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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2024 Workiva-->
<!--r:4faadb36-cbbc-4ac9-93d2-9cef5dc656fe,g:3c1c114b-7f49-4d90-b499-62d56c8bc0f4-->
<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.arrowheadresearch.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="arwr-20240930.xsd#ConsolidatedStatementsofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/ConsolidatedStatementsofStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_1f5bfb46-803d-49a7-b337-3e42eaa6b48a" 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_4e08f666-f996-4c95-8e09-dac7734d5a0d" 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_1f5bfb46-803d-49a7-b337-3e42eaa6b48a" xlink:to="loc_us-gaap_StatementTable_4e08f666-f996-4c95-8e09-dac7734d5a0d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_c0e8e552-8372-4aea-8373-932482d32127" 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_4e08f666-f996-4c95-8e09-dac7734d5a0d" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_c0e8e552-8372-4aea-8373-932482d32127" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_c0e8e552-8372-4aea-8373-932482d32127_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_c0e8e552-8372-4aea-8373-932482d32127" xlink:to="loc_us-gaap_EquityComponentDomain_c0e8e552-8372-4aea-8373-932482d32127_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_55c67701-46f7-4b43-8943-239999593da1" 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_c0e8e552-8372-4aea-8373-932482d32127" xlink:to="loc_us-gaap_EquityComponentDomain_55c67701-46f7-4b43-8943-239999593da1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_c4dc11bb-2f94-4672-80ce-55fddff59e14" 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_55c67701-46f7-4b43-8943-239999593da1" xlink:to="loc_us-gaap_CommonStockMember_c4dc11bb-2f94-4672-80ce-55fddff59e14" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_5a61e94c-ddee-47bf-ace9-fc92d49b700d" 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_55c67701-46f7-4b43-8943-239999593da1" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_5a61e94c-ddee-47bf-ace9-fc92d49b700d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_07c5c6e7-aae9-4adf-b23d-387b8af6bf2b" 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_55c67701-46f7-4b43-8943-239999593da1" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_07c5c6e7-aae9-4adf-b23d-387b8af6bf2b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_363d3e4d-37ce-4809-a516-75d5b0ff23ea" 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_55c67701-46f7-4b43-8943-239999593da1" xlink:to="loc_us-gaap_RetainedEarningsMember_363d3e4d-37ce-4809-a516-75d5b0ff23ea" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncontrollingInterestMember_56b06c2d-6509-4e77-b426-9fad2958f62d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NoncontrollingInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_55c67701-46f7-4b43-8943-239999593da1" xlink:to="loc_us-gaap_NoncontrollingInterestMember_56b06c2d-6509-4e77-b426-9fad2958f62d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" 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_1f5bfb46-803d-49a7-b337-3e42eaa6b48a" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_19478453-016f-4858-b628-ae6e86f15293" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_SharesOutstanding_19478453-016f-4858-b628-ae6e86f15293" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_c18f9d43-7237-4a4c-9a77-493a2f3de57d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_c18f9d43-7237-4a4c-9a77-493a2f3de57d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_dc2a7675-814f-4098-9f34-628013d76df4" 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_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_dc2a7675-814f-4098-9f34-628013d76df4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9eee6650-a5c5-46be-bad7-6385999b0466" 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_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_9eee6650-a5c5-46be-bad7-6385999b0466" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_c570ae3e-cf68-4320-92eb-283492085fe9" 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_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueStockOptionsExercised_c570ae3e-cf68-4320-92eb-283492085fe9" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_9e4915c9-0094-4983-973c-5c47dd56cca7" 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_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesRestrictedStockAwardGross_9e4915c9-0094-4983-973c-5c47dd56cca7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_d1463247-ed83-4a5a-a387-e5d5a514c28e" 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_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueRestrictedStockAwardGross_d1463247-ed83-4a5a-a387-e5d5a514c28e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_645daaf9-b1a0-4be2-8ad6-fea057c3ef96" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_645daaf9-b1a0-4be2-8ad6-fea057c3ef96" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_73f8a5a0-1d09-43a6-b043-c447d96eb8c9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_73f8a5a0-1d09-43a6-b043-c447d96eb8c9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_ee310919-37b0-4aa9-bbe9-b4257a66e93a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_ee310919-37b0-4aa9-bbe9-b4257a66e93a" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_2d13af19-d81e-475b-9f52-eb8bcfc443ac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossForeignCurrencyTransactionAndTranslationAdjustmentNetOfTax_2d13af19-d81e-475b-9f52-eb8bcfc443ac" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncontrollingInterestIncreaseFromSubsidiaryEquityIssuance_b1490cb1-9396-4608-aab7-902e03e89c3d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NoncontrollingInterestIncreaseFromSubsidiaryEquityIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_NoncontrollingInterestIncreaseFromSubsidiaryEquityIssuance_b1490cb1-9396-4608-aab7-902e03e89c3d" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProfitLoss_4b671531-6a22-466e-8c4e-b1c8f9b45a97" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProfitLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_1b8ca5c0-599b-4e7d-b709-84a1faa98e17" xlink:to="loc_us-gaap_ProfitLoss_4b671531-6a22-466e-8c4e-b1c8f9b45a97" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesOutstanding_2360de0a-14ce-41de-bb0e-25354cf1e631" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_94f2d4dc-e75d-4972-8413-fc56f418b938" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#OrganizationandSignificantAccountingPoliciesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:href="arwr-20240930.xsd#arwr_OrganizationAndSignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:href="arwr-20240930.xsd#arwr_OrganizationAndSignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_1e98d315-5548-4171-a1cc-aea721786970" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:to="loc_us-gaap_CreditFacilityAxis_1e98d315-5548-4171-a1cc-aea721786970" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_1e98d315-5548-4171-a1cc-aea721786970_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_1e98d315-5548-4171-a1cc-aea721786970" xlink:to="loc_us-gaap_CreditFacilityDomain_1e98d315-5548-4171-a1cc-aea721786970_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_078a3745-6d18-4810-9ea7-a1298c5a4e34" 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_1e98d315-5548-4171-a1cc-aea721786970" xlink:to="loc_us-gaap_CreditFacilityDomain_078a3745-6d18-4810-9ea7-a1298c5a4e34" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredDebtMember_82b28f41-66ce-49b9-bab8-25d5c5e8d01d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_078a3745-6d18-4810-9ea7-a1298c5a4e34" xlink:to="loc_us-gaap_SecuredDebtMember_82b28f41-66ce-49b9-bab8-25d5c5e8d01d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_14e7208e-24c9-4ebc-b206-798a228d6462" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:to="loc_us-gaap_DebtInstrumentAxis_14e7208e-24c9-4ebc-b206-798a228d6462" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_14e7208e-24c9-4ebc-b206-798a228d6462_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_14e7208e-24c9-4ebc-b206-798a228d6462" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_14e7208e-24c9-4ebc-b206-798a228d6462_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_eacd7999-6bf5-4511-a678-4925af26af52" 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_14e7208e-24c9-4ebc-b206-798a228d6462" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_eacd7999-6bf5-4511-a678-4925af26af52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementMember_b328ef7b-2187-4f4a-bec9-68b4faa297c9" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_eacd7999-6bf5-4511-a678-4925af26af52" xlink:to="loc_arwr_FinancingAgreementMember_b328ef7b-2187-4f4a-bec9-68b4faa297c9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_189a1892-b5e2-4bcd-af5b-e69cccfd14ca" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_189a1892-b5e2-4bcd-af5b-e69cccfd14ca" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_189a1892-b5e2-4bcd-af5b-e69cccfd14ca_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_189a1892-b5e2-4bcd-af5b-e69cccfd14ca" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_189a1892-b5e2-4bcd-af5b-e69cccfd14ca_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_d6052e7a-895d-4685-bacf-d1e2c922a73a" 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_189a1892-b5e2-4bcd-af5b-e69cccfd14ca" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_d6052e7a-895d-4685-bacf-d1e2c922a73a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_126d26d4-d1df-4b62-aed5-e0ef645d5f93" 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_d6052e7a-895d-4685-bacf-d1e2c922a73a" xlink:to="loc_us-gaap_LineOfCreditMember_126d26d4-d1df-4b62-aed5-e0ef645d5f93" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_a8fbbf61-e305-46ea-8f01-ff7722418dc6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_a8fbbf61-e305-46ea-8f01-ff7722418dc6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_a8fbbf61-e305-46ea-8f01-ff7722418dc6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_a8fbbf61-e305-46ea-8f01-ff7722418dc6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_a8fbbf61-e305-46ea-8f01-ff7722418dc6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_44193b0b-b636-4166-9355-d95f9ec084e2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_a8fbbf61-e305-46ea-8f01-ff7722418dc6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_44193b0b-b636-4166-9355-d95f9ec084e2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UnderwritingAgreementMember_8c6b87d7-c4e5-46ad-a487-b8489ae49f4c" xlink:href="arwr-20240930.xsd#arwr_UnderwritingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_44193b0b-b636-4166-9355-d95f9ec084e2" xlink:to="loc_arwr_UnderwritingAgreementMember_8c6b87d7-c4e5-46ad-a487-b8489ae49f4c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_2ad1422e-240d-481a-b1e3-a587b20ee988" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_05ebae0a-ace8-4021-be80-d3b44c9ddb58" xlink:to="loc_srt_RangeAxis_2ad1422e-240d-481a-b1e3-a587b20ee988" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2ad1422e-240d-481a-b1e3-a587b20ee988_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_2ad1422e-240d-481a-b1e3-a587b20ee988" xlink:to="loc_srt_RangeMember_2ad1422e-240d-481a-b1e3-a587b20ee988_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_d7f506e1-b9d2-42d9-abe2-61b12b6781dc" 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_2ad1422e-240d-481a-b1e3-a587b20ee988" xlink:to="loc_srt_RangeMember_d7f506e1-b9d2-42d9-abe2-61b12b6781dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_d6f5fe32-02a5-4810-9465-30a564e92146" 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_d7f506e1-b9d2-42d9-abe2-61b12b6781dc" xlink:to="loc_srt_MaximumMember_d6f5fe32-02a5-4810-9465-30a564e92146" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_2ada0d12-d875-4e8f-88ac-23506829cabd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalents_2ada0d12-d875-4e8f-88ac-23506829cabd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_8b595dba-0719-445e-a5aa-6a27c2d94ebf" 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_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsAtCarryingValue_8b595dba-0719-445e-a5aa-6a27c2d94ebf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_2bf80388-6321-4543-9906-7a08e00b3de0" 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_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_2bf80388-6321-4543-9906-7a08e00b3de0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_IncreaseDecreaseInCashAndInvestments_b1da6193-f98b-468e-8958-ade891bf3a0f" xlink:href="arwr-20240930.xsd#arwr_IncreaseDecreaseInCashAndInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_arwr_IncreaseDecreaseInCashAndInvestments_b1da6193-f98b-468e-8958-ade891bf3a0f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_04d743af-9159-43fe-9ce6-8478e3845288" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_04d743af-9159-43fe-9ce6-8478e3845288" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_386973bc-5347-48aa-9004-93f90eaca505" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_LineOfCredit_386973bc-5347-48aa-9004-93f90eaca505" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_bc9b0ec4-b7ea-4745-a2a2-1a2955cb0de9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_bc9b0ec4-b7ea-4745-a2a2-1a2955cb0de9" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTerm_1eb17c29-f8c5-4021-a802-0e40895e24b6" 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_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_DebtInstrumentTerm_1eb17c29-f8c5-4021-a802-0e40895e24b6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_b4c9b0ce-08a8-44aa-94bb-0f68a62ed7fb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_b4c9b0ce-08a8-44aa-94bb-0f68a62ed7fb" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_f769f254-a0b3-4998-a88f-37610d28c458" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_f769f254-a0b3-4998-a88f-37610d28c458" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_e49efe2e-8baa-4de5-b00e-cb95724f058c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_e49efe2e-8baa-4de5-b00e-cb95724f058c" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SaleOfStockAggregatePurchasePrice_c20dbbf6-c740-4133-912d-0b2a86730763" xlink:href="arwr-20240930.xsd#arwr_SaleOfStockAggregatePurchasePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_arwr_SaleOfStockAggregatePurchasePrice_c20dbbf6-c740-4133-912d-0b2a86730763" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_8d689bf1-4987-4bb9-a7e4-4b6734895fc6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_8d689bf1-4987-4bb9-a7e4-4b6734895fc6" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_89ee1aad-d898-469e-8632-2335336b4b75" xlink:href="arwr-20240930.xsd#arwr_DevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_89ee1aad-d898-469e-8632-2335336b4b75" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashFDICInsuredAmount_35bb84e1-ac2e-4acc-b234-7342e19b259b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashFDICInsuredAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_CashFDICInsuredAmount_35bb84e1-ac2e-4acc-b234-7342e19b259b" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ImpairmentOfIntangibleAssetsFinitelived_1ce3f0ee-ccf9-4f21-bbef-f64cb2825dc7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ImpairmentOfIntangibleAssetsFinitelived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_72693121-ae0f-4ec7-8c88-aac245e7f5fd" xlink:to="loc_us-gaap_ImpairmentOfIntangibleAssetsFinitelived_1ce3f0ee-ccf9-4f21-bbef-f64cb2825dc7" xlink:type="arc" order="15"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesUsefulLivesofPropertyPlantandEquipmentDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#OrganizationandSignificantAccountingPoliciesUsefulLivesofPropertyPlantandEquipmentDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/OrganizationandSignificantAccountingPoliciesUsefulLivesofPropertyPlantandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_e65d07e4-4f35-4955-8fea-5d775b264b61" xlink:href="arwr-20240930.xsd#arwr_OrganizationAndSignificantAccountingPoliciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_bc9a41f7-a8f4-4f6e-a21b-1f25b38baedb" xlink:href="arwr-20240930.xsd#arwr_OrganizationAndSignificantAccountingPoliciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_e65d07e4-4f35-4955-8fea-5d775b264b61" xlink:to="loc_arwr_OrganizationAndSignificantAccountingPoliciesTable_bc9a41f7-a8f4-4f6e-a21b-1f25b38baedb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_8dabfb4a-d82f-4bd1-9fba-0cb320528272" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_bc9a41f7-a8f4-4f6e-a21b-1f25b38baedb" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_8dabfb4a-d82f-4bd1-9fba-0cb320528272" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8dabfb4a-d82f-4bd1-9fba-0cb320528272_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_8dabfb4a-d82f-4bd1-9fba-0cb320528272" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8dabfb4a-d82f-4bd1-9fba-0cb320528272_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" 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_8dabfb4a-d82f-4bd1-9fba-0cb320528272" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BuildingMember_52debb97-595b-450f-a689-308044aee7f1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BuildingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:to="loc_us-gaap_BuildingMember_52debb97-595b-450f-a689-308044aee7f1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_4c9657fe-bfc5-4236-92ab-d246c28d1bdc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:to="loc_us-gaap_EquipmentMember_4c9657fe-bfc5-4236-92ab-d246c28d1bdc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_e9d86c3f-2e08-4d97-af64-7fa093876239" 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_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_e9d86c3f-2e08-4d97-af64-7fa093876239" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ComputersAndSoftwareMember_56f60e42-61dc-461c-8a71-f9dad3cac64f" xlink:href="arwr-20240930.xsd#arwr_ComputersAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:to="loc_arwr_ComputersAndSoftwareMember_56f60e42-61dc-461c-8a71-f9dad3cac64f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_1d8436da-c3d2-4b34-9e1a-de88041c3479" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_1cf9337f-7aaa-4671-b536-f3bf16a6407e" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_1d8436da-c3d2-4b34-9e1a-de88041c3479" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_3aa870f4-62e5-4908-bb0b-addf16e0c132" 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_arwr_OrganizationAndSignificantAccountingPoliciesTable_bc9a41f7-a8f4-4f6e-a21b-1f25b38baedb" xlink:to="loc_srt_RangeAxis_3aa870f4-62e5-4908-bb0b-addf16e0c132" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_3aa870f4-62e5-4908-bb0b-addf16e0c132_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_3aa870f4-62e5-4908-bb0b-addf16e0c132" xlink:to="loc_srt_RangeMember_3aa870f4-62e5-4908-bb0b-addf16e0c132_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_3d7a188f-7646-4f6e-a4e4-8356045400f5" 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_3aa870f4-62e5-4908-bb0b-addf16e0c132" xlink:to="loc_srt_RangeMember_3d7a188f-7646-4f6e-a4e4-8356045400f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_b7843c12-1492-46a1-9a3b-729dc02c9e6e" 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_3d7a188f-7646-4f6e-a4e4-8356045400f5" xlink:to="loc_srt_MinimumMember_b7843c12-1492-46a1-9a3b-729dc02c9e6e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_96ca8628-9e8c-49c1-b438-49e408c9c0c4" 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_3d7a188f-7646-4f6e-a4e4-8356045400f5" xlink:to="loc_srt_MaximumMember_96ca8628-9e8c-49c1-b438-49e408c9c0c4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_6817fbfd-5718-46a4-887c-ecffaf13ae77" 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_arwr_OrganizationAndSignificantAccountingPoliciesLineItems_e65d07e4-4f35-4955-8fea-5d775b264b61" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_6817fbfd-5718-46a4-887c-ecffaf13ae77" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsRevenueDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CollaborationandLicenseAgreementsRevenueDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsRevenueDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_39b70596-20aa-4461-9f08-0cd8ff120058" 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_829977bd-2126-45b9-9f26-b38454c17205" 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_39b70596-20aa-4461-9f08-0cd8ff120058" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_829977bd-2126-45b9-9f26-b38454c17205" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_fecacd37-3184-48e4-8f5f-96a3e6d90e2b" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_829977bd-2126-45b9-9f26-b38454c17205" xlink:to="loc_srt_MajorCustomersAxis_fecacd37-3184-48e4-8f5f-96a3e6d90e2b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_fecacd37-3184-48e4-8f5f-96a3e6d90e2b_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_fecacd37-3184-48e4-8f5f-96a3e6d90e2b" xlink:to="loc_srt_NameOfMajorCustomerDomain_fecacd37-3184-48e4-8f5f-96a3e6d90e2b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_fecacd37-3184-48e4-8f5f-96a3e6d90e2b" xlink:to="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_0f87ffc0-d14d-46d4-b030-c478f0519640" xlink:href="arwr-20240930.xsd#arwr_GlaxosmithklineIntellectualPropertyLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:to="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_0f87ffc0-d14d-46d4-b030-c478f0519640" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonTherapeuticsIrelandDACMember_c52fc86f-8c4e-410b-8688-174fd5908541" xlink:href="arwr-20240930.xsd#arwr_HorizonTherapeuticsIrelandDACMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:to="loc_arwr_HorizonTherapeuticsIrelandDACMember_c52fc86f-8c4e-410b-8688-174fd5908541" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_e00d2d10-b8f2-47f7-a229-85e362d61300" xlink:href="arwr-20240930.xsd#arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:to="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_e00d2d10-b8f2-47f7-a229-85e362d61300" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_JanssenPharmaceuticalsIncorporationMember_c3ceffc9-09cc-4734-86d3-5097c815a595" xlink:href="arwr-20240930.xsd#arwr_JanssenPharmaceuticalsIncorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:to="loc_arwr_JanssenPharmaceuticalsIncorporationMember_c3ceffc9-09cc-4734-86d3-5097c815a595" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmgenIncorporatedMember_8f52d47e-1504-4648-8a7b-d1ec528fafcd" xlink:href="arwr-20240930.xsd#arwr_AmgenIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_12db6b84-172d-43a8-8387-8583ac31a288" xlink:to="loc_arwr_AmgenIncorporatedMember_8f52d47e-1504-4648-8a7b-d1ec528fafcd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_ed2140f9-ae1a-4381-8d58-e5633535c1c5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_39b70596-20aa-4461-9f08-0cd8ff120058" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_ed2140f9-ae1a-4381-8d58-e5633535c1c5" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsGlaxosmithklineIntellectualPropertyNo3LimitedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ca34c9fb-59e1-47e8-b894-f7ab8c5d02d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ca34c9fb-59e1-47e8-b894-f7ab8c5d02d6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_0157b4c7-f828-4278-b8df-e3016f88f066" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ca34c9fb-59e1-47e8-b894-f7ab8c5d02d6" xlink:to="loc_srt_CounterpartyNameAxis_0157b4c7-f828-4278-b8df-e3016f88f066" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0157b4c7-f828-4278-b8df-e3016f88f066_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_0157b4c7-f828-4278-b8df-e3016f88f066" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0157b4c7-f828-4278-b8df-e3016f88f066_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_70ab83d0-e780-4fb4-b290-24006bec889a" 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_0157b4c7-f828-4278-b8df-e3016f88f066" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_70ab83d0-e780-4fb4-b290-24006bec889a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_6b778367-5ed1-4b51-a6f1-b41edd28424c" xlink:href="arwr-20240930.xsd#arwr_GlaxosmithklineIntellectualPropertyLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_70ab83d0-e780-4fb4-b290-24006bec889a" xlink:to="loc_arwr_GlaxosmithklineIntellectualPropertyLimitedMember_6b778367-5ed1-4b51-a6f1-b41edd28424c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ca34c9fb-59e1-47e8-b894-f7ab8c5d02d6" xlink:to="loc_us-gaap_TypeOfArrangementAxis_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4aec910d-ff1d-4e92-ab2a-7bca5a9f7442" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_6ac1b41c-a307-4f3b-a3ab-ed2c647f177b" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4aec910d-ff1d-4e92-ab2a-7bca5a9f7442" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GSKHSDLicenseAgreementMember_2220ab73-5d75-453d-b30c-f678fc582c41" xlink:href="arwr-20240930.xsd#arwr_GSKHSDLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4aec910d-ff1d-4e92-ab2a-7bca5a9f7442" xlink:to="loc_arwr_GSKHSDLicenseAgreementMember_2220ab73-5d75-453d-b30c-f678fc582c41" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_GSKHBVAgreementMember_d14518a1-6427-4edb-9eab-e7a8237f958f" xlink:href="arwr-20240930.xsd#arwr_GSKHBVAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4aec910d-ff1d-4e92-ab2a-7bca5a9f7442" xlink:to="loc_arwr_GSKHBVAgreementMember_d14518a1-6427-4edb-9eab-e7a8237f958f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_fd95f530-0ab0-4058-837e-27945d0e1209" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ca34c9fb-59e1-47e8-b894-f7ab8c5d02d6" xlink:to="loc_srt_RangeAxis_fd95f530-0ab0-4058-837e-27945d0e1209" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_fd95f530-0ab0-4058-837e-27945d0e1209_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_fd95f530-0ab0-4058-837e-27945d0e1209" xlink:to="loc_srt_RangeMember_fd95f530-0ab0-4058-837e-27945d0e1209_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_6319dc06-1cf4-4ed5-8c23-675814fa9d99" 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_fd95f530-0ab0-4058-837e-27945d0e1209" xlink:to="loc_srt_RangeMember_6319dc06-1cf4-4ed5-8c23-675814fa9d99" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_36f1e49b-5845-43e4-9802-3f1b10f7a376" 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_6319dc06-1cf4-4ed5-8c23-675814fa9d99" xlink:to="loc_srt_MaximumMember_36f1e49b-5845-43e4-9802-3f1b10f7a376" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_4b994108-110a-4239-9232-39df6e0a6343" xlink:href="arwr-20240930.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_InitialTransactionPrice_4b994108-110a-4239-9232-39df6e0a6343" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivable_6075a712-fa00-4e4f-8631-b3422dd08a61" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_MilestonePaymentReceivable_6075a712-fa00-4e4f-8631-b3422dd08a61" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree_145d6a7f-7adf-4a4b-86c0-b2a86eb13ad7" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_MilestonePaymentReceivableUponAchievementOfPhaseTwoAndFirstPatientDosedInPhaseThree_145d6a7f-7adf-4a4b-86c0-b2a86eb13ad7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommercialMilestonePaymentsAtFirstCommercialSale_d6a1b5d2-04d5-4b92-88b6-88eb12cfe077" xlink:href="arwr-20240930.xsd#arwr_CommercialMilestonePaymentsAtFirstCommercialSale"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_CommercialMilestonePaymentsAtFirstCommercialSale_d6a1b5d2-04d5-4b92-88b6-88eb12cfe077" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SalesRelatedMilestonePayments_e23549fa-df77-4b22-b28c-96776e188a9f" xlink:href="arwr-20240930.xsd#arwr_SalesRelatedMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_SalesRelatedMilestonePayments_e23549fa-df77-4b22-b28c-96776e188a9f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentAndSalesMilestonesPayments_40512f0f-533f-4104-a30d-545bf858d318" xlink:href="arwr-20240930.xsd#arwr_DevelopmentAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_arwr_DevelopmentAndSalesMilestonesPayments_40512f0f-533f-4104-a30d-545bf858d318" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNetCurrent_d4ef06a4-3270-4d0f-8672-3d5071eceaae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerAssetNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_us-gaap_ContractWithCustomerAssetNetCurrent_d4ef06a4-3270-4d0f-8672-3d5071eceaae" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1ebe51a3-070f-478e-b9dc-61ea771f4a7c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_5ea4235a-12f4-454e-9152-9d840d36ca57" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1ebe51a3-070f-478e-b9dc-61ea771f4a7c" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsHorizonTherapeuticsIrelandDACDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9539450c-2837-4670-ae6a-479a0c763e70" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ff266701-6bef-4262-a440-a44f17c3560c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9539450c-2837-4670-ae6a-479a0c763e70" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ff266701-6bef-4262-a440-a44f17c3560c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_fb458d2d-9f11-45c3-848d-5d6988236152" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ff266701-6bef-4262-a440-a44f17c3560c" xlink:to="loc_srt_CounterpartyNameAxis_fb458d2d-9f11-45c3-848d-5d6988236152" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_fb458d2d-9f11-45c3-848d-5d6988236152_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_fb458d2d-9f11-45c3-848d-5d6988236152" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_fb458d2d-9f11-45c3-848d-5d6988236152_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_706f06a7-82ab-4bc9-9053-af0d9961379e" 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_fb458d2d-9f11-45c3-848d-5d6988236152" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_706f06a7-82ab-4bc9-9053-af0d9961379e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonTherapeuticsIrelandDACMember_9b359ea2-dff0-41df-9e5a-b900502a8e66" xlink:href="arwr-20240930.xsd#arwr_HorizonTherapeuticsIrelandDACMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_706f06a7-82ab-4bc9-9053-af0d9961379e" xlink:to="loc_arwr_HorizonTherapeuticsIrelandDACMember_9b359ea2-dff0-41df-9e5a-b900502a8e66" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_51fe9895-d420-423d-bed0-0d5842ab2c28" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ff266701-6bef-4262-a440-a44f17c3560c" xlink:to="loc_us-gaap_TypeOfArrangementAxis_51fe9895-d420-423d-bed0-0d5842ab2c28" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_51fe9895-d420-423d-bed0-0d5842ab2c28_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_51fe9895-d420-423d-bed0-0d5842ab2c28" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_51fe9895-d420-423d-bed0-0d5842ab2c28_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_78869155-df37-4729-af0f-878634a651a3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_51fe9895-d420-423d-bed0-0d5842ab2c28" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_78869155-df37-4729-af0f-878634a651a3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_HorizonLicenseAgreementMember_b53134af-cd52-46a3-8e60-9de7a53678d5" xlink:href="arwr-20240930.xsd#arwr_HorizonLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_78869155-df37-4729-af0f-878634a651a3" xlink:to="loc_arwr_HorizonLicenseAgreementMember_b53134af-cd52-46a3-8e60-9de7a53678d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctPerformanceObligations_9e3954d3-6527-4265-b2f1-6c46ff2fca0a" xlink:href="arwr-20240930.xsd#arwr_NumberOfDistinctPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9539450c-2837-4670-ae6a-479a0c763e70" xlink:to="loc_arwr_NumberOfDistinctPerformanceObligations_9e3954d3-6527-4265-b2f1-6c46ff2fca0a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_7cef30eb-9bb3-4c2a-a494-bf49979fb03f" xlink:href="arwr-20240930.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9539450c-2837-4670-ae6a-479a0c763e70" xlink:to="loc_arwr_InitialTransactionPrice_7cef30eb-9bb3-4c2a-a494-bf49979fb03f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentEarned_9c1172f3-18f5-4bd8-bbf7-f894a0e7c612" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentEarned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_9539450c-2837-4670-ae6a-479a0c763e70" xlink:to="loc_arwr_MilestonePaymentEarned_9c1172f3-18f5-4bd8-bbf7-f894a0e7c612" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsTakedaPharmaceuticalCompanyLimitedDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_94987c95-a1b3-4c90-bc05-71fb6bce5814" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_94987c95-a1b3-4c90-bc05-71fb6bce5814" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_e68a683e-7591-4bbf-b0a0-03ca20bbd15d" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_94987c95-a1b3-4c90-bc05-71fb6bce5814" xlink:to="loc_srt_CounterpartyNameAxis_e68a683e-7591-4bbf-b0a0-03ca20bbd15d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e68a683e-7591-4bbf-b0a0-03ca20bbd15d_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_e68a683e-7591-4bbf-b0a0-03ca20bbd15d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_e68a683e-7591-4bbf-b0a0-03ca20bbd15d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_84590eaf-5371-4917-a2d3-54d88bf868e3" 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_e68a683e-7591-4bbf-b0a0-03ca20bbd15d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_84590eaf-5371-4917-a2d3-54d88bf868e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_a68a8f31-b7a0-4013-a97b-cfc176a02760" xlink:href="arwr-20240930.xsd#arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_84590eaf-5371-4917-a2d3-54d88bf868e3" xlink:to="loc_arwr_TakedaPharmaceuticalsUnitedStatesOfAmericaIncorporatedMember_a68a8f31-b7a0-4013-a97b-cfc176a02760" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_18030dec-47d9-4674-9c19-e403c12eb166" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_94987c95-a1b3-4c90-bc05-71fb6bce5814" xlink:to="loc_us-gaap_TypeOfArrangementAxis_18030dec-47d9-4674-9c19-e403c12eb166" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_18030dec-47d9-4674-9c19-e403c12eb166_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_18030dec-47d9-4674-9c19-e403c12eb166" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_18030dec-47d9-4674-9c19-e403c12eb166_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_fe4aecdf-73ed-4a12-bfc1-567914adb513" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_18030dec-47d9-4674-9c19-e403c12eb166" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_fe4aecdf-73ed-4a12-bfc1-567914adb513" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LicenseAndCoFundingAgreementMember_ab839150-dad1-42fb-89f7-2b8ac390daf9" xlink:href="arwr-20240930.xsd#arwr_LicenseAndCoFundingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_fe4aecdf-73ed-4a12-bfc1-567914adb513" xlink:to="loc_arwr_LicenseAndCoFundingAgreementMember_ab839150-dad1-42fb-89f7-2b8ac390daf9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_9651e8d6-39bc-411b-9ec6-f82b8fc36d55" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_94987c95-a1b3-4c90-bc05-71fb6bce5814" xlink:to="loc_srt_RangeAxis_9651e8d6-39bc-411b-9ec6-f82b8fc36d55" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9651e8d6-39bc-411b-9ec6-f82b8fc36d55_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_9651e8d6-39bc-411b-9ec6-f82b8fc36d55" xlink:to="loc_srt_RangeMember_9651e8d6-39bc-411b-9ec6-f82b8fc36d55_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_4f82ac33-097c-47be-8b04-3a745685972d" 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_9651e8d6-39bc-411b-9ec6-f82b8fc36d55" xlink:to="loc_srt_RangeMember_4f82ac33-097c-47be-8b04-3a745685972d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_b616789b-4738-487a-9e55-1445a4b8c267" 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_4f82ac33-097c-47be-8b04-3a745685972d" xlink:to="loc_srt_MinimumMember_b616789b-4738-487a-9e55-1445a4b8c267" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_1be77717-a089-421d-a6fe-ef06b80a3493" 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_4f82ac33-097c-47be-8b04-3a745685972d" xlink:to="loc_srt_MaximumMember_1be77717-a089-421d-a6fe-ef06b80a3493" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales_b73709fe-6daf-49dc-a159-43e47c681d55" xlink:href="arwr-20240930.xsd#arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_PercentageOfEligibleToReceiveTieredRoyaltiesOnNetSales_b73709fe-6daf-49dc-a159-43e47c681d55" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctPerformanceObligations_244af3de-721d-417f-ae1e-2258cdf7dd56" xlink:href="arwr-20240930.xsd#arwr_NumberOfDistinctPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_NumberOfDistinctPerformanceObligations_244af3de-721d-417f-ae1e-2258cdf7dd56" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfDistinctBundle_6d51cf3b-8d24-484b-b875-4befd2cd9b32" xlink:href="arwr-20240930.xsd#arwr_NumberOfDistinctBundle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_NumberOfDistinctBundle_6d51cf3b-8d24-484b-b875-4befd2cd9b32" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_42f5a6d5-4566-43b1-bb11-dfaa4f16671d" xlink:href="arwr-20240930.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_InitialTransactionPrice_42f5a6d5-4566-43b1-bb11-dfaa4f16671d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentEarned_71c08034-4e7f-4d0f-a9a7-046e626e6f1f" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentEarned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_MilestonePaymentEarned_71c08034-4e7f-4d0f-a9a7-046e626e6f1f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_00a229e7-b6d5-44d1-b22e-ccd15d98b6c7" xlink:href="arwr-20240930.xsd#arwr_DevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_arwr_DevelopmentRegulatoryAndSalesMilestonesPayments_00a229e7-b6d5-44d1-b22e-ccd15d98b6c7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_3b8d15db-4828-490e-bc02-505eefd2e9a5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_6334a09d-0180-4b36-b3bd-755a793827ea" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_3b8d15db-4828-490e-bc02-505eefd2e9a5" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsAmgenIncDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CollaborationandLicenseAgreementsAmgenIncDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CollaborationandLicenseAgreementsAmgenIncDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1de59289-b21d-40de-b3ad-796aea977d30" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1de59289-b21d-40de-b3ad-796aea977d30" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_798c7e28-c2b8-41e1-b974-5437fc426fee" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1de59289-b21d-40de-b3ad-796aea977d30" xlink:to="loc_srt_CounterpartyNameAxis_798c7e28-c2b8-41e1-b974-5437fc426fee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_798c7e28-c2b8-41e1-b974-5437fc426fee_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_798c7e28-c2b8-41e1-b974-5437fc426fee" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_798c7e28-c2b8-41e1-b974-5437fc426fee_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68a8aea7-ac35-4d9c-b32d-e2c774a39ff3" 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_798c7e28-c2b8-41e1-b974-5437fc426fee" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68a8aea7-ac35-4d9c-b32d-e2c774a39ff3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmgenIncorporatedMember_2f215031-c99f-475d-8eb4-85eac0fc0e48" xlink:href="arwr-20240930.xsd#arwr_AmgenIncorporatedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68a8aea7-ac35-4d9c-b32d-e2c774a39ff3" xlink:to="loc_arwr_AmgenIncorporatedMember_2f215031-c99f-475d-8eb4-85eac0fc0e48" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_1b078795-75c3-4b66-86b2-9858efde539d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1de59289-b21d-40de-b3ad-796aea977d30" xlink:to="loc_us-gaap_TypeOfArrangementAxis_1b078795-75c3-4b66-86b2-9858efde539d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_1b078795-75c3-4b66-86b2-9858efde539d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_1b078795-75c3-4b66-86b2-9858efde539d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_1b078795-75c3-4b66-86b2-9858efde539d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_666bb467-e92d-447f-b827-d5e3a8e85618" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_1b078795-75c3-4b66-86b2-9858efde539d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_666bb467-e92d-447f-b827-d5e3a8e85618" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OlpasiranAgreementMember_a7541a1a-81fc-4980-9e5c-27196b82e269" xlink:href="arwr-20240930.xsd#arwr_OlpasiranAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_666bb467-e92d-447f-b827-d5e3a8e85618" xlink:to="loc_arwr_OlpasiranAgreementMember_a7541a1a-81fc-4980-9e5c-27196b82e269" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPharmaAgreementMember_c5985414-3d9e-497d-aea4-d9d6e048c876" xlink:href="arwr-20240930.xsd#arwr_RoyaltyPharmaAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_666bb467-e92d-447f-b827-d5e3a8e85618" xlink:to="loc_arwr_RoyaltyPharmaAgreementMember_c5985414-3d9e-497d-aea4-d9d6e048c876" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_5dee0c89-d9a4-431a-8779-1d33c30b2f63" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_1de59289-b21d-40de-b3ad-796aea977d30" xlink:to="loc_srt_RangeAxis_5dee0c89-d9a4-431a-8779-1d33c30b2f63" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_5dee0c89-d9a4-431a-8779-1d33c30b2f63_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_5dee0c89-d9a4-431a-8779-1d33c30b2f63" xlink:to="loc_srt_RangeMember_5dee0c89-d9a4-431a-8779-1d33c30b2f63_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_865d5d58-ff78-4cac-9055-a5c6bed01ba4" 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_5dee0c89-d9a4-431a-8779-1d33c30b2f63" xlink:to="loc_srt_RangeMember_865d5d58-ff78-4cac-9055-a5c6bed01ba4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_81ffdddb-144d-4b89-b11f-666691f59744" 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_865d5d58-ff78-4cac-9055-a5c6bed01ba4" xlink:to="loc_srt_MaximumMember_81ffdddb-144d-4b89-b11f-666691f59744" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfAgreements_f6fbd4bb-b30a-45d0-b960-016b60da5ca3" xlink:href="arwr-20240930.xsd#arwr_NumberOfAgreements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_NumberOfAgreements_f6fbd4bb-b30a-45d0-b960-016b60da5ca3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_fe3a4eca-374d-43bd-9ccb-7a619a7c9c49" xlink:href="arwr-20240930.xsd#arwr_CashReceivedAsDueUnderCollaborationAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_CashReceivedAsDueUnderCollaborationAgreement_fe3a4eca-374d-43bd-9ccb-7a619a7c9c49" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_f68b87f5-d1d5-489d-ab48-fd27ec5742e1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_f68b87f5-d1d5-489d-ab48-fd27ec5742e1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceived_dd6e8b8a-7bd1-4783-a9e7-b1713574b1d9" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceived"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_MilestonePaymentReceived_dd6e8b8a-7bd1-4783-a9e7-b1713574b1d9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerAssetNetCurrent_d1caaa60-97f2-4a5c-b268-33ee087fec42" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerAssetNetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_us-gaap_ContractWithCustomerAssetNetCurrent_d1caaa60-97f2-4a5c-b268-33ee087fec42" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_ed5f094a-ee5c-4332-a058-34baae1173df" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_ed5f094a-ee5c-4332-a058-34baae1173df" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_71a3ec41-db85-49bc-abc5-ce83e4f1d6fc" xlink:href="arwr-20240930.xsd#arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_71a3ec41-db85-49bc-abc5-ce83e4f1d6fc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_9d27c776-3151-4030-b3bc-4f970e63e91a" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_9d27c776-3151-4030-b3bc-4f970e63e91a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments_163e6fda-01c8-48e2-85fd-17186467bb8a" xlink:href="arwr-20240930.xsd#arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_f0bc89f0-c2cb-43a9-9679-61e183549084" xlink:to="loc_arwr_AdditionalRemainingDevelopmentRegulatoryAndSalesMilestonesPayments_163e6fda-01c8-48e2-85fd-17186467bb8a" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/BalanceSheetAccountsSummaryofPropertyandEquipmentDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#BalanceSheetAccountsSummaryofPropertyandEquipmentDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/BalanceSheetAccountsSummaryofPropertyandEquipmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a37fbc9b-7fad-468a-aeb7-ff25aaf76253" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a37fbc9b-7fad-468a-aeb7-ff25aaf76253" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_284f3fe1-3e9c-4bff-ad66-46911c381697" 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_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_a37fbc9b-7fad-468a-aeb7-ff25aaf76253" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_284f3fe1-3e9c-4bff-ad66-46911c381697" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_284f3fe1-3e9c-4bff-ad66-46911c381697_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_284f3fe1-3e9c-4bff-ad66-46911c381697" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_284f3fe1-3e9c-4bff-ad66-46911c381697_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" 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_284f3fe1-3e9c-4bff-ad66-46911c381697" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandMember_208a4ac1-ea98-4f33-b936-dbad0cb6d2b4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LandMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_LandMember_208a4ac1-ea98-4f33-b936-dbad0cb6d2b4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BuildingMember_e1a8db0e-0c1a-494f-acc3-bce127c4f634" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_BuildingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_BuildingMember_e1a8db0e-0c1a-494f-acc3-bce127c4f634" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_0a3da5ed-0edc-439e-80ed-9ee1377dbfdb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_EquipmentMember_0a3da5ed-0edc-439e-80ed-9ee1377dbfdb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_e5acf72a-5a22-4208-9950-44864d6b6bce" 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_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_e5acf72a-5a22-4208-9950-44864d6b6bce" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ComputersAndSoftwareMember_b81d8739-ea38-4d53-8387-d1fcb794f5a6" xlink:href="arwr-20240930.xsd#arwr_ComputersAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_arwr_ComputersAndSoftwareMember_b81d8739-ea38-4d53-8387-d1fcb794f5a6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_a9ee0aed-aab2-4871-b825-67c97ca66ffb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_a9ee0aed-aab2-4871-b825-67c97ca66ffb" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressMember_b262551f-7147-4a0c-bef6-f8bbe3560226" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ConstructionInProgressMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a4f2bab-3343-4717-bffd-cd8de48bf4b8" xlink:to="loc_us-gaap_ConstructionInProgressMember_b262551f-7147-4a0c-bef6-f8bbe3560226" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_d4e41bba-cf75-4576-8051-da3edc1ff340" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_d4e41bba-cf75-4576-8051-da3edc1ff340" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_783ae63c-7613-4253-a28d-8474093cd2d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_783ae63c-7613-4253-a28d-8474093cd2d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_b5822034-9b3c-496a-a48a-39db7fc6a740" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_b5822034-9b3c-496a-a48a-39db7fc6a740" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_467d9832-d0a3-4566-aec4-cf34e2f0b90e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_467d9832-d0a3-4566-aec4-cf34e2f0b90e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTransfersAndChanges_9fe56bb3-5a0e-450d-b2b0-28e3c948ee73" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentTransfersAndChanges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTransfersAndChanges_9fe56bb3-5a0e-450d-b2b0-28e3c948ee73" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_8c41c163-ad19-4589-beec-27cb4214e684" 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_us-gaap_PropertyPlantAndEquipmentLineItems_ce198675-1b57-4549-9dc6-711538a0ed78" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_8c41c163-ad19-4589-beec-27cb4214e684" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/InvestmentsSummaryofShorttermLongtermInvestmentsandMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:href="arwr-20240930.xsd#arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_d24ac4d7-fcb7-4cfd-971f-997c8d85ed8b" xlink:href="arwr-20240930.xsd#arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_d24ac4d7-fcb7-4cfd-971f-997c8d85ed8b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_82bd9316-a3fe-4f2c-b422-9e748865d406" 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_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesTable_d24ac4d7-fcb7-4cfd-971f-997c8d85ed8b" xlink:to="loc_us-gaap_FinancialInstrumentAxis_82bd9316-a3fe-4f2c-b422-9e748865d406" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_82bd9316-a3fe-4f2c-b422-9e748865d406_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_82bd9316-a3fe-4f2c-b422-9e748865d406" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_82bd9316-a3fe-4f2c-b422-9e748865d406_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a7737ef1-f0fe-49b6-95e2-5cb9688ecf92" 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_82bd9316-a3fe-4f2c-b422-9e748865d406" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a7737ef1-f0fe-49b6-95e2-5cb9688ecf92" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesMember_382a383b-984c-4160-b2fb-a3a5f002c97b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_a7737ef1-f0fe-49b6-95e2-5cb9688ecf92" xlink:to="loc_us-gaap_DebtSecuritiesMember_382a383b-984c-4160-b2fb-a3a5f002c97b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_827d7433-7891-4ac3-b0e0-9d5ff8d4f8f0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostCurrent_827d7433-7891-4ac3-b0e0-9d5ff8d4f8f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent_bbce6fd5-6cf9-41d8-a8f6-3a35890e202f" xlink:href="arwr-20240930.xsd#arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedGainCurrent_bbce6fd5-6cf9-41d8-a8f6-3a35890e202f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent_62909865-3142-4d8a-9d86-6c205592a643" xlink:href="arwr-20240930.xsd#arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_arwr_DebtSecuritiesAvailableForSaleAccumulatedGrossUnrealizedLossCurrent_62909865-3142-4d8a-9d86-6c205592a643" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_d86697b3-a53b-4ef5-af8f-92e5e0595294" 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_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_d86697b3-a53b-4ef5-af8f-92e5e0595294" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_fcf738bf-06f8-41e0-a9f5-df5b38ab0620" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_fcf738bf-06f8-41e0-a9f5-df5b38ab0620" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeReclassificationAdjustmentForHeldToMaturityTransferredToAvailableForSaleSecuritiesBeforeTax_caa4dc53-26fa-4ceb-bb60-812961876158" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeReclassificationAdjustmentForHeldToMaturityTransferredToAvailableForSaleSecuritiesBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_ScheduleOfHeldToMaturitySecuritiesAndMarketableSecuritiesLineItems_a52feb8b-2266-41d0-9142-814601b6e421" xlink:to="loc_us-gaap_OtherComprehensiveIncomeReclassificationAdjustmentForHeldToMaturityTransferredToAvailableForSaleSecuritiesBeforeTax_caa4dc53-26fa-4ceb-bb60-812961876158" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#IntangibleAssetsScheduleofIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/IntangibleAssetsScheduleofIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_ddcd6da4-51b2-4d5b-bd4c-875c29907a72" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_ddcd6da4-51b2-4d5b-bd4c-875c29907a72" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_96e183a0-7a24-47d6-acef-19afcd8734a6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_ddcd6da4-51b2-4d5b-bd4c-875c29907a72" xlink:to="loc_us-gaap_AssetAcquisitionAxis_96e183a0-7a24-47d6-acef-19afcd8734a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_96e183a0-7a24-47d6-acef-19afcd8734a6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_96e183a0-7a24-47d6-acef-19afcd8734a6" xlink:to="loc_us-gaap_AssetAcquisitionDomain_96e183a0-7a24-47d6-acef-19afcd8734a6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_f7fc9900-097e-4368-afb2-be711d77ae1c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_96e183a0-7a24-47d6-acef-19afcd8734a6" xlink:to="loc_us-gaap_AssetAcquisitionDomain_f7fc9900-097e-4368-afb2-be711d77ae1c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NovartisMember_dc3218c2-ccfa-499d-a132-8a20f996f5ab" xlink:href="arwr-20240930.xsd#arwr_NovartisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_f7fc9900-097e-4368-afb2-be711d77ae1c" xlink:to="loc_arwr_NovartisMember_dc3218c2-ccfa-499d-a132-8a20f996f5ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_ddcd6da4-51b2-4d5b-bd4c-875c29907a72" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bf2adee6-fab8-4e68-8fc7-de21f0fd0183" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_acf6bde7-f4c8-4e01-bf91-62cefc7e2b21" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bf2adee6-fab8-4e68-8fc7-de21f0fd0183" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PatentsMember_8824cacd-92d5-4658-9617-928eb67401d4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PatentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bf2adee6-fab8-4e68-8fc7-de21f0fd0183" xlink:to="loc_us-gaap_PatentsMember_8824cacd-92d5-4658-9617-928eb67401d4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LicensingAgreementsMember_e4fb481d-6cd2-4dea-91aa-47061fb3aded" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LicensingAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_bf2adee6-fab8-4e68-8fc7-de21f0fd0183" xlink:to="loc_us-gaap_LicensingAgreementsMember_e4fb481d-6cd2-4dea-91aa-47061fb3aded" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_4deaa125-1ce3-4dc9-9446-dfd1f3753e25" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_4deaa125-1ce3-4dc9-9446-dfd1f3753e25" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_2b3f0a4b-8db3-4c18-91d7-1def83c3ecef" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_2b3f0a4b-8db3-4c18-91d7-1def83c3ecef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FiniteLivedIntangibleAssetsImpairment_465c59e9-8722-49b8-87f1-ba0ebc33b303" xlink:href="arwr-20240930.xsd#arwr_FiniteLivedIntangibleAssetsImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_arwr_FiniteLivedIntangibleAssetsImpairment_465c59e9-8722-49b8-87f1-ba0ebc33b303" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_792d65c2-c82b-4846-a5df-9a9cb06e453e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_792d65c2-c82b-4846-a5df-9a9cb06e453e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_f45da499-c525-4a38-a42a-abc02af5a0d7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_d55e3072-e2ab-4c0e-aa4c-cf3d3acdae82" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetUsefulLife_f45da499-c525-4a38-a42a-abc02af5a0d7" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_92fdc9cd-12d0-4817-8d5d-4082be3d514f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_92fdc9cd-12d0-4817-8d5d-4082be3d514f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_f81b1d18-aa8a-4c75-af27-df57b56b30c5" 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_ScheduleOfStockByClassTable_92fdc9cd-12d0-4817-8d5d-4082be3d514f" xlink:to="loc_us-gaap_PlanNameAxis_f81b1d18-aa8a-4c75-af27-df57b56b30c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_f81b1d18-aa8a-4c75-af27-df57b56b30c5_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_f81b1d18-aa8a-4c75-af27-df57b56b30c5" xlink:to="loc_us-gaap_PlanNameDomain_f81b1d18-aa8a-4c75-af27-df57b56b30c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_566965f3-d3ad-4b58-afdf-545201161d3d" 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_f81b1d18-aa8a-4c75-af27-df57b56b30c5" xlink:to="loc_us-gaap_PlanNameDomain_566965f3-d3ad-4b58-afdf-545201161d3d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember_484fb5e1-2443-4bd0-822a-9cd04e8e44fc" xlink:href="arwr-20240930.xsd#arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_566965f3-d3ad-4b58-afdf-545201161d3d" xlink:to="loc_arwr_TwoThousandFourEquityIncentivePlanTwoThousandThirteenEquityIncentivePlanTwoThousandTwentyOneEquityIncentivePlanAndInducementGrantsMember_484fb5e1-2443-4bd0-822a-9cd04e8e44fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_3106035d-3b67-41fa-8673-2a5ac3f8a5c6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_92fdc9cd-12d0-4817-8d5d-4082be3d514f" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_3106035d-3b67-41fa-8673-2a5ac3f8a5c6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_3106035d-3b67-41fa-8673-2a5ac3f8a5c6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_3106035d-3b67-41fa-8673-2a5ac3f8a5c6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_3106035d-3b67-41fa-8673-2a5ac3f8a5c6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ecf8bbaf-7052-49f7-b43f-bd04bd38d447" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_3106035d-3b67-41fa-8673-2a5ac3f8a5c6" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ecf8bbaf-7052-49f7-b43f-bd04bd38d447" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AtTheMarketAgreementMember_024b5bbe-9261-4493-b80b-562b92c7b701" xlink:href="arwr-20240930.xsd#arwr_AtTheMarketAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ecf8bbaf-7052-49f7-b43f-bd04bd38d447" xlink:to="loc_arwr_AtTheMarketAgreementMember_024b5bbe-9261-4493-b80b-562b92c7b701" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UnderwritingAgreementMember_5294690e-2dea-4a57-b1f2-7883ca9a5bcb" xlink:href="arwr-20240930.xsd#arwr_UnderwritingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_ecf8bbaf-7052-49f7-b43f-bd04bd38d447" xlink:to="loc_arwr_UnderwritingAgreementMember_5294690e-2dea-4a57-b1f2-7883ca9a5bcb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_6faac78f-7604-4d18-a18c-81a3fc0d5a7d" 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_ScheduleOfStockByClassTable_92fdc9cd-12d0-4817-8d5d-4082be3d514f" xlink:to="loc_srt_RangeAxis_6faac78f-7604-4d18-a18c-81a3fc0d5a7d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_6faac78f-7604-4d18-a18c-81a3fc0d5a7d_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_6faac78f-7604-4d18-a18c-81a3fc0d5a7d" xlink:to="loc_srt_RangeMember_6faac78f-7604-4d18-a18c-81a3fc0d5a7d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_2168582b-e9d7-4442-9433-e1ee008790ce" 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_6faac78f-7604-4d18-a18c-81a3fc0d5a7d" xlink:to="loc_srt_RangeMember_2168582b-e9d7-4442-9433-e1ee008790ce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_26199fe5-f147-4cc6-92eb-31c3d2a4726f" 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_2168582b-e9d7-4442-9433-e1ee008790ce" xlink:to="loc_srt_MaximumMember_26199fe5-f147-4cc6-92eb-31c3d2a4726f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_5741943f-5c1c-4ab2-b871-d54552402be8" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_5741943f-5c1c-4ab2-b871-d54552402be8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_c1f7f91c-1292-4dcd-9707-873f67a1c04e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_c1f7f91c-1292-4dcd-9707-873f67a1c04e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_bf9090b4-c386-4c7c-9494-f18beeab6e47" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_CommonStockSharesIssued_bf9090b4-c386-4c7c-9494-f18beeab6e47" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_4452a8bd-8334-4488-a157-f66205edcb3b" 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_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_4452a8bd-8334-4488-a157-f66205edcb3b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_f1a880d0-951c-4a09-9df6-0786caac1538" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_f1a880d0-951c-4a09-9df6-0786caac1538" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_ca895791-b6ad-42b4-b0d1-e5364f0b9a89" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_ca895791-b6ad-42b4-b0d1-e5364f0b9a89" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_da8eb904-7019-479f-9a01-6511c808b927" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_PreferredStockSharesIssued_da8eb904-7019-479f-9a01-6511c808b927" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_e26fc79c-4874-4c8f-bf7f-d5db015d1d1e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_e26fc79c-4874-4c8f-bf7f-d5db015d1d1e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_cef3aefd-6140-4650-ae5e-6680589b528a" 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_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_cef3aefd-6140-4650-ae5e-6680589b528a" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_ea842fc6-8e92-451a-9126-13433080d2f4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_ea842fc6-8e92-451a-9126-13433080d2f4" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_8029ae98-9627-4e17-93d7-24d99e114ccf" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_8029ae98-9627-4e17-93d7-24d99e114ccf" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SaleOfStockAggregatePurchasePrice_94ea83af-88e9-4584-9268-2cf55b44347f" xlink:href="arwr-20240930.xsd#arwr_SaleOfStockAggregatePurchasePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_arwr_SaleOfStockAggregatePurchasePrice_94ea83af-88e9-4584-9268-2cf55b44347f" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_69f43892-88e6-4a00-8ab2-33bbf05a7f8e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_69f43892-88e6-4a00-8ab2-33bbf05a7f8e" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommonStockCapitalSharesValueReservedForFutureIssuance_8d32ef4d-8fd8-4587-8350-7e7f304cc099" xlink:href="arwr-20240930.xsd#arwr_CommonStockCapitalSharesValueReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_arwr_CommonStockCapitalSharesValueReservedForFutureIssuance_8d32ef4d-8fd8-4587-8350-7e7f304cc099" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock_38d8a36b-dca3-4a99-939d-3f074fb0a311" xlink:href="arwr-20240930.xsd#arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_arwr_PercentageOfCommissionOnAggregateGrossProceedsFromSaleOfCommonStock_38d8a36b-dca3-4a99-939d-3f074fb0a311" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_2ee3a4b5-f8f6-4021-909b-5fc880784b52" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_9c44fb8e-b658-458e-9ddf-f47ff409739a" xlink:to="loc_us-gaap_SharesIssued_2ee3a4b5-f8f6-4021-909b-5fc880784b52" xlink:type="arc" order="15"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/CommitmentsandContingenciesDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#CommitmentsandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/CommitmentsandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCommitmentsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsTable_29aa085e-3d95-4b2d-8d82-8c31e3dd7f12" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherCommitmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:to="loc_us-gaap_OtherCommitmentsTable_29aa085e-3d95-4b2d-8d82-8c31e3dd7f12" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397" 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_us-gaap_OtherCommitmentsTable_29aa085e-3d95-4b2d-8d82-8c31e3dd7f12" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397_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_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8bff9077-af50-4ad6-ace3-a64828662223" 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_4d1fdbf0-ef9c-4b4b-bb85-d1a609ccc397" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8bff9077-af50-4ad6-ace3-a64828662223" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DrugManufacturingFacilityMember_bd861175-120e-4b82-bf7b-35e9a8a68582" xlink:href="arwr-20240930.xsd#arwr_DrugManufacturingFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8bff9077-af50-4ad6-ace3-a64828662223" xlink:to="loc_arwr_DrugManufacturingFacilityMember_bd861175-120e-4b82-bf7b-35e9a8a68582" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LaboratoryAndOfficeFacilityMember_222f7844-3bc0-42e6-8f50-f40f7cc25aea" xlink:href="arwr-20240930.xsd#arwr_LaboratoryAndOfficeFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8bff9077-af50-4ad6-ace3-a64828662223" xlink:to="loc_arwr_LaboratoryAndOfficeFacilityMember_222f7844-3bc0-42e6-8f50-f40f7cc25aea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FacilitiesMember_92a54204-ef80-4854-aa61-100ff7e185d5" xlink:href="arwr-20240930.xsd#arwr_FacilitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8bff9077-af50-4ad6-ace3-a64828662223" xlink:to="loc_arwr_FacilitiesMember_92a54204-ef80-4854-aa61-100ff7e185d5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OtherCommitmentsTable_29aa085e-3d95-4b2d-8d82-8c31e3dd7f12" xlink:to="loc_srt_StatementGeographicalAxis_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7" xlink:to="loc_srt_SegmentGeographicalDomain_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_b04dd8c5-9eeb-44c0-b975-bfbd0fb7875a" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_0eaa1b9d-d153-41c7-afac-eb5bcb68dae7" xlink:to="loc_srt_SegmentGeographicalDomain_b04dd8c5-9eeb-44c0-b975-bfbd0fb7875a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_WI_8cc3c6ac-e074-4366-b952-4cc17e27007f" xlink:href="https://xbrl.sec.gov/stpr/2024/stpr-2024.xsd#stpr_WI"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_b04dd8c5-9eeb-44c0-b975-bfbd0fb7875a" xlink:to="loc_stpr_WI_8cc3c6ac-e074-4366-b952-4cc17e27007f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyAccrualAtCarryingValue_3e5a8722-17a5-4eb0-acc7-23a88f544e2c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LossContingencyAccrualAtCarryingValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:to="loc_us-gaap_LossContingencyAccrualAtCarryingValue_3e5a8722-17a5-4eb0-acc7-23a88f544e2c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AreaOfLand_4fd805a7-4686-41a7-bc80-75c33a4b3f0e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AreaOfLand"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:to="loc_us-gaap_AreaOfLand_4fd805a7-4686-41a7-bc80-75c33a4b3f0e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommitmentsCapitalExpendituresIncurredToDate_ac1ee77c-559a-42d6-ba9f-6996fe673ca0" xlink:href="arwr-20240930.xsd#arwr_CommitmentsCapitalExpendituresIncurredToDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:to="loc_arwr_CommitmentsCapitalExpendituresIncurredToDate_ac1ee77c-559a-42d6-ba9f-6996fe673ca0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AmountIntendsToInvestForBuildoutOfFacilities_8f87a05b-a009-4fca-95dd-777726ed7fb1" xlink:href="arwr-20240930.xsd#arwr_AmountIntendsToInvestForBuildoutOfFacilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsLineItems_fbf63e14-7421-4d08-bb6d-677f578776b4" xlink:to="loc_arwr_AmountIntendsToInvestForBuildoutOfFacilities_8f87a05b-a009-4fca-95dd-777726ed7fb1" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LeasesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3" 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_us-gaap_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3_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_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c9b904e8-3872-4706-936d-f216d3a2f66a" 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_bbe33cb7-79a1-4f2b-b729-5a8fcb952ea3" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c9b904e8-3872-4706-936d-f216d3a2f66a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CorporateHeadquartersInPasadenaMember_497120d5-40a9-458d-a8e1-42eb56cad7ef" xlink:href="arwr-20240930.xsd#arwr_CorporateHeadquartersInPasadenaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c9b904e8-3872-4706-936d-f216d3a2f66a" xlink:to="loc_arwr_CorporateHeadquartersInPasadenaMember_497120d5-40a9-458d-a8e1-42eb56cad7ef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ResearchFacilityInSanDiegoMember_8e3a1152-c8f0-42a8-8d3e-3e7925336891" xlink:href="arwr-20240930.xsd#arwr_ResearchFacilityInSanDiegoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c9b904e8-3872-4706-936d-f216d3a2f66a" xlink:to="loc_arwr_ResearchFacilityInSanDiegoMember_8e3a1152-c8f0-42a8-8d3e-3e7925336891" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ResearchFacilityInMadisonMember_c6561e0d-562d-46d9-a0cd-1e0ada351444" xlink:href="arwr-20240930.xsd#arwr_ResearchFacilityInMadisonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_c9b904e8-3872-4706-936d-f216d3a2f66a" xlink:to="loc_arwr_ResearchFacilityInMadisonMember_c6561e0d-562d-46d9-a0cd-1e0ada351444" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_21826969-e60e-4b75-aa9e-8bd0a611ff38" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:to="loc_srt_StatementGeographicalAxis_21826969-e60e-4b75-aa9e-8bd0a611ff38" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_21826969-e60e-4b75-aa9e-8bd0a611ff38_default" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_21826969-e60e-4b75-aa9e-8bd0a611ff38" xlink:to="loc_srt_SegmentGeographicalDomain_21826969-e60e-4b75-aa9e-8bd0a611ff38_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_5bab1f46-e3be-4836-82a7-3889000dbeab" xlink:href="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_21826969-e60e-4b75-aa9e-8bd0a611ff38" xlink:to="loc_srt_SegmentGeographicalDomain_5bab1f46-e3be-4836-82a7-3889000dbeab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_CA_b0b2dd1b-418b-4107-ab92-0a14bc9a26a1" xlink:href="https://xbrl.sec.gov/stpr/2024/stpr-2024.xsd#stpr_CA"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_5bab1f46-e3be-4836-82a7-3889000dbeab" xlink:to="loc_stpr_CA_b0b2dd1b-418b-4107-ab92-0a14bc9a26a1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_WI_d36f8a10-3482-43a3-9b9c-5d404a232c4c" xlink:href="https://xbrl.sec.gov/stpr/2024/stpr-2024.xsd#stpr_WI"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_5bab1f46-e3be-4836-82a7-3889000dbeab" xlink:to="loc_stpr_WI_d36f8a10-3482-43a3-9b9c-5d404a232c4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_85155cc5-5ad7-4844-ae0d-b2d74a84376a" 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_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:to="loc_srt_RangeAxis_85155cc5-5ad7-4844-ae0d-b2d74a84376a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_85155cc5-5ad7-4844-ae0d-b2d74a84376a_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_85155cc5-5ad7-4844-ae0d-b2d74a84376a" xlink:to="loc_srt_RangeMember_85155cc5-5ad7-4844-ae0d-b2d74a84376a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_bdaeaef3-e9d7-4755-96d4-0a65d0726e17" 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_85155cc5-5ad7-4844-ae0d-b2d74a84376a" xlink:to="loc_srt_RangeMember_bdaeaef3-e9d7-4755-96d4-0a65d0726e17" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_61b0c8f6-8fc1-4847-a706-889c9e1b588c" 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_bdaeaef3-e9d7-4755-96d4-0a65d0726e17" xlink:to="loc_srt_MaximumMember_61b0c8f6-8fc1-4847-a706-889c9e1b588c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_ddc7a872-9ea1-43b8-a697-1cc93cba64c5" 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_LesseeLeaseDescriptionTable_d8d77010-f5ee-48a4-9edd-bcc67e9b29ca" xlink:to="loc_srt_CounterpartyNameAxis_ddc7a872-9ea1-43b8-a697-1cc93cba64c5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ddc7a872-9ea1-43b8-a697-1cc93cba64c5_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_ddc7a872-9ea1-43b8-a697-1cc93cba64c5" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_ddc7a872-9ea1-43b8-a697-1cc93cba64c5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f90eddd0-fe21-42e7-a83f-457b751b31a6" 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_ddc7a872-9ea1-43b8-a697-1cc93cba64c5" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f90eddd0-fe21-42e7-a83f-457b751b31a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ColoradoOwnerLLCMember_e50d7bef-600f-4672-af89-d89214512980" xlink:href="arwr-20240930.xsd#arwr_ColoradoOwnerLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_f90eddd0-fe21-42e7-a83f-457b751b31a6" xlink:to="loc_arwr_ColoradoOwnerLLCMember_e50d7bef-600f-4672-af89-d89214512980" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LandSubjectToGroundLeases_49a9d359-09a8-4452-93f2-8a37fec65524" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LandSubjectToGroundLeases"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_us-gaap_LandSubjectToGroundLeases_49a9d359-09a8-4452-93f2-8a37fec65524" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfOptionsToRenew_720ced70-feef-43c8-802c-2a2d9eae2595" xlink:href="arwr-20240930.xsd#arwr_NumberOfOptionsToRenew"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_arwr_NumberOfOptionsToRenew_720ced70-feef-43c8-802c-2a2d9eae2595" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_410433ed-a2f2-4e78-8336-0d681c4b6859" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_410433ed-a2f2-4e78-8336-0d681c4b6859" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseTermOfContract_88f2b1b9-b0ae-467f-bd9b-963a89f82ab7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LesseeOperatingLeaseTermOfContract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_us-gaap_LesseeOperatingLeaseTermOfContract_88f2b1b9-b0ae-467f-bd9b-963a89f82ab7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MaximumAdditionalTenantImprovementAllowance_2e7057c0-6066-4525-90b5-b127f28bb5b2" xlink:href="arwr-20240930.xsd#arwr_MaximumAdditionalTenantImprovementAllowance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_arwr_MaximumAdditionalTenantImprovementAllowance_2e7057c0-6066-4525-90b5-b127f28bb5b2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum_0cf53755-d33b-4522-aba1-c47a3bf8faf0" xlink:href="arwr-20240930.xsd#arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum_0cf53755-d33b-4522-aba1-c47a3bf8faf0" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalTenantImprovementAllowanceLiability_b1f38317-71ca-41ff-84a0-12ac779a36d7" xlink:href="arwr-20240930.xsd#arwr_AdditionalTenantImprovementAllowanceLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_arwr_AdditionalTenantImprovementAllowanceLiability_b1f38317-71ca-41ff-84a0-12ac779a36d7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum_6ed7633d-a919-4c1e-bc31-ac92279ef198" xlink:href="arwr-20240930.xsd#arwr_AdditionalTenantImprovementAllowanceInterestPerAnnum"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermLeaseCost_1786616c-6955-483b-bf23-707118ce6bdb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShortTermLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_067bee66-c884-4f6c-95c0-f3c183d1fb8b" xlink:to="loc_us-gaap_ShortTermLeaseCost_1786616c-6955-483b-bf23-707118ce6bdb" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LeasesComponentsofLeaseAssetsandLiabilitiesDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#LeasesComponentsofLeaseAssetsandLiabilitiesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LeasesComponentsofLeaseAssetsandLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeasedAssetsLineItems_99276b5a-fad6-43dd-a7c5-f39cb7c7cda7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeasedAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfOperatingLeasedAssetsTable_f1025be9-dc28-4a15-a1f3-4881bb370e05" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfOperatingLeasedAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_99276b5a-fad6-43dd-a7c5-f39cb7c7cda7" xlink:to="loc_us-gaap_ScheduleOfOperatingLeasedAssetsTable_f1025be9-dc28-4a15-a1f3-4881bb370e05" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f" 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_ScheduleOfOperatingLeasedAssetsTable_f1025be9-dc28-4a15-a1f3-4881bb370e05" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f_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_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_5061e656-a32c-4dc5-b1e3-d957a7adb74a" 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_bf8b86b3-8f03-4985-9edc-ffd1a3b0383f" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_5061e656-a32c-4dc5-b1e3-d957a7adb74a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_e071bda0-1f67-473b-9fb6-ed358e38bb1e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_5061e656-a32c-4dc5-b1e3-d957a7adb74a" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_e071bda0-1f67-473b-9fb6-ed358e38bb1e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_3d263305-adf7-4ea1-9cdd-a09931d7556e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_5061e656-a32c-4dc5-b1e3-d957a7adb74a" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_3d263305-adf7-4ea1-9cdd-a09931d7556e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_3f4fb394-33a4-4f31-b22e-6b72fc630d0e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsAndLiabilitiesLesseeAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_99276b5a-fad6-43dd-a7c5-f39cb7c7cda7" xlink:to="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_3f4fb394-33a4-4f31-b22e-6b72fc630d0e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_9be5fdc6-8f34-4946-bcad-d858a57575d0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_3f4fb394-33a4-4f31-b22e-6b72fc630d0e" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_9be5fdc6-8f34-4946-bcad-d858a57575d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_352a7cd5-33b8-4419-8ae6-14a249ca2c06" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_3f4fb394-33a4-4f31-b22e-6b72fc630d0e" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_352a7cd5-33b8-4419-8ae6-14a249ca2c06" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_52507bc7-2310-47d8-a402-2548d22ceac3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAndLiabilitiesLesseeAbstract_3f4fb394-33a4-4f31-b22e-6b72fc630d0e" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_52507bc7-2310-47d8-a402-2548d22ceac3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCostAbstract_46aaac6d-a3ea-47c5-8308-492d36699f6b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseCostAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLeasedAssetsLineItems_99276b5a-fad6-43dd-a7c5-f39cb7c7cda7" xlink:to="loc_us-gaap_LeaseCostAbstract_46aaac6d-a3ea-47c5-8308-492d36699f6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseCost_4874e43a-37e5-4774-b396-cdaabed0b9b1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_46aaac6d-a3ea-47c5-8308-492d36699f6b" xlink:to="loc_us-gaap_OperatingLeaseCost_4874e43a-37e5-4774-b396-cdaabed0b9b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableLeaseCost_291dfd04-c503-4ee8-8283-b1b4aca224e3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_VariableLeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_46aaac6d-a3ea-47c5-8308-492d36699f6b" xlink:to="loc_us-gaap_VariableLeaseCost_291dfd04-c503-4ee8-8283-b1b4aca224e3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseCost_3cfb4aeb-7df4-4360-be43-23972a4123ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LeaseCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LeaseCostAbstract_46aaac6d-a3ea-47c5-8308-492d36699f6b" xlink:to="loc_us-gaap_LeaseCost_3cfb4aeb-7df4-4360-be43-23972a4123ba" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#StockBasedCompensationNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" 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_635ff164-0948-4bb9-b33a-36eea38bde49" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_635ff164-0948-4bb9-b33a-36eea38bde49" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88" 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_635ff164-0948-4bb9-b33a-36eea38bde49" xlink:to="loc_us-gaap_PlanNameAxis_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88_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_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88" xlink:to="loc_us-gaap_PlanNameDomain_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" 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_1b54b7b3-d8cc-44d9-b043-9c09d6f98e88" xlink:to="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsThirteenIncentivePlanMember_630d3c3f-0030-4071-a2c5-d9ec0097075e" xlink:href="arwr-20240930.xsd#arwr_TwoThousandsThirteenIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" xlink:to="loc_arwr_TwoThousandsThirteenIncentivePlanMember_630d3c3f-0030-4071-a2c5-d9ec0097075e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_2151ba8e-c2fb-424d-b60d-7323da43ae55" xlink:href="arwr-20240930.xsd#arwr_TwoThousandTwentyOneIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" xlink:to="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_2151ba8e-c2fb-424d-b60d-7323da43ae55" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InducementPlanMember_96367a79-2883-4243-b8cd-45a3c36b52be" xlink:href="arwr-20240930.xsd#arwr_InducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" xlink:to="loc_arwr_InducementPlanMember_96367a79-2883-4243-b8cd-45a3c36b52be" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_VisirnaESOPMember_ed554a45-462f-4e10-ae40-148757015f83" xlink:href="arwr-20240930.xsd#arwr_VisirnaESOPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_c18d0ccc-5193-4254-9046-92532a9f7cdb" xlink:to="loc_arwr_VisirnaESOPMember_ed554a45-462f-4e10-ae40-148757015f83" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8" 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_635ff164-0948-4bb9-b33a-36eea38bde49" xlink:to="loc_us-gaap_AwardTypeAxis_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8_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_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7b9acf5c-2765-4cde-abee-dc3683f1f1cb" 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_6af0b6bf-8db2-421e-acfe-2b9f10da8cd8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_7b9acf5c-2765-4cde-abee-dc3683f1f1cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_7bec4fe0-3972-47c2-b04f-1112fbb1c88a" 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_7b9acf5c-2765-4cde-abee-dc3683f1f1cb" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_7bec4fe0-3972-47c2-b04f-1112fbb1c88a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_eff300e0-6380-430c-b85c-10e45cbe9dee" 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_7b9acf5c-2765-4cde-abee-dc3683f1f1cb" xlink:to="loc_us-gaap_EmployeeStockOptionMember_eff300e0-6380-430c-b85c-10e45cbe9dee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_2d1c0549-8eb9-44fb-b515-76c5772712a7" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_2d1c0549-8eb9-44fb-b515-76c5772712a7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_a8061e43-1168-4900-9583-cb7984755b8f" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_a8061e43-1168-4900-9583-cb7984755b8f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_96b642c8-731a-464b-a514-9542ca2e9c72" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant_96b642c8-731a-464b-a514-9542ca2e9c72" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_bff81efb-7c38-44d3-be93-26b9e4c4c42e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_bff81efb-7c38-44d3-be93-26b9e4c4c42e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_43510141-41a4-4dd2-b55e-375a0e81730c" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_43510141-41a4-4dd2-b55e-375a0e81730c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_7ea4344f-05a5-4ce2-95ae-cb92cd3c759a" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_7ea4344f-05a5-4ce2-95ae-cb92cd3c759a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2d0dc051-b8b9-4045-a406-302b46a44fd8" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2d0dc051-b8b9-4045-a406-302b46a44fd8" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_53f4626e-6035-4fb2-a1bd-6b5299456de4" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_53f4626e-6035-4fb2-a1bd-6b5299456de4" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_54270821-8e08-4ea2-bfa4-a70a589b5400" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_54270821-8e08-4ea2-bfa4-a70a589b5400" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_5b2efc32-645c-47b9-a8c1-d424d088c51d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_5b2efc32-645c-47b9-a8c1-d424d088c51d" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_696ad4d4-05b0-4823-8d8d-abf98e87f643" 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_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_696ad4d4-05b0-4823-8d8d-abf98e87f643" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_1e674a7a-47a7-407f-a2a9-b693f6d703c7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_49d31d73-c39c-4cb8-ba4f-19004015485d" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_1e674a7a-47a7-407f-a2a9-b693f6d703c7" xlink:type="arc" order="11"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofGrantedandOutstandingSharesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_758c269f-3234-4ff5-9b5b-54e5a8426ada" 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_7170f9cc-9d1c-4077-ae64-b3f5a8a65287" 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_758c269f-3234-4ff5-9b5b-54e5a8426ada" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_7170f9cc-9d1c-4077-ae64-b3f5a8a65287" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_23d6b479-851b-4b98-ada5-835708620281" 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_7170f9cc-9d1c-4077-ae64-b3f5a8a65287" xlink:to="loc_us-gaap_AwardTypeAxis_23d6b479-851b-4b98-ada5-835708620281" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_23d6b479-851b-4b98-ada5-835708620281_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_23d6b479-851b-4b98-ada5-835708620281" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_23d6b479-851b-4b98-ada5-835708620281_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_329d6cde-5db3-4f01-a54b-338777259315" 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_23d6b479-851b-4b98-ada5-835708620281" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_329d6cde-5db3-4f01-a54b-338777259315" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_41ff3af3-f644-40c1-b007-f43dca6a04ef" 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_329d6cde-5db3-4f01-a54b-338777259315" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_41ff3af3-f644-40c1-b007-f43dca6a04ef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_6426058c-4309-40dd-8815-02da2d2cf949" 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_7170f9cc-9d1c-4077-ae64-b3f5a8a65287" xlink:to="loc_us-gaap_PlanNameAxis_6426058c-4309-40dd-8815-02da2d2cf949" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_6426058c-4309-40dd-8815-02da2d2cf949_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_6426058c-4309-40dd-8815-02da2d2cf949" xlink:to="loc_us-gaap_PlanNameDomain_6426058c-4309-40dd-8815-02da2d2cf949_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_aa4e678b-56be-4ff2-acd1-a090b7ba7bc7" 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_6426058c-4309-40dd-8815-02da2d2cf949" xlink:to="loc_us-gaap_PlanNameDomain_aa4e678b-56be-4ff2-acd1-a090b7ba7bc7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandsThirteenIncentivePlanMember_cf9d43ce-f8a6-4ec6-8a29-546632262210" xlink:href="arwr-20240930.xsd#arwr_TwoThousandsThirteenIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_aa4e678b-56be-4ff2-acd1-a090b7ba7bc7" xlink:to="loc_arwr_TwoThousandsThirteenIncentivePlanMember_cf9d43ce-f8a6-4ec6-8a29-546632262210" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_fa6e8bc8-3366-4764-a5d3-2d9921631d67" xlink:href="arwr-20240930.xsd#arwr_TwoThousandTwentyOneIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_aa4e678b-56be-4ff2-acd1-a090b7ba7bc7" xlink:to="loc_arwr_TwoThousandTwentyOneIncentivePlanMember_fa6e8bc8-3366-4764-a5d3-2d9921631d67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InducementAwardsMember_15e2fcc8-66d9-4741-b08c-a7f4391bb283" xlink:href="arwr-20240930.xsd#arwr_InducementAwardsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_aa4e678b-56be-4ff2-acd1-a090b7ba7bc7" xlink:to="loc_arwr_InducementAwardsMember_15e2fcc8-66d9-4741-b08c-a7f4391bb283" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_d698a796-f41c-4cad-a87a-578aefae0d74" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_758c269f-3234-4ff5-9b5b-54e5a8426ada" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_d698a796-f41c-4cad-a87a-578aefae0d74" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_5baba030-01f1-4e80-96a7-25a5bd21c306" 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_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_758c269f-3234-4ff5-9b5b-54e5a8426ada" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_5baba030-01f1-4e80-96a7-25a5bd21c306" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding_b415e340-df4f-4ac2-8f1c-de29d491e352" xlink:href="arwr-20240930.xsd#arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_758c269f-3234-4ff5-9b5b-54e5a8426ada" xlink:to="loc_arwr_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAndEquityInstrumentsOtherThanOptionsOutstanding_b415e340-df4f-4ac2-8f1c-de29d491e352" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationExpensesIncludedinOperatingExpensesDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#StockBasedCompensationExpensesIncludedinOperatingExpensesDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationExpensesIncludedinOperatingExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_7c9aadef-863c-470b-81f3-13325d72b5c7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_6e233f7e-c8f5-4cb8-853e-6b8d5bfa478c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_7c9aadef-863c-470b-81f3-13325d72b5c7" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_6e233f7e-c8f5-4cb8-853e-6b8d5bfa478c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_2f53300e-fc58-4af4-a96e-eb2e024bbd88" 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_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_6e233f7e-c8f5-4cb8-853e-6b8d5bfa478c" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_2f53300e-fc58-4af4-a96e-eb2e024bbd88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_2f53300e-fc58-4af4-a96e-eb2e024bbd88_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_2f53300e-fc58-4af4-a96e-eb2e024bbd88" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_2f53300e-fc58-4af4-a96e-eb2e024bbd88_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_73d7bf57-413f-4fb8-8ff9-fbde3beca143" 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_2f53300e-fc58-4af4-a96e-eb2e024bbd88" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_73d7bf57-413f-4fb8-8ff9-fbde3beca143" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_e4df72f4-d766-4d75-bbd9-d56a1914c64f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_73d7bf57-413f-4fb8-8ff9-fbde3beca143" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_e4df72f4-d766-4d75-bbd9-d56a1914c64f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_7caa6940-c46e-46f0-ae9b-6d6b83187cb0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_73d7bf57-413f-4fb8-8ff9-fbde3beca143" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_7caa6940-c46e-46f0-ae9b-6d6b83187cb0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_f7bbb715-7911-4628-b2ca-c7c510b01ea4" 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_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_7c9aadef-863c-470b-81f3-13325d72b5c7" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_f7bbb715-7911-4628-b2ca-c7c510b01ea4" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofRSUsActivityDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#StockBasedCompensationSummaryofRSUsActivityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/StockBasedCompensationSummaryofRSUsActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_d112830e-d821-4140-8099-cfc458cdc466" 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_d9e2c5c4-0dee-4303-a829-fd20234c7611" 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_d112830e-d821-4140-8099-cfc458cdc466" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d9e2c5c4-0dee-4303-a829-fd20234c7611" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_4269ac0a-8d11-465d-890b-533a35f61675" 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_d9e2c5c4-0dee-4303-a829-fd20234c7611" xlink:to="loc_us-gaap_AwardTypeAxis_4269ac0a-8d11-465d-890b-533a35f61675" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_4269ac0a-8d11-465d-890b-533a35f61675_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_4269ac0a-8d11-465d-890b-533a35f61675" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_4269ac0a-8d11-465d-890b-533a35f61675_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2e244c6d-68d2-4be2-8bc3-2bc14b4b6c92" 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_4269ac0a-8d11-465d-890b-533a35f61675" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_2e244c6d-68d2-4be2-8bc3-2bc14b4b6c92" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_2f4cb937-a05f-49e4-989a-a91f1f201367" 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_2e244c6d-68d2-4be2-8bc3-2bc14b4b6c92" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_2f4cb937-a05f-49e4-989a-a91f1f201367" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_498e8449-e797-435f-99be-03711d74c2c9" 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_d112830e-d821-4140-8099-cfc458cdc466" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_498e8449-e797-435f-99be-03711d74c2c9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2bfdc073-6780-42db-bcd0-15405a183788" 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_498e8449-e797-435f-99be-03711d74c2c9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_2bfdc073-6780-42db-bcd0-15405a183788" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_35567ac6-5192-4b31-b285-6dfb4b33cb91" 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_498e8449-e797-435f-99be-03711d74c2c9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_35567ac6-5192-4b31-b285-6dfb4b33cb91" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_352a63fa-442e-4e74-ad28-37ecb9ae283d" 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_498e8449-e797-435f-99be-03711d74c2c9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_352a63fa-442e-4e74-ad28-37ecb9ae283d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_79366c08-2fe7-4112-b0eb-5746811bd98f" 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_498e8449-e797-435f-99be-03711d74c2c9" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_79366c08-2fe7-4112-b0eb-5746811bd98f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_c1f65d45-e97b-44b1-990c-6e2a2c4c3396" 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_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" 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_d112830e-d821-4140-8099-cfc458cdc466" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_1e898110-f6b5-47c7-a960-2d871290dbed" 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_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_1e898110-f6b5-47c7-a960-2d871290dbed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0a2ef385-bade-492c-b0d0-c5ee7ee2faca" 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_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0a2ef385-bade-492c-b0d0-c5ee7ee2faca" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_56062683-3339-4b18-8c3a-2820e4bafd37" 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_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_56062683-3339-4b18-8c3a-2820e4bafd37" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_b7e6f3f1-f8c1-4e05-9391-3d62a194096a" 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_4c54f55f-8d9b-44c8-b0a4-9b7f174fafae" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_b7e6f3f1-f8c1-4e05-9391-3d62a194096a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_c54bca92-fa41-43a4-b85f-d5ba8a4b4245" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FairValueMeasurementsFairValueMeasurementsforAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_bc02cdae-d667-4b0c-9bd7-e8bc4d0a0da6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_bc02cdae-d667-4b0c-9bd7-e8bc4d0a0da6" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_febe0918-103b-4530-b798-c5dcf4fce336" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_febe0918-103b-4530-b798-c5dcf4fce336" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_febe0918-103b-4530-b798-c5dcf4fce336_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_febe0918-103b-4530-b798-c5dcf4fce336" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_febe0918-103b-4530-b798-c5dcf4fce336_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_097ad4c9-be85-48d2-b7b2-ffc50805ffe6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_febe0918-103b-4530-b798-c5dcf4fce336" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_097ad4c9-be85-48d2-b7b2-ffc50805ffe6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_e0dbd5b6-f388-481c-8fd4-5e6c16b0c844" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_097ad4c9-be85-48d2-b7b2-ffc50805ffe6" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_e0dbd5b6-f388-481c-8fd4-5e6c16b0c844" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_892e418b-0e67-4ce8-852f-038cf9d5401f" 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_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_892e418b-0e67-4ce8-852f-038cf9d5401f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_892e418b-0e67-4ce8-852f-038cf9d5401f_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_892e418b-0e67-4ce8-852f-038cf9d5401f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_892e418b-0e67-4ce8-852f-038cf9d5401f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_adb142bd-2e08-4918-9935-8f831a038a7b" 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_892e418b-0e67-4ce8-852f-038cf9d5401f" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_adb142bd-2e08-4918-9935-8f831a038a7b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_cf8d6a9e-2790-4cf6-81be-1ce17a6c6384" 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_adb142bd-2e08-4918-9935-8f831a038a7b" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_cf8d6a9e-2790-4cf6-81be-1ce17a6c6384" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_612d66c6-7142-4018-9959-7c3b40a78f18" 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_adb142bd-2e08-4918-9935-8f831a038a7b" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_612d66c6-7142-4018-9959-7c3b40a78f18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_44e71b15-bf2b-4a4b-b6de-98a606728645" 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_adb142bd-2e08-4918-9935-8f831a038a7b" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_44e71b15-bf2b-4a4b-b6de-98a606728645" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_5416e598-691a-4657-b0b8-16b821cfacc3" 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_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:to="loc_us-gaap_FinancialInstrumentAxis_5416e598-691a-4657-b0b8-16b821cfacc3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5416e598-691a-4657-b0b8-16b821cfacc3_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_5416e598-691a-4657-b0b8-16b821cfacc3" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_5416e598-691a-4657-b0b8-16b821cfacc3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" 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_5416e598-691a-4657-b0b8-16b821cfacc3" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_417eed72-e83a-4610-be2f-9b395c615682" 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_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_417eed72-e83a-4610-be2f-9b395c615682" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentDebtSecuritiesMember_4f330d7e-7e8b-47d3-ae52-a9c035730bfe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_USGovernmentDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:to="loc_us-gaap_USGovernmentDebtSecuritiesMember_4f330d7e-7e8b-47d3-ae52-a9c035730bfe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MunicipalBondsMember_9fdb2c32-7549-4db7-bc92-b63a67aa5c2e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MunicipalBondsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:to="loc_us-gaap_MunicipalBondsMember_9fdb2c32-7549-4db7-bc92-b63a67aa5c2e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CommercialNotesMember_8e90ff6e-c2a9-4a75-a513-834a2c8e329e" xlink:href="arwr-20240930.xsd#arwr_CommercialNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:to="loc_arwr_CommercialNotesMember_8e90ff6e-c2a9-4a75-a513-834a2c8e329e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_62dfca3a-ed6c-47ae-ba11-6fbe9f6a23b7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_1a957b35-ed03-4637-a2bc-ac74b2e880cd" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_62dfca3a-ed6c-47ae-ba11-6fbe9f6a23b7" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_1eae8872-f0fa-4d4d-8974-bc14f34f6add" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_d519f5f1-3ea5-4958-906f-320253bf4795" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_1eae8872-f0fa-4d4d-8974-bc14f34f6add" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1eae8872-f0fa-4d4d-8974-bc14f34f6add_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_CashAndCashEquivalentsAxis_1eae8872-f0fa-4d4d-8974-bc14f34f6add" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_1eae8872-f0fa-4d4d-8974-bc14f34f6add_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e3d62673-b115-4cbb-9de8-06683343af48" 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_CashAndCashEquivalentsAxis_1eae8872-f0fa-4d4d-8974-bc14f34f6add" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e3d62673-b115-4cbb-9de8-06683343af48" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_3fe5e303-7526-4d98-ba0a-3728d35e01d5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_e3d62673-b115-4cbb-9de8-06683343af48" xlink:to="loc_us-gaap_MoneyMarketFundsMember_3fe5e303-7526-4d98-ba0a-3728d35e01d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_d69facc6-56c3-4c4e-9b7a-a98e9849ff97" 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_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_bc02cdae-d667-4b0c-9bd7-e8bc4d0a0da6" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_d69facc6-56c3-4c4e-9b7a-a98e9849ff97" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_c2a331f5-3307-41d6-9c63-42098f87a7d5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_bc02cdae-d667-4b0c-9bd7-e8bc4d0a0da6" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_c2a331f5-3307-41d6-9c63-42098f87a7d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_b2139cd6-afae-4bc9-a541-3c2463d60542" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_bc02cdae-d667-4b0c-9bd7-e8bc4d0a0da6" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_b2139cd6-afae-4bc9-a541-3c2463d60542" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/IncomeTaxesNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#IncomeTaxesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/IncomeTaxesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwardsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_71e523db-f73a-4324-b0fb-c668bffb7bc5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_71e523db-f73a-4324-b0fb-c668bffb7bc5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_fdf3a11d-4233-4c56-bc0b-b3705cbf847e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_71e523db-f73a-4324-b0fb-c668bffb7bc5" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_fdf3a11d-4233-4c56-bc0b-b3705cbf847e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_fdf3a11d-4233-4c56-bc0b-b3705cbf847e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_fdf3a11d-4233-4c56-bc0b-b3705cbf847e" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_fdf3a11d-4233-4c56-bc0b-b3705cbf847e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_329321fb-e5fb-4006-af71-d06e440cea57" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_fdf3a11d-4233-4c56-bc0b-b3705cbf847e" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_329321fb-e5fb-4006-af71-d06e440cea57" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_4f44b34e-e017-4dc5-9fff-fb5e43050fbc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DomesticCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_329321fb-e5fb-4006-af71-d06e440cea57" xlink:to="loc_us-gaap_DomesticCountryMember_4f44b34e-e017-4dc5-9fff-fb5e43050fbc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StateAndLocalJurisdictionMember_ca3a3082-0739-47ab-8ae4-d83bb7e642ea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StateAndLocalJurisdictionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_329321fb-e5fb-4006-af71-d06e440cea57" xlink:to="loc_us-gaap_StateAndLocalJurisdictionMember_ca3a3082-0739-47ab-8ae4-d83bb7e642ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ForeignCountryMember_dd1f0f22-83e3-4fd3-a15a-814bd21ff19e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ForeignCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_329321fb-e5fb-4006-af71-d06e440cea57" xlink:to="loc_us-gaap_ForeignCountryMember_dd1f0f22-83e3-4fd3-a15a-814bd21ff19e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsValuationAllowance_e54c9f5c-ab41-485d-95b2-5ef20a77fde2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DeferredTaxAssetsValuationAllowance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_DeferredTaxAssetsValuationAllowance_e54c9f5c-ab41-485d-95b2-5ef20a77fde2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwards_cbe0dece-5607-4036-83a7-02b653869ad3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLossCarryforwards"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_OperatingLossCarryforwards_cbe0dece-5607-4036-83a7-02b653869ad3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OperatingLossCarryforwardsSubjectToExpiration_14357983-0ce5-430a-8b6c-00cd8a47654e" xlink:href="arwr-20240930.xsd#arwr_OperatingLossCarryforwardsSubjectToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_arwr_OperatingLossCarryforwardsSubjectToExpiration_14357983-0ce5-430a-8b6c-00cd8a47654e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_OperatingLossCarryforwardsNotSubjectToExpiration_15f6d5e9-84f3-45c7-afa6-78502ad1f1b4" xlink:href="arwr-20240930.xsd#arwr_OperatingLossCarryforwardsNotSubjectToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_arwr_OperatingLossCarryforwardsNotSubjectToExpiration_15f6d5e9-84f3-45c7-afa6-78502ad1f1b4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardAmount_956fcd52-b3a9-4118-9bc2-9ed4e8fe9f02" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TaxCreditCarryforwardAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_TaxCreditCarryforwardAmount_956fcd52-b3a9-4118-9bc2-9ed4e8fe9f02" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_TaxCreditCarryforwardAmountSubjectToExpiration_2cfcaa2e-235a-4169-b660-d4e4073ab4b8" xlink:href="arwr-20240930.xsd#arwr_TaxCreditCarryforwardAmountSubjectToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_arwr_TaxCreditCarryforwardAmountSubjectToExpiration_2cfcaa2e-235a-4169-b660-d4e4073ab4b8" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_d5eb7517-b42d-42af-a773-108383ab2109" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_d5eb7517-b42d-42af-a773-108383ab2109" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UndistributedEarningsOfForeignSubsidiaries_4719fead-024d-483d-a60b-115b0c783f62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_UndistributedEarningsOfForeignSubsidiaries"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingLossCarryforwardsLineItems_fe113b56-238d-4da3-a2c7-6bb20a5355ba" xlink:to="loc_us-gaap_UndistributedEarningsOfForeignSubsidiaries_4719fead-024d-483d-a60b-115b0c783f62" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/EmployeeBenefitPlansDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#EmployeeBenefitPlansDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/EmployeeBenefitPlansDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedBenefitPlanDisclosureLineItems_e811ff3d-7d81-4205-87af-27dc61d93894" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedBenefitPlanDisclosureLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable_f59e6e11-731b-4f1d-b2d9-8429a4b5e340" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DefinedBenefitPlanDisclosureLineItems_e811ff3d-7d81-4205-87af-27dc61d93894" xlink:to="loc_us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable_f59e6e11-731b-4f1d-b2d9-8429a4b5e340" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanTypeAxis_312d96bd-9cd3-4da2-8a76-cccf45c30ae6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetirementPlanTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfDefinedBenefitPlansDisclosuresTable_f59e6e11-731b-4f1d-b2d9-8429a4b5e340" xlink:to="loc_us-gaap_RetirementPlanTypeAxis_312d96bd-9cd3-4da2-8a76-cccf45c30ae6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanTypeDomain_312d96bd-9cd3-4da2-8a76-cccf45c30ae6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetirementPlanTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RetirementPlanTypeAxis_312d96bd-9cd3-4da2-8a76-cccf45c30ae6" xlink:to="loc_us-gaap_RetirementPlanTypeDomain_312d96bd-9cd3-4da2-8a76-cccf45c30ae6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetirementPlanTypeDomain_1b90ec5c-a404-470e-b036-812f3c0821bb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetirementPlanTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RetirementPlanTypeAxis_312d96bd-9cd3-4da2-8a76-cccf45c30ae6" xlink:to="loc_us-gaap_RetirementPlanTypeDomain_1b90ec5c-a404-470e-b036-812f3c0821bb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_EmployeeContributionsUpToThreePercentMember_88b47869-25bf-440f-99d8-838c239e97f0" xlink:href="arwr-20240930.xsd#arwr_EmployeeContributionsUpToThreePercentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RetirementPlanTypeDomain_1b90ec5c-a404-470e-b036-812f3c0821bb" xlink:to="loc_arwr_EmployeeContributionsUpToThreePercentMember_88b47869-25bf-440f-99d8-838c239e97f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_EmployeeContributionNextTwoPercentMember_1367ba26-9dfc-4309-b299-b1edbac8cfd7" xlink:href="arwr-20240930.xsd#arwr_EmployeeContributionNextTwoPercentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RetirementPlanTypeDomain_1b90ec5c-a404-470e-b036-812f3c0821bb" xlink:to="loc_arwr_EmployeeContributionNextTwoPercentMember_1367ba26-9dfc-4309-b299-b1edbac8cfd7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch_0cb930a1-c7be-4630-a88a-ce4878abba3c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedBenefitPlanDisclosureLineItems_e811ff3d-7d81-4205-87af-27dc61d93894" xlink:to="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercentOfMatch_0cb930a1-c7be-4630-a88a-ce4878abba3c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent_cfd4d6ea-40da-490b-9854-67066cbab39a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedBenefitPlanDisclosureLineItems_e811ff3d-7d81-4205-87af-27dc61d93894" xlink:to="loc_us-gaap_DefinedContributionPlanEmployerMatchingContributionPercent_cfd4d6ea-40da-490b-9854-67066cbab39a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DefinedContributionPlanCostRecognized_66c3fbd0-a0f8-4434-a95e-670ae3bad3f6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DefinedContributionPlanCostRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DefinedBenefitPlanDisclosureLineItems_e811ff3d-7d81-4205-87af-27dc61d93894" xlink:to="loc_us-gaap_DefinedContributionPlanCostRecognized_66c3fbd0-a0f8-4434-a95e-670ae3bad3f6" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/LiabilityRelatedtotheSaleofFutureRoyaltiesNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#LiabilityRelatedtotheSaleofFutureRoyaltiesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/LiabilityRelatedtotheSaleofFutureRoyaltiesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_602ba645-d546-468e-ad46-8193eac075f9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_602ba645-d546-468e-ad46-8193eac075f9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_3177cd4a-8c45-43e4-835d-5cb1c8077e0a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_602ba645-d546-468e-ad46-8193eac075f9" xlink:to="loc_us-gaap_TypeOfArrangementAxis_3177cd4a-8c45-43e4-835d-5cb1c8077e0a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3177cd4a-8c45-43e4-835d-5cb1c8077e0a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3177cd4a-8c45-43e4-835d-5cb1c8077e0a" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_3177cd4a-8c45-43e4-835d-5cb1c8077e0a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4ec207b7-c574-4948-8165-5c9831cba189" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_3177cd4a-8c45-43e4-835d-5cb1c8077e0a" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4ec207b7-c574-4948-8165-5c9831cba189" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPharmaAgreementMember_ec6b710b-ff57-4dfc-8516-9d2806c73321" xlink:href="arwr-20240930.xsd#arwr_RoyaltyPharmaAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_4ec207b7-c574-4948-8165-5c9831cba189" xlink:to="loc_arwr_RoyaltyPharmaAgreementMember_ec6b710b-ff57-4dfc-8516-9d2806c73321" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_94f3d2ca-471f-4675-8e98-2b4bba3a8198" 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_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_602ba645-d546-468e-ad46-8193eac075f9" xlink:to="loc_srt_RangeAxis_94f3d2ca-471f-4675-8e98-2b4bba3a8198" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_94f3d2ca-471f-4675-8e98-2b4bba3a8198_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_94f3d2ca-471f-4675-8e98-2b4bba3a8198" xlink:to="loc_srt_RangeMember_94f3d2ca-471f-4675-8e98-2b4bba3a8198_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_47075564-fd10-484c-a3b2-9db1736b7666" 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_94f3d2ca-471f-4675-8e98-2b4bba3a8198" xlink:to="loc_srt_RangeMember_47075564-fd10-484c-a3b2-9db1736b7666" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_8648eab6-1df3-4384-87a4-e55a9cd94cad" 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_47075564-fd10-484c-a3b2-9db1736b7666" xlink:to="loc_srt_MaximumMember_8648eab6-1df3-4384-87a4-e55a9cd94cad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_8a5a3781-cf58-483f-b1a9-f3529caab970" xlink:href="arwr-20240930.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_InitialTransactionPrice_8a5a3781-cf58-483f-b1a9-f3529caab970" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_5ca0b82e-b80e-4eec-b91d-d5c135e7cf67" xlink:href="arwr-20240930.xsd#arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_UpfrontPaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_5ca0b82e-b80e-4eec-b91d-d5c135e7cf67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivable_4afe5085-7e8f-48e1-bcfe-d340fc97dc2a" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_MilestonePaymentReceivable_4afe5085-7e8f-48e1-bcfe-d340fc97dc2a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial_182b26b6-3fdf-4432-b877-fee7509b7ad7" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_MilestonePaymentReceivableUponAchievementOfEnrollmentInPhase3ClinicalTrial_182b26b6-3fdf-4432-b877-fee7509b7ad7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponFDAApproval_5bd262b6-6472-4879-8733-6a55b34717ce" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivableUponFDAApproval"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_MilestonePaymentReceivableUponFDAApproval_5bd262b6-6472-4879-8733-6a55b34717ce" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments_f3850077-a32d-490b-b875-3be0043c7a68" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_MilestonePaymentReceivableUponReceiptOfRoyaltyPayments_f3850077-a32d-490b-b875-3be0043c7a68" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_RoyaltyPaymentThreshold_ebd8c9c2-37e0-4216-9672-6d19c7ce7ed7" xlink:href="arwr-20240930.xsd#arwr_RoyaltyPaymentThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_RoyaltyPaymentThreshold_ebd8c9c2-37e0-4216-9672-6d19c7ce7ed7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_6bf39a41-b86c-431b-a10b-49dfb76db64c" xlink:href="arwr-20240930.xsd#arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_MilestonePaymentReceivedLiabilityRelatedToSaleOfFutureRoyalties_6bf39a41-b86c-431b-a10b-49dfb76db64c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_LiabilitySaleOfFutureRoyaltiesInterestRate_4a253a91-c393-4ce8-b51c-4c0ff8223681" xlink:href="arwr-20240930.xsd#arwr_LiabilitySaleOfFutureRoyaltiesInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_4c94e5fe-2d69-402a-9555-3ba0140ec237" xlink:to="loc_arwr_LiabilitySaleOfFutureRoyaltiesInterestRate_4a253a91-c393-4ce8-b51c-4c0ff8223681" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FinancialAgreementNarrativeDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#FinancialAgreementNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FinancialAgreementNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_d6bdaa1f-1317-4130-8bb8-c4ff7f90475d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_d6bdaa1f-1317-4130-8bb8-c4ff7f90475d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296" 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_LineOfCreditFacilityTable_d6bdaa1f-1317-4130-8bb8-c4ff7f90475d" xlink:to="loc_us-gaap_CreditFacilityAxis_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296_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_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296" xlink:to="loc_us-gaap_CreditFacilityDomain_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_90615642-2805-46b6-8ea3-e69c9dfa5a5b" 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_75fdfc9e-92c5-4cbb-b4c9-3572c6fd9296" xlink:to="loc_us-gaap_CreditFacilityDomain_90615642-2805-46b6-8ea3-e69c9dfa5a5b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredDebtMember_6f88b8bf-38ff-460d-a920-34ba37227a31" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_90615642-2805-46b6-8ea3-e69c9dfa5a5b" xlink:to="loc_us-gaap_SecuredDebtMember_6f88b8bf-38ff-460d-a920-34ba37227a31" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_72e838d5-141f-4f22-b20c-c5809f46d203" 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_LineOfCreditFacilityTable_d6bdaa1f-1317-4130-8bb8-c4ff7f90475d" xlink:to="loc_us-gaap_DebtInstrumentAxis_72e838d5-141f-4f22-b20c-c5809f46d203" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_72e838d5-141f-4f22-b20c-c5809f46d203_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_72e838d5-141f-4f22-b20c-c5809f46d203" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_72e838d5-141f-4f22-b20c-c5809f46d203_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_1fd32d9d-f20b-4540-a1c4-281e2e5959c1" 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_72e838d5-141f-4f22-b20c-c5809f46d203" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_1fd32d9d-f20b-4540-a1c4-281e2e5959c1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementMember_9f13e28c-e297-4bab-98ca-933cd3c7f2f4" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_1fd32d9d-f20b-4540-a1c4-281e2e5959c1" xlink:to="loc_arwr_FinancingAgreementMember_9f13e28c-e297-4bab-98ca-933cd3c7f2f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_34b774d4-97bf-4c2c-84ba-b5305b772584" 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_LineOfCreditFacilityTable_d6bdaa1f-1317-4130-8bb8-c4ff7f90475d" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_34b774d4-97bf-4c2c-84ba-b5305b772584" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_34b774d4-97bf-4c2c-84ba-b5305b772584_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_34b774d4-97bf-4c2c-84ba-b5305b772584" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_34b774d4-97bf-4c2c-84ba-b5305b772584_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_5b4371ec-4208-49e5-a6fc-b83d65095ac1" 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_34b774d4-97bf-4c2c-84ba-b5305b772584" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_5b4371ec-4208-49e5-a6fc-b83d65095ac1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_69831188-ddcb-4012-aa07-c746078c6f18" 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_5b4371ec-4208-49e5-a6fc-b83d65095ac1" xlink:to="loc_us-gaap_LineOfCreditMember_69831188-ddcb-4012-aa07-c746078c6f18" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_c7be085e-12ae-4b16-84e4-1dc04c94a941" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_c7be085e-12ae-4b16-84e4-1dc04c94a941" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_22c6af3c-813f-4129-b5e4-0aa3bb4dd346" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_LineOfCredit_22c6af3c-813f-4129-b5e4-0aa3bb4dd346" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_2667cd41-b070-4610-98ac-78b6ccc6fef1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_2667cd41-b070-4610-98ac-78b6ccc6fef1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTerm_903fdd65-6015-4bab-ab78-bfdb68116a1c" 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_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_DebtInstrumentTerm_903fdd65-6015-4bab-ab78-bfdb68116a1c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_db551b63-de7a-4793-a2b6-a3fa71c00b88" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_db551b63-de7a-4793-a2b6-a3fa71c00b88" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_fae5231c-6f55-4b8d-bb62-b53c1ce42ff4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_fae5231c-6f55-4b8d-bb62-b53c1ce42ff4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtInstrumentCovenantMinimumLiquidityIfCapitalizationIsAboveThreshold_6bd1f770-37af-45d0-a119-8ef7c8bc0a23" xlink:href="arwr-20240930.xsd#arwr_DebtInstrumentCovenantMinimumLiquidityIfCapitalizationIsAboveThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_arwr_DebtInstrumentCovenantMinimumLiquidityIfCapitalizationIsAboveThreshold_6bd1f770-37af-45d0-a119-8ef7c8bc0a23" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DebtInstrumentCovenantMarketCapitalizationThreshold_3564d09a-812e-40f8-b13e-3aa93b0feec6" xlink:href="arwr-20240930.xsd#arwr_DebtInstrumentCovenantMarketCapitalizationThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_arwr_DebtInstrumentCovenantMarketCapitalizationThreshold_3564d09a-812e-40f8-b13e-3aa93b0feec6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_18b66bc4-1c7b-4788-802a-b769cf77a4d7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_af8b4f73-38db-42b8-b4fa-6e0e0aa1d65d" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_18b66bc4-1c7b-4788-802a-b769cf77a4d7" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FinancingAgreementOutstandingBalanceofCreditFacilityDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#FinancingAgreementOutstandingBalanceofCreditFacilityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FinancingAgreementOutstandingBalanceofCreditFacilityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_b4ffe965-8d14-439d-a3ba-5563b938c5fe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_0899b492-63d4-47b3-a786-8ad68923881e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_b4ffe965-8d14-439d-a3ba-5563b938c5fe" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_0899b492-63d4-47b3-a786-8ad68923881e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_c7609dcf-e9d7-43d4-8ac8-295e31149225" 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_LineOfCreditFacilityTable_0899b492-63d4-47b3-a786-8ad68923881e" xlink:to="loc_us-gaap_CreditFacilityAxis_c7609dcf-e9d7-43d4-8ac8-295e31149225" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_c7609dcf-e9d7-43d4-8ac8-295e31149225_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_c7609dcf-e9d7-43d4-8ac8-295e31149225" xlink:to="loc_us-gaap_CreditFacilityDomain_c7609dcf-e9d7-43d4-8ac8-295e31149225_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_277574ea-914e-4377-af9f-bf3e2c9f3a25" 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_c7609dcf-e9d7-43d4-8ac8-295e31149225" xlink:to="loc_us-gaap_CreditFacilityDomain_277574ea-914e-4377-af9f-bf3e2c9f3a25" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredDebtMember_89c003c7-85c9-4aa2-a013-dd8df963a137" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_277574ea-914e-4377-af9f-bf3e2c9f3a25" xlink:to="loc_us-gaap_SecuredDebtMember_89c003c7-85c9-4aa2-a013-dd8df963a137" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5" 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_LineOfCreditFacilityTable_0899b492-63d4-47b3-a786-8ad68923881e" xlink:to="loc_us-gaap_DebtInstrumentAxis_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5_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_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_ae5f9e78-8c92-417e-a83f-9268969c1cee" 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_28e8f9d7-c727-4462-94b1-8dbd6d1f5ac5" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_ae5f9e78-8c92-417e-a83f-9268969c1cee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementMember_8e8b6a9d-a234-4458-9a59-ff99eb316d72" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_ae5f9e78-8c92-417e-a83f-9268969c1cee" xlink:to="loc_arwr_FinancingAgreementMember_8e8b6a9d-a234-4458-9a59-ff99eb316d72" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementInitialTermLoanMember_cd72d53a-3143-4d73-baf0-bdda81f53e62" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementInitialTermLoanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_FinancingAgreementMember_8e8b6a9d-a234-4458-9a59-ff99eb316d72" xlink:to="loc_arwr_FinancingAgreementInitialTermLoanMember_cd72d53a-3143-4d73-baf0-bdda81f53e62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementInitialTermLoanInterestMember_9027b1d9-934d-4aa0-96e6-73958a52e8e2" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementInitialTermLoanInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_arwr_FinancingAgreementMember_8e8b6a9d-a234-4458-9a59-ff99eb316d72" xlink:to="loc_arwr_FinancingAgreementInitialTermLoanInterestMember_9027b1d9-934d-4aa0-96e6-73958a52e8e2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1" 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_LineOfCreditFacilityTable_0899b492-63d4-47b3-a786-8ad68923881e" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1_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_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_d45873af-cf53-4272-a910-efa7157629ee" 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_40ed2feb-bdf9-4d57-b7f0-7836ed36a4c1" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_d45873af-cf53-4272-a910-efa7157629ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_ad17300b-8257-497e-b253-4fc3215d9f68" 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_d45873af-cf53-4272-a910-efa7157629ee" xlink:to="loc_us-gaap_LineOfCreditMember_ad17300b-8257-497e-b253-4fc3215d9f68" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_3d31bd22-c4ff-4db3-ab39-0e69bb986f9d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_b4ffe965-8d14-439d-a3ba-5563b938c5fe" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_3d31bd22-c4ff-4db3-ab39-0e69bb986f9d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_936572cb-f611-4244-acd3-f0096a5fe54c" 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_LineOfCreditFacilityLineItems_b4ffe965-8d14-439d-a3ba-5563b938c5fe" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_936572cb-f611-4244-acd3-f0096a5fe54c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_2ce759fc-1cff-4e6d-9c16-c5a3dbe229cc" 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_LineOfCreditFacilityLineItems_b4ffe965-8d14-439d-a3ba-5563b938c5fe" xlink:to="loc_us-gaap_LongTermDebt_2ce759fc-1cff-4e6d-9c16-c5a3dbe229cc" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FinancingAgreementInterestExpenseRecognizedRelatedtoCreditFacilityDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#FinancingAgreementInterestExpenseRecognizedRelatedtoCreditFacilityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FinancingAgreementInterestExpenseRecognizedRelatedtoCreditFacilityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_ca76d150-6c25-4eac-ba39-5284ff5e49d6" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_8d9fcd6e-b589-4cc2-aaac-346bd8c60978" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_ca76d150-6c25-4eac-ba39-5284ff5e49d6" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_8d9fcd6e-b589-4cc2-aaac-346bd8c60978" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0" 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_LineOfCreditFacilityTable_8d9fcd6e-b589-4cc2-aaac-346bd8c60978" xlink:to="loc_us-gaap_CreditFacilityAxis_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0_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_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0" xlink:to="loc_us-gaap_CreditFacilityDomain_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_3b2e6e55-ef63-4580-950e-67d5cec497cc" 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_836c2d69-29de-49fc-ade1-b1c2bd7ec6f0" xlink:to="loc_us-gaap_CreditFacilityDomain_3b2e6e55-ef63-4580-950e-67d5cec497cc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredDebtMember_c8e96c80-8ad9-48f6-9f14-a9505ff6836e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_3b2e6e55-ef63-4580-950e-67d5cec497cc" xlink:to="loc_us-gaap_SecuredDebtMember_c8e96c80-8ad9-48f6-9f14-a9505ff6836e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_71ef71e6-affa-4867-be12-0ab432c6e58a" 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_LineOfCreditFacilityTable_8d9fcd6e-b589-4cc2-aaac-346bd8c60978" xlink:to="loc_us-gaap_DebtInstrumentAxis_71ef71e6-affa-4867-be12-0ab432c6e58a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_71ef71e6-affa-4867-be12-0ab432c6e58a_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_71ef71e6-affa-4867-be12-0ab432c6e58a" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_71ef71e6-affa-4867-be12-0ab432c6e58a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_8f56e418-da83-4248-aeff-4f75d87c6a2d" 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_71ef71e6-affa-4867-be12-0ab432c6e58a" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_8f56e418-da83-4248-aeff-4f75d87c6a2d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementMember_7470d0b8-f983-45f3-bfcc-bc67f5bbf8d0" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_8f56e418-da83-4248-aeff-4f75d87c6a2d" xlink:to="loc_arwr_FinancingAgreementMember_7470d0b8-f983-45f3-bfcc-bc67f5bbf8d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_b3801b3b-7582-45e1-93a7-4f047412af13" 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_LineOfCreditFacilityTable_8d9fcd6e-b589-4cc2-aaac-346bd8c60978" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_b3801b3b-7582-45e1-93a7-4f047412af13" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_b3801b3b-7582-45e1-93a7-4f047412af13_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_b3801b3b-7582-45e1-93a7-4f047412af13" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_b3801b3b-7582-45e1-93a7-4f047412af13_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_fc900f8b-ad2b-40f2-ac57-b13e5fa2af5a" 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_b3801b3b-7582-45e1-93a7-4f047412af13" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_fc900f8b-ad2b-40f2-ac57-b13e5fa2af5a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_a189c1b2-dbe2-4de5-9aa3-aa8a1d8c68e8" 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_fc900f8b-ad2b-40f2-ac57-b13e5fa2af5a" xlink:to="loc_us-gaap_LineOfCreditMember_a189c1b2-dbe2-4de5-9aa3-aa8a1d8c68e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_dbc01178-3b67-485b-a481-f651821cb723" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AmortizationOfFinancingCostsAndDiscounts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_ca76d150-6c25-4eac-ba39-5284ff5e49d6" xlink:to="loc_us-gaap_AmortizationOfFinancingCostsAndDiscounts_dbc01178-3b67-485b-a481-f651821cb723" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebtExcludingAmortization_9c9381d8-e8dc-4d9c-b602-5d2676186b50" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestExpenseDebtExcludingAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_ca76d150-6c25-4eac-ba39-5284ff5e49d6" xlink:to="loc_us-gaap_InterestExpenseDebtExcludingAmortization_9c9381d8-e8dc-4d9c-b602-5d2676186b50" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_7a82cfb7-d2c8-4f40-8181-c338539deef5" 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_LineOfCreditFacilityLineItems_ca76d150-6c25-4eac-ba39-5284ff5e49d6" xlink:to="loc_us-gaap_InterestExpenseDebt_7a82cfb7-d2c8-4f40-8181-c338539deef5" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/FinancingAgreementPrincipalRepaymentRelatedtoCreditFacilityDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#FinancingAgreementPrincipalRepaymentRelatedtoCreditFacilityDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/FinancingAgreementPrincipalRepaymentRelatedtoCreditFacilityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_3bf32aa8-9003-4635-8f02-0499a5b1e1cb" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LineOfCreditFacilityTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_3bf32aa8-9003-4635-8f02-0499a5b1e1cb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_22f83987-21fa-4ca4-aa82-432a23fe2f58" 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_LineOfCreditFacilityTable_3bf32aa8-9003-4635-8f02-0499a5b1e1cb" xlink:to="loc_us-gaap_DebtInstrumentAxis_22f83987-21fa-4ca4-aa82-432a23fe2f58" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_22f83987-21fa-4ca4-aa82-432a23fe2f58_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_22f83987-21fa-4ca4-aa82-432a23fe2f58" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_22f83987-21fa-4ca4-aa82-432a23fe2f58_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_72e5df17-9539-4424-abc3-fb96793d181e" 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_22f83987-21fa-4ca4-aa82-432a23fe2f58" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_72e5df17-9539-4424-abc3-fb96793d181e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_FinancingAgreementMember_76885861-2afd-4714-8522-fc99bf8954ea" xlink:href="arwr-20240930.xsd#arwr_FinancingAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_72e5df17-9539-4424-abc3-fb96793d181e" xlink:to="loc_arwr_FinancingAgreementMember_76885861-2afd-4714-8522-fc99bf8954ea" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_8d1e6a54-3366-43de-86df-799828f33102" 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_LineOfCreditFacilityTable_3bf32aa8-9003-4635-8f02-0499a5b1e1cb" xlink:to="loc_us-gaap_CreditFacilityAxis_8d1e6a54-3366-43de-86df-799828f33102" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_8d1e6a54-3366-43de-86df-799828f33102_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_8d1e6a54-3366-43de-86df-799828f33102" xlink:to="loc_us-gaap_CreditFacilityDomain_8d1e6a54-3366-43de-86df-799828f33102_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_99b48fa5-7043-465c-9348-c7ad2e3f8e36" 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_8d1e6a54-3366-43de-86df-799828f33102" xlink:to="loc_us-gaap_CreditFacilityDomain_99b48fa5-7043-465c-9348-c7ad2e3f8e36" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SecuredDebtMember_97df30c8-7936-4e86-9468-f9612b211ecd" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SecuredDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_99b48fa5-7043-465c-9348-c7ad2e3f8e36" xlink:to="loc_us-gaap_SecuredDebtMember_97df30c8-7936-4e86-9468-f9612b211ecd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_145adb39-7101-4b11-b013-23345cc4e2c2" 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_LineOfCreditFacilityTable_3bf32aa8-9003-4635-8f02-0499a5b1e1cb" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_145adb39-7101-4b11-b013-23345cc4e2c2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_145adb39-7101-4b11-b013-23345cc4e2c2_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_145adb39-7101-4b11-b013-23345cc4e2c2" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_145adb39-7101-4b11-b013-23345cc4e2c2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_47c240c5-509b-4b2a-addb-518e3b282156" 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_145adb39-7101-4b11-b013-23345cc4e2c2" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_47c240c5-509b-4b2a-addb-518e3b282156" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_4e833645-b9ba-4350-8a68-0a4a00f4cdcb" 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_47c240c5-509b-4b2a-addb-518e3b282156" xlink:to="loc_us-gaap_LineOfCreditMember_4e833645-b9ba-4350-8a68-0a4a00f4cdcb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_84bfb7f3-c559-41c8-9487-f3565811c505" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInNextTwelveMonths_84bfb7f3-c559-41c8-9487-f3565811c505" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_f92b10b9-7f3f-4d03-9822-0c1d76d160d1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearTwo_f92b10b9-7f3f-4d03-9822-0c1d76d160d1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_6bdc2f7c-34e4-4784-aaaf-09977321c169" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearThree_6bdc2f7c-34e4-4784-aaaf-09977321c169" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_4c05df2b-44ab-458c-b8c4-678c7b751d8f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFour_4c05df2b-44ab-458c-b8c4-678c7b751d8f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_9f346e4d-4aeb-4be7-ac7d-da1769ba8e42" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalInYearFive_9f346e4d-4aeb-4be7-ac7d-da1769ba8e42" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_14f1d46b-0e07-48ee-8956-833c146a3364" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_LongTermDebtMaturitiesRepaymentsOfPrincipalAfterYearFive_14f1d46b-0e07-48ee-8956-833c146a3364" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_a31f1eaa-b356-45da-ab6a-a6ff6a7848a9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_8c20993f-b2b0-4dbf-a671-9e8d3dc58b1c" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_a31f1eaa-b356-45da-ab6a-a6ff6a7848a9" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/NetLossPerShareAntidulitiveDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#NetLossPerShareAntidulitiveDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/NetLossPerShareAntidulitiveDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a4b8aa8a-07b6-46b3-9182-b826738ecb41" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_51636512-ebd8-4957-a382-2c0d816c3ba2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a4b8aa8a-07b6-46b3-9182-b826738ecb41" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_51636512-ebd8-4957-a382-2c0d816c3ba2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_70b0ed2e-9d65-41d7-836d-85bfd6535c6b" 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_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_51636512-ebd8-4957-a382-2c0d816c3ba2" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_70b0ed2e-9d65-41d7-836d-85bfd6535c6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_70b0ed2e-9d65-41d7-836d-85bfd6535c6b_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_70b0ed2e-9d65-41d7-836d-85bfd6535c6b" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_70b0ed2e-9d65-41d7-836d-85bfd6535c6b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_9a3dba9c-9c7b-4bee-81da-cc04c04d9431" 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_70b0ed2e-9d65-41d7-836d-85bfd6535c6b" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_9a3dba9c-9c7b-4bee-81da-cc04c04d9431" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_8dd04559-0524-44c8-81fc-ee62343b4a8c" 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_9a3dba9c-9c7b-4bee-81da-cc04c04d9431" xlink:to="loc_us-gaap_EmployeeStockOptionMember_8dd04559-0524-44c8-81fc-ee62343b4a8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_65dd5bd5-e852-4879-96f4-fccba3694ff2" 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_9a3dba9c-9c7b-4bee-81da-cc04c04d9431" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_65dd5bd5-e852-4879-96f4-fccba3694ff2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4f1adb67-08db-435e-9f7b-5b5bbb3cd945" 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_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_a4b8aa8a-07b6-46b3-9182-b826738ecb41" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_4f1adb67-08db-435e-9f7b-5b5bbb3cd945" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.arrowheadresearch.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="arwr-20240930.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.arrowheadresearch.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_8b8928b0-677b-4f41-a4c0-1b55b6ac339b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_8b8928b0-677b-4f41-a4c0-1b55b6ac339b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_8b8928b0-677b-4f41-a4c0-1b55b6ac339b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_8b8928b0-677b-4f41-a4c0-1b55b6ac339b" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_8b8928b0-677b-4f41-a4c0-1b55b6ac339b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_8168f9f1-b5c1-495d-915f-06abf23a11dc" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_8b8928b0-677b-4f41-a4c0-1b55b6ac339b" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_8168f9f1-b5c1-495d-915f-06abf23a11dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_c391f0b7-e431-4ba3-bf08-3b0b0a408d00" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_8168f9f1-b5c1-495d-915f-06abf23a11dc" xlink:to="loc_us-gaap_SubsequentEventMember_c391f0b7-e431-4ba3-bf08-3b0b0a408d00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_781d352a-9fe7-46f6-92aa-18feb7ff1789" 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_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_srt_CounterpartyNameAxis_781d352a-9fe7-46f6-92aa-18feb7ff1789" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_781d352a-9fe7-46f6-92aa-18feb7ff1789_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_781d352a-9fe7-46f6-92aa-18feb7ff1789" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_781d352a-9fe7-46f6-92aa-18feb7ff1789_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7a05f262-bc99-4196-99c9-dee882fe8575" 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_781d352a-9fe7-46f6-92aa-18feb7ff1789" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7a05f262-bc99-4196-99c9-dee882fe8575" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SareptaMember_5261c222-3ab2-4e60-a84e-faf3d2d53232" xlink:href="arwr-20240930.xsd#arwr_SareptaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7a05f262-bc99-4196-99c9-dee882fe8575" xlink:to="loc_arwr_SareptaMember_5261c222-3ab2-4e60-a84e-faf3d2d53232" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_6bf522b2-07cf-4c80-a186-835d96cc398d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_us-gaap_TypeOfArrangementAxis_6bf522b2-07cf-4c80-a186-835d96cc398d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_6bf522b2-07cf-4c80-a186-835d96cc398d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_6bf522b2-07cf-4c80-a186-835d96cc398d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_6bf522b2-07cf-4c80-a186-835d96cc398d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_40475f7c-e334-468d-80c4-a5f72595c49d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_6bf522b2-07cf-4c80-a186-835d96cc398d" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_40475f7c-e334-468d-80c4-a5f72595c49d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SareptaCollaborationAgreementMember_889b14c2-2769-46a9-b5a6-863d29e59841" xlink:href="arwr-20240930.xsd#arwr_SareptaCollaborationAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_40475f7c-e334-468d-80c4-a5f72595c49d" xlink:to="loc_arwr_SareptaCollaborationAgreementMember_889b14c2-2769-46a9-b5a6-863d29e59841" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_5be55e79-35ae-4dec-b2f8-72e32c16fa49" 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_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_srt_RangeAxis_5be55e79-35ae-4dec-b2f8-72e32c16fa49" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_5be55e79-35ae-4dec-b2f8-72e32c16fa49_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_5be55e79-35ae-4dec-b2f8-72e32c16fa49" xlink:to="loc_srt_RangeMember_5be55e79-35ae-4dec-b2f8-72e32c16fa49_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e9fda4cd-8571-4c1c-a5e6-38ac097670e8" 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_5be55e79-35ae-4dec-b2f8-72e32c16fa49" xlink:to="loc_srt_RangeMember_e9fda4cd-8571-4c1c-a5e6-38ac097670e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_cca276a0-8cf3-478d-b182-307eac7da6ef" 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_e9fda4cd-8571-4c1c-a5e6-38ac097670e8" xlink:to="loc_srt_MaximumMember_cca276a0-8cf3-478d-b182-307eac7da6ef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_4f7b5bd8-45df-409e-8a31-cc598de94d03" 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_e9fda4cd-8571-4c1c-a5e6-38ac097670e8" xlink:to="loc_srt_MinimumMember_4f7b5bd8-45df-409e-8a31-cc598de94d03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_1b6866c0-8291-4635-90eb-6a6596ab3db0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_1b6866c0-8291-4635-90eb-6a6596ab3db0" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_1b6866c0-8291-4635-90eb-6a6596ab3db0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_1b6866c0-8291-4635-90eb-6a6596ab3db0" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_1b6866c0-8291-4635-90eb-6a6596ab3db0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_08a6594d-211e-4ad3-8c55-dde8c8fcd402" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_1b6866c0-8291-4635-90eb-6a6596ab3db0" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_08a6594d-211e-4ad3-8c55-dde8c8fcd402" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrivatePlacementMember_22c4d3dc-19ae-425f-b31e-d2c3568ae893" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PrivatePlacementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_08a6594d-211e-4ad3-8c55-dde8c8fcd402" xlink:to="loc_us-gaap_PrivatePlacementMember_22c4d3dc-19ae-425f-b31e-d2c3568ae893" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_c1fa840e-ccaf-44dd-8d07-66617f578ec5" 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_SubsequentEventTable_7eb43dbd-a410-4f4c-8097-1eeeebb23cf0" xlink:to="loc_srt_StatementScenarioAxis_c1fa840e-ccaf-44dd-8d07-66617f578ec5" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_c1fa840e-ccaf-44dd-8d07-66617f578ec5_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_c1fa840e-ccaf-44dd-8d07-66617f578ec5" xlink:to="loc_srt_ScenarioUnspecifiedDomain_c1fa840e-ccaf-44dd-8d07-66617f578ec5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_58a5cb61-9e4c-47b1-8cc3-e8313339b3f8" 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_c1fa840e-ccaf-44dd-8d07-66617f578ec5" xlink:to="loc_srt_ScenarioUnspecifiedDomain_58a5cb61-9e4c-47b1-8cc3-e8313339b3f8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_0ac5e656-8027-430b-9f96-5667fcfd7e5d" 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_58a5cb61-9e4c-47b1-8cc3-e8313339b3f8" xlink:to="loc_srt_ScenarioForecastMember_0ac5e656-8027-430b-9f96-5667fcfd7e5d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfNewTargetPrograms_297c3d44-f47a-4e53-a4b2-9ef62e2a809a" xlink:href="arwr-20240930.xsd#arwr_NumberOfNewTargetPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_NumberOfNewTargetPrograms_297c3d44-f47a-4e53-a4b2-9ef62e2a809a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_3921f95e-8c9c-456e-8145-d19ab735e90a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_3921f95e-8c9c-456e-8145-d19ab735e90a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_f3e8f99e-19be-4b71-b15b-7264cd29cc7e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_f3e8f99e-19be-4b71-b15b-7264cd29cc7e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_ac236460-1164-4d29-80a4-1684c9645650" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_ac236460-1164-4d29-80a4-1684c9645650" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_InitialTransactionPrice_622d3b3d-d86c-4015-bd8e-bf009304fbe8" xlink:href="arwr-20240930.xsd#arwr_InitialTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_InitialTransactionPrice_622d3b3d-d86c-4015-bd8e-bf009304fbe8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivableUnderCollaborationAgreement_a937d8b8-e4f2-407f-a83d-9a3bf93b5e2b" xlink:href="arwr-20240930.xsd#arwr_CashReceivableUnderCollaborationAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_CashReceivableUnderCollaborationAgreement_a937d8b8-e4f2-407f-a83d-9a3bf93b5e2b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivableUnderCollaborationAgreementAnnualInstallments_e49190c1-521e-4a0c-9a1c-3d187e9f44fc" xlink:href="arwr-20240930.xsd#arwr_CashReceivableUnderCollaborationAgreementAnnualInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_CashReceivableUnderCollaborationAgreementAnnualInstallments_e49190c1-521e-4a0c-9a1c-3d187e9f44fc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_CashReceivableUnderCollaborationAgreementAnnualInstallmentsPeriod_4a8846b6-d903-4287-acbe-5f800d55a68b" xlink:href="arwr-20240930.xsd#arwr_CashReceivableUnderCollaborationAgreementAnnualInstallmentsPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_CashReceivableUnderCollaborationAgreementAnnualInstallmentsPeriod_4a8846b6-d903-4287-acbe-5f800d55a68b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_EnrollmentRelatedMilestonePayments_b6c5f603-c182-4eec-a376-2e0550af3330" xlink:href="arwr-20240930.xsd#arwr_EnrollmentRelatedMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_EnrollmentRelatedMilestonePayments_b6c5f603-c182-4eec-a376-2e0550af3330" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_NumberOfCollaborationPrograms_34dc3f17-4241-428d-8047-29da2ed2fff4" xlink:href="arwr-20240930.xsd#arwr_NumberOfCollaborationPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_NumberOfCollaborationPrograms_34dc3f17-4241-428d-8047-29da2ed2fff4" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DevelopmentMilestonePayments_1237d596-63ce-425a-8b30-a7627efdcfb9" xlink:href="arwr-20240930.xsd#arwr_DevelopmentMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_DevelopmentMilestonePayments_1237d596-63ce-425a-8b30-a7627efdcfb9" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_SalesRelatedMilestonePayments_c3f158eb-3a2f-45d6-8e1b-bbb252156f24" xlink:href="arwr-20240930.xsd#arwr_SalesRelatedMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_SalesRelatedMilestonePayments_c3f158eb-3a2f-45d6-8e1b-bbb252156f24" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_4cade1ae-ffae-4a55-a65b-e9575cf0dca2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_4cade1ae-ffae-4a55-a65b-e9575cf0dca2" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_4476cfb8-26e8-47e0-b25f-4c92740cd36d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_4476cfb8-26e8-47e0-b25f-4c92740cd36d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_eb3894cd-5b82-4573-8e28-b9c4033b737b" xlink:href="arwr-20240930.xsd#arwr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_arwr_ClassOfWarrantOrRightPurchasePriceOfWarrantsOrRights_eb3894cd-5b82-4573-8e28-b9c4033b737b" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfWarrants_2fc61656-0c5b-4bc0-ba52-54e0df068ed7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_0b90e343-92e6-4acb-b400-51096efd39f2" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfWarrants_2fc61656-0c5b-4bc0-ba52-54e0df068ed7" xlink:type="arc" order="15"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/TradingArrangementsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#TradingArrangmentsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/TradingArrangementsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllTradingArrangementsMember" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllTradingArrangementsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ChristopherAnzaloneAugust162024PlanMember_46186b3c-b814-4814-84e2-354e7919b0dd" xlink:href="arwr-20240930.xsd#arwr_ChristopherAnzaloneAugust162024PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllTradingArrangementsMember" xlink:to="loc_arwr_ChristopherAnzaloneAugust162024PlanMember_46186b3c-b814-4814-84e2-354e7919b0dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ChristopherAnzaloneAugust222024PlanMember_a1411133-6c19-468d-abb9-9ba97d8f0d63" xlink:href="arwr-20240930.xsd#arwr_ChristopherAnzaloneAugust222024PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllTradingArrangementsMember" xlink:to="loc_arwr_ChristopherAnzaloneAugust222024PlanMember_a1411133-6c19-468d-abb9-9ba97d8f0d63" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ChristopherAnzaloneSeptember2024PlanMember_d899e331-6fd8-4c64-af75-62b73dfe0432" xlink:href="arwr-20240930.xsd#arwr_ChristopherAnzaloneSeptember2024PlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllTradingArrangementsMember" xlink:to="loc_arwr_ChristopherAnzaloneSeptember2024PlanMember_d899e331-6fd8-4c64-af75-62b73dfe0432" xlink:type="arc" order="3"/>
  </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://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_AdeoyeOlukotunMember_d82278ff-b2cc-4824-a59a-134b811860cc" xlink:href="arwr-20240930.xsd#arwr_AdeoyeOlukotunMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_arwr_AdeoyeOlukotunMember_d82278ff-b2cc-4824-a59a-134b811860cc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_ChristopherAnzaloneMember_de24dc27-be9a-49f9-a57a-889cd54b3e2c" xlink:href="arwr-20240930.xsd#arwr_ChristopherAnzaloneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_arwr_ChristopherAnzaloneMember_de24dc27-be9a-49f9-a57a-889cd54b3e2c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_DouglassGivenMember_5809861d-ad0f-4ffe-8cc7-02c26b3fae40" xlink:href="arwr-20240930.xsd#arwr_DouglassGivenMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_arwr_DouglassGivenMember_5809861d-ad0f-4ffe-8cc7-02c26b3fae40" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_arwr_JamesHamiltonMember_ba8ebf1d-b815-452b-85e1-b4778f50ea82" xlink:href="arwr-20240930.xsd#arwr_JamesHamiltonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_arwr_JamesHamiltonMember_ba8ebf1d-b815-452b-85e1-b4778f50ea82" xlink:type="arc" order="5"/>
  </link:definitionLink>
</link:linkbase>
