a" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_440a4db7-93be-4c6b-abbe-53493827571a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_d7cd852f-5a2f-49c2-9b71-cb15796be0d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_440a4db7-93be-4c6b-abbe-53493827571a" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_d7cd852f-5a2f-49c2-9b71-cb15796be0d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_d7cd852f-5a2f-49c2-9b71-cb15796be0d4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_d7cd852f-5a2f-49c2-9b71-cb15796be0d4" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_d7cd852f-5a2f-49c2-9b71-cb15796be0d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3297d802-d33f-4f49-9113-344961a068a4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_d7cd852f-5a2f-49c2-9b71-cb15796be0d4" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3297d802-d33f-4f49-9113-344961a068a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_CollateralForCreditMember_8873304e-28e8-4933-906d-f15914480550" xlink:href="bcrx-20240930.xsd#bcrx_CollateralForCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_3297d802-d33f-4f49-9113-344961a068a4" xlink:to="loc_bcrx_CollateralForCreditMember_8873304e-28e8-4933-906d-f15914480550" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_90fc1bfe-cf43-4c57-88dc-c4235d98b008" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_440a4db7-93be-4c6b-abbe-53493827571a" xlink:to="loc_srt_RangeAxis_90fc1bfe-cf43-4c57-88dc-c4235d98b008" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_90fc1bfe-cf43-4c57-88dc-c4235d98b008_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_90fc1bfe-cf43-4c57-88dc-c4235d98b008" xlink:to="loc_srt_RangeMember_90fc1bfe-cf43-4c57-88dc-c4235d98b008_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_982a54a6-d4d6-4e4d-8a05-580fa6c9d0ed" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_90fc1bfe-cf43-4c57-88dc-c4235d98b008" xlink:to="loc_srt_RangeMember_982a54a6-d4d6-4e4d-8a05-580fa6c9d0ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_4080035c-578f-4e32-ad20-c6014372c44a" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_982a54a6-d4d6-4e4d-8a05-580fa6c9d0ed" xlink:to="loc_srt_MaximumMember_4080035c-578f-4e32-ad20-c6014372c44a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_279fb083-7990-40b0-8142-9abca1142d5f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_440a4db7-93be-4c6b-abbe-53493827571a" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_279fb083-7990-40b0-8142-9abca1142d5f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_279fb083-7990-40b0-8142-9abca1142d5f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_279fb083-7990-40b0-8142-9abca1142d5f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_279fb083-7990-40b0-8142-9abca1142d5f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_22e199be-a5b8-4d7f-b644-4cba9b137b7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_279fb083-7990-40b0-8142-9abca1142d5f" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_22e199be-a5b8-4d7f-b644-4cba9b137b7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_25a1d189-3c2e-4d8e-ab3d-78266c019cf2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_22e199be-a5b8-4d7f-b644-4cba9b137b7e" xlink:to="loc_us-gaap_ComputerEquipmentMember_25a1d189-3c2e-4d8e-ab3d-78266c019cf2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LaboratoryEquipmentOfficeEquipmentAndSoftwareMember_4692e89b-daca-4ee2-bdbf-06d5c832d3ad" xlink:href="bcrx-20240930.xsd#bcrx_LaboratoryEquipmentOfficeEquipmentAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_22e199be-a5b8-4d7f-b644-4cba9b137b7e" xlink:to="loc_bcrx_LaboratoryEquipmentOfficeEquipmentAndSoftwareMember_4692e89b-daca-4ee2-bdbf-06d5c832d3ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_2c4bba65-e36a-41ce-812c-23809fc144b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_22e199be-a5b8-4d7f-b644-4cba9b137b7e" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_2c4bba65-e36a-41ce-812c-23809fc144b2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalents_198ea020-6726-4af8-a860-0d7fd4eca3db" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalents_198ea020-6726-4af8-a860-0d7fd4eca3db" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_543fda25-9f55-4cc7-b7db-0d9f5c3ef946" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsNoncurrent_543fda25-9f55-4cc7-b7db-0d9f5c3ef946" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_593d335a-7c36-4070-934a-b9a6049bc02e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_593d335a-7c36-4070-934a-b9a6049bc02e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MaturityPeriodOfHighQualityMarketableSecurities_7eabcd14-2fef-431b-893c-bf3c5326cb7f" xlink:href="bcrx-20240930.xsd#bcrx_MaturityPeriodOfHighQualityMarketableSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_bcrx_MaturityPeriodOfHighQualityMarketableSecurities_7eabcd14-2fef-431b-893c-bf3c5326cb7f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AverageMaturityPeriodOfHighQualityMarketableSecurities_4be82930-ab4f-4c45-bf48-7763ccfd30c2" xlink:href="bcrx-20240930.xsd#bcrx_AverageMaturityPeriodOfHighQualityMarketableSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_bcrx_AverageMaturityPeriodOfHighQualityMarketableSecurities_4be82930-ab4f-4c45-bf48-7763ccfd30c2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MaturityPeriodOfShortTermInvestment_24643690-feca-49e0-89da-83c972bc7179" xlink:href="bcrx-20240930.xsd#bcrx_MaturityPeriodOfShortTermInvestment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_bcrx_MaturityPeriodOfShortTermInvestment_24643690-feca-49e0-89da-83c972bc7179" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LongTermInvestmentMaturityMinimum_99a48430-16c4-4071-bcd8-ee6fd523172b" xlink:href="bcrx-20240930.xsd#bcrx_LongTermInvestmentMaturityMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_bcrx_LongTermInvestmentMaturityMinimum_99a48430-16c4-4071-bcd8-ee6fd523172b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_0abcd5af-7dd8-4ad6-b1f6-a20043ff7089" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_0abcd5af-7dd8-4ad6-b1f6-a20043ff7089" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4d8eb02f-bbc5-4262-a128-47e63317ee24" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4d8eb02f-bbc5-4262-a128-47e63317ee24" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodBeforeTax_0d6a616b-02a8-4e45-be1e-7552d678bd6d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_75d12ddb-e8bc-471b-8e5b-3588012dbf02" xlink:to="loc_us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodBeforeTax_0d6a616b-02a8-4e45-be1e-7552d678bd6d" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskSummaryofRevenuesDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#SignificantAccountingPoliciesandConcentrationsofRiskSummaryofRevenuesDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskSummaryofRevenuesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_43cbf620-2245-4214-89e6-f659e0f22f5a" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_0d43fb10-885c-4e98-9e87-540ba414cac6" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_43cbf620-2245-4214-89e6-f659e0f22f5a" xlink:to="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_0d43fb10-885c-4e98-9e87-540ba414cac6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_b029d4cf-8cf1-462d-9c20-189308f15c19" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_0d43fb10-885c-4e98-9e87-540ba414cac6" xlink:to="loc_srt_ProductOrServiceAxis_b029d4cf-8cf1-462d-9c20-189308f15c19" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_b029d4cf-8cf1-462d-9c20-189308f15c19_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_b029d4cf-8cf1-462d-9c20-189308f15c19" xlink:to="loc_srt_ProductsAndServicesDomain_b029d4cf-8cf1-462d-9c20-189308f15c19_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_c8b7f035-2669-464d-aae9-85f2d01374b5" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_b029d4cf-8cf1-462d-9c20-189308f15c19" xlink:to="loc_srt_ProductsAndServicesDomain_c8b7f035-2669-464d-aae9-85f2d01374b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_9118ed50-d701-47c8-8967-5eceb75954c8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c8b7f035-2669-464d-aae9-85f2d01374b5" xlink:to="loc_us-gaap_ProductMember_9118ed50-d701-47c8-8967-5eceb75954c8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_CollaborativeAndOtherResearchAndDevelopmentMember_545bf6cf-3bf3-4768-8182-06ca053f9f6b" xlink:href="bcrx-20240930.xsd#bcrx_CollaborativeAndOtherResearchAndDevelopmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c8b7f035-2669-464d-aae9-85f2d01374b5" xlink:to="loc_bcrx_CollaborativeAndOtherResearchAndDevelopmentMember_545bf6cf-3bf3-4768-8182-06ca053f9f6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_f83a8054-6373-4d8f-867c-ab7f7acd40d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_43cbf620-2245-4214-89e6-f659e0f22f5a" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_f83a8054-6373-4d8f-867c-ab7f7acd40d3" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskNetLossPerShareDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#SignificantAccountingPoliciesandConcentrationsofRiskNetLossPerShareDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/SignificantAccountingPoliciesandConcentrationsofRiskNetLossPerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_895677fc-fc01-4e8d-9887-dfdb339d4e05" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_e437833c-1686-46f6-8c6b-94a52ec79b48" xlink:href="bcrx-20240930.xsd#bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_895677fc-fc01-4e8d-9887-dfdb339d4e05" xlink:to="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_e437833c-1686-46f6-8c6b-94a52ec79b48" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_90c2323d-d2eb-4f53-8391-2680633b5d9a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskTable_e437833c-1686-46f6-8c6b-94a52ec79b48" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_90c2323d-d2eb-4f53-8391-2680633b5d9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_90c2323d-d2eb-4f53-8391-2680633b5d9a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_90c2323d-d2eb-4f53-8391-2680633b5d9a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_90c2323d-d2eb-4f53-8391-2680633b5d9a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7c10a7d0-bcb1-4406-ac8e-5d098fc90d1d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_90c2323d-d2eb-4f53-8391-2680633b5d9a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7c10a7d0-bcb1-4406-ac8e-5d098fc90d1d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_7e335b40-9141-4dd7-a0cb-2b9aa4bbacd4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7c10a7d0-bcb1-4406-ac8e-5d098fc90d1d" xlink:to="loc_us-gaap_EmployeeStockOptionMember_7e335b40-9141-4dd7-a0cb-2b9aa4bbacd4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_4080e198-1607-4455-af84-da879078aa35" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7c10a7d0-bcb1-4406-ac8e-5d098fc90d1d" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_4080e198-1607-4455-af84-da879078aa35" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_31b5a19e-e2bc-4c25-8075-33626fe62903" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7c10a7d0-bcb1-4406-ac8e-5d098fc90d1d" xlink:to="loc_us-gaap_WarrantMember_31b5a19e-e2bc-4c25-8075-33626fe62903" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_759b9bca-d962-44ff-b20f-34c4c30d4cd1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_SignificantAccountingPoliciesAndConcentrationsOfRiskLineItems_895677fc-fc01-4e8d-9887-dfdb339d4e05" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_759b9bca-d962-44ff-b20f-34c4c30d4cd1" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/RevenueDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#RevenueDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/RevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_262d2cf5-f9a1-4a7c-966c-4cec6e3e609e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_2bd6f9df-2482-47aa-be6d-46339eb83f92" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_262d2cf5-f9a1-4a7c-966c-4cec6e3e609e" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_2bd6f9df-2482-47aa-be6d-46339eb83f92" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_16fdf213-adc9-41a0-8411-138a4ad69ddc" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_2bd6f9df-2482-47aa-be6d-46339eb83f92" xlink:to="loc_srt_ProductOrServiceAxis_16fdf213-adc9-41a0-8411-138a4ad69ddc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_16fdf213-adc9-41a0-8411-138a4ad69ddc_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_16fdf213-adc9-41a0-8411-138a4ad69ddc" xlink:to="loc_srt_ProductsAndServicesDomain_16fdf213-adc9-41a0-8411-138a4ad69ddc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_89d90998-5a3d-49d6-90b4-ada348a53f48" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_16fdf213-adc9-41a0-8411-138a4ad69ddc" xlink:to="loc_srt_ProductsAndServicesDomain_89d90998-5a3d-49d6-90b4-ada348a53f48" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_e888e591-0737-4419-b1c2-79d6c7f52f47" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_89d90998-5a3d-49d6-90b4-ada348a53f48" xlink:to="loc_us-gaap_ProductMember_e888e591-0737-4419-b1c2-79d6c7f52f47" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ORLADEYOMember_e63db6e7-29b9-4a0e-a0d2-b5267b936c1a" xlink:href="bcrx-20240930.xsd#bcrx_ORLADEYOMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_89d90998-5a3d-49d6-90b4-ada348a53f48" xlink:to="loc_bcrx_ORLADEYOMember_e63db6e7-29b9-4a0e-a0d2-b5267b936c1a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_OtherIncomeFromContractWithCustomerMember_724a44cd-1f41-4490-941f-3445837d1aca" xlink:href="bcrx-20240930.xsd#bcrx_OtherIncomeFromContractWithCustomerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_89d90998-5a3d-49d6-90b4-ada348a53f48" xlink:to="loc_bcrx_OtherIncomeFromContractWithCustomerMember_724a44cd-1f41-4490-941f-3445837d1aca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicDistributionAxis_37142f2c-197f-4584-9311-2140ab6fe7d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeographicDistributionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_2bd6f9df-2482-47aa-be6d-46339eb83f92" xlink:to="loc_us-gaap_GeographicDistributionAxis_37142f2c-197f-4584-9311-2140ab6fe7d6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicDistributionDomain_37142f2c-197f-4584-9311-2140ab6fe7d6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeographicDistributionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_GeographicDistributionAxis_37142f2c-197f-4584-9311-2140ab6fe7d6" xlink:to="loc_us-gaap_GeographicDistributionDomain_37142f2c-197f-4584-9311-2140ab6fe7d6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicDistributionDomain_94badb50-a092-4af6-b98e-16e7e9939090" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeographicDistributionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_GeographicDistributionAxis_37142f2c-197f-4584-9311-2140ab6fe7d6" xlink:to="loc_us-gaap_GeographicDistributionDomain_94badb50-a092-4af6-b98e-16e7e9939090" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicDistributionDomesticMember_ecc08574-b850-4d82-bb5d-e30498eb013f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeographicDistributionDomesticMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GeographicDistributionDomain_94badb50-a092-4af6-b98e-16e7e9939090" xlink:to="loc_us-gaap_GeographicDistributionDomesticMember_ecc08574-b850-4d82-bb5d-e30498eb013f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeographicDistributionForeignMember_624b81a5-ba0a-452d-8593-b5c17ff99843" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeographicDistributionForeignMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_GeographicDistributionDomain_94badb50-a092-4af6-b98e-16e7e9939090" xlink:to="loc_us-gaap_GeographicDistributionForeignMember_624b81a5-ba0a-452d-8593-b5c17ff99843" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_5f80e8d3-9d34-4c0a-a276-5020b6109f54" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_262d2cf5-f9a1-4a7c-966c-4cec6e3e609e" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_5f80e8d3-9d34-4c0a-a276-5020b6109f54" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/InvestmentsFairValueRecurringBasisDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#InvestmentsFairValueRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/InvestmentsFairValueRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesLineItems_28909371-8a64-4185-af44-7455318a011c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesTable_46990d51-9bfc-43de-8151-ed2b02b91a1a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_28909371-8a64-4185-af44-7455318a011c" xlink:to="loc_us-gaap_MarketableSecuritiesTable_46990d51-9bfc-43de-8151-ed2b02b91a1a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ab43681e-6d57-4fe9-9950-a1402597d544" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_MarketableSecuritiesTable_46990d51-9bfc-43de-8151-ed2b02b91a1a" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ab43681e-6d57-4fe9-9950-a1402597d544" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ab43681e-6d57-4fe9-9950-a1402597d544_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ab43681e-6d57-4fe9-9950-a1402597d544" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ab43681e-6d57-4fe9-9950-a1402597d544_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_84eadc9b-9f8f-427d-a2d3-af0a1bab8691" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ab43681e-6d57-4fe9-9950-a1402597d544" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_84eadc9b-9f8f-427d-a2d3-af0a1bab8691" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_b694a35c-d728-4c3c-b4ce-abd2080a3d6c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_84eadc9b-9f8f-427d-a2d3-af0a1bab8691" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_b694a35c-d728-4c3c-b4ce-abd2080a3d6c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_14d972b2-d977-4e4d-9379-479b1e117e43" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_84eadc9b-9f8f-427d-a2d3-af0a1bab8691" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_14d972b2-d977-4e4d-9379-479b1e117e43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_8d3cf336-5f48-41b7-97ca-eeb4259ba0cc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_84eadc9b-9f8f-427d-a2d3-af0a1bab8691" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_8d3cf336-5f48-41b7-97ca-eeb4259ba0cc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_f6a1c512-511b-4e03-8a1f-a6978032884c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_MarketableSecuritiesTable_46990d51-9bfc-43de-8151-ed2b02b91a1a" xlink:to="loc_us-gaap_FinancialInstrumentAxis_f6a1c512-511b-4e03-8a1f-a6978032884c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f6a1c512-511b-4e03-8a1f-a6978032884c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_f6a1c512-511b-4e03-8a1f-a6978032884c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f6a1c512-511b-4e03-8a1f-a6978032884c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9fa7ddac-02a1-436d-8b26-04c78933b2ab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_f6a1c512-511b-4e03-8a1f-a6978032884c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9fa7ddac-02a1-436d-8b26-04c78933b2ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_124393f5-e4f3-4e50-9888-c23bdd89dc95" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9fa7ddac-02a1-436d-8b26-04c78933b2ab" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_124393f5-e4f3-4e50-9888-c23bdd89dc95" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_f465484d-ceaf-4d4f-b723-5b1ab4ef4630" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_9fa7ddac-02a1-436d-8b26-04c78933b2ab" xlink:to="loc_us-gaap_CertificatesOfDepositMember_f465484d-ceaf-4d4f-b723-5b1ab4ef4630" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_9ef8a47b-58f8-44c8-ba72-733aa29783fd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_28909371-8a64-4185-af44-7455318a011c" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_9ef8a47b-58f8-44c8-ba72-733aa29783fd" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/InvestmentsFairValueoftheCompanysInvestmentsbyTypeDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#InvestmentsFairValueoftheCompanysInvestmentsbyTypeDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/InvestmentsFairValueoftheCompanysInvestmentsbyTypeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MarketableSecuritiesTable_615cfc72-0c1f-4bb2-8906-41ec8f73e7f8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MarketableSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_MarketableSecuritiesTable_615cfc72-0c1f-4bb2-8906-41ec8f73e7f8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_37e53427-2731-4880-b627-638b4424086c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_MarketableSecuritiesTable_615cfc72-0c1f-4bb2-8906-41ec8f73e7f8" xlink:to="loc_us-gaap_FinancialInstrumentAxis_37e53427-2731-4880-b627-638b4424086c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_37e53427-2731-4880-b627-638b4424086c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_37e53427-2731-4880-b627-638b4424086c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_37e53427-2731-4880-b627-638b4424086c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f81b3ba3-b7c2-42b0-ae78-e4a27236042f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_37e53427-2731-4880-b627-638b4424086c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f81b3ba3-b7c2-42b0-ae78-e4a27236042f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_efc11fe6-5630-47c4-a533-e0095d898e42" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f81b3ba3-b7c2-42b0-ae78-e4a27236042f" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_efc11fe6-5630-47c4-a533-e0095d898e42" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CertificatesOfDepositMember_4b03a28d-f5cf-4c54-ab62-cceb93e621fe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CertificatesOfDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f81b3ba3-b7c2-42b0-ae78-e4a27236042f" xlink:to="loc_us-gaap_CertificatesOfDepositMember_4b03a28d-f5cf-4c54-ab62-cceb93e621fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss_2420164f-93f9-44f4-848e-f2f8b15743d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestAfterAllowanceForCreditLoss_2420164f-93f9-44f4-848e-f2f8b15743d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLoss_c80f61fd-a85d-4fb6-9e01-471456e80c71" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLoss_c80f61fd-a85d-4fb6-9e01-471456e80c71" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_41b9fed0-5614-44a4-b089-ac7ebeedb7c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_41b9fed0-5614-44a4-b089-ac7ebeedb7c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019783b2-5345-4156-87e3-68d7082b423d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019783b2-5345-4156-87e3-68d7082b423d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4ce8596f-fae8-429e-95e0-7174f35419a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_4ce8596f-fae8-429e-95e0-7174f35419a8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLossStatementOfFinancialPositionExtensibleList_84c8f3b7-810c-4179-91fc-0b24eb8b7555" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLossStatementOfFinancialPositionExtensibleList"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MarketableSecuritiesLineItems_562701ed-ec14-4974-b5bd-ea83756d9acf" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAccruedInterestAfterAllowanceForCreditLossStatementOfFinancialPositionExtensibleList_84c8f3b7-810c-4179-91fc-0b24eb8b7555" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/TradeReceivablesDetailsTextual" xlink:type="simple" xlink:href="bcrx-20240930.xsd#TradeReceivablesDetailsTextual"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/TradeReceivablesDetailsTextual" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_f346361c-9192-428d-93a2-15fa2e5e4257" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsNotesAndLoansReceivableLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_9f5d73fe-7391-41a4-acc0-f7b7f235b1d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_f346361c-9192-428d-93a2-15fa2e5e4257" xlink:to="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_9f5d73fe-7391-41a4-acc0-f7b7f235b1d4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_056c73c9-ee20-4c7a-a544-05158d4f3bb7" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_9f5d73fe-7391-41a4-acc0-f7b7f235b1d4" xlink:to="loc_srt_ProductOrServiceAxis_056c73c9-ee20-4c7a-a544-05158d4f3bb7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_056c73c9-ee20-4c7a-a544-05158d4f3bb7_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_056c73c9-ee20-4c7a-a544-05158d4f3bb7" xlink:to="loc_srt_ProductsAndServicesDomain_056c73c9-ee20-4c7a-a544-05158d4f3bb7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_4b62426f-2643-4e05-a9a0-0404c29cb5bf" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_056c73c9-ee20-4c7a-a544-05158d4f3bb7" xlink:to="loc_srt_ProductsAndServicesDomain_4b62426f-2643-4e05-a9a0-0404c29cb5bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ORLADEYOMember_f2d55599-d50d-4e62-8d3b-607f7c052867" xlink:href="bcrx-20240930.xsd#bcrx_ORLADEYOMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4b62426f-2643-4e05-a9a0-0404c29cb5bf" xlink:to="loc_bcrx_ORLADEYOMember_f2d55599-d50d-4e62-8d3b-607f7c052867" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RAPIVABMember_f6d97677-f809-40d2-8a4a-da8c1ab8b60c" xlink:href="bcrx-20240930.xsd#bcrx_RAPIVABMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_4b62426f-2643-4e05-a9a0-0404c29cb5bf" xlink:to="loc_bcrx_RAPIVABMember_f6d97677-f809-40d2-8a4a-da8c1ab8b60c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_b5a4bfe1-8405-490d-8bd1-c02ac1164c58" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_9f5d73fe-7391-41a4-acc0-f7b7f235b1d4" xlink:to="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_b5a4bfe1-8405-490d-8bd1-c02ac1164c58" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableTypeDomain_b5a4bfe1-8405-490d-8bd1-c02ac1164c58_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivableTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_b5a4bfe1-8405-490d-8bd1-c02ac1164c58" xlink:to="loc_us-gaap_ReceivableTypeDomain_b5a4bfe1-8405-490d-8bd1-c02ac1164c58_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableTypeDomain_ef50fd5a-ae1f-4bbf-a6af-7c6ee88713e8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivableTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_b5a4bfe1-8405-490d-8bd1-c02ac1164c58" xlink:to="loc_us-gaap_ReceivableTypeDomain_ef50fd5a-ae1f-4bbf-a6af-7c6ee88713e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeAccountsReceivableMember_15f40f44-a134-45f8-8483-3119c3db63d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TradeAccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReceivableTypeDomain_ef50fd5a-ae1f-4bbf-a6af-7c6ee88713e8" xlink:to="loc_us-gaap_TradeAccountsReceivableMember_15f40f44-a134-45f8-8483-3119c3db63d4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableNet_657d2880-659f-4da5-b7a1-f7e664c9605b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsReceivableNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_f346361c-9192-428d-93a2-15fa2e5e4257" xlink:to="loc_us-gaap_AccountsReceivableNet_657d2880-659f-4da5-b7a1-f7e664c9605b" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/TradeReceivablesSummaryofReceivablesDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#TradeReceivablesSummaryofReceivablesDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/TradeReceivablesSummaryofReceivablesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_9380d603-9157-4307-ace9-cfca0ac5a9ad" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsNotesAndLoansReceivableLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_e294b1ee-e9b3-4af0-a54d-242eade4c5d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_9380d603-9157-4307-ace9-cfca0ac5a9ad" xlink:to="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_e294b1ee-e9b3-4af0-a54d-242eade4c5d4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis_db2ee196-91a1-4b92-9bd8-b358a52f93de" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_e294b1ee-e9b3-4af0-a54d-242eade4c5d4" xlink:to="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis_db2ee196-91a1-4b92-9bd8-b358a52f93de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LegalEntityTypeOfCounterpartyDomain_db2ee196-91a1-4b92-9bd8-b358a52f93de_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis_db2ee196-91a1-4b92-9bd8-b358a52f93de" xlink:to="loc_us-gaap_LegalEntityTypeOfCounterpartyDomain_db2ee196-91a1-4b92-9bd8-b358a52f93de_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LegalEntityTypeOfCounterpartyDomain_c383f4d4-57a1-4ed5-ba9a-8bdb4f11fe16" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LegalEntityTypeOfCounterpartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByLegalEntityOfCounterpartyTypeAxis_db2ee196-91a1-4b92-9bd8-b358a52f93de" xlink:to="loc_us-gaap_LegalEntityTypeOfCounterpartyDomain_c383f4d4-57a1-4ed5-ba9a-8bdb4f11fe16" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyReceivablesFromPartnersMember_96dec098-0104-46f1-b345-04f0d3c362b2" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyReceivablesFromPartnersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LegalEntityTypeOfCounterpartyDomain_c383f4d4-57a1-4ed5-ba9a-8bdb4f11fe16" xlink:to="loc_bcrx_RoyaltyReceivablesFromPartnersMember_96dec098-0104-46f1-b345-04f0d3c362b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByBillingStatusTypeAxis_6b373e17-5dff-4c9d-bcb0-f90aa43651b2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivablesByBillingStatusTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAccountsNotesLoansAndFinancingReceivableTable_e294b1ee-e9b3-4af0-a54d-242eade4c5d4" xlink:to="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByBillingStatusTypeAxis_6b373e17-5dff-4c9d-bcb0-f90aa43651b2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivablesBillingStatusDomain_6b373e17-5dff-4c9d-bcb0-f90aa43651b2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivablesBillingStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByBillingStatusTypeAxis_6b373e17-5dff-4c9d-bcb0-f90aa43651b2" xlink:to="loc_us-gaap_ReceivablesBillingStatusDomain_6b373e17-5dff-4c9d-bcb0-f90aa43651b2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivablesBillingStatusDomain_94595eb0-a133-45d5-b5bc-879735129d68" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivablesBillingStatusDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivablesByBillingStatusTypeAxis_6b373e17-5dff-4c9d-bcb0-f90aa43651b2" xlink:to="loc_us-gaap_ReceivablesBillingStatusDomain_94595eb0-a133-45d5-b5bc-879735129d68" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BilledRevenuesMember_93590031-badc-4911-abec-d4d261dcdb99" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BilledRevenuesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReceivablesBillingStatusDomain_94595eb0-a133-45d5-b5bc-879735129d68" xlink:to="loc_us-gaap_BilledRevenuesMember_93590031-badc-4911-abec-d4d261dcdb99" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnbilledRevenuesMember_71051e33-c153-4801-99f2-6d7307644ce3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_UnbilledRevenuesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReceivablesBillingStatusDomain_94595eb0-a133-45d5-b5bc-879735129d68" xlink:to="loc_us-gaap_UnbilledRevenuesMember_71051e33-c153-4801-99f2-6d7307644ce3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivablesNetCurrent_3b7df70c-2f03-466b-9f63-11619a552a1d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ReceivablesNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AccountsNotesAndLoansReceivableLineItems_9380d603-9157-4307-ace9-cfca0ac5a9ad" xlink:to="loc_us-gaap_ReceivablesNetCurrent_3b7df70c-2f03-466b-9f63-11619a552a1d" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/RoyaltyFinancingObligationsDetailsTextual" xlink:type="simple" xlink:href="bcrx-20240930.xsd#RoyaltyFinancingObligationsDetailsTextual"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/RoyaltyFinancingObligationsDetailsTextual" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyMonetizationsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltiesMonetizationsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_a39310e0-c417-427f-8ca7-50f2f0bc32e8" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:to="loc_srt_CounterpartyNameAxis_a39310e0-c417-427f-8ca7-50f2f0bc32e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a39310e0-c417-427f-8ca7-50f2f0bc32e8_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_a39310e0-c417-427f-8ca7-50f2f0bc32e8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a39310e0-c417-427f-8ca7-50f2f0bc32e8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_a39310e0-c417-427f-8ca7-50f2f0bc32e8" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RPI2019IntermediateFinanceTrustMember_36b48f9a-7dfa-4d2e-bee3-e0a86958df8c" xlink:href="bcrx-20240930.xsd#bcrx_RPI2019IntermediateFinanceTrustMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:to="loc_bcrx_RPI2019IntermediateFinanceTrustMember_36b48f9a-7dfa-4d2e-bee3-e0a86958df8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RPI2021And2020IntermediateFinanceTrustMember_4d045d73-e74d-4144-b87e-b4d66e322150" xlink:href="bcrx-20240930.xsd#bcrx_RPI2021And2020IntermediateFinanceTrustMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:to="loc_bcrx_RPI2021And2020IntermediateFinanceTrustMember_4d045d73-e74d-4144-b87e-b4d66e322150" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_The2021RPIRoyaltyPurchaseAgreementMember_018f1a0a-775c-49fc-9400-6d11f8e8b5d6" xlink:href="bcrx-20240930.xsd#bcrx_The2021RPIRoyaltyPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:to="loc_bcrx_The2021RPIRoyaltyPurchaseAgreementMember_018f1a0a-775c-49fc-9400-6d11f8e8b5d6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_OMERSCapitalMarketsMember_acede72d-e475-404e-a22b-69f15a552a49" xlink:href="bcrx-20240930.xsd#bcrx_OMERSCapitalMarketsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_4be34e83-cb0b-4eab-b41b-c29f36d493c5" xlink:to="loc_bcrx_OMERSCapitalMarketsMember_acede72d-e475-404e-a22b-69f15a552a49" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_120aa86a-d90b-4858-8d77-923dc194982f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_120aa86a-d90b-4858-8d77-923dc194982f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_120aa86a-d90b-4858-8d77-923dc194982f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_120aa86a-d90b-4858-8d77-923dc194982f" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_120aa86a-d90b-4858-8d77-923dc194982f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01517272-fb70-47fe-ac84-51570ca26db8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_120aa86a-d90b-4858-8d77-923dc194982f" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01517272-fb70-47fe-ac84-51570ca26db8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_FutureRoyaltiesPayableMember_a803aab3-7d51-4880-a9e7-82eab848bd2f" xlink:href="bcrx-20240930.xsd#bcrx_FutureRoyaltiesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01517272-fb70-47fe-ac84-51570ca26db8" xlink:to="loc_bcrx_FutureRoyaltiesPayableMember_a803aab3-7d51-4880-a9e7-82eab848bd2f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_c226071f-cfaa-43fb-978a-b636049b2284" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:to="loc_srt_ProductOrServiceAxis_c226071f-cfaa-43fb-978a-b636049b2284" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_c226071f-cfaa-43fb-978a-b636049b2284_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_c226071f-cfaa-43fb-978a-b636049b2284" xlink:to="loc_srt_ProductsAndServicesDomain_c226071f-cfaa-43fb-978a-b636049b2284_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_de5b4961-3a6b-4663-8d94-f112703ebda7" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_c226071f-cfaa-43fb-978a-b636049b2284" xlink:to="loc_srt_ProductsAndServicesDomain_de5b4961-3a6b-4663-8d94-f112703ebda7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ORLADEYOMember_ba06e46a-737f-4a46-87aa-be2c85742960" xlink:href="bcrx-20240930.xsd#bcrx_ORLADEYOMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_de5b4961-3a6b-4663-8d94-f112703ebda7" xlink:to="loc_bcrx_ORLADEYOMember_ba06e46a-737f-4a46-87aa-be2c85742960" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_BCX10013Member_00602efb-1ddd-442b-beff-f81c8148ce8c" xlink:href="bcrx-20240930.xsd#bcrx_BCX10013Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_de5b4961-3a6b-4663-8d94-f112703ebda7" xlink:to="loc_bcrx_BCX10013Member_00602efb-1ddd-442b-beff-f81c8148ce8c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeAxis_e9d44d9a-d371-41c2-9c27-80ebca4ebd33" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_RoyaltiesMonetizationsTable_e5b3ab3b-c8ad-4d26-b9de-c9e2595d2e13" xlink:to="loc_bcrx_AnnualNetSalesRangeAxis_e9d44d9a-d371-41c2-9c27-80ebca4ebd33" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeDomain_e9d44d9a-d371-41c2-9c27-80ebca4ebd33_default" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_bcrx_AnnualNetSalesRangeAxis_e9d44d9a-d371-41c2-9c27-80ebca4ebd33" xlink:to="loc_bcrx_AnnualNetSalesRangeDomain_e9d44d9a-d371-41c2-9c27-80ebca4ebd33_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_bcrx_AnnualNetSalesRangeAxis_e9d44d9a-d371-41c2-9c27-80ebca4ebd33" xlink:to="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesUnder350000Member_1db04a17-d134-44a1-aa5b-ea1c59ef31ef" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesUnder350000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesUnder350000Member_1db04a17-d134-44a1-aa5b-ea1c59ef31ef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesBetween350000And550000Member_1bfa7a57-88be-470e-8188-f6efa780fdca" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesBetween350000And550000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesBetween350000And550000Member_1bfa7a57-88be-470e-8188-f6efa780fdca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesOver550000Member_7c65f11b-25eb-4b5e-bbe7-17911d8cbf14" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesOver550000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesOver550000Member_7c65f11b-25eb-4b5e-bbe7-17911d8cbf14" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesUnder150000Member_4e39b39f-d28c-4f21-a03c-0643048a7930" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesUnder150000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesUnder150000Member_4e39b39f-d28c-4f21-a03c-0643048a7930" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesBetween150000And230000Member_bfdf4a23-c511-4132-9d24-fa9a679b98cf" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesBetween150000And230000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesBetween150000And230000Member_bfdf4a23-c511-4132-9d24-fa9a679b98cf" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesOver230000Member_ccb48d4e-1576-4275-b1b6-12d0553fe640" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesOver230000Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesOver230000Member_ccb48d4e-1576-4275-b1b6-12d0553fe640" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesUnder15BillionMember_5f835cd7-12c4-4d2c-a08b-f5014de47521" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesUnder15BillionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesUnder15BillionMember_5f835cd7-12c4-4d2c-a08b-f5014de47521" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesBetween15And3BillionsMember_fd0e127a-f9b8-4c2b-af2d-c357dd5e9f8c" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesBetween15And3BillionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesBetween15And3BillionsMember_fd0e127a-f9b8-4c2b-af2d-c357dd5e9f8c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesOver3BillionsMember_eec093b2-9c8a-4570-9ddd-d99a12048344" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesOver3BillionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_2e2ad034-ddc8-4b2b-9436-92f677a7f0fc" xlink:to="loc_bcrx_AnnualNetSalesOver3BillionsMember_eec093b2-9c8a-4570-9ddd-d99a12048344" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfDebt_911041d9-be35-4ed1-8c59-b671def1d9ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfDebt_911041d9-be35-4ed1-8c59-b671def1d9ec" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInKeyTerritories_bc7c41d8-8132-4965-9c6e-db3e0b4fb18c" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInKeyTerritories"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInKeyTerritories_bc7c41d8-8132-4965-9c6e-db3e0b4fb18c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfSublicenseRevenueInOtherMarkets_93d60eb5-b294-4436-a89a-e16066f0a7d7" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfSublicenseRevenueInOtherMarkets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfSublicenseRevenueInOtherMarkets_93d60eb5-b294-4436-a89a-e16066f0a7d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInOtherMarkets_b6c6ac4e-a3fb-41e9-bdf5-f664ed834044" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInOtherMarkets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesInOtherMarkets_b6c6ac4e-a3fb-41e9-bdf5-f664ed834044" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SharesIssuedCommonStockPremium_f524bc67-2513-4440-879b-4c82d664ef14" xlink:href="bcrx-20240930.xsd#bcrx_SharesIssuedCommonStockPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_SharesIssuedCommonStockPremium_f524bc67-2513-4440-879b-4c82d664ef14" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesMaximumTieredProfitSharePercentageOnPermittedSalesInOtherMarkets_25357c63-5444-4db7-aeaf-e9e7dd179289" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesMaximumTieredProfitSharePercentageOnPermittedSalesInOtherMarkets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesMaximumTieredProfitSharePercentageOnPermittedSalesInOtherMarkets_25357c63-5444-4db7-aeaf-e9e7dd179289" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSales_246670c0-a4a7-4d97-9de0-01054b07c4af" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSales_246670c0-a4a7-4d97-9de0-01054b07c4af" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesBasedOnReductionInSales_e3e3f88f-8d8a-4ec9-aa74-ea55c2616814" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesBasedOnReductionInSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfAnnualNetSalesBasedOnReductionInSales_e3e3f88f-8d8a-4ec9-aa74-ea55c2616814" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfPurchasePrice_d697ad31-9c00-4a7c-bd6c-bbf68e1bdf22" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfPurchasePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPercentageOfPurchasePrice_d697ad31-9c00-4a7c-bd6c-bbf68e1bdf22" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPurchasePriceAmount_b9b06af5-3cca-4b95-9cec-548f11243fe9" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyPurchaseAgreementRoyaltiesPurchasePriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_40e1caa8-7cd8-46ed-b7c2-752228298a4e" xlink:to="loc_bcrx_RoyaltyPurchaseAgreementRoyaltiesPurchasePriceAmount_b9b06af5-3cca-4b95-9cec-548f11243fe9" xlink:type="arc" order="9"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/RoyaltyFinancingObligationsScheduleofRoyaltyFinancingObligationsDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#RoyaltyFinancingObligationsScheduleofRoyaltyFinancingObligationsDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/RoyaltyFinancingObligationsScheduleofRoyaltyFinancingObligationsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyMonetizationsLineItems_5a98ad7c-e13b-4554-9834-8510f8abbf2b" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyMonetizationsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltiesMonetizationsTable_f2b39cbc-d920-4608-8941-3e93fbfbcfef" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltiesMonetizationsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_5a98ad7c-e13b-4554-9834-8510f8abbf2b" xlink:to="loc_bcrx_RoyaltiesMonetizationsTable_f2b39cbc-d920-4608-8941-3e93fbfbcfef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_84f81bb2-f169-4487-859d-d0f2fe6d01c9" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_bcrx_RoyaltiesMonetizationsTable_f2b39cbc-d920-4608-8941-3e93fbfbcfef" xlink:to="loc_srt_CounterpartyNameAxis_84f81bb2-f169-4487-859d-d0f2fe6d01c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_84f81bb2-f169-4487-859d-d0f2fe6d01c9_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_84f81bb2-f169-4487-859d-d0f2fe6d01c9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_84f81bb2-f169-4487-859d-d0f2fe6d01c9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6902078d-94dd-47cf-a155-479a5f41bc27" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_84f81bb2-f169-4487-859d-d0f2fe6d01c9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6902078d-94dd-47cf-a155-479a5f41bc27" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TwentyTwentyRPIRoyaltyAgreementMember_75395e34-dfb6-4911-a407-52eb41cf8eb6" xlink:href="bcrx-20240930.xsd#bcrx_TwentyTwentyRPIRoyaltyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6902078d-94dd-47cf-a155-479a5f41bc27" xlink:to="loc_bcrx_TwentyTwentyRPIRoyaltyAgreementMember_75395e34-dfb6-4911-a407-52eb41cf8eb6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TwentyTwentyOneRPIRoyaltyAgreementMember_8bb70e8c-68fb-45f5-aace-bd8dd6ede350" xlink:href="bcrx-20240930.xsd#bcrx_TwentyTwentyOneRPIRoyaltyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6902078d-94dd-47cf-a155-479a5f41bc27" xlink:to="loc_bcrx_TwentyTwentyOneRPIRoyaltyAgreementMember_8bb70e8c-68fb-45f5-aace-bd8dd6ede350" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_OMERSRoyaltyAgreementMember_6d716a06-f79a-476d-b631-cd164bf976bd" xlink:href="bcrx-20240930.xsd#bcrx_OMERSRoyaltyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6902078d-94dd-47cf-a155-479a5f41bc27" xlink:to="loc_bcrx_OMERSRoyaltyAgreementMember_6d716a06-f79a-476d-b631-cd164bf976bd" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyMontizationsRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMonetizationsLineItems_5a98ad7c-e13b-4554-9834-8510f8abbf2b" xlink:to="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyFinancingLiabilities_95b7442c-f4f3-409e-b366-c8168c0ae61b" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyFinancingLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:to="loc_bcrx_RoyaltyFinancingLiabilities_95b7442c-f4f3-409e-b366-c8168c0ae61b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilities_cc7c1aaa-a0da-4be4-88f3-391f4f2b4477" xlink:href="bcrx-20240930.xsd#bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:to="loc_bcrx_NonCashInterestExpenseOnRoyaltyFinancingLiabilities_cc7c1aaa-a0da-4be4-88f3-391f4f2b4477" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyRevenuesPaidAndPayable_0d8ed6ad-18ba-41ff-a9c6-858fca300ee9" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyRevenuesPaidAndPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:to="loc_bcrx_RoyaltyRevenuesPaidAndPayable_0d8ed6ad-18ba-41ff-a9c6-858fca300ee9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyFinancingLiabilities_68dfe83e-21f2-4d04-9305-fba68247bbb1" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyFinancingLiabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_519ab273-4432-4610-9144-523072a992b7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_RoyaltyMontizationsRollForward_1649d349-c1e9-4c2b-9aa1-d161c38e10ff" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_519ab273-4432-4610-9144-523072a992b7" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/DebtDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#DebtDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/DebtDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_4bcd8412-d683-4059-864e-a06197295c4b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_us-gaap_DebtInstrumentAxis_4bcd8412-d683-4059-864e-a06197295c4b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_4bcd8412-d683-4059-864e-a06197295c4b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_4bcd8412-d683-4059-864e-a06197295c4b" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_4bcd8412-d683-4059-864e-a06197295c4b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_4bcd8412-d683-4059-864e-a06197295c4b" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermLoanTrancheAMember_74148ec7-5418-4968-b30b-f2d64356f81a" xlink:href="bcrx-20240930.xsd#bcrx_TermLoanTrancheAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_TermLoanTrancheAMember_74148ec7-5418-4968-b30b-f2d64356f81a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LoanAgreementMember_1860920e-49ce-4710-afc3-e0b8364cae18" xlink:href="bcrx-20240930.xsd#bcrx_LoanAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_LoanAgreementMember_1860920e-49ce-4710-afc3-e0b8364cae18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_CreditAgreementMember_634c8b68-96b8-4f5d-b70c-7bf7796945e4" xlink:href="bcrx-20240930.xsd#bcrx_CreditAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_CreditAgreementMember_634c8b68-96b8-4f5d-b70c-7bf7796945e4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermLoanTrancheBMember_f69e7ab8-1f7d-41f9-afd8-f7b0293332e0" xlink:href="bcrx-20240930.xsd#bcrx_TermLoanTrancheBMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_TermLoanTrancheBMember_f69e7ab8-1f7d-41f9-afd8-f7b0293332e0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermLoanTrancheCMember_5bd1a60c-520d-440b-ba84-bd2a37c1def0" xlink:href="bcrx-20240930.xsd#bcrx_TermLoanTrancheCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_TermLoanTrancheCMember_5bd1a60c-520d-440b-ba84-bd2a37c1def0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermLoanTrancheDMember_8d147e68-f31e-4726-aeff-e87c1b1cf277" xlink:href="bcrx-20240930.xsd#bcrx_TermLoanTrancheDMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_7cd035bd-8e1a-4b13-83fd-8303d1b1977b" xlink:to="loc_bcrx_TermLoanTrancheDMember_8d147e68-f31e-4726-aeff-e87c1b1cf277" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_c9a28972-ae4f-4efc-ba47-ea15b86c7aac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_9a2e77d6-f767-4eef-a258-1f76d1bc5fd0" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_c9a28972-ae4f-4efc-ba47-ea15b86c7aac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PharmakonAdvisorsLPMember_0f2f94dc-735f-46a7-9c0f-dabf06ec631b" xlink:href="bcrx-20240930.xsd#bcrx_PharmakonAdvisorsLPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_c9a28972-ae4f-4efc-ba47-ea15b86c7aac" xlink:to="loc_bcrx_PharmakonAdvisorsLPMember_0f2f94dc-735f-46a7-9c0f-dabf06ec631b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AthyriumMember_1abade98-226b-4957-846c-10f6067147c6" xlink:href="bcrx-20240930.xsd#bcrx_AthyriumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_c9a28972-ae4f-4efc-ba47-ea15b86c7aac" xlink:to="loc_bcrx_AthyriumMember_1abade98-226b-4957-846c-10f6067147c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MidCapFinancialServicesLLCMember_4a533f67-2339-4c49-97d2-2599aa946afc" xlink:href="bcrx-20240930.xsd#bcrx_MidCapFinancialServicesLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_c9a28972-ae4f-4efc-ba47-ea15b86c7aac" xlink:to="loc_bcrx_MidCapFinancialServicesLLCMember_4a533f67-2339-4c49-97d2-2599aa946afc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_96eb7cc9-0e3e-465a-a2a8-8062c29670df" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_96eb7cc9-0e3e-465a-a2a8-8062c29670df" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_96eb7cc9-0e3e-465a-a2a8-8062c29670df_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_96eb7cc9-0e3e-465a-a2a8-8062c29670df" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_96eb7cc9-0e3e-465a-a2a8-8062c29670df_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_96eb7cc9-0e3e-465a-a2a8-8062c29670df" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_d322aee4-34e0-46cd-ad68-105c94cd781c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:to="loc_us-gaap_LineOfCreditMember_d322aee4-34e0-46cd-ad68-105c94cd781c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermALoanMember_d31b259e-2b8f-475d-a3bd-4348652130ca" xlink:href="bcrx-20240930.xsd#bcrx_TermALoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:to="loc_bcrx_TermALoanMember_d31b259e-2b8f-475d-a3bd-4348652130ca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermBLoanMember_fb745cbf-51af-4dff-8a78-4405d1112ed4" xlink:href="bcrx-20240930.xsd#bcrx_TermBLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:to="loc_bcrx_TermBLoanMember_fb745cbf-51af-4dff-8a78-4405d1112ed4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermCLoanMember_ec4dd4e1-5a83-48bd-8d30-4c5a73114c0e" xlink:href="bcrx-20240930.xsd#bcrx_TermCLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:to="loc_bcrx_TermCLoanMember_ec4dd4e1-5a83-48bd-8d30-4c5a73114c0e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_TermBAndCLoanMember_cc080b32-df21-40e8-bdf1-45e0216801ca" xlink:href="bcrx-20240930.xsd#bcrx_TermBAndCLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_6e2c00df-69bc-4e79-bdd0-9301133ffb30" xlink:to="loc_bcrx_TermBAndCLoanMember_cc080b32-df21-40e8-bdf1-45e0216801ca" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_1e90531c-6b3b-4eac-8675-f7efb3b843af" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_us-gaap_CreditFacilityAxis_1e90531c-6b3b-4eac-8675-f7efb3b843af" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_1e90531c-6b3b-4eac-8675-f7efb3b843af_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_1e90531c-6b3b-4eac-8675-f7efb3b843af" xlink:to="loc_us-gaap_CreditFacilityDomain_1e90531c-6b3b-4eac-8675-f7efb3b843af_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_94f5b321-4dea-4a0f-8863-d23ce12213e5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_1e90531c-6b3b-4eac-8675-f7efb3b843af" xlink:to="loc_us-gaap_CreditFacilityDomain_94f5b321-4dea-4a0f-8863-d23ce12213e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_SeniorCreditFacilityMember_2df072ba-60c1-424e-a536-12d603cf141f" xlink:href="bcrx-20240930.xsd#bcrx_SeniorCreditFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_94f5b321-4dea-4a0f-8863-d23ce12213e5" xlink:to="loc_bcrx_SeniorCreditFacilityMember_2df072ba-60c1-424e-a536-12d603cf141f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateAxis_adf9edc1-e901-48f9-8971-963074727a22" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableRateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_us-gaap_VariableRateAxis_adf9edc1-e901-48f9-8971-963074727a22" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_adf9edc1-e901-48f9-8971-963074727a22_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_VariableRateAxis_adf9edc1-e901-48f9-8971-963074727a22" xlink:to="loc_us-gaap_VariableRateDomain_adf9edc1-e901-48f9-8971-963074727a22_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableRateDomain_331b693a-c271-452d-ab76-302a69956469" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableRateDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_VariableRateAxis_adf9edc1-e901-48f9-8971-963074727a22" xlink:to="loc_us-gaap_VariableRateDomain_331b693a-c271-452d-ab76-302a69956469" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember_67d6a3e6-e18c-47c4-83bc-e86fa2734624" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_331b693a-c271-452d-ab76-302a69956469" xlink:to="loc_us-gaap_SecuredOvernightFinancingRateSofrOvernightIndexSwapRateMember_67d6a3e6-e18c-47c4-83bc-e86fa2734624" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LondonInterbankOfferedRateMember_b4fc7e47-23d3-4c66-ba52-c9aa22ac3815" xlink:href="bcrx-20240930.xsd#bcrx_LondonInterbankOfferedRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_VariableRateDomain_331b693a-c271-452d-ab76-302a69956469" xlink:to="loc_bcrx_LondonInterbankOfferedRateMember_b4fc7e47-23d3-4c66-ba52-c9aa22ac3815" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtCovenantTermsAxis_e73a171c-bf40-4009-a034-709c2aedf952" xlink:href="bcrx-20240930.xsd#bcrx_DebtCovenantTermsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_36fa8a93-bec8-40b6-b9bb-65f236c8d13f" xlink:to="loc_bcrx_DebtCovenantTermsAxis_e73a171c-bf40-4009-a034-709c2aedf952" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtCovenantTermsDomain_e73a171c-bf40-4009-a034-709c2aedf952_default" xlink:href="bcrx-20240930.xsd#bcrx_DebtCovenantTermsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_bcrx_DebtCovenantTermsAxis_e73a171c-bf40-4009-a034-709c2aedf952" xlink:to="loc_bcrx_DebtCovenantTermsDomain_e73a171c-bf40-4009-a034-709c2aedf952_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:href="bcrx-20240930.xsd#bcrx_DebtCovenantTermsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_bcrx_DebtCovenantTermsAxis_e73a171c-bf40-4009-a034-709c2aedf952" xlink:to="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PikInterestPaymentIsMadeMember_7460c063-5a48-45f5-bf1c-3e396848d102" xlink:href="bcrx-20240930.xsd#bcrx_PikInterestPaymentIsMadeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:to="loc_bcrx_PikInterestPaymentIsMadeMember_7460c063-5a48-45f5-bf1c-3e396848d102" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_BetweenTheSecondAndThirdAnniversariesMember_5deabfff-7b32-4844-b75b-101e4f8026d9" xlink:href="bcrx-20240930.xsd#bcrx_BetweenTheSecondAndThirdAnniversariesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:to="loc_bcrx_BetweenTheSecondAndThirdAnniversariesMember_5deabfff-7b32-4844-b75b-101e4f8026d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AfterFourthAnniversaryMember_56ee17b1-bf2b-4365-a636-9b14c0785a36" xlink:href="bcrx-20240930.xsd#bcrx_AfterFourthAnniversaryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:to="loc_bcrx_AfterFourthAnniversaryMember_56ee17b1-bf2b-4365-a636-9b14c0785a36" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AfterThirdAnniversaryMember_bf16c27e-b715-40e7-94c3-d2fe3f45f2e7" xlink:href="bcrx-20240930.xsd#bcrx_AfterThirdAnniversaryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_DebtCovenantTermsDomain_5f072640-af5d-4b90-8ef4-bb0e0a55418d" xlink:to="loc_bcrx_AfterThirdAnniversaryMember_bf16c27e-b715-40e7-94c3-d2fe3f45f2e7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_9389a89e-aeba-4965-b5f7-5294731aee26" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_9389a89e-aeba-4965-b5f7-5294731aee26" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfLinesOfCredit_8f595e3e-cca4-4fcd-950b-9fc37cbbb9a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RepaymentsOfLinesOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_RepaymentsOfLinesOfCredit_8f595e3e-cca4-4fcd-950b-9fc37cbbb9a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_f16c337a-61d7-48a4-96b8-9e790302c01e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfLongTermDebt_f16c337a-61d7-48a4-96b8-9e790302c01e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTerm_44d5110f-5a06-4bb0-b1f5-91400b437b63" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentTerm_44d5110f-5a06-4bb0-b1f5-91400b437b63" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentCapitalizedInterestRate_bdb2f87c-f618-4572-bf5a-3c1f2b7f9a30" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentCapitalizedInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentCapitalizedInterestRate_bdb2f87c-f618-4572-bf5a-3c1f2b7f9a30" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentVariableRateFloor_205297bb-aff2-465c-9fa3-3677991e42e7" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentVariableRateFloor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentVariableRateFloor_205297bb-aff2-465c-9fa3-3677991e42e7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_bbacb0f2-bd0d-49e6-b85a-45b8c2ec9fca" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentBasisSpreadOnVariableRate1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentBasisSpreadOnVariableRate1_bbacb0f2-bd0d-49e6-b85a-45b8c2ec9fca" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_80f9742e-4987-4f9b-8734-870540a7172b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_80f9742e-4987-4f9b-8734-870540a7172b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_795d4d3e-26bf-46e7-af4d-cec6ae2c55c0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_InterestExpenseDebt_795d4d3e-26bf-46e7-af4d-cec6ae2c55c0" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PercentOfInterestPayment_62f21878-28e8-4e13-ae69-10c160e5d45a" xlink:href="bcrx-20240930.xsd#bcrx_PercentOfInterestPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_PercentOfInterestPayment_62f21878-28e8-4e13-ae69-10c160e5d45a" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentPeriodicPaymentInterest_655d317d-d6d1-45e9-83a3-1258f13b05a5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentPeriodicPaymentInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentPeriodicPaymentInterest_655d317d-d6d1-45e9-83a3-1258f13b05a5" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFairValue_fcdcccb5-9398-4d89-95f7-fd6cba29bbeb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentFairValue_fcdcccb5-9398-4d89-95f7-fd6cba29bbeb" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_d0e6019e-1fed-471f-954b-f0bd6d671549" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_d0e6019e-1fed-471f-954b-f0bd6d671549" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_ceb91d7d-0cf5-4d3a-b72c-32a06392333b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_ceb91d7d-0cf5-4d3a-b72c-32a06392333b" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentLiborFloor_c9eb56f4-c581-4878-940b-c37606683aa8" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentLiborFloor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentLiborFloor_c9eb56f4-c581-4878-940b-c37606683aa8" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentLiborCap_ea605ee0-f6ad-4de8-8f34-a56b9fac0495" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentLiborCap"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentLiborCap_ea605ee0-f6ad-4de8-8f34-a56b9fac0495" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentPeriodicPayment_8b3066ec-a6ba-4001-b189-b0fabd425293" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentPeriodicPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentPeriodicPayment_8b3066ec-a6ba-4001-b189-b0fabd425293" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentPrepaymentFeePercentageOfPrincipalVoluntaryPayments_538339f4-a641-4ba9-8af4-a961d94146db" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentPrepaymentFeePercentageOfPrincipalVoluntaryPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentPrepaymentFeePercentageOfPrincipalVoluntaryPayments_538339f4-a641-4ba9-8af4-a961d94146db" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaidInKindInterest_2c078ab9-18bc-41c4-a76d-3fb05666832b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaidInKindInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_PaidInKindInterest_2c078ab9-18bc-41c4-a76d-3fb05666832b" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_e1f2e8f2-2523-45e4-bd02-dc369a7d6181" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_LongTermDebt_e1f2e8f2-2523-45e4-bd02-dc369a7d6181" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseLongTermDebt_1c88ffa7-80ba-48ff-89dc-f1ec2c8c1902" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseLongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_InterestExpenseLongTermDebt_1c88ffa7-80ba-48ff-89dc-f1ec2c8c1902" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentExitFeePercentageOfPrincipal_17884f3a-e14a-4d96-8a0b-263eea86747a" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentExitFeePercentageOfPrincipal"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentExitFeePercentageOfPrincipal_17884f3a-e14a-4d96-8a0b-263eea86747a" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_DebtInstrumentCommitmentFeePercentage_2b42c1dd-5526-45eb-b693-57bc28344aca" xlink:href="bcrx-20240930.xsd#bcrx_DebtInstrumentCommitmentFeePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_bcrx_DebtInstrumentCommitmentFeePercentage_2b42c1dd-5526-45eb-b693-57bc28344aca" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFeeAmount_40ffdd1d-6001-478b-a33a-88d51ded5b10" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentFeeAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DebtInstrumentFeeAmount_40ffdd1d-6001-478b-a33a-88d51ded5b10" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_f95cf2ef-e63f-49be-a9f9-c516d6337318" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredFinanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_DeferredFinanceCostsNet_f95cf2ef-e63f-49be-a9f9-c516d6337318" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_68719425-19d9-4620-bcc9-6bf0940a36fb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GainsLossesOnExtinguishmentOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_5a5fbfa9-2a18-461e-8072-87c72517e394" xlink:to="loc_us-gaap_GainsLossesOnExtinguishmentOfDebt_68719425-19d9-4620-bcc9-6bf0940a36fb" xlink:type="arc" order="25"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockLineItems_080cdbf3-0b57-4325-a074-a56149f495a0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_b87f2342-b2ab-4b70-827b-5fd242c16629" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_080cdbf3-0b57-4325-a074-a56149f495a0" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_b87f2342-b2ab-4b70-827b-5fd242c16629" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_6789f226-6793-4439-989e-1770db824db5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_b87f2342-b2ab-4b70-827b-5fd242c16629" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_6789f226-6793-4439-989e-1770db824db5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_6789f226-6793-4439-989e-1770db824db5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_6789f226-6793-4439-989e-1770db824db5" xlink:to="loc_us-gaap_EquityComponentDomain_6789f226-6793-4439-989e-1770db824db5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_635e6442-e93c-4cf7-8b54-27ab6d663115" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_6789f226-6793-4439-989e-1770db824db5" xlink:to="loc_us-gaap_EquityComponentDomain_635e6442-e93c-4cf7-8b54-27ab6d663115" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_f06f18a0-ed08-4210-8309-78e9c87e42bc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_635e6442-e93c-4cf7-8b54-27ab6d663115" xlink:to="loc_us-gaap_CommonStockMember_f06f18a0-ed08-4210-8309-78e9c87e42bc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_0ea43f79-c66c-498c-b685-961e979554a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_635e6442-e93c-4cf7-8b54-27ab6d663115" xlink:to="loc_us-gaap_WarrantMember_0ea43f79-c66c-498c-b685-961e979554a2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_StockIssuedDuringPeriodSharesWarrantsExercised_14e664c4-81a6-473e-b151-4a46b3964d83" xlink:href="bcrx-20240930.xsd#bcrx_StockIssuedDuringPeriodSharesWarrantsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_080cdbf3-0b57-4325-a074-a56149f495a0" xlink:to="loc_bcrx_StockIssuedDuringPeriodSharesWarrantsExercised_14e664c4-81a6-473e-b151-4a46b3964d83" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightOutstanding_f59786c2-931b-47b7-8fe5-433300385899" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_080cdbf3-0b57-4325-a074-a56149f495a0" xlink:to="loc_us-gaap_ClassOfWarrantOrRightOutstanding_f59786c2-931b-47b7-8fe5-433300385899" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockholdersEquitySharesReservedforFutureIssuanceDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockholdersEquitySharesReservedforFutureIssuanceDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockholdersEquitySharesReservedforFutureIssuanceDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockLineItems_ea5d26a2-b6e2-41fe-ace3-d85c58250dc7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_1a049006-3af6-463c-9ccd-455bc3713690" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_ea5d26a2-b6e2-41fe-ace3-d85c58250dc7" xlink:to="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_1a049006-3af6-463c-9ccd-455bc3713690" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_18f87794-4fd8-4f5a-b2d3-be92e49453f1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_1a049006-3af6-463c-9ccd-455bc3713690" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_18f87794-4fd8-4f5a-b2d3-be92e49453f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18f87794-4fd8-4f5a-b2d3-be92e49453f1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_18f87794-4fd8-4f5a-b2d3-be92e49453f1" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_18f87794-4fd8-4f5a-b2d3-be92e49453f1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7473d0e9-b69b-4c10-b250-d887844c6771" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_18f87794-4fd8-4f5a-b2d3-be92e49453f1" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7473d0e9-b69b-4c10-b250-d887844c6771" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_22013fe1-30ab-494d-a9a0-e5837762560f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7473d0e9-b69b-4c10-b250-d887844c6771" xlink:to="loc_us-gaap_EmployeeStockOptionMember_22013fe1-30ab-494d-a9a0-e5837762560f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_8e5a200e-a21d-46d8-b5db-5012bc0f6f81" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7473d0e9-b69b-4c10-b250-d887844c6771" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_8e5a200e-a21d-46d8-b5db-5012bc0f6f81" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_7646c445-4d64-4f5f-86bd-fccb27ecad38" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_7473d0e9-b69b-4c10-b250-d887844c6771" xlink:to="loc_us-gaap_WarrantMember_7646c445-4d64-4f5f-86bd-fccb27ecad38" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_1a049006-3af6-463c-9ccd-455bc3713690" xlink:to="loc_us-gaap_PlanNameAxis_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7" xlink:to="loc_us-gaap_PlanNameDomain_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_49433560-74a1-421b-80e8-7f25b259150a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_abb7ef33-9b03-4ee6-ac2f-307b2f0dccf7" xlink:to="loc_us-gaap_PlanNameDomain_49433560-74a1-421b-80e8-7f25b259150a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_d8de1b14-3538-4f4e-b40e-aa32769d89ca" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_49433560-74a1-421b-80e8-7f25b259150a" xlink:to="loc_bcrx_IncentivePlanMember_d8de1b14-3538-4f4e-b40e-aa32769d89ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_802f2c1d-16bb-4b70-bf07-741d33aa11f2" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_49433560-74a1-421b-80e8-7f25b259150a" xlink:to="loc_bcrx_InducementPlanMember_802f2c1d-16bb-4b70-bf07-741d33aa11f2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_EmployeeStockPurchasePlanMember_f69df241-7779-417a-878f-27f4516bd115" xlink:href="bcrx-20240930.xsd#bcrx_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_49433560-74a1-421b-80e8-7f25b259150a" xlink:to="loc_bcrx_EmployeeStockPurchasePlanMember_f69df241-7779-417a-878f-27f4516bd115" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_ac3f2a15-b2dd-4583-8c53-91e82109a121" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsidiaryOrEquityMethodInvesteeSaleOfStockBySubsidiaryOrEquityInvesteeTable_1a049006-3af6-463c-9ccd-455bc3713690" xlink:to="loc_us-gaap_AwardTypeAxis_ac3f2a15-b2dd-4583-8c53-91e82109a121" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ac3f2a15-b2dd-4583-8c53-91e82109a121_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_ac3f2a15-b2dd-4583-8c53-91e82109a121" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_ac3f2a15-b2dd-4583-8c53-91e82109a121_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e189c71f-2266-4ffd-a6b6-c6835ec4145b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_ac3f2a15-b2dd-4583-8c53-91e82109a121" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e189c71f-2266-4ffd-a6b6-c6835ec4145b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_78eaede7-012e-4f46-87de-2fb8651ea4f3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e189c71f-2266-4ffd-a6b6-c6835ec4145b" xlink:to="loc_us-gaap_EmployeeStockOptionMember_78eaede7-012e-4f46-87de-2fb8651ea4f3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_084e010c-28db-4b89-bad0-580807370d52" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e189c71f-2266-4ffd-a6b6-c6835ec4145b" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_084e010c-28db-4b89-bad0-580807370d52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_7141b30f-6d87-4278-9bd2-47d3f9ee24c0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e189c71f-2266-4ffd-a6b6-c6835ec4145b" xlink:to="loc_us-gaap_WarrantMember_7141b30f-6d87-4278-9bd2-47d3f9ee24c0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_70c95b03-dc88-4754-a97f-009b3335ceb0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsidiarySaleOfStockLineItems_ea5d26a2-b6e2-41fe-ace3-d85c58250dc7" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_70c95b03-dc88-4754-a97f-009b3335ceb0" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockbasedCompensationDetailsTextual" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockbasedCompensationDetailsTextual"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockbasedCompensationDetailsTextual" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_34de44e5-1b1c-4b51-8f78-8fd6507c4238" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_34de44e5-1b1c-4b51-8f78-8fd6507c4238" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_70a0b859-56db-41c7-a9b6-8fe90149b3e5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_34de44e5-1b1c-4b51-8f78-8fd6507c4238" xlink:to="loc_us-gaap_PlanNameAxis_70a0b859-56db-41c7-a9b6-8fe90149b3e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_70a0b859-56db-41c7-a9b6-8fe90149b3e5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_70a0b859-56db-41c7-a9b6-8fe90149b3e5" xlink:to="loc_us-gaap_PlanNameDomain_70a0b859-56db-41c7-a9b6-8fe90149b3e5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_70a0b859-56db-41c7-a9b6-8fe90149b3e5" xlink:to="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RetirementPolicyMember_b754630b-fe86-462b-8737-53adb3a44177" xlink:href="bcrx-20240930.xsd#bcrx_RetirementPolicyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:to="loc_bcrx_RetirementPolicyMember_b754630b-fe86-462b-8737-53adb3a44177" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_31363756-94eb-49e1-b74f-1b4a36a001f5" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:to="loc_bcrx_IncentivePlanMember_31363756-94eb-49e1-b74f-1b4a36a001f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_1f7dc47d-2f5c-414e-8884-cdac0b43f06e" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:to="loc_bcrx_InducementPlanMember_1f7dc47d-2f5c-414e-8884-cdac0b43f06e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_EmployeeStockPurchasePlanMember_d1fc656d-8926-4c60-9348-23db9a082506" xlink:href="bcrx-20240930.xsd#bcrx_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_2b3a88a3-915d-4d45-a853-eea78e1ce8e9" xlink:to="loc_bcrx_EmployeeStockPurchasePlanMember_d1fc656d-8926-4c60-9348-23db9a082506" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_90a8026d-7a57-4e09-b190-bb88d0420145" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_34de44e5-1b1c-4b51-8f78-8fd6507c4238" xlink:to="loc_us-gaap_AwardTypeAxis_90a8026d-7a57-4e09-b190-bb88d0420145" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_90a8026d-7a57-4e09-b190-bb88d0420145_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_90a8026d-7a57-4e09-b190-bb88d0420145" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_90a8026d-7a57-4e09-b190-bb88d0420145_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e4785045-68b6-450e-8d63-e624c48bf17a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_90a8026d-7a57-4e09-b190-bb88d0420145" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e4785045-68b6-450e-8d63-e624c48bf17a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_c2443806-6106-4c18-8a47-2ecddd1ccae9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_e4785045-68b6-450e-8d63-e624c48bf17a" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_c2443806-6106-4c18-8a47-2ecddd1ccae9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ShareBasedPaymentArrangementNumberOfPlans_d02ea3e6-8996-4dc8-a119-cfc9bf9ba31c" xlink:href="bcrx-20240930.xsd#bcrx_ShareBasedPaymentArrangementNumberOfPlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_bcrx_ShareBasedPaymentArrangementNumberOfPlans_d02ea3e6-8996-4dc8-a119-cfc9bf9ba31c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_56d38ee8-a998-474d-8d5d-571aca6e1416" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_56d38ee8-a998-474d-8d5d-571aca6e1416" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_bdf2e74e-5feb-42ec-9221-32ff31999d56" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_bdf2e74e-5feb-42ec-9221-32ff31999d56" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_33c9eda9-0a8b-4076-ac51-a5b3d3143c7f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_33c9eda9-0a8b-4076-ac51-a5b3d3143c7f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_ae9d41fe-0ce5-4d48-bccc-d710d496a8e7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_ae9d41fe-0ce5-4d48-bccc-d710d496a8e7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_e56dc39f-b435-4b72-92c3-76b0eea309d7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_e56dc39f-b435-4b72-92c3-76b0eea309d7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_b899b1e7-ac80-4816-b19d-9a70696689ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_b899b1e7-ac80-4816-b19d-9a70696689ae" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_f4e13af4-31ab-439a-82fd-76e94050f626" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_f4e13af4-31ab-439a-82fd-76e94050f626" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_c9163914-611e-4400-96f9-307839ef75d3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed4e94e9-1e20-4f3f-9124-cf6684f68e8f" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeStockPurchasePlans_c9163914-611e-4400-96f9-307839ef75d3" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockbasedCompensationShareBasedCompensationDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockbasedCompensationShareBasedCompensationDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockbasedCompensationShareBasedCompensationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_961bd37a-f599-42ac-ab6c-5c3b6808da77" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_44c8ea51-d95b-491e-b65e-8e6662c03588" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_961bd37a-f599-42ac-ab6c-5c3b6808da77" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_44c8ea51-d95b-491e-b65e-8e6662c03588" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_ed94bb25-adc9-4d21-9d70-08df9ebd0178" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_44c8ea51-d95b-491e-b65e-8e6662c03588" xlink:to="loc_us-gaap_PlanNameAxis_ed94bb25-adc9-4d21-9d70-08df9ebd0178" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_ed94bb25-adc9-4d21-9d70-08df9ebd0178_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_ed94bb25-adc9-4d21-9d70-08df9ebd0178" xlink:to="loc_us-gaap_PlanNameDomain_ed94bb25-adc9-4d21-9d70-08df9ebd0178_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_d4cc6cd1-6a8e-4db0-b80f-a72a28497c0b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_ed94bb25-adc9-4d21-9d70-08df9ebd0178" xlink:to="loc_us-gaap_PlanNameDomain_d4cc6cd1-6a8e-4db0-b80f-a72a28497c0b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_6c5f1b14-c2e0-494d-bb28-0423405d06ca" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d4cc6cd1-6a8e-4db0-b80f-a72a28497c0b" xlink:to="loc_bcrx_IncentivePlanMember_6c5f1b14-c2e0-494d-bb28-0423405d06ca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_c7bf1716-6f61-4543-a5ce-e6c7ed32e010" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d4cc6cd1-6a8e-4db0-b80f-a72a28497c0b" xlink:to="loc_bcrx_InducementPlanMember_c7bf1716-6f61-4543-a5ce-e6c7ed32e010" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_EmployeeStockPurchasePlanMember_dce4ef9d-9346-4392-a23f-7ef0f8da2f9d" xlink:href="bcrx-20240930.xsd#bcrx_EmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_d4cc6cd1-6a8e-4db0-b80f-a72a28497c0b" xlink:to="loc_bcrx_EmployeeStockPurchasePlanMember_dce4ef9d-9346-4392-a23f-7ef0f8da2f9d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_53854610-dd32-4151-b0ef-8864c9675789" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_961bd37a-f599-42ac-ab6c-5c3b6808da77" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_53854610-dd32-4151-b0ef-8864c9675789" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockbasedCompensationWeightedAverageAssumptionsforStockOptionAwardsGrantedtoEmployeesandDirectorsUnderthePlansDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockbasedCompensationWeightedAverageAssumptionsforStockOptionAwardsGrantedtoEmployeesandDirectorsUnderthePlansDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockbasedCompensationWeightedAverageAssumptionsforStockOptionAwardsGrantedtoEmployeesandDirectorsUnderthePlansDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ea392851-66f4-42ba-8f3f-65ed740d02fa" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ea392851-66f4-42ba-8f3f-65ed740d02fa" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_0f9e9018-69ae-4894-9db4-b45b27fa3665" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_ea392851-66f4-42ba-8f3f-65ed740d02fa" xlink:to="loc_us-gaap_PlanNameAxis_0f9e9018-69ae-4894-9db4-b45b27fa3665" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_0f9e9018-69ae-4894-9db4-b45b27fa3665_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_0f9e9018-69ae-4894-9db4-b45b27fa3665" xlink:to="loc_us-gaap_PlanNameDomain_0f9e9018-69ae-4894-9db4-b45b27fa3665_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_e1e46186-cca6-40d6-994a-ddaa363bf65c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_0f9e9018-69ae-4894-9db4-b45b27fa3665" xlink:to="loc_us-gaap_PlanNameDomain_e1e46186-cca6-40d6-994a-ddaa363bf65c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_de6b5ec1-2dcf-401f-b96f-1b0a22431ac7" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_e1e46186-cca6-40d6-994a-ddaa363bf65c" xlink:to="loc_bcrx_IncentivePlanMember_de6b5ec1-2dcf-401f-b96f-1b0a22431ac7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_1ff65bcc-dc8a-4041-89e0-f0f4ee06f6bf" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_e1e46186-cca6-40d6-994a-ddaa363bf65c" xlink:to="loc_bcrx_InducementPlanMember_1ff65bcc-dc8a-4041-89e0-f0f4ee06f6bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_6461226d-6fa9-4448-875b-ecb5c510fb61" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_6461226d-6fa9-4448-875b-ecb5c510fb61" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_21b229f5-b6a7-4500-897e-bf769764fb11" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_21b229f5-b6a7-4500-897e-bf769764fb11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_ee4fb0f0-0da6-4c52-9bc1-bd082de479ab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_ee4fb0f0-0da6-4c52-9bc1-bd082de479ab" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_4b8d2a1a-0be9-4619-b433-4b90e567f862" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_4b8d2a1a-0be9-4619-b433-4b90e567f862" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0d6bf120-463c-4d82-a28c-5dc5fc9004be" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6254cff4-0ecc-4a05-9104-d929a7d86794" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0d6bf120-463c-4d82-a28c-5dc5fc9004be" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockbasedCompensationOptionActivityDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockbasedCompensationOptionActivityDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockbasedCompensationOptionActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d628fe65-ad01-47a1-9820-fca3c6b8412f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d628fe65-ad01-47a1-9820-fca3c6b8412f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_47cf8e44-0fdb-4c11-9be0-ca203746906b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d628fe65-ad01-47a1-9820-fca3c6b8412f" xlink:to="loc_us-gaap_AwardTypeAxis_47cf8e44-0fdb-4c11-9be0-ca203746906b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_47cf8e44-0fdb-4c11-9be0-ca203746906b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_47cf8e44-0fdb-4c11-9be0-ca203746906b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_47cf8e44-0fdb-4c11-9be0-ca203746906b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_73a57eae-f9df-4556-b4f8-9c62f8cb7009" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_47cf8e44-0fdb-4c11-9be0-ca203746906b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_73a57eae-f9df-4556-b4f8-9c62f8cb7009" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_1cc7dc74-b2c6-4317-8d8d-5250a02c513b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_73a57eae-f9df-4556-b4f8-9c62f8cb7009" xlink:to="loc_us-gaap_EmployeeStockOptionMember_1cc7dc74-b2c6-4317-8d8d-5250a02c513b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_364a565b-96dd-4791-8edd-f0dea765d564" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d628fe65-ad01-47a1-9820-fca3c6b8412f" xlink:to="loc_us-gaap_PlanNameAxis_364a565b-96dd-4791-8edd-f0dea765d564" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_364a565b-96dd-4791-8edd-f0dea765d564_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_364a565b-96dd-4791-8edd-f0dea765d564" xlink:to="loc_us-gaap_PlanNameDomain_364a565b-96dd-4791-8edd-f0dea765d564_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_7a7aa8ca-2a2d-4998-9347-b8f0c8f872d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_364a565b-96dd-4791-8edd-f0dea765d564" xlink:to="loc_us-gaap_PlanNameDomain_7a7aa8ca-2a2d-4998-9347-b8f0c8f872d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_8aa30045-5438-4211-bd8b-b6705799f7cf" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_7a7aa8ca-2a2d-4998-9347-b8f0c8f872d8" xlink:to="loc_bcrx_IncentivePlanMember_8aa30045-5438-4211-bd8b-b6705799f7cf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_fe472a44-e441-46b8-997f-b169f9916340" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_7a7aa8ca-2a2d-4998-9347-b8f0c8f872d8" xlink:to="loc_bcrx_InducementPlanMember_fe472a44-e441-46b8-997f-b169f9916340" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_7d092dcf-82aa-4486-bd07-4ed6baf82845" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_7d092dcf-82aa-4486-bd07-4ed6baf82845" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_4fe22ac1-55c1-437d-b624-56b3e33efade" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_4fe22ac1-55c1-437d-b624-56b3e33efade" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_add03af5-083c-47e0-b1bb-2b8e755cb18d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_add03af5-083c-47e0-b1bb-2b8e755cb18d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_c92f5ddd-5e42-44a4-aaf1-44062366e6be" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_31d1e490-5652-4e7f-b166-3546a1e8d2cd" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriod_c92f5ddd-5e42-44a4-aaf1-44062366e6be" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_06a7b5f7-aede-4391-bd8d-2a1fcbd73611" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_14119fb2-7bff-4b53-a8ac-d65ddebfea72" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_14119fb2-7bff-4b53-a8ac-d65ddebfea72" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_711efff1-941e-4a38-bb8b-dd092e289e6c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_711efff1-941e-4a38-bb8b-dd092e289e6c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_25baaf5d-1163-48cc-92a2-6fe956bcb88f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_25baaf5d-1163-48cc-92a2-6fe956bcb88f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_ab477ea6-24d7-49e8-9779-c0b21df21a88" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_ab477ea6-24d7-49e8-9779-c0b21df21a88" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_0a4d047f-ba2a-44d9-9e2f-6969fe48c305" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_0a4d047f-ba2a-44d9-9e2f-6969fe48c305" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_e06cd4ea-3b54-4f44-8691-9404ea7fa382" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_ea5dd6ae-afc8-4344-a20f-88231a7605c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePrice_e06cd4ea-3b54-4f44-8691-9404ea7fa382" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_15728d53-3e74-4ddc-ae33-2e0ea4cff4eb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_efc3918f-4afc-4020-932b-d172e96033ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_efc3918f-4afc-4020-932b-d172e96033ae" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_894cf8ef-7a7c-4238-a861-d84a30de122a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_894cf8ef-7a7c-4238-a861-d84a30de122a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_9918318b-ec3c-4341-a2f2-1964c678830b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_9918318b-ec3c-4341-a2f2-1964c678830b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_fd981f25-e55b-4ee6-a079-b19ab7a7ccf0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_9918318b-ec3c-4341-a2f2-1964c678830b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_fd981f25-e55b-4ee6-a079-b19ab7a7ccf0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_49b917e3-4323-4bdd-8284-92d388960dba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_9918318b-ec3c-4341-a2f2-1964c678830b" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_49b917e3-4323-4bdd-8284-92d388960dba" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_97e39f02-e827-44b4-b183-11b4094872ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_9918318b-ec3c-4341-a2f2-1964c678830b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_97e39f02-e827-44b4-b183-11b4094872ae" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_5357506c-1b39-40e9-8259-d48af6e00479" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_5357506c-1b39-40e9-8259-d48af6e00479" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_593668a8-70f4-47a4-8bec-b8baa761ea84" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_593668a8-70f4-47a4-8bec-b8baa761ea84" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_34f609ca-fcb0-49af-ac96-cb7a1745203a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_34f609ca-fcb0-49af-ac96-cb7a1745203a" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_671c6a60-1006-4d5c-a986-1e1895a959cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_304ee02b-89b2-4004-a4ed-2b052aed6099" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_671c6a60-1006-4d5c-a986-1e1895a959cb" xlink:type="arc" order="10"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#StockbasedCompensationRestrictedStockUnitActivityDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_a25f85ca-6dc3-47f6-8973-3b178e8791a8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_9bbc9412-dd62-4820-9e69-0afcce8b2276" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_a25f85ca-6dc3-47f6-8973-3b178e8791a8" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_9bbc9412-dd62-4820-9e69-0afcce8b2276" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_35ae69f7-1ded-4a4b-a539-c30e10b79a43" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_9bbc9412-dd62-4820-9e69-0afcce8b2276" xlink:to="loc_us-gaap_AwardTypeAxis_35ae69f7-1ded-4a4b-a539-c30e10b79a43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_35ae69f7-1ded-4a4b-a539-c30e10b79a43_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_35ae69f7-1ded-4a4b-a539-c30e10b79a43" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_35ae69f7-1ded-4a4b-a539-c30e10b79a43_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_814a4869-fe00-409b-859c-a33277b25c74" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_35ae69f7-1ded-4a4b-a539-c30e10b79a43" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_814a4869-fe00-409b-859c-a33277b25c74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_26b45fc9-8425-4714-a882-d0b5dccc00a2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_814a4869-fe00-409b-859c-a33277b25c74" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_26b45fc9-8425-4714-a882-d0b5dccc00a2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_2caf4d72-ec61-4194-a8d7-49519dbb7033" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_9bbc9412-dd62-4820-9e69-0afcce8b2276" xlink:to="loc_us-gaap_PlanNameAxis_2caf4d72-ec61-4194-a8d7-49519dbb7033" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_2caf4d72-ec61-4194-a8d7-49519dbb7033_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_2caf4d72-ec61-4194-a8d7-49519dbb7033" xlink:to="loc_us-gaap_PlanNameDomain_2caf4d72-ec61-4194-a8d7-49519dbb7033_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_e504b48d-cb30-4f1e-9027-dd34b5f70c4b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_2caf4d72-ec61-4194-a8d7-49519dbb7033" xlink:to="loc_us-gaap_PlanNameDomain_e504b48d-cb30-4f1e-9027-dd34b5f70c4b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_IncentivePlanMember_88b235b6-fa05-4d11-8b72-88b0cd1b9457" xlink:href="bcrx-20240930.xsd#bcrx_IncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_e504b48d-cb30-4f1e-9027-dd34b5f70c4b" xlink:to="loc_bcrx_IncentivePlanMember_88b235b6-fa05-4d11-8b72-88b0cd1b9457" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_InducementPlanMember_b8389210-0b5e-469f-ad46-e5e2ee302085" xlink:href="bcrx-20240930.xsd#bcrx_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_e504b48d-cb30-4f1e-9027-dd34b5f70c4b" xlink:to="loc_bcrx_InducementPlanMember_b8389210-0b5e-469f-ad46-e5e2ee302085" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_a25f85ca-6dc3-47f6-8973-3b178e8791a8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d5fc6d6d-e37f-4f50-a96f-01cbf35377d8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_d5fc6d6d-e37f-4f50-a96f-01cbf35377d8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_98474f30-957c-44c4-b3d4-109786003a68" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_98474f30-957c-44c4-b3d4-109786003a68" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_94cfa581-8c6b-4f43-bcc4-82c973f47463" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_94cfa581-8c6b-4f43-bcc4-82c973f47463" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_4b8c369d-34ac-4e0d-8a9b-a563150d09b0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_44e81bdd-3b6b-433c-933a-63fb1edd7aa6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_4b8c369d-34ac-4e0d-8a9b-a563150d09b0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2e39a701-e62f-49e4-b1f1-8ef5c3ce4144" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_a25f85ca-6dc3-47f6-8973-3b178e8791a8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_39455bd5-e216-4f3a-a337-2e0966c88f2c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_39455bd5-e216-4f3a-a337-2e0966c88f2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_5c7cb70e-47a4-4e2d-af63-f48ac299be50" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_5c7cb70e-47a4-4e2d-af63-f48ac299be50" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_745c722f-ad99-4f7c-be82-6b07c3097c52" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_745c722f-ad99-4f7c-be82-6b07c3097c52" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_95e98dd7-6b1c-46a2-bef5-e3bd8c111fa7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_f3a7243c-7413-47a7-be5b-31aba561ea89" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_95e98dd7-6b1c-46a2-bef5-e3bd8c111fa7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_7194bcfe-c411-4abc-a4aa-c20e38600c7c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/CollaborativeandOtherRelationshipsDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#CollaborativeandOtherRelationshipsDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/CollaborativeandOtherRelationshipsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_846cb1ad-284e-4f86-99ef-7c654589da62" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:to="loc_srt_CounterpartyNameAxis_846cb1ad-284e-4f86-99ef-7c654589da62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_846cb1ad-284e-4f86-99ef-7c654589da62_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_846cb1ad-284e-4f86-99ef-7c654589da62" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_846cb1ad-284e-4f86-99ef-7c654589da62_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_56d4cdb9-2671-436a-9c53-62e92d39f241" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_846cb1ad-284e-4f86-99ef-7c654589da62" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_56d4cdb9-2671-436a-9c53-62e92d39f241" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ToriiPharmaceuticalCoMember_2c967612-63df-4aac-910b-a0f5f7bfb26b" xlink:href="bcrx-20240930.xsd#bcrx_ToriiPharmaceuticalCoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_56d4cdb9-2671-436a-9c53-62e92d39f241" xlink:to="loc_bcrx_ToriiPharmaceuticalCoMember_2c967612-63df-4aac-910b-a0f5f7bfb26b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ClearsideBiomedicalIncMember_7b2535cd-a30e-427f-8455-2fe30e82670d" xlink:href="bcrx-20240930.xsd#bcrx_ClearsideBiomedicalIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_56d4cdb9-2671-436a-9c53-62e92d39f241" xlink:to="loc_bcrx_ClearsideBiomedicalIncMember_7b2535cd-a30e-427f-8455-2fe30e82670d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_HHSOfficeOfTheAdministrationForStrategicPreparednessAndResponseMember_23376f53-4b09-4e74-8220-19324b14a268" xlink:href="bcrx-20240930.xsd#bcrx_HHSOfficeOfTheAdministrationForStrategicPreparednessAndResponseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_56d4cdb9-2671-436a-9c53-62e92d39f241" xlink:to="loc_bcrx_HHSOfficeOfTheAdministrationForStrategicPreparednessAndResponseMember_23376f53-4b09-4e74-8220-19324b14a268" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_e36f8157-da99-4df6-a015-70a0145c8687" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:to="loc_srt_RangeAxis_e36f8157-da99-4df6-a015-70a0145c8687" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e36f8157-da99-4df6-a015-70a0145c8687_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_e36f8157-da99-4df6-a015-70a0145c8687" xlink:to="loc_srt_RangeMember_e36f8157-da99-4df6-a015-70a0145c8687_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2fcc9683-b3a6-430c-bc06-8a6c0c478a46" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_e36f8157-da99-4df6-a015-70a0145c8687" xlink:to="loc_srt_RangeMember_2fcc9683-b3a6-430c-bc06-8a6c0c478a46" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_b10d52f5-3807-4c8e-9110-eb513ca4389a" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2fcc9683-b3a6-430c-bc06-8a6c0c478a46" xlink:to="loc_srt_MinimumMember_b10d52f5-3807-4c8e-9110-eb513ca4389a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_b4f7f087-aa49-4d96-b7ed-8c9f145e745c" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_2fcc9683-b3a6-430c-bc06-8a6c0c478a46" xlink:to="loc_srt_MaximumMember_b4f7f087-aa49-4d96-b7ed-8c9f145e745c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeAxis_abadf3aa-f518-423a-9522-ccc84017b325" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:to="loc_bcrx_AnnualNetSalesRangeAxis_abadf3aa-f518-423a-9522-ccc84017b325" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeDomain_abadf3aa-f518-423a-9522-ccc84017b325_default" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_bcrx_AnnualNetSalesRangeAxis_abadf3aa-f518-423a-9522-ccc84017b325" xlink:to="loc_bcrx_AnnualNetSalesRangeDomain_abadf3aa-f518-423a-9522-ccc84017b325_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesRangeDomain_f33d97ce-4a97-4c8d-bb85-5146c7b0f7c9" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesRangeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_bcrx_AnnualNetSalesRangeAxis_abadf3aa-f518-423a-9522-ccc84017b325" xlink:to="loc_bcrx_AnnualNetSalesRangeDomain_f33d97ce-4a97-4c8d-bb85-5146c7b0f7c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesOf2MillionMember_bdf903e6-31a8-4870-ae2f-af009bd3b0c2" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesOf2MillionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_f33d97ce-4a97-4c8d-bb85-5146c7b0f7c9" xlink:to="loc_bcrx_AnnualNetSalesOf2MillionMember_bdf903e6-31a8-4870-ae2f-af009bd3b0c2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_AnnualNetSalesGreaterThan15MillionMember_9b9f9418-575d-492c-b1a7-01623cd94e43" xlink:href="bcrx-20240930.xsd#bcrx_AnnualNetSalesGreaterThan15MillionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_bcrx_AnnualNetSalesRangeDomain_f33d97ce-4a97-4c8d-bb85-5146c7b0f7c9" xlink:to="loc_bcrx_AnnualNetSalesGreaterThan15MillionMember_9b9f9418-575d-492c-b1a7-01623cd94e43" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_aad2fe62-10e4-45d5-a455-70f1e6777c35" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:to="loc_srt_ProductOrServiceAxis_aad2fe62-10e4-45d5-a455-70f1e6777c35" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_aad2fe62-10e4-45d5-a455-70f1e6777c35_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_aad2fe62-10e4-45d5-a455-70f1e6777c35" xlink:to="loc_srt_ProductsAndServicesDomain_aad2fe62-10e4-45d5-a455-70f1e6777c35_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_3455e0b7-80f8-4d20-9894-0cdb156c7dde" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_aad2fe62-10e4-45d5-a455-70f1e6777c35" xlink:to="loc_srt_ProductsAndServicesDomain_3455e0b7-80f8-4d20-9894-0cdb156c7dde" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RAPIVABMember_12595244-b08b-4a9f-b1c1-1dfdfd9dda30" xlink:href="bcrx-20240930.xsd#bcrx_RAPIVABMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_3455e0b7-80f8-4d20-9894-0cdb156c7dde" xlink:to="loc_bcrx_RAPIVABMember_12595244-b08b-4a9f-b1c1-1dfdfd9dda30" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_e6b50dff-5698-4c18-a408-235a903a60a1" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfResearchAndDevelopmentArrangementContractToPerformForOthersTable_a220f2e5-6f98-4c1f-b98a-876bd469e624" xlink:to="loc_srt_StatementScenarioAxis_e6b50dff-5698-4c18-a408-235a903a60a1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_e6b50dff-5698-4c18-a408-235a903a60a1_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_e6b50dff-5698-4c18-a408-235a903a60a1" xlink:to="loc_srt_ScenarioUnspecifiedDomain_e6b50dff-5698-4c18-a408-235a903a60a1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_5353ec3d-acd5-421f-b73f-5e8722fef3cb" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_e6b50dff-5698-4c18-a408-235a903a60a1" xlink:to="loc_srt_ScenarioUnspecifiedDomain_5353ec3d-acd5-421f-b73f-5e8722fef3cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_bcc18de7-a993-44c8-874e-00dbd0520bef" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_5353ec3d-acd5-421f-b73f-5e8722fef3cb" xlink:to="loc_srt_ScenarioForecastMember_bcc18de7-a993-44c8-874e-00dbd0520bef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_20697330-6bb9-4c78-9acb-b37341a67ad6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_20697330-6bb9-4c78-9acb-b37341a67ad6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PotentialMilestonePaymentsReceivableIfRegulatoryApprovalBeforeMilestone_062a93ac-d6c7-4279-b219-950acc731e60" xlink:href="bcrx-20240930.xsd#bcrx_PotentialMilestonePaymentsReceivableIfRegulatoryApprovalBeforeMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_PotentialMilestonePaymentsReceivableIfRegulatoryApprovalBeforeMilestone_062a93ac-d6c7-4279-b219-950acc731e60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyRateIfMaintainsSakigakeDesignation_5fc122a9-c158-4069-b816-41ae5cfbab27" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyRateIfMaintainsSakigakeDesignation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_RoyaltyRateIfMaintainsSakigakeDesignation_5fc122a9-c158-4069-b816-41ae5cfbab27" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MaximumCustomaryReductionOnRoyaltyRate_b04c8dcf-6d6d-4cd8-8151-93e5c3ee5cd7" xlink:href="bcrx-20240930.xsd#bcrx_MaximumCustomaryReductionOnRoyaltyRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_MaximumCustomaryReductionOnRoyaltyRate_b04c8dcf-6d6d-4cd8-8151-93e5c3ee5cd7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_RoyaltyRate_ed862908-4e91-40fd-a4db-fbca56c9069d" xlink:href="bcrx-20240930.xsd#bcrx_RoyaltyRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_RoyaltyRate_ed862908-4e91-40fd-a4db-fbca56c9069d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_CollaborativeAgreementContractValue_6765973b-9e2f-42ed-9afc-006a9effce77" xlink:href="bcrx-20240930.xsd#bcrx_CollaborativeAgreementContractValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_CollaborativeAgreementContractValue_6765973b-9e2f-42ed-9afc-006a9effce77" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_MaximumNumberOfProductsPermittedToBeObtainedDoses_a6695c8b-13bb-4dbc-8c32-efc3506d50d7" xlink:href="bcrx-20240930.xsd#bcrx_MaximumNumberOfProductsPermittedToBeObtainedDoses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_MaximumNumberOfProductsPermittedToBeObtainedDoses_a6695c8b-13bb-4dbc-8c32-efc3506d50d7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ContractTerm_228be77c-13a4-4b63-890c-93aa5c38861d" xlink:href="bcrx-20240930.xsd#bcrx_ContractTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_ContractTerm_228be77c-13a4-4b63-890c-93aa5c38861d" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_NumberOfOptionalOrderingPeriods_4fccb348-1f0f-4124-83c6-0587f4dfe257" xlink:href="bcrx-20240930.xsd#bcrx_NumberOfOptionalOrderingPeriods"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_NumberOfOptionalOrderingPeriods_4fccb348-1f0f-4124-83c6-0587f4dfe257" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromCollaborators_dd70cd72-e0f9-468a-ad05-0adb5fca29c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromCollaborators"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_us-gaap_ProceedsFromCollaborators_dd70cd72-e0f9-468a-ad05-0adb5fca29c5" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_NumberOfProductDeliveredDoses_fa7ebe4d-0882-40a6-a15f-e40aed71d00d" xlink:href="bcrx-20240930.xsd#bcrx_NumberOfProductDeliveredDoses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_NumberOfProductDeliveredDoses_fa7ebe4d-0882-40a6-a15f-e40aed71d00d" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LicenseAgreementUpfrontPayment_33ba0c92-96e1-4244-9a24-6825f7e5ffac" xlink:href="bcrx-20240930.xsd#bcrx_LicenseAgreementUpfrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_LicenseAgreementUpfrontPayment_33ba0c92-96e1-4244-9a24-6825f7e5ffac" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PotentialMilestonePaymentsPayable_030f606c-4176-4cea-9d69-fbda96f20c34" xlink:href="bcrx-20240930.xsd#bcrx_PotentialMilestonePaymentsPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_PotentialMilestonePaymentsPayable_030f606c-4176-4cea-9d69-fbda96f20c34" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PotentialMilestonePaymentsPayableIfRegulatoryApprovalBeforeMilestone_8d3414a2-d150-48bc-96cc-9957a6455d2d" xlink:href="bcrx-20240930.xsd#bcrx_PotentialMilestonePaymentsPayableIfRegulatoryApprovalBeforeMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_PotentialMilestonePaymentsPayableIfRegulatoryApprovalBeforeMilestone_8d3414a2-d150-48bc-96cc-9957a6455d2d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LicenseAgreementNumberOfMilestonePayments_cd22973c-ab5a-401b-81dd-b68f281ad09a" xlink:href="bcrx-20240930.xsd#bcrx_LicenseAgreementNumberOfMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_LicenseAgreementNumberOfMilestonePayments_cd22973c-ab5a-401b-81dd-b68f281ad09a" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LicenseAgreementAnnualGlobalNetSales_42b6d980-f556-476e-9d0a-3e370f1950ad" xlink:href="bcrx-20240930.xsd#bcrx_LicenseAgreementAnnualGlobalNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_LicenseAgreementAnnualGlobalNetSales_42b6d980-f556-476e-9d0a-3e370f1950ad" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_LicenseAgreementRoyaltyPaymentNumberOfTiers_4c251f8a-b318-438d-80b3-b0f762e41590" xlink:href="bcrx-20240930.xsd#bcrx_LicenseAgreementRoyaltyPaymentNumberOfTiers"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersLineItems_b44c7fc9-31c9-4de3-be43-a1c45239f4eb" xlink:to="loc_bcrx_LicenseAgreementRoyaltyPaymentNumberOfTiers_4c251f8a-b318-438d-80b3-b0f762e41590" xlink:type="arc" order="16"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.biocryst.com/role/WorkforceReductionDetails" xlink:type="simple" xlink:href="bcrx-20240930.xsd#WorkforceReductionDetails"/>
  <link:definitionLink xlink:role="http://www.biocryst.com/role/WorkforceReductionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveLineItems_6b525e9a-cca4-4272-8285-14f5f8b5c856" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringCostAndReserveLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_4f8bb930-40d3-47ba-a672-14d056e9c03a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfRestructuringAndRelatedCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_6b525e9a-cca4-4272-8285-14f5f8b5c856" xlink:to="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_4f8bb930-40d3-47ba-a672-14d056e9c03a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveAxis_dcd55e0f-fae2-4d56-94bc-5800705617db" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringCostAndReserveAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_4f8bb930-40d3-47ba-a672-14d056e9c03a" xlink:to="loc_us-gaap_RestructuringCostAndReserveAxis_dcd55e0f-fae2-4d56-94bc-5800705617db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_dcd55e0f-fae2-4d56-94bc-5800705617db_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_dcd55e0f-fae2-4d56-94bc-5800705617db" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_dcd55e0f-fae2-4d56-94bc-5800705617db_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_95945732-46b3-4a8e-bc25-6513e0074831" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_dcd55e0f-fae2-4d56-94bc-5800705617db" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_95945732-46b3-4a8e-bc25-6513e0074831" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeSeveranceMember_a8d70272-6573-4692-8b8b-218fe2cabb57" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeSeveranceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_95945732-46b3-4a8e-bc25-6513e0074831" xlink:to="loc_us-gaap_EmployeeSeveranceMember_a8d70272-6573-4692-8b8b-218fe2cabb57" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OneTimeTerminationBenefitsMember_2b6c1d2e-dcf1-4aee-8f36-c0eff37a11ee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OneTimeTerminationBenefitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_95945732-46b3-4a8e-bc25-6513e0074831" xlink:to="loc_us-gaap_OneTimeTerminationBenefitsMember_2b6c1d2e-dcf1-4aee-8f36-c0eff37a11ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_df2c970e-f269-42fa-a720-ddd33d7f5df5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestructuringAndRelatedCostsTable_4f8bb930-40d3-47ba-a672-14d056e9c03a" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_df2c970e-f269-42fa-a720-ddd33d7f5df5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_df2c970e-f269-42fa-a720-ddd33d7f5df5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_df2c970e-f269-42fa-a720-ddd33d7f5df5" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_df2c970e-f269-42fa-a720-ddd33d7f5df5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_56a5e9f6-0a61-4f73-b5d1-ec22af7f95c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_df2c970e-f269-42fa-a720-ddd33d7f5df5" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_56a5e9f6-0a61-4f73-b5d1-ec22af7f95c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_ResearchAndDevelopementMember_34810763-12b4-4cdd-a5d7-f8f73ec959da" xlink:href="bcrx-20240930.xsd#bcrx_ResearchAndDevelopementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_56a5e9f6-0a61-4f73-b5d1-ec22af7f95c5" xlink:to="loc_bcrx_ResearchAndDevelopementMember_34810763-12b4-4cdd-a5d7-f8f73ec959da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_0f1a1f2a-5c49-412d-bb60-ad0e09825a86" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SellingGeneralAndAdministrativeExpensesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_56a5e9f6-0a61-4f73-b5d1-ec22af7f95c5" xlink:to="loc_us-gaap_SellingGeneralAndAdministrativeExpensesMember_0f1a1f2a-5c49-412d-bb60-ad0e09825a86" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCosts_db0ee34a-9a12-4045-8a30-0d52ddb4beb1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_6b525e9a-cca4-4272-8285-14f5f8b5c856" xlink:to="loc_us-gaap_RestructuringCosts_db0ee34a-9a12-4045-8a30-0d52ddb4beb1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_bcrx_PaymentsForRestructuringNet_869e7b82-b374-408e-bbd6-47d7df6532f1" xlink:href="bcrx-20240930.xsd#bcrx_PaymentsForRestructuringNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_6b525e9a-cca4-4272-8285-14f5f8b5c856" xlink:to="loc_bcrx_PaymentsForRestructuringNet_869e7b82-b374-408e-bbd6-47d7df6532f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserve_fa8519d6-9e74-44bb-8ec5-42d0e43753e5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestructuringReserve"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestructuringCostAndReserveLineItems_6b525e9a-cca4-4272-8285-14f5f8b5c856" xlink:to="loc_us-gaap_RestructuringReserve_fa8519d6-9e74-44bb-8ec5-42d0e43753e5" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/AwardTypeOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#AwardTypeOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/AwardTypeOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-roles-2024.xsd#eedm"/>
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract" xlink:to="loc_us-gaap_OtherAssetsNoncurrent" xlink:type="arc" order="2"/>
  </link:definitionLink>
</link:linkbase>
