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        <link:definition>40901 - Disclosure - Income Taxes (Details)</link:definition>
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        <link:definition>41401 - Disclosure - Commitments and Contingencies (Details)</link:definition>
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        <link:usedOn>link:calculationLink</link:usedOn>
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      <link:linkbaseRef xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="rytm-20240331_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple" />
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  <xsd:element name="EmploymentInducementPlan2022Member" id="rytm_EmploymentInducementPlan2022Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
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  <xsd:element name="LicenseAgreementUpfrontConsideration" id="rytm_LicenseAgreementUpfrontConsideration" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
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  <xsd:element name="AnnualNetRevenuesBetween125MillionAnd300MillionMember" id="rytm_AnnualNetRevenuesBetween125MillionAnd300MillionMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="AnnualNetRevenuesExceeding300MillionMember" id="rytm_AnnualNetRevenuesExceeding300MillionMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" id="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" id="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" id="rytm_PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="ThresholdAnnualNetRevenuesForRoyaltyInterest" id="rytm_ThresholdAnnualNetRevenuesForRoyaltyInterest" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" id="rytm_ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="RevenueInterestsPayableCapAsPercentOfInvestmentAmount" id="rytm_RevenueInterestsPayableCapAsPercentOfInvestmentAmount" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="RevenueInterestPaymentPeriodFromInitialClosing" id="rytm_RevenueInterestPaymentPeriodFromInitialClosing" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
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  <xsd:element name="NonCashInterestExpenseAndAmortizationOfDebtIssuanceCosts" id="rytm_NonCashInterestExpenseAndAmortizationOfDebtIssuanceCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
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  <xsd:element name="NumberOfIndependentSubStudiesInPatients" id="rytm_NumberOfIndependentSubStudiesInPatients" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
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  <xsd:element name="CommercialRegulatoryApprovalAndMilestonePayments" id="rytm_CommercialRegulatoryApprovalAndMilestonePayments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
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  <xsd:element name="ProceedsFromRoyaltyFinancingAgreement" id="rytm_ProceedsFromRoyaltyFinancingAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
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  <xsd:element name="AcquiredInProcessResearchAndDevelopmentAssetsClassifiedAsInvestingActivities" id="rytm_AcquiredInProcessResearchAndDevelopmentAssetsClassifiedAsInvestingActivities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
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  <xsd:element name="RightsOfCompoundLB54640Member" id="rytm_RightsOfCompoundLB54640Member" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
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  <xsd:element name="DurationToCheckPrimaryEndPointOfTreatmentInSignalTrial" id="rytm_DurationToCheckPrimaryEndPointOfTreatmentInSignalTrial" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
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  <xsd:element name="NoncashOrPartNoncashAcquisitionNoncashFinancialOrEquityInstrumentConsiderationValueSharesIssued" id="rytm_NoncashOrPartNoncashAcquisitionNoncashFinancialOrEquityInstrumentConsiderationValueSharesIssued" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="InvestorsAndAffiliatedEntitiesPercentageOfOwnershipBeforeTransaction" id="rytm_InvestorsAndAffiliatedEntitiesPercentageOfOwnershipBeforeTransaction" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="DurationMilestonePaymentsNotExpectingToBePaid" id="rytm_DurationMilestonePaymentsNotExpectingToBePaid" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LiquidationPreference" id="rytm_LiquidationPreference" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="StepUpInterestRatePercentage" id="rytm_StepUpInterestRatePercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
  <xsd:element name="LimitedVotingRightsShares" id="rytm_LimitedVotingRightsShares" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" />
</xsd:schema>
