Form 10-K FIBROGEN INC For: Dec 31

March 1, 2021 4:25 PM EST

News and research before you hear about it on CNBC and others. Claim your 1-week free trial to StreetInsider Premium here.
fgen-10k_20201231.htm
false FY 0000921299 --12-31 P3Y P3Y P3Y P3Y 0 0 0 true false 0 0 0 0 fgen:AccruedAndOtherCurrentLiabilitiesMember fgen:AccruedAndOtherCurrentLiabilitiesMember us-gaap:OtherNoncurrentLiabilitiesMember us-gaap:OtherNoncurrentLiabilitiesMember P2Y10M24D P3Y7M6D P1Y9M18D P2Y1M6D P6Y7M6D P6Y6M P5Y1M6D P5Y8M12D P5Y3M18D P5Y4M24D P6M P6M P6M 0.475 0.481 0.473 0.001 0.013 0.008 P2Y P2Y P2Y 0.771 0.621 0.753 0.029 0.029 0.029 us-gaap:ProductMember us-gaap:ProductMember us-gaap:ProductMember 0000921299 2020-01-01 2020-12-31 xbrli:shares 0000921299 2021-01-31 iso4217:USD 0000921299 2020-06-30 0000921299 2020-12-31 0000921299 2019-12-31 iso4217:USD xbrli:shares 0000921299 us-gaap:LicenseMember 2020-01-01 2020-12-31 0000921299 us-gaap:LicenseMember 2019-01-01 2019-12-31 0000921299 us-gaap:LicenseMember 2018-01-01 2018-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember 2020-01-01 2020-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember 2019-01-01 2019-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember 2018-01-01 2018-12-31 0000921299 us-gaap:ProductMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember 2019-01-01 2019-12-31 0000921299 us-gaap:ProductMember 2018-01-01 2018-12-31 0000921299 fgen:DrugProductRevenueMember 2020-01-01 2020-12-31 0000921299 fgen:DrugProductRevenueMember 2019-01-01 2019-12-31 0000921299 fgen:DrugProductRevenueMember 2018-01-01 2018-12-31 0000921299 2019-01-01 2019-12-31 0000921299 2018-01-01 2018-12-31 0000921299 fgen:AstellasCollaborationAgreementMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasCollaborationAgreementMember 2018-01-01 2018-12-31 0000921299 us-gaap:CommonStockMember 2017-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2017-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2017-12-31 0000921299 us-gaap:RetainedEarningsMember 2017-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2017-12-31 0000921299 2017-12-31 0000921299 us-gaap:CommonStockMember us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:RetainedEarningsMember us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:NoncontrollingInterestMember us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:AccountingStandardsUpdate201601Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2017-12-31 0000921299 us-gaap:CommonStockMember 2018-01-01 2018-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2018-01-01 2018-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2018-01-01 2018-12-31 0000921299 us-gaap:RetainedEarningsMember 2018-01-01 2018-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2018-01-01 2018-12-31 0000921299 us-gaap:CommonStockMember 2018-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2018-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2018-12-31 0000921299 us-gaap:RetainedEarningsMember 2018-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2018-12-31 0000921299 2018-12-31 0000921299 us-gaap:CommonStockMember us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:RetainedEarningsMember us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:NoncontrollingInterestMember us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AccountingStandardsUpdate201602Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:CommonStockMember us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:RetainedEarningsMember us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:NoncontrollingInterestMember us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:AccountingStandardsUpdate201802Member srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember 2018-12-31 0000921299 us-gaap:CommonStockMember 2019-01-01 2019-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2019-01-01 2019-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2019-01-01 2019-12-31 0000921299 us-gaap:RetainedEarningsMember 2019-01-01 2019-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2019-01-01 2019-12-31 0000921299 us-gaap:CommonStockMember 2019-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2019-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2019-12-31 0000921299 us-gaap:RetainedEarningsMember 2019-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2019-12-31 0000921299 us-gaap:CommonStockMember 2020-01-01 2020-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2020-01-01 2020-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2020-01-01 2020-12-31 0000921299 us-gaap:RetainedEarningsMember 2020-01-01 2020-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2020-01-01 2020-12-31 0000921299 us-gaap:CommonStockMember 2020-12-31 0000921299 us-gaap:AdditionalPaidInCapitalMember 2020-12-31 0000921299 us-gaap:AccumulatedOtherComprehensiveIncomeMember 2020-12-31 0000921299 us-gaap:RetainedEarningsMember 2020-12-31 0000921299 us-gaap:NoncontrollingInterestMember 2020-12-31 0000921299 country:JP 2020-01-01 2020-12-31 0000921299 srt:EuropeMember 2020-01-01 2020-12-31 0000921299 fgen:UnitedStatesRestOfWorldAndChinaMember 2020-01-01 2020-12-31 fgen:Segment 0000921299 2020-04-01 xbrli:pure 0000921299 us-gaap:AccountsReceivableMember us-gaap:CreditConcentrationRiskMember fgen:AstellasCollaborationAgreementMember 2020-01-01 2020-12-31 0000921299 us-gaap:AccountsReceivableMember us-gaap:CreditConcentrationRiskMember fgen:AstellasCollaborationAgreementMember 2019-01-01 2019-12-31 0000921299 us-gaap:AccountsReceivableMember us-gaap:CreditConcentrationRiskMember fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 us-gaap:AccountsReceivableMember us-gaap:CreditConcentrationRiskMember fgen:AstraZenecaAgreementsMember 2019-01-01 2019-12-31 0000921299 fgen:AccountsReceivableFromDistributorsMember us-gaap:CreditConcentrationRiskMember 2020-01-01 2020-12-31 0000921299 us-gaap:GeographicDistributionForeignMember 2020-12-31 0000921299 us-gaap:GeographicDistributionForeignMember 2019-12-31 0000921299 srt:MinimumMember us-gaap:ComputerEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MaximumMember us-gaap:ComputerEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MinimumMember fgen:LaboratoryEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MaximumMember fgen:LaboratoryEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MinimumMember us-gaap:MachineryAndEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MaximumMember us-gaap:MachineryAndEquipmentMember 2020-01-01 2020-12-31 0000921299 srt:MinimumMember us-gaap:FurnitureAndFixturesMember 2020-01-01 2020-12-31 0000921299 srt:MaximumMember us-gaap:FurnitureAndFixturesMember 2020-01-01 2020-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2020-01-01 2020-12-31 0000921299 srt:CumulativeEffectPeriodOfAdoptionAdjustmentMember us-gaap:AccountingStandardsUpdate201602Member 2019-01-01 0000921299 fgen:ImpactOfChangeInAccountingPrincipleUponAdoptionOfASU201802Member us-gaap:AccountingStandardsUpdate201802Member 2019-01-01 0000921299 us-gaap:DifferenceBetweenRevenueGuidanceInEffectBeforeAndAfterTopic606Member us-gaap:AccountingStandardsUpdate201601Member 2018-01-01 0000921299 fgen:BeijingKangdaYongfuPharmaceuticalCoLTDMember fgen:FibroGenBeijingMember 2020-07-31 iso4217:CNY 0000921299 fgen:BeijingKangdaYongfuPharmaceuticalCoLTDMember fgen:FibroGenBeijingMember 2020-07-01 2020-07-31 0000921299 fgen:BeijingKangdaYongfuPharmaceuticalCoLTDMember fgen:FibroGenBeijingMember fgen:AcquiredLicenseMember 2020-07-01 2020-07-31 0000921299 fgen:BeijingKangdaYongfuPharmaceuticalCoLTDMember fgen:FibroGenBeijingMember fgen:AstraZenecaABMember fgen:BeijingFalikangPharmaceuticalCoLtdMember 2020-09-15 2020-09-15 0000921299 fgen:FibroGenBeijingMember fgen:BeijingFalikangPharmaceuticalCoLtdMember 2020-01-01 2020-12-31 0000921299 fgen:FibroGenBeijingMember fgen:BeijingFalikangPharmaceuticalCoLtdMember 2020-12-31 0000921299 fgen:BeijingFalikangPharmaceuticalCoLtdMember us-gaap:VariableInterestEntityNotPrimaryBeneficiaryMember 2020-01-01 2020-12-31 0000921299 fgen:BeijingFalikangPharmaceuticalCoLtdMember 2020-01-01 2020-12-31 0000921299 fgen:BeijingFalikangPharmaceuticalCoLtdMember 2020-12-31 0000921299 fgen:BeijingFalikangPharmaceuticalCoLtdMember 2019-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2005-06-01 2009-02-28 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2005-06-01 2005-06-30 0000921299 country:JP fgen:AstellasCollaborationAgreementMember fgen:ClinicalDevelopmentMilestonesMember 2005-06-01 2005-06-30 0000921299 country:JP fgen:AstellasCollaborationAgreementMember fgen:RegulatoryMilestonesMember 2005-06-01 2005-06-30 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2020-01-01 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2020-12-01 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2019-09-01 2019-09-30 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2019-09-30 0000921299 country:JP fgen:AstellasCollaborationAgreementMember 2018-04-01 2018-06-30 0000921299 fgen:AstellasCollaborationAgreementMember fgen:DrugProductRevenueMember country:JP 2020-01-01 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember fgen:DrugProductRevenueMember country:JP 2019-01-01 2019-12-31 0000921299 fgen:AstellasCollaborationAgreementMember fgen:DrugProductRevenueMember country:JP 2018-01-01 2018-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2006-04-01 2009-02-28 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2006-04-30 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember fgen:ClinicalDevelopmentMilestonesMember 2006-04-01 2006-04-30 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember fgen:RegulatoryMilestonesMember 2006-04-01 2006-04-30 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2006-04-01 2006-04-30 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2020-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2019-06-30 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2019-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember 2020-04-01 2020-06-30 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember 2013-07-29 2013-07-30 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember fgen:ClinicalDevelopmentMilestonesMember 2013-07-29 2013-07-30 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember fgen:RegulatoryMilestonesMember 2013-07-29 2013-07-30 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember fgen:DeferredApprovalMilestoneMember 2013-07-29 2013-07-30 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember 2015-01-01 2015-12-31 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember fgen:FibroGenIncMember 2015-01-01 2015-12-31 0000921299 fgen:UnitedStatesAndRestOfWorldMember fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 fgen:AstraZenecaAgreementsMember 2019-06-30 0000921299 fgen:AstraZenecaAgreementsMember 2019-12-31 0000921299 fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 fgen:AstraZenecaAgreementsMember fgen:DrugProductRevenueMember 2020-01-01 2020-12-31 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2013-07-29 2013-07-30 0000921299 country:CN fgen:AstraZenecaAgreementsMember fgen:ClinicalDevelopmentMilestonesMember 2013-07-29 2013-07-30 0000921299 country:CN fgen:AstraZenecaAgreementsMember fgen:RegulatoryMilestonesMember 2013-07-29 2013-07-30 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2019-01-01 2019-12-31 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2018-12-16 2018-12-17 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2018-12-28 2018-12-29 0000921299 country:CN fgen:AstraZenecaAgreementsMember 2018-01-01 2018-12-31 0000921299 fgen:AstraZenecaAgreementsMember us-gaap:SellingGeneralAndAdministrativeExpensesMember 2020-10-01 2020-12-31 0000921299 fgen:AstraZenecaAgreementsMember us-gaap:SellingGeneralAndAdministrativeExpensesMember 2020-01-01 2020-12-31 0000921299 us-gaap:OtherNoncurrentLiabilitiesMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 us-gaap:AccountsPayableMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 us-gaap:AccruedLiabilitiesMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 country:CN fgen:AstraZenecaAgreementsMember fgen:AccruedAndOtherCurrentLiabilitiesMember 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember srt:MinimumMember us-gaap:MeasurementInputDiscountRateMember us-gaap:ValuationTechniqueDiscountedCashFlowMember 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember srt:MaximumMember us-gaap:MeasurementInputDiscountRateMember us-gaap:ValuationTechniqueDiscountedCashFlowMember 2020-12-31 0000921299 fgen:UnitedStatesAndRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 us-gaap:MeasurementInputDiscountRateMember us-gaap:ValuationTechniqueDiscountedCashFlowMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2020-01-01 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2019-01-01 2019-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2018-01-01 2018-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2020-01-01 2020-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2019-01-01 2019-12-31 0000921299 country:JP fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2018-01-01 2018-12-31 0000921299 fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember country:JP 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember country:JP 2020-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2020-01-01 2020-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2019-01-01 2019-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember 2018-01-01 2018-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2020-01-01 2020-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2019-01-01 2019-12-31 0000921299 srt:EuropeMember fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember 2018-01-01 2018-12-31 0000921299 fgen:AstellasCollaborationAgreementMember us-gaap:LicenseMember srt:EuropeMember 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember fgen:DevelopmentAndOtherRevenueMember srt:EuropeMember 2020-12-31 0000921299 us-gaap:LicenseMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 us-gaap:LicenseMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2019-01-01 2019-12-31 0000921299 us-gaap:LicenseMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2018-01-01 2018-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-01-01 2020-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2019-01-01 2019-12-31 0000921299 fgen:DevelopmentAndOtherRevenueMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2018-01-01 2018-12-31 0000921299 us-gaap:LicenseMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:CoDevelopmentInformationSharingAndCommitteeServicesMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:ChinaPerformanceObligationMember fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:UnitedStatesRestOfWorldAndChinaMember fgen:AstraZenecaAgreementsMember 2020-12-31 0000921299 fgen:AstellasCollaborationAgreementMember fgen:UnitedStatesRestOfWorldAndChinaMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember fgen:PriceAdjustmentMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember fgen:PriceAdjustmentMember 2019-01-01 2019-12-31 0000921299 us-gaap:ProductMember fgen:NonKeyAccountHospitalListingAwardMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember fgen:NonKeyAccountHospitalListingAwardMember 2019-01-01 2019-12-31 0000921299 us-gaap:ProductMember fgen:ContractualSalesRebateMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember fgen:ContractualSalesRebateMember 2019-01-01 2019-12-31 0000921299 us-gaap:ProductMember fgen:OtherDiscountsAndRebatesMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember fgen:OtherDiscountsAndRebatesMember 2019-01-01 2019-12-31 0000921299 us-gaap:ProductMember us-gaap:SalesReturnsAndAllowancesMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember us-gaap:SalesReturnsAndAllowancesMember 2019-01-01 2019-12-31 0000921299 fgen:NonKeyAccountHospitalListingAwardMember 2020-01-01 2020-12-31 0000921299 fgen:ContractualSalesRebateMember 2020-01-01 2020-12-31 0000921299 fgen:ContractualSalesRebateMember 2019-01-01 2019-12-31 0000921299 fgen:PriceAdjustmentMember 2020-01-01 2020-12-31 0000921299 us-gaap:ProductMember 2019-12-31 0000921299 us-gaap:ProductMember 2020-12-31 0000921299 fgen:RebatesAndDiscountsMember 2019-01-01 2019-12-31 0000921299 fgen:RebatesAndDiscountsMember fgen:GrossAccountsReceivableMember 2020-01-01 2020-12-31 0000921299 fgen:RebatesAndDiscountsMember fgen:GrossAccountsReceivableMember 2019-01-01 2019-12-31 0000921299 fgen:RebatesAndDiscountsMember fgen:ContractLiabilitiesMember 2020-01-01 2020-12-31 0000921299 fgen:RebatesAndDiscountsMember fgen:ContractLiabilitiesMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasAgreementMember fgen:DrugProductRevenueMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasAgreementMember fgen:DrugProductRevenueMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasAgreementMember fgen:DrugProductRevenueMember 2018-01-01 2018-12-31 0000921299 fgen:AstraZenecaAgreementsMember fgen:DrugProductRevenueMember 2019-01-01 2019-12-31 0000921299 fgen:AstraZenecaAgreementsMember fgen:DrugProductRevenueMember 2018-01-01 2018-12-31 0000921299 fgen:DrugProductRevenueMember 2020-01-01 2020-12-31 0000921299 fgen:DrugProductRevenueMember 2019-01-01 2019-12-31 0000921299 fgen:DrugProductRevenueMember 2018-01-01 2018-12-31 0000921299 fgen:DrugProductRevenueMember country:JP 2018-01-01 2018-12-31 0000921299 fgen:DrugProductRevenueMember 2019-12-31 0000921299 fgen:DrugProductRevenueMember fgen:APIShipmentMember 2020-01-01 2020-12-31 0000921299 fgen:DrugProductRevenueMember country:JP 2020-04-01 2020-06-30 0000921299 fgen:DrugProductRevenueMember fgen:AstellasCollaborationAgreementMember srt:EuropeMember 2020-12-31 0000921299 fgen:DrugProductRevenueMember fgen:AstellasCollaborationAgreementMember 2019-12-31 0000921299 fgen:DrugProductRevenueMember fgen:AstellasCollaborationAgreementMember 2020-01-01 2020-12-31 0000921299 fgen:DrugProductRevenueMember fgen:AstellasCollaborationAgreementMember 2020-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2020-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2020-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2020-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember 2020-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2020-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2020-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2020-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember 2020-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2020-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2020-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2020-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember 2020-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2020-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2020-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2020-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember 2020-12-31 0000921299 us-gaap:USTreasurySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 us-gaap:USTreasurySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 us-gaap:USTreasurySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 us-gaap:USTreasurySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 fgen:BondAndMutualFundsMember us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 us-gaap:EquitySecuritiesMember us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 us-gaap:MoneyMarketFundsMember us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 us-gaap:CertificatesOfDepositMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 us-gaap:CertificatesOfDepositMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 us-gaap:CertificatesOfDepositMember us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 us-gaap:CertificatesOfDepositMember us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel1Member 2019-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel2Member 2019-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember us-gaap:FairValueInputsLevel3Member 2019-12-31 0000921299 us-gaap:FairValueMeasurementsRecurringMember 2019-12-31 0000921299 us-gaap:FairValueInputsLevel1Member fgen:LeaseObligationsMember 2020-12-31 0000921299 us-gaap:FairValueInputsLevel2Member fgen:LeaseObligationsMember 2020-12-31 0000921299 us-gaap:FairValueInputsLevel3Member fgen:LeaseObligationsMember 2020-12-31 0000921299 fgen:LeaseObligationsMember 2020-12-31 0000921299 us-gaap:FairValueInputsLevel1Member fgen:LeaseObligationsMember 2019-12-31 0000921299 us-gaap:FairValueInputsLevel2Member fgen:LeaseObligationsMember 2019-12-31 0000921299 us-gaap:FairValueInputsLevel3Member fgen:LeaseObligationsMember 2019-12-31 0000921299 fgen:LeaseObligationsMember 2019-12-31 fgen:Lease 0000921299 us-gaap:BuildingMember 2020-01-01 2020-12-31 0000921299 fgen:ShorensteinPropertiesLLCMember 2006-12-31 0000921299 fgen:ShorensteinPropertiesLLCMember 2006-01-01 2006-12-31 0000921299 fgen:ShorensteinPropertiesLLCMember 2020-01-01 2020-12-31 0000921299 fgen:BeijingEconomicTechnologicalDevelopmentAreaMember 2013-12-31 0000921299 fgen:BeijingEconomicTechnologicalDevelopmentAreaMember 2013-01-01 2013-12-31 0000921299 fgen:OfficeSpacesMember 2020-01-01 2020-12-31 0000921299 srt:MinimumMember 2020-12-31 0000921299 srt:MaximumMember 2020-12-31 0000921299 us-gaap:OfficeEquipmentMember srt:MinimumMember 2020-12-31 0000921299 us-gaap:OfficeEquipmentMember srt:MaximumMember 2020-12-31 0000921299 fgen:BondAndMutualFundsMember 2020-12-31 0000921299 us-gaap:EquitySecuritiesMember 2020-12-31 0000921299 us-gaap:USTreasurySecuritiesMember 2019-12-31 0000921299 us-gaap:CertificatesOfDepositMember 2019-12-31 0000921299 fgen:BondAndMutualFundsMember 2019-12-31 0000921299 us-gaap:EquitySecuritiesMember 2019-12-31 0000921299 2018-01-01 2020-12-31 fgen:Milestone 0000921299 fgen:AstraZenecaAgreementsMember fgen:UnitedStatesAndRestOfWorldMember 2019-12-31 0000921299 us-gaap:LeaseholdImprovementsMember 2020-12-31 0000921299 us-gaap:LeaseholdImprovementsMember 2019-12-31 0000921299 fgen:LaboratoryEquipmentMember 2020-12-31 0000921299 fgen:LaboratoryEquipmentMember 2019-12-31 0000921299 us-gaap:MachineryAndEquipmentMember 2020-12-31 0000921299 us-gaap:MachineryAndEquipmentMember 2019-12-31 0000921299 us-gaap:ComputerEquipmentMember 2020-12-31 0000921299 us-gaap:ComputerEquipmentMember 2019-12-31 0000921299 us-gaap:FurnitureAndFixturesMember 2020-12-31 0000921299 us-gaap:FurnitureAndFixturesMember 2019-12-31 0000921299 us-gaap:ConstructionInProgressMember 2020-12-31 0000921299 us-gaap:ConstructionInProgressMember 2019-12-31 0000921299 fgen:AstraZenecaAgreementsMember 2020-07-01 2020-09-30 fgen:DevelopmentObligation 0000921299 fgen:BankOfFinlandInterestRateMember 2020-12-31 0000921299 fgen:ManufactureAndSupplyOfRoxadustatMember 2020-12-31 0000921299 fgen:ManufactureAndSupplyOfPamrevlumabMember 2020-12-31 0000921299 fgen:OtherPurchasesMember 2020-12-31 0000921299 fgen:ResearchAndPreClinicalStageDevelopmentProgramsMember 2020-01-01 2020-12-31 0000921299 fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesAPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesAPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesBPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesBPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesCPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesCPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesDPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesDPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesEPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesEPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesFPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesFPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesGPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesGPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 us-gaap:SeriesHPreferredStockMember fgen:FibrogenEuropeOyMember 2020-12-31 0000921299 us-gaap:SeriesHPreferredStockMember fgen:FibrogenEuropeOyMember 2019-12-31 0000921299 fgen:FibrogenEuropeOyMember 2020-01-01 2020-12-31 0000921299 fgen:FibroGenCaymanMember us-gaap:SeriesAPreferredStockMember 2020-12-31 0000921299 fgen:FibroGenCaymanMember us-gaap:SeriesAPreferredStockMember 2019-12-31 0000921299 fgen:FibroGenCaymanMember 2020-12-31 0000921299 fgen:FibroGenCaymanMember us-gaap:SeriesAPreferredStockMember 2020-01-01 2020-12-31 0000921299 us-gaap:IPOMember 2014-11-19 0000921299 us-gaap:EmployeeStockMember 2020-12-31 0000921299 us-gaap:EmployeeStockMember 2019-12-31 0000921299 fgen:TwoThousandAndFiveStockPlanMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFiveStockPlanMember srt:MaximumMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember srt:MaximumMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember us-gaap:ShareBasedCompensationAwardTrancheOneMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2014-09-01 2014-09-30 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2019-01-01 2019-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2019-12-31 0000921299 fgen:TwoThousandAndFourteenEquityIncentivePlanMember 2018-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2019-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2020-01-01 2020-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEmployeeStockPurchasePlanMember 2014-09-01 2014-09-30 0000921299 fgen:TwoThousandAndFourteenEmployeeStockPurchasePlanMember 2014-09-30 0000921299 fgen:TwoThousandAndFourteenEmployeeStockPurchasePlanMember 2020-01-01 2020-12-31 0000921299 fgen:TwoThousandAndFourteenEmployeeStockPurchasePlanMember 2019-01-01 2019-12-31 0000921299 fgen:TwoThousandAndFourteenEmployeeStockPurchasePlanMember 2018-01-01 2018-12-31 0000921299 us-gaap:ResearchAndDevelopmentExpenseMember 2020-01-01 2020-12-31 0000921299 us-gaap:ResearchAndDevelopmentExpenseMember 2019-01-01 2019-12-31 0000921299 us-gaap:ResearchAndDevelopmentExpenseMember 2018-01-01 2018-12-31 0000921299 us-gaap:SellingGeneralAndAdministrativeExpensesMember 2020-01-01 2020-12-31 0000921299 us-gaap:SellingGeneralAndAdministrativeExpensesMember 2019-01-01 2019-12-31 0000921299 us-gaap:SellingGeneralAndAdministrativeExpensesMember 2018-01-01 2018-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2020-01-01 2020-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2019-01-01 2019-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2018-01-01 2018-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MinimumMember 2020-01-01 2020-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MinimumMember 2019-01-01 2019-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MinimumMember 2018-01-01 2018-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MaximumMember 2020-01-01 2020-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MaximumMember 2019-01-01 2019-12-31 0000921299 us-gaap:StockCompensationPlanMember srt:MaximumMember 2018-01-01 2018-12-31 0000921299 us-gaap:StockCompensationPlanMember 2020-01-01 2020-12-31 0000921299 us-gaap:StockCompensationPlanMember 2019-01-01 2019-12-31 0000921299 us-gaap:StockCompensationPlanMember 2018-01-01 2018-12-31 0000921299 fgen:StockOptionAwardsMember 2020-12-31 0000921299 fgen:StockOptionAwardsMember 2020-01-01 2020-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2020-01-01 2020-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2019-01-01 2019-12-31 0000921299 us-gaap:EmployeeStockOptionMember 2018-01-01 2018-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2020-01-01 2020-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2019-01-01 2019-12-31 0000921299 us-gaap:RestrictedStockUnitsRSUMember 2018-01-01 2018-12-31 0000921299 us-gaap:EmployeeStockMember 2020-01-01 2020-12-31 0000921299 us-gaap:EmployeeStockMember 2019-01-01 2019-12-31 0000921299 us-gaap:EmployeeStockMember 2018-01-01 2018-12-31 0000921299 us-gaap:WarrantMember 2020-01-01 2020-12-31 0000921299 us-gaap:WarrantMember 2019-01-01 2019-12-31 0000921299 us-gaap:WarrantMember 2018-01-01 2018-12-31 0000921299 us-gaap:DomesticCountryMember 2020-12-31 0000921299 us-gaap:StateAndLocalJurisdictionMember 2020-12-31 0000921299 us-gaap:DomesticCountryMember 2020-01-01 2020-12-31 0000921299 us-gaap:StateAndLocalJurisdictionMember 2020-01-01 2020-12-31 0000921299 us-gaap:ForeignCountryMember 2020-12-31 0000921299 us-gaap:ForeignCountryMember srt:MinimumMember 2020-01-01 2020-12-31 0000921299 us-gaap:ForeignCountryMember srt:MaximumMember 2020-01-01 2020-12-31 0000921299 us-gaap:StateAndLocalJurisdictionMember stpr:CA 2020-12-31 0000921299 fgen:FederalAndStateMember 2017-12-31 0000921299 fgen:FederalAndStateMember 2018-01-01 2018-12-31 0000921299 fgen:FederalAndStateMember 2018-12-31 0000921299 fgen:FederalAndStateMember 2019-01-01 2019-12-31 0000921299 fgen:FederalAndStateMember 2019-12-31 0000921299 fgen:FederalAndStateMember 2020-01-01 2020-12-31 0000921299 fgen:FederalAndStateMember 2020-12-31 0000921299 us-gaap:EarliestTaxYearMember 2020-01-01 2020-12-31 0000921299 us-gaap:LatestTaxYearMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember fgen:LicenseAndDevelopmentMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember fgen:LicenseAndDevelopmentMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember fgen:LicenseAndDevelopmentMember 2018-01-01 2018-12-31 0000921299 fgen:AstellasMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasMember 2018-01-01 2018-12-31 0000921299 fgen:AstellasMember country:JP 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember fgen:APIShipmentMember country:JP 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember fgen:APIShipmentMember country:JP 2019-01-01 2019-12-31 0000921299 fgen:AstellasMember fgen:APIShipmentMember country:JP 2018-01-01 2018-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember 2020-01-01 2020-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember 2019-01-01 2019-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember 2018-01-01 2018-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember 2020-12-31 0000921299 fgen:AstellasMember us-gaap:CollaborativeArrangementMember 2019-12-31 0000921299 fgen:AstellasMember srt:EuropeMember 2019-12-31 0000921299 fgen:AstellasMember srt:EuropeMember 2020-12-31 0000921299 srt:EuropeMember 2020-06-30 0000921299 fgen:AstellasMember 2020-12-31 0000921299 fgen:AstellasMember 2019-12-31 0000921299 fgen:APIShipmentMember 2019-01-01 2019-12-31 0000921299 fgen:FalikangMember 2020-09-01 2020-09-30 0000921299 fgen:FalikangMember 2020-12-31 0000921299 srt:EuropeMember 2019-01-01 2019-12-31 0000921299 srt:EuropeMember 2018-01-01 2018-12-31 0000921299 country:JP 2019-01-01 2019-12-31 0000921299 country:JP 2018-01-01 2018-12-31 0000921299 country:CN 2020-01-01 2020-12-31 0000921299 country:CN 2019-01-01 2019-12-31 0000921299 country:CN 2018-01-01 2018-12-31 0000921299 fgen:AllOtherMember 2020-01-01 2020-12-31 0000921299 fgen:AllOtherMember 2019-01-01 2019-12-31 0000921299 fgen:AllOtherMember 2018-01-01 2018-12-31 0000921299 country:US 2020-12-31 0000921299 country:US 2019-12-31 0000921299 country:CN 2020-12-31 0000921299 country:CN 2019-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstellasCollaborationAgreementMember us-gaap:SalesRevenueNetMember 2020-01-01 2020-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstellasCollaborationAgreementMember us-gaap:SalesRevenueNetMember 2019-01-01 2019-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstellasCollaborationAgreementMember us-gaap:SalesRevenueNetMember 2018-01-01 2018-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstellasCollaborationAgreementMember us-gaap:AccountsReceivableMember 2020-01-01 2020-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstellasCollaborationAgreementMember us-gaap:AccountsReceivableMember 2019-01-01 2019-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstraZenecaAgreementsMember us-gaap:SalesRevenueNetMember 2020-01-01 2020-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstraZenecaAgreementsMember us-gaap:SalesRevenueNetMember 2019-01-01 2019-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstraZenecaAgreementsMember us-gaap:SalesRevenueNetMember 2018-01-01 2018-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstraZenecaAgreementsMember us-gaap:AccountsReceivableMember 2020-01-01 2020-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember fgen:AstraZenecaAgreementsMember us-gaap:AccountsReceivableMember 2019-01-01 2019-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember us-gaap:SalesRevenueNetMember 2020-01-01 2020-12-31 0000921299 us-gaap:CustomerConcentrationRiskMember us-gaap:AccountsReceivableMember 2020-01-01 2020-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2019-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2018-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2017-12-31 0000921299 fgen:ValuationAllowanceForRebatesAndDiscountsMember 2019-12-31 0000921299 fgen:ValuationAllowanceForRebatesAndDiscountsMember 2018-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2020-01-01 2020-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2019-01-01 2019-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2018-01-01 2018-12-31 0000921299 fgen:ValuationAllowanceForRebatesAndDiscountsMember 2020-01-01 2020-12-31 0000921299 fgen:ValuationAllowanceForRebatesAndDiscountsMember 2019-01-01 2019-12-31 0000921299 us-gaap:ValuationAllowanceOfDeferredTaxAssetsMember 2020-12-31 0000921299 fgen:ValuationAllowanceForRebatesAndDiscountsMember 2020-12-31

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

Form 10-K 

 

(Mark One)

ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2020

OR

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from            to           .

Commission file number: 001-36740 

 

FIBROGEN, INC.

(Exact name of registrant as specified in its charter) 

 

 

Delaware

 

77-0357827

(State or other jurisdiction of incorporation or organization)

 

(I.R.S. Employer Identification No.)

409 Illinois Street

San Francisco, CA

 

94158

(Address of principal executive offices)

 

(zip code)

 

Registrant’s telephone number, including area code:

(415) 978-1200 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

Trading Symbol

Name of each exchange on which registered

Common Stock, $0.01 par value

FGEN

The NASDAQ Global Select Market

 

Securities registered pursuant to Section 12(g) of the Act:

None

 

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.    Yes      No  

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.    Yes       No  

Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.    Yes       No  

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).    Yes       No  

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act:

 

Large accelerated filer

 

  

Accelerated filer

 

Non-accelerated filer

 

  

  

Smaller reporting company

 

Emerging growth company

 

  

 

 

 

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.         

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report.         

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act).    Yes      No  

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant, computed by reference to the closing price as of the last business day of the registrant’s most recently completed second fiscal quarter, June 30, 2020, was approximately $2,127.6 million. Shares of Common Stock held by each executive officer and director and stockholders known by the registrant to own 10% or more of the outstanding stock based on public filings and other information known to the registrant have been excluded since such persons may be deemed affiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

The number of shares of common stock outstanding as of January 31, 2021 was 91,560,468.

DOCUMENTS INCORPORATED BY REFERENCE

Items 10, 11, 12, 13 and 14 of Part III of this Annual Report on Form 10-K incorporate information by reference from the definitive proxy statement for the registrant’s 2021 Annual Meeting of Stockholders to be filed with the Securities and Exchange Commission pursuant to Regulation 14A not later than after 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K.

 

 

 


 

 

TABLE OF CONTENTS

 

 

 

 

 

Page

PART I

 

 

 

5

 

 

 

 

 

Item 1.

 

Business

  

5

Item 1A.

 

Risk Factors

  

49

Item 1B.

 

Unresolved Staff Comments

  

87

Item 2.

 

Properties

  

87

Item 3.

 

Legal Proceedings

  

87

Item 4.

 

Mine Safety Disclosures

  

87

 

 

 

 

 

PART II

 

 

 

88

 

 

 

 

 

Item 5.

 

 

Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

  

88

Item 6.

 

Selected Financial Data

  

89

Item 7.

 

Management’s Discussion and Analysis of Financial Condition and Results of Operations

  

90

Item 7A.

 

Quantitative and Qualitative Disclosure About Market Risk

  

114

Item 8.

 

Consolidated Financial Statements and Supplementary Data

  

115

Item 9.

 

Changes in and Disagreements with Accountants on Accounting and Financial Disclosures

  

169

Item 9A.

 

Controls and Procedures

  

169

Item 9B.

 

Other Information

  

170

 

 

 

 

 

PART III

 

 

 

171

 

 

 

 

 

Item 10.

 

Directors, Executive Officers and Corporate Governance

  

171

Item 11.

 

Executive Compensation

  

171

Item 12.

 

Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

  

171

Item 13.

 

Certain Relationships and Related Transactions, and Director Independence

  

171

Item 14.

 

Principal Accounting Fees and Services

  

171

 

 

 

 

 

PART IV

 

 

 

172

 

 

 

 

 

Item 15.

 

Exhibits and Financial Statement Schedules

  

172

 

 

Signatures

  

181

 

1


 

FORWARD-LOOKING STATEMENTS

This Annual Report filed on Form 10-K and the information incorporated herein by reference, particularly in the sections captioned “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and “Business,” contains forward-looking statements, which involve substantial risks and uncertainties. In this Annual Report, all statements other than statements of historical or present facts contained in this Annual Report, including statements regarding our future financial condition, business strategy and plans and objectives of management for future operations, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “believe,” “will,” “may,” “estimate,” “continue,” “anticipate,” “contemplate,” “intend,” “target,” “project,” “should,” “plan,” “expect,” “predict,” “could,” “potentially” or the negative of these terms or other similar terms or expressions that concern our expectations, strategy, plans or intentions. Forward-looking statements appear in a number of places throughout this Annual Report and include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things, our ongoing and planned preclinical development and clinical trials, the timing of and our ability to make regulatory filings and obtain and maintain regulatory approvals for roxadustat, pamrevlumab and our other product candidates, our intellectual property position, the potential safety, efficacy, reimbursement, convenience clinical and pharmaco-economic benefits of our product candidates, the potential markets for any of our product candidates, our ability to develop commercial functions, our ability to operate in China, expectations regarding clinical trial data, our results of operations, cash needs, spending of the proceeds from our initial public offering, financial condition, liquidity, prospects, growth and strategies, the industry in which we operate and the trends that may affect the industry or us. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy and financial needs.

These forward-looking statements are subject to a number of risks, uncertainties and assumptions described in the section of this Annual Report captioned “Risk Factors” and elsewhere in this Annual Report. A summary of these risk factors can be found in the following section, however please refer to the full risk factors in Item 1A “Risk Factors”. These risks are not exhaustive. Other sections of this Annual Report may include additional factors that could adversely impact our business and financial performance. Moreover, we operate in a very competitive and rapidly changing environment. New risk factors emerge from time to time, and it is not possible for our management to predict all risk factors nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in, or implied by, any forward-looking statements.

You should not rely upon forward-looking statements as predictions of future events. We cannot assure you that the events and circumstances reflected in the forward-looking statements will be achieved or occur. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements. The forward-looking statements made in this Annual Report are based on circumstances as of the date on which the statements are made. Except as required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this Annual Report or to conform these statements to actual results or to changes in our expectations.

This Annual Report also contains market data, research, industry forecasts and other similar information obtained from or based on industry reports and publications, including information concerning our industry, our business, and the potential markets for our product candidates, including data regarding the estimated size and patient populations of those and related markets, their projected growth rates and the incidence of certain medical conditions, as well as physician and patient practices within the related markets. Such data and information involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates.

You should read this Annual Report with the understanding that our actual future results, levels of activity, performance and achievements may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary statements.


2


 

 

SUMMARY RISK FACTOR

The success of the Company will depend on a number of factors, many of which are beyond our control and involve risks, including but not limited to the following:

Risks Related to the Development and Commercialization of Our Product Candidates

We are substantially dependent on the success of our lead product, roxadustat, and our second compound in development, pamrevlumab.

As a company, we have limited commercialization experience, and the time and resources to develop such experience are significant. If we fail to achieve and sustain commercial success for roxadustat with our collaboration partners, our business would be harmed.

Although regulatory approval has been obtained for roxadustat in China, Japan, and Chile, we may be unable to obtain regulatory approval for other countries, or such approval may be delayed or limited, due to a number of factors, many of which are beyond our control.

The results of the FDA Cardiovascular and Renal Drugs Advisory Committee meeting may affect roxadustat’s approvability or label in CKD anemia.

Preclinical, Phase 1 and Phase 2 clinical trial results may not be indicative of the results that may be obtained in larger clinical trials.

We do not know whether our ongoing or planned clinical trials of roxadustat or pamrevlumab will need to be redesigned based on interim results or if we will be able to achieve sufficient patient enrollment or complete planned clinical trials on schedule.

Our product candidates may cause or have attributed to them undesirable side effects or have other properties that delay or prevent their regulatory approval or limit their commercial potential.

Clinical trials of our product candidates may not uncover all possible adverse effects that patients may experience.

If we or our manufacturers cannot properly manufacture sufficient product, we may experience delays in development, regulatory approval, launch or successful commercialization.

Regulatory authorities will do their own benefit risk analysis and may reach a different conclusion than we or our partners have, and these regulatory authorities may base their approval decision on different analyses, data, and statistical methods than ours.

Even if we are able to obtain regulatory approval of our product candidates, the label we obtain may limit the indicated uses for which our product candidates may be marketed.

We face substantial competition in the discovery, development and commercialization of product candidates.

No or limited reimbursement or insurance coverage of our approved products, if any, by third-party payors may render our products less attractive to patients and healthcare providers.

Risks Related to Severe Acute Respiratory Syndrome Coronavirus 2 and the Resulting Coronavirus Disease (“COVID-19”)

Our business could continue to be adversely affected by the ongoing COVID-19 global pandemic.

Risks Related to Our Reliance on Third Parties

If our collaborations were terminated or if Astellas or AstraZeneca were to prioritize other initiatives over their collaborations with us, our ability to successfully develop and commercialize our product candidates would suffer.

If our preclinical and clinical trial contractors do not properly perform their agreed upon obligations, we may not be able to obtain or may be delayed in receiving regulatory approvals for our product candidates.

We currently rely, and expect to continue to rely, on third parties to conduct many aspects of our product manufacturing and distribution, and these third parties may terminate these agreements or not perform satisfactorily.

Certain components of our products are acquired from single-source suppliers or without long-term supply agreements. The loss of these suppliers, or their failure to supply, would materially and adversely affect our business.

Risks Related to Our Intellectual Property

If our efforts to protect our proprietary technologies are not adequate, we may not be able to compete effectively in our market.

Intellectual property disputes may be costly, time consuming, and may negatively affect our competitive position.

Our reliance on third parties and agreements with collaboration partners requires us to share our trade secrets, which increases the possibility that a competitor may discover them or that our trade secrets will be misappropriated or disclosed.

The cost of maintaining our patent protection is high and requires continuous review and diligence. We may not be able to effectively maintain our intellectual property position throughout the major markets of the world.

The laws of some foreign countries do not protect proprietary rights to the same extent as do the laws of the U.S., and we may encounter significant problems in securing and defending our intellectual property rights outside the U.S.

Intellectual property rights do not address all potential threats to any competitive advantage we may have.

3


 

 

The existence of counterfeit pharmaceutical products in pharmaceutical markets may compromise our brand and reputation and have a material adverse effect on our business, operations and prospects.

Risks Related to Government Regulation

The regulatory approval process is highly uncertain and we may not obtain regulatory approval for our product candidates.

Our product candidates could fail to receive regulatory approval from the FDA or other regulatory authorities.

Our current and future relationships with customers, physicians, and third-party payors are subject to healthcare fraud and abuse laws, false claims laws, transparency laws, privacy and security laws, and other regulations. If we are unable to comply with such laws, we could face substantial penalties.

We are subject to laws and regulations governing corruption, which will require us to maintain costly compliance programs.

We have identified material weaknesses in our internal control over financial reporting. If we are unable to remediate these, or if we otherwise fail to maintain an effective system of internal control, it may result in material misstatements in our financial statements.

The impact of recent U.S. healthcare reform, its potential partial or full repeal, and other changes in the healthcare industry and in healthcare spending is currently unknown, and may adversely affect our business model.

Roxadustat is considered a Class 2 substance on the 2019 World Anti-Doping Agency Prohibited List that could limit sales and increase security and distribution costs for our partners and us.

Our employees may engage in misconduct or improper activities, which could result in significant liability or harm our reputation.

If we fail to comply with environmental, health or safety laws and regulations, we could incur fines, penalties or other costs.

Risks Related to Our International Operations

We have established operations in China and are seeking approval to commercialize our product candidates outside of the U.S., and a number of risks associated with international operations could materially and adversely affect our business.

The pharmaceutical industry in China is highly regulated and such regulations are subject to change.

We have limited experience distributing drugs in China.

We use our own manufacturing facilities in China to produce roxadustat API and drug product. There are risks inherent to operating commercial manufacturing facilities, and with these being our single source suppliers, we may not be able to continually meet market demand.

As a company, we have limited experience in pharmacovigilance, medical affairs, and management of the third-party distribution logistics, and cannot assure you we will be able to meet regulatory requirements or operate in these capacities successfully.

We and our collaboration partner in China, AstraZeneca, may experience difficulties in successfully growing and sustaining sales of roxadustat in China.

The retail prices of any product candidates that we develop may be subject to pricing control in China and elsewhere.

FibroGen (China) Medical Technology Development Co., Ltd. (“FibroGen Beijing”) would be subject to restrictions on paying dividends or making other payments to us, which may restrict our ability to satisfy our liquidity requirements.

Any capital contributions from us to FibroGen Beijing must be approved by the Ministry of Commerce in China, and failure to obtain such approval may materially and adversely affect the liquidity position of FibroGen Beijing.

We may be subject to currency exchange rate fluctuations and currency exchange restrictions with respect to our operations in China, which could adversely affect our financial performance.

Because FibroGen Beijing’s funds are held in banks that do not provide insurance, the failure of any bank in which FibroGen Beijing deposits its funds could adversely affect our business.

We may be subject to tax inefficiencies associated with our offshore corporate structure.

Our foreign operations, particularly those in China, are subject to significant risks involving the protection of intellectual property.

Uncertainties with respect to the China legal system could have a material adverse effect on us.

Changes in China’s economic, governmental, or social conditions could have a material adverse effect on our business.

Our operations in China subject us to various Chinese labor and social insurance laws, and our failure to comply with such laws may materially and adversely affect our business, financial condition and results of operations.

Risks Related to the Operation of Our Business

Please see below for additional risk factors related to the operation of our Business.  

There are also a variety of Risks Related to Our Common Stock

Please see below for additional risk factors to our Common Stock.

 

4


 

 

PART I

ITEM 1. BUSINESS

OVERVIEW

We are a leading biopharmaceutical company discovering, developing and commercializing a pipeline of first-in-class therapeutics. We apply our pioneering expertise in hypoxia-inducible factor (“HIF”) biology, 2-oxoglutarate enzymology, and connective tissue growth factor (“CTGF”) biology to advance innovative medicines for the treatment of anemia, fibrotic disease, and cancer.

Roxadustat, our most advanced product, is an oral small molecule inhibitor of HIF-prolyl hydroxylase (“HIF-PH”) activity that acts by stimulating the body’s natural pathway of erythropoiesis, or red blood cell production.

We and our collaboration partner AstraZeneca AB (“AstraZeneca”) continue to expand the commercialization of roxadustat (tradename: 爱瑞卓®) in the People’s Republic of China (“China”) where it is approved for the treatment of anemia caused by chronic kidney disease (“CKD”) in non-dialysis and dialysis patients. Roxadustat was added to the National Reimbursement Drug List (“NRDL”), effective January 1, 2020. As of the end of 2020, roxadustat was listed at hospitals that represent approximately 70% of the CKD anemia market opportunity in China and we continue to focus on adding additional temporary and permanent hospital listings for roxadustat.

In Japan, our partner Astellas Pharma Inc. (“Astellas”) continues the commercial launch of EVRENZO® (roxadustat). Astellas received approval of the supplemental New Drug Application (“NDA”) for the use of EVRENZO in patients with anemia of CKD not on dialysis from the Pharmaceuticals and Medical Devices Agency in November 2020, and it is now approved for the treatment of anemia associated with CKD in both non-dialysis and dialysis patients.

With respect to our United States (“U.S.”) NDA for roxadustat for the treatment of anemia due to CKD submitted for review in December 2019 to the U.S. Food and Drug Administration (“FDA”), in December 2020, the FDA extended the review period of the NDA by three months for FibroGen to submit additional analyses of existing roxadustat clinical data, and set a new Prescription Drug User Fee Act (“PDUFA”) goal date of March 20, 2021. On March 1, 2021, the FDA informed us that the Cardiovascular and Renal Drugs Advisory Committee will hold an advisory committee meeting to review the NDA for roxadustat. The date of the advisory committee meeting has not been set. As a result of this communication, we will not receive an approval decision by the PDUFA goal date.

In May 2020, the Marketing Authorization Application (“MAA”) for roxadustat for the treatment of anemia in patients with CKD, submitted by our partner Astellas, was accepted for regulatory review by the European Medicines Agency (“EMA”). Astellas expects an approval decision mid-2021.

EVRENZO® (roxadustat) has also been approved for the treatment of anemia in CKD patients on dialysis and patients not on dialysis in Chile. In collaboration with AstraZeneca, applications for marketing approval of roxadustat in CKD anemia have been submitted in Canada, Australia, Mexico, Brazil, Taiwan, South Korea, Philippines, Singapore, India, Colombia, and Thailand.

Beyond anemia in CKD, roxadustat is in Phase 3 clinical development in the U.S. and Europe and in Phase 2/3 development in China for anemia associated with myelodysplastic syndromes (“MDS”).

We have completed enrollment in our Phase 2 clinical trial of roxadustat in the U.S. in chemotherapy-induced anemia (“CIA”), and we expect topline data from this study in the second half of 2021.

Pamrevlumab is our first-in-class antibody developed to inhibit the activity of CTGF, a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. Pamrevlumab is in Phase 3 clinical development for the treatment of idiopathic pulmonary fibrosis (“IPF”), locally advanced unresectable pancreatic cancer (“LAPC”), and Duchenne muscular dystrophy (“DMD”).

5


 

ROXADUSTAT FOR THE TREATMENT OF ANEMIA IN CHRONIC KIDNEY DISEASE

In collaboration with our partners AstraZeneca and Astellas, we have completed 16 Phase 3 studies worldwide in over 11,000 patients to support our regulatory filings in the U.S., Europe, China, and Japan.

After describing the mechanism of action of roxadustat, which is the first in a new class of potential anemia drugs, we provide some background on the CKD anemia market and a summary of our Phase 3 program along with some of the most important results.

Roxadustat Mechanism of Action

Roxadustat is an orally administered reversible inhibitor of HIF-PH. Inhibition of prolyl hydroxylase stabilizes HIF, which stimulates a coordinated erythropoietic response that includes the increase of plasma endogenous erythropoietin (“EPO”) levels and reduction of hepcidin, a key regulator of iron homeostasis. In healthy individuals under normal oxygen conditions, HIF-PH tags HIF-alpha for degradation and the HIF pathway is not activated. However, under low oxygen conditions, the HIF-PH enzymes cannot function and HIF-alpha accumulates. HIF-alpha then combines with HIF-beta, and the newly formed HIF complex initiates transcription of a number of genes involved in the erythropoietic process, which ultimately leads to increased oxygen delivery to tissues.

In anemia of CKD, roxadustat temporarily inhibits HIF-PH, preventing degradation of HIF-alpha and activating the HIF pathway, which stimulates a coordinated erythropoietic response that includes EPO production and the reduction of hepcidin.

The coordinated erythropoiesis activated by roxadustat includes both the stimulation of erythroid maturation, by increasing the body’s production of EPO, and an increase in iron availability for hemoglobin synthesis in part through a decrease in hepcidin levels, which is particularly important in patients with inflammation. Patients taking roxadustat typically have a transient increase in circulating endogenous EPO levels at peak concentration within or near the physiologic range naturally experienced by humans adapting to hypoxic conditions such as at high altitude, following blood donation, or impaired lung function, such as pulmonary edema.

6


 

By contrast, erythropoiesis stimulating agents (“ESAs”) act only to stimulate erythroid maturation without a corresponding increase in iron availability, and are typically dosed at well above the natural physiologic range of EPO. The sudden demand for iron stimulated by ESA-induced erythropoiesis can lead to functional or absolute iron deficiency. We believe these high doses of ESAs are a main cause of the significant safety issues that have been attributed to this class of drugs. In addition, the lack of a coordinated increase in iron availability with ESAs may explain the hyporesponsiveness of patients with inflammation to this class of drugs. It also explains why patients taking ESAs need more IV iron supplementation and red blood cell transfusions than patients taking roxadustat do. Not only are IV iron and blood transfusions more costly than oral iron, but both are also associated with increased risk of hospitalization and death.

The differentiated mechanism of action of roxadustat, which involves induction of the body’s own natural pathways to achieve a more complete erythropoiesis, has the potential to provide a safe and effective treatment for anemia, including in the presence of inflammation, which normally limits iron availability.

Background of Anemia in Chronic Kidney Disease

Chronic kidney disease is a progressive disease characterized by gradual loss of kidney function that may eventually lead to kidney failure or end-stage renal disease requiring dialysis or a kidney transplant to survive. CKD affects 12% to 14% of the global adult population. CKD is more prevalent in developed countries but is also growing rapidly in emerging markets such as China.  

Anemia is a complication of CKD and can be a serious medical condition in which patients have insufficient red blood cells and low levels of hemoglobin, a protein in red blood cells that carries oxygen to cells throughout the body. Anemia becomes increasingly common as kidney function declines and is associated with increased risk of hospitalization, cardiovascular complications and death, and frequently causes significant fatigue, cognitive dysfunction, and considerable reduction of quality of life.

There are approximately 39 million1 CKD patients in the U.S., an estimated 6 million of whom have anemia2.

When ESAs were introduced in 1989, they dramatically reduced the need for blood transfusions in CKD patients, which was a material development since transfusions reduce the patient’s opportunity for a kidney transplant and increase the risk of infections and complications such as heart failure and allergic reactions. However, multiple randomized clinical trials with ESAs suggested safety risks of ESA therapies, and as a result, the anemia guidelines and approved labels have changed to more restrictive use of ESAs.

 

1 

Bikbov B et al. “Global regional and national burden of chronic kidney disease 1990-2017 - a systematic analysis for the Global Burden of Disease Study 2017.” The Lancet, 395 (2020): 709-33. Web. 13 Feb. 2020.

2 

Based on 15.4% of CKD patients having anemia, (where anemia is defined as hemoglobin levels of ≤ 12 g/dL in women and ≤ 13 g/dL in men.

7


 

 

In the dialysis-dependent population, most patients start receiving ESAs when the patient is transitioning to dialysis care. As of the end of 2018, there were over 550,000 CKD patients on dialysis in the U.S., a large majority of whom required anemia therapy.

There were approximately 127,000 incident dialysis patients in 2018.  Despite the higher risk of blood transfusions, cardiovascular events, and hospitalization in patients with anemia, only 14.6% of patients in 2018 were treated with ESAs prior to initiating dialysis notwithstanding a mean hemoglobin level of 9.3 g/dL at the time of dialysis initiation.

These treatment figures at the time of dialysis initiation demonstrate how undertreated CKD anemia is currently in non-dialysis patients. However, we believe there will be approximately 2 million addressable non-dialysis CKD anemia patients in the U.S. annually, based on the hemoglobin entry criteria in our Phase 3 clinical trials recommending initiation of treatment when a patient’s hemoglobin level is less than 10 g/dL. In addition to the safety concerns raised for ESAs, which may have been a greater impediment to treatment in the non-dialysis setting, other factors which contribute to the recent historical under-treatment of anemia in non-dialysis patients are related to the form of administration and accessibility of ESA products. ESAs are typically administered by subcutaneous injections, which is more difficult outside of dialysis centers or nephrology practices where non-dialysis patients are typically treated.

8


 

Roxadustat Phase 3 CKD Anemia Clinical Program

 

 

 

 

 

Number of Patients

 

Study Sponsor, Number

 

Comparator

 

U.S.

 

 

Europe

 

 

China

 

 

Japan

 

NON-DIALYSIS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FibroGen - FGCL-4592-060 (ANDES)

 

Placebo

 

-------- 922 --------

 

 

 

 

 

 

 

 

 

Astellas - 1517-CL-0608 (ALPS)

 

Placebo

 

-------- 597 --------

 

 

 

 

 

 

 

 

 

AstraZeneca - D5740C00001 (OLYMPUS)

 

Placebo

 

-------- 2,781 --------

 

 

 

 

 

 

 

 

 

Astellas - 1517-CL-0610

 

Darbepoetin alfa

 

 

 

 

 

 

616

 

 

 

 

 

 

 

 

 

FibroGen - FGCL-4592-808

 

Placebo

 

 

 

 

 

 

 

 

 

 

151

 

 

 

 

 

Astellas - 1517-CL-0310

 

Darbepoetin alfa

 

 

 

 

 

 

 

 

 

 

 

 

 

 

334

 

Astellas - 1517-CL-0314

 

None

 

 

 

 

 

 

 

 

 

 

 

 

 

 

99

 

Non-Dialysis-Dependent CKD Subtotal by Region

 

 

 

 

4,300

 

 

 

4,916

 

 

 

151

 

 

 

433

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STABLE DIALYSIS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Astellas - 1517-CL-0613 (PYRENEES)

 

Epoetin alfa or Darbepoetin alfa

 

 

 

 

 

 

838

 

 

 

 

 

 

 

 

 

FibroGen - FGCL-4592-806

 

Epoetin alfa

 

 

 

 

 

 

 

 

 

 

304

 

 

 

 

 

Astellas - 1517-CL-0302

 

None

 

 

 

 

 

 

 

 

 

 

 

 

 

 

56

 

Astellas - 1517-CL-0307

 

Darbepoetin alfa

 

 

 

 

 

 

 

 

 

 

 

 

 

 

303

 

Astellas - 1517-CL-0308

 

None

 

 

 

 

 

 

 

 

 

 

 

 

 

 

75

 

Astellas - 1517-CL-0312

 

None

 

 

 

 

 

 

 

 

 

 

 

 

 

 

164

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

STABLE AND INCIDENT DIALYSIS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

AstraZeneca - D5740C00002 (ROCKIES)

 

Epoetin alfa

 

-------- 2,133 --------

 

 

 

 

 

 

 

 

 

FibroGen - FGCL-4592-064 (SIERRAS)

 

Epoetin alfa

 

-------- 741 --------

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

INCIDENT DIALYSIS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

FibroGen - FGCL-4592-063 (HIMALAYAS)

 

Epoetin alfa

 

-------- 1,043 --------

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Dialysis-Dependent-CKD Subtotal by Region

 

 

 

 

3,917

 

 

 

4,755

 

 

 

304

 

 

 

598

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Total by Regulatory Approval Region

 

 

 

 

8,217

 

 

 

9,671

 

 

 

455

 

 

 

1,031

 

Combined Total to Support U.S. and Europe Approvals

 

 

 

9,671

 

 

 

 

 

 

 

 

 

 

9


 

 

The primary efficacy endpoint was met in each of the pivotal studies for the U.S. NDA and Europe MAA, as shown below:

Summary of Results from Individual Phase 3 Studies of Roxadustat in CKD Anemia

Summary of Roxadustat U.S. and Europe Phase 3 Primary Efficacy Results

 

Study Sponsor, Number

U.S. Primary Endpoint

Endpoint

Met

Europe Primary Endpoint

Endpoint

Met

NON-DIALYSIS

 

 

 

 

FibroGen - FGCL-4592-060 (ANDES)

Superior to Placebo (p<0.0001)

Superior to Placebo (p<0.0001)

Astellas - 1517-CL-0608 (ALPS)

 

Superior to Placebo (p<0.001)

 

Superior to Placebo (p<0.001)

AstraZeneca - D5740C00001 (OLYMPUS)

 

Statistically-Significant Improvement in Hb Change Compared to Placebo

 

Statistically-Significant Improvement in Hb Change Compared to Placebo

 

 

 

 

 

STABLE DIALYSIS

 

 

 

 

Astellas - 1517-CL-0613 (PYRENEES)

Non-Inferior to ESAs

Non-Inferior to ESAs

 

 

 

 

 

STABLE AND INCIDENT DIALYSIS

 

 

 

 

AstraZeneca - D5740C00002 (ROCKIES)

Statistically-Significant Larger Hb Increase Compared to Epoetin Alfa

Statistically-Significant Larger Hb Increase Compared to Epoetin Alfa

FibroGen - FGCL-4592-064 (SIERRAS)

Superior to Epoetin Alfa (p<0.0001)

Superior to Epoetin Alfa (p<0.0001)

 

 

 

 

 

INCIDENT DIALYSIS

 

 

 

 

FibroGen - FGCL-4592-063 (HIMALAYAS)

Superior to Epoetin Alfa (p=0.0005)

Non-Inferior to Epoetin Alfa

Additional Highlights from Recent Publications and Presentations of Roxadustat in CKD Anemia

Pooled Cardiovascular Safety Results

In the U.S., the primary safety endpoint is time to first major adverse cardiovascular event (“MACE”), a composite endpoint of all-cause mortality, stroke and myocardial infarction, with secondary safety endpoint of “MACE+”, a composite endpoint consisting of the three components in MACE plus heart failure or unstable angina requiring hospitalization.The below cardiovascular safety analyses reflect the pooling strategy and analytical approach that was agreed upon with the FDA and presented in scientific journals/professional meetings.

10


 

Non-Dialysis - Pooled Cardiovascular Safety Data

The intent-to-treat analyses, inclusive of data during on-treatment and post treatment long term follow-up (until a common study end date), was used in our primary cardiovascular safety analysis method for non-dialysis in the U.S. This approach accounts for the higher drop-out rate in the placebo arm. The figure below shows that in the 4,270 pooled non-dialysis patients (OLYMPUS, ANDES, and ALPS), the risk of MACE, MACE+, and all-cause mortality in roxadustat patients were comparable to that in placebo patients based on a reference non-inferiority margin of 1.3.  

 

 

Dialysis - Pooled Cardiovascular Safety Data

In the pooled on-treatment analysis of 3,880 dialysis patients (HIMALAYAS, SIERRAS, and ROCKIES), the risk of MACE and all-cause mortality in roxadustat patients were comparable to epoetin alfa, based on a reference non-inferiority margin of 1.3. Roxadustat lowered the risk of MACE+ by 14% compared to epoetin alfa based on a hazard ratio of 0.86 and an upper bound of 95% CI under 1.0. The hazard ratios represent a point estimate of relative risk.  

11


 

 

Incident Dialysis Subgroup - Pooled Cardiovascular Safety Data

Data from the pooled incident dialysis patients were recently published in Kidney International Reports. (Provenzano R et al. Pooled Analysis of Roxadustat for Anemia in Patients with Kidney Failure Incident to Dialysis. KI Reports 2021. Available at https://www.kireports.org/article/S2468-0249(20)31851-9/fulltext.  Accessed on 11FEB2021.)

This is a clinically important subgroup of dialysis patients who started participation in roxadustat Phase 3 studies within their first four months of dialysis initiation. In these 1,526 incident dialysis patients, roxadustat reduced the risk of MACE by 30% and MACE+ by 34%, with a trend towards lower all-cause mortality. The lower MACE and MACE+ risks (compared to epoetin alfa) are based on hazard ratios of 0.70 and 0.66, respectively, with the upper bound of 95% CI under 1.0 for both endpoints. We believe this incident dialysis subpopulation provides clinically and commercially relevant and generalizable results for comparison of roxadustat versus epoetin alfa because most incident dialysis patients (as opposed to stable dialysis patients) were ESA-naïve or had only limited exposure to ESAs prior to study entry. In addition, the initiation of anemia therapy in this incident dialysis subgroup resembles clinical practice as the vast majority of U.S. patients start anemia therapy early in dialysis treatment (during the first four months of treatment).  

Iron-Metabolism Data

In non-dialysis patients, roxadustat was effective regardless of whether the “iron-repletion” criteria (ferritin >=100 ng/mL AND TSAT >=20%) were met, including the 40% of patients whose iron stores were below those required for ESA treatment. Roxadustat also increased both serum iron and transferrin, resulting in the long-term clinical stability of TSAT while increasing the absolute amount of iron available for erythropoiesis.

In dialysis patients, roxadustat treated patients required less IV iron supplementation than patients treated with ESA. Roxadustat facilitated iron transport and utilization by increasing both serum iron and iron-carrying capacity (TIBC), whereas these parameters were decreased and unchanged, respectively, with epoetin alfa. We believe these changes were most likely driven by the downstream effects of reduced hepcidin in roxadustat treated patients.

Efficacy at Raising Hemoglobin Irrespective of Iron Replete Status

In the non-dialysis pool (4,277 patients from ANDES, OLYMPUS, and ALPS), roxadustat increased hemoglobin (by 1.94 g/dL) regardless of whether patients were iron-replete (patients shown to have sufficient baseline stores of iron in their body, TSAT ≥20% and Ferritin ≥100 ng/mL) or not iron-replete.

12


 

Sierras – U.S. Only Dialysis Study

In the U.S. dialysis study SIERRAS, roxadustat raised and maintained Hb levels with stable mean doses over time regardless of baseline inflammation status, as measured by CRP levels. The dose requirement of roxadustat was not impacted by inflammation.

Mean Hb and Mean Weekly Dose of roxadustat (Top Figure) and Epoetin Alfa (Bottom Figure) Over Time in Patients with hsCRP ≤ULN or >ULN (SIERRAS)

 

hsCRP: high-sensitivity C-reactive protein; SE: standard error; ULN: upper limit of normal.

The proportion of patients who required at least one red blood cell transfusion in the first 52 weeks was 12.5% with roxadustat compared to 21.1% with epoetin alfa (p<0.05) in SIERRAS.

13


 

ROXADUSTAT FOR THE TREATMENT OF ANEMIA IN CHRONIC KIDNEY DISEASE IN CHINA

In August 2019, roxadustat (China tradename: 爱瑞卓®) received marketing authorization in China for the treatment of anemia caused by CKD in non-dialysis-dependent patients. Treatment for anemia caused by CKD in dialysis-dependent patients was approved in December 2018.

In July 2019, results from our two China Phase 3 clinical trials were published in the New England Journal of Medicine.3 4

In December 2019, roxadustat was included on the updated NRDL released by China’s National Healthcare Security Administration. Roxadustat is included on the NRDL for the treatment of anemia in CKD.  

Market Opportunity

The currently available forms of treatment in China for anemia in CKD include ESAs, oral iron, intravenous iron, traditional Chinese medicine, and combinations thereof. ESAs are the largest segment, which we estimate to be approximately $275 million in sales, or approximately 80% of the total ESA market based on data from IQVIA China Hospital Pharmaceutical Audit. With the unique benefits of roxadustat to treat previously unaddressable patient populations, we believe the overall CKD anemia market will increase.

China is experiencing epidemiological changes in metabolic diseases due to economic development, urbanization and an aging population. Diabetes and hypertension are the leading causes of CKD in China, and rates have been growing over past two decades. We believe the increase in diabetes and hypertension prevalence will result in an increase of CKD anemia patients.

Dialysis-Dependent CKD

Based on the latest estimates and published data, we believe there are over 600,000 dialysis patients in China, making it the largest single-country dialysis population in the world. With the substantial growth rate of dialysis patients (over 10% per year from 2011 to 2017), the Ministry of Health and the Chinese Society of Nephrology have publicly recognized the need for further investment in dialysis infrastructure.  

The prevalence of CKD dialysis patients that have anemia (defined as hemoglobin < 10g/dL) is estimated to be over 90%.

Dialysis treatment is delivered in the form of hemodialysis or peritoneal dialysis. In China, approximately 85% of dialysis patients with CKD are on hemodialysis. Hemodialysis is performed primarily in dialysis clinics within hospitals, most of which are publicly owned. This is in contrast to the U.S. where freestanding dialysis centers located outside of hospitals is common practice. With recent regulatory changes, the number of privately owned dialysis clinics is growing at a rapid pace, a trend that has provided additional capacity to meet the growing demand. The remaining 14-15% of CKD patients (approximately 100,000) are on peritoneal dialysis, which is self-administered at home by patients, a setting which roxadustat is particularly well-suited for due to its oral administration. Peritoneal dialysis patients typically visit their nephrologists on a monthly basis at the hospital for monitoring and follow-up.  

 

3 

N. Chen, et al. “Roxadustat Treatment for Anemia in Patients Undergoing Long-Term Dialysis” N Engl J Med 381 (2019): 1011-22. DOI: 10.1056/NEJMoa1901713

4 

N. Chen, et al. “Roxadustat for Anemia in Patients with Kidney Disease Not Receiving Dialysis” N Engl J Med 381 (2019): 1001-1010. DOI: 10.1056/NEJMoa1813599

14


 

 

Non-Dialysis-Dependent CKD

We estimate that there are over 10 million Stage 3-5 non-dialysis CKD patients in China with anemia (defined as hemoglobin < 10g/dL). We believe the addressable population of non-dialysis patients with anemia (anemic patients that have been diagnosed and treated for CKD) is approximately 2-3 million, with 1-2 million of these addressable patients in Stages 3 and 4 and 1 million in Stage 5 non-dialysis. This Stage 5 population that is dialysis-eligible but not receiving dialysis is characteristic of developing markets like China, and presents a particular opportunity for roxadustat, as many patients have severe anemia.  

Unmet Medical Need and Roxadustat Differentiation in China

We believe there is a particularly significant unmet medical need for the treatment of anemia in CKD in China. Anemia is considered a risk multiplier for CKD patients and is commonly associated with increased rates of cardiovascular events, hospitalizations, CKD progression, and death. Several of the advantages that roxadustat, as an oral therapeutic, potentially offers over ESAs are particularly suited to address the unmet medical need in each of the three categories of CKD patients in China.

We believe there is chronic under-treatment of anemia within the CKD patient population on dialysis in China due in part to under-prescription of IV iron (often necessary for ESA treatment), and lack of efficacy in patients with inflammation. The most recent treatment guidelines published by the Chinese Society of Nephrology in 2018 recommended treatment to hemoglobin 11.0 g/dL to 12.0 g/dL. Even though over 70% of hemodialysis CKD patients, and approximately 60% of peritoneal dialysis CKD patients are treated with ESAs, based on the Chinese Renal Data System in 2015, less than 60% of dialysis patients reached 10.2 g/dL.

In the non-dialysis population and peritoneal dialysis population, only a small percentage of patients receive anemia treatment, and those who do, they receive only a minimal level of treatment, including patients who are eligible for dialysis and who have severe anemia. Roxadustat, as an oral medication, can be easily administered in any setting and stored at room temperature. Injectable drugs like ESAs present a challenge in China because even subcutaneous administration is performed at hospitals and not in the home, in part due to the difficulty in refrigeration and administration of injectable medicines. Frequent hospital visits, for the sole purpose of receiving injectable ESA treatment (as well as IV iron, which is often necessary with ESA treatment), can present a substantial logistical and financial burden to patients.

In the context of the rapidly growing China pharmaceutical market, we believe that the demand for anemia therapy will continue to grow as a result of an expanding CKD population, as well as the central government’s mandate to make dialysis more available through government reimbursement and build-out of dialysis facilities. In addition, as the standard of living improves in China, the demand for access to innovative drugs increases. In this context, we believe that roxadustat is a particularly promising product for this market.

Commercialization

AstraZeneca is our commercialization partner for roxadustat in China. Under our collaboration agreement, AstraZeneca leads commercialization activities and has responsibility for sales and marketing, and market access. FibroGen has responsibility for medical affairs, manufacturing (as the Marketing Authorization Holder), and pharmacovigilance.

Pricing and Reimbursement

In December 2019, roxadustat was included for the treatment of anemia in CKD on the updated NRDL released by China’s National Healthcare Security Administration. The list is effective for a standard two-year period from January 1, 2020 to December 31, 2021. Roxadustat will be subject to price re-negotiation at the end of 2021.

We believe reimbursement is one of the two most critical market access factors for commercialization success in China, with the other being hospital listings. China is mostly a single-payor market with near universal healthcare provided by the government. Over 95% of the population receives healthcare coverage under one government-funded medical reimbursement plan or another, each with different levels of reimbursement. Commercial health insurance is available but is minimally adopted, and is seen as a supplement above and beyond government reimbursement.  

15


 

Reimbursement for roxadustat will differ based on multiple factors including the CKD patient population (dialysis vs. non-dialysis), location, patient employment status, and if roxadustat is qualified into the “Critical Disease” or “Chronic Disease” insurance programs for such locations. We expect roxadustat reimbursement rates will be largely consistent with those ESAs listed on the NRDL. We believe in the next few years and in many parts of the country, reimbursement will reach a level where patient out-of-pocket costs will be in the range of 10-20% for dialysis and 30-50% for non-dialysis.

Hospital Listing

Before roxadustat can be prescribed at a government hospital, which is 90% of the market in China, it has to be carried in the hospital formulary. The process of entry into the formulary is commonly referred to as “hospital listing”. Decisions are made on a hospital-by-hospital basis, where hospital listing committees meet anywhere from every six months to every five years. Temporary listings can be used in the interim, where the head of the department could place an ad-hoc order with the formulary for a single or handful of patients for small quantities of roxadustat. These market access constraints impact all drugs, not just roxadustat. Consistent with the experience of other product launches in China, significant market uptake is usually seen a few years after launch, although in the case of roxadustat, it could be sooner given the inclusion in NRDL within 12 months of market approval.

Tendering

Tendering is a provincial level procedure. For drugs with multiple brands, it is a collective tender process for purchases by government hospitals of a medicine included in provincial or local medicine procurement catalogs. In the case of roxadustat, it is a more administrative process than for most drugs as roxadustat is currently the only drug of its class (HIF-PHI) available on the market. The tendering process of roxadustat is substantially complete in all 31 provinces in China.

ROXADUSTAT FOR THE TREATMENT OF ANEMIA IN CHRONIC KIDNEY DISEASE IN JAPAN

In Japan, our partner Astellas continues the commercial launch of EVRENZO® (roxadustat), targeting healthcare providers that care for approximately 330,000 dialysis patients across Japan. EVRENZO is now approved for the treatment of anemia associated with CKD in both non-dialysis and dialysis patients. The supplemental NDA for the use of roxadustat in patients with anemia of CKD not on dialysis was approved in November 2020 by the Pharmaceuticals and Medical Devices Agency.

In addition, the 14-day Prescription Rule that is typically in place for the first 12 months of a product’s availability in Japan was lifted in December of 2020, creating a potential catalyst for EVRENZO utilization given it is the first HIF-PH inhibitor to no longer have this limitation.

ROXADUSTAT FOR THE TREATMENT OF CHEMOTHERAPY-INDUCED ANEMIA AND ANEMIA ASSOCIATED WITH MYELODYSPLASTIC SYNDROMES

Based on roxadustat’s mechanism of action and safety and efficacy profile to date, we believe it has the potential to treat anemia associated with many other conditions, including CIA and MDS.

Background of Chemotherapy-Induced Anemia

As blood cell production in bone marrow is highly prolific, it is particularly vulnerable to the cytotoxic effects of chemotherapy used to treat cancer patients. Many chemotherapy agents directly impair hematopoiesis in bone marrow, including disruption of red blood cell production. The nephrotoxic effects of some cytotoxic agents, such as platinum-containing agents, can also result in decreased production of erythropoietin by the kidneys, further contributing to reduced red blood cell production. Radiation therapy has also been associated with hematologic toxicity.  

Approximately 40% of total solid tumor cancer patients, or approximately 6.8 million people, undergo chemotherapy each year globally, including 1.7 million in the U.S. and 3.2 million in China. Between 60% and 80% of these patients develop anemia. The incidence and severity of CIA depend on a variety of factors, including the tumor type or the level of toxicity of the therapy, and further increases with each successive chemotherapy round. We believe the addressable population is approximately 600,000 in the U.S. and 500,000 in China.

16


 

ESAs have been recommended for patients experiencing CIA with the desirable goals of improvement in anemia-related symptoms and the avoidance of blood transfusion, which increases risk of infections and the risk of complications such as heart failure and allergic reactions. However, not all CIA patients respond to ESA therapy, which may be due to the etiology of their CIA or inflammatory comorbidity. ESA use also has associated toxicities, including increased thrombotic events, possible decreased survival and accelerated tumor progression, as published from randomized clinical trials and meta-analyses, that led to label restrictions and boxed warnings for ESAs in cancer populations in 2007, followed by the ESA Risk Evaluation and Mitigation Strategy (“REMS”) program.

Market Opportunity for Roxadustat in Chemotherapy-Induced Anemia

ESA sales for CIA dropped significantly in the U.S. since the reported safety risks of ESA use in cancer patients in 2006, from estimated $2.5 billion in 2006 to less than $0.5 billion in 2019. During the same period, the prevalence of diagnosed CIA remained at similar levels, and is expected to grow slightly.

We believe that if our clinical program shows an acceptable safety and efficacy profile, roxadustat would have the potential to address anemia in this population of patients undergoing chemotherapy.

Clinical Development of Roxadustat in Chemotherapy-Induced Anemia

We have completed enrollment in WHITNEY, our Phase 2 clinical trial of roxadustat in the U.S. in CIA. This is a single-arm open label study investigating the efficacy and safety of roxadustat for the treatment of anemia in 92 patients receiving myelosuppressive chemotherapy treatment for non-myeloid malignancies, with a treatment duration of 16 weeks. We expect topline data from this study in the second half of 2021.

Background of Anemia in Myelodysplastic Syndromes

Myelodysplastic syndromes are a diverse group of bone marrow disorders characterized by ineffective production of healthy blood cells and premature destruction of blood cells in the bone marrow, leading to anemia. In most MDS patients, the cause of the disease is unknown.

The prevalence of MDS in the U.S. is estimated to be between 60,000 and 170,000, and continues to rise as more therapies become available and patients are living longer with MDS. Annual incidence rates are estimated to be 4.9/100,000 adults in the U.S., and 1.51/100,000 adults in China.

Anemia is the most common clinical presentation in MDS, seen in approximately 80% of MDS patients, and producing symptoms, including fatigue, weakness, exercise intolerance, shortness of breath, dizziness, and cognitive impairment.

Limitations of the Current Standard of Care for Anemia in Myelodysplastic Syndromes

Stem cell transplant is the only potentially curative therapy for MDS, but it is not feasible in most patients due to their advanced age and frailty. The high rate of severe anemia leaves recurring red blood cell transfusions as the mainstay of care in MDS patients. Transfusion can result in direct organ damage through transfusional iron overload. Transfusion dependent MDS patients suffer higher rates of cardiac events, infections and transformation to acute leukemia, and a decreased overall survival rate when compared with non-transfused patients with MDS, and decreased survival compared to an age-matched elderly population. Patients receiving red blood cell transfusions may require an iron chelator in order to address toxic elements of iron overload such as lipid peroxidation and cell membrane, protein, DNA, and organ damage.  

Lower-risk MDS patients represent approximately 77% of total diagnosed MDS population. Most national and international guidelines recommend use of ESAs for anemia only in lower-risk MDS patients presenting with symptomatic anemia with serum EPO levels at or below 500 mU/mL.  

Even among the eligible subpopulation, the effectiveness of ESAs in treating anemia in MDS remains limited, with the best clinical study results showing 40% to 60% erythroid response rates, in studies where significantly high doses of ESAs were used, enrolled patients had low serum EPO levels, and in lower-risk categories. New strategies to broaden the eligible population, improve anemia and maintain adequate iron balance, as well as avoidance of transfusions, are highly desired in managing patients with MDS.  

17


 

Reblozyl® (luspatercept) was approved by the FDA in April 2020 for the treatment of anemia in adults with MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis who need regular red blood cell transfusions and have not responded well to or cannot receive an ESA. It is the first and only erythroid maturation agent approved in the U.S., Europe, and Canada and is part of a global collaboration between Acceleron Pharma, Inc. and Bristol Myers Squibb. In 2020, Reblozyl net revenue was $274 million, including $115 million in Q4 2020.

Market Opportunity for Roxadustat in Myelodysplastic Syndromes

We believe there is a significant need for a safer, more effective, and more convenient option to address anemia in patients with lower-risk MDS. Roxadustat, our orally administered small molecule HIF-PH inhibitor, stimulates the body’s natural mechanism of red blood cell production and iron hemostasis based on cellular-level oxygen-sensing and iron-regulation mechanisms. Unlike ESAs which are limited to providing exogenous EPO, roxadustat activates a coordinated erythropoietic response in the body that includes the stimulation of red blood cell progenitors, an increase in the body’s production of endogenous EPO, and an increase in iron availability for hemoglobin synthesis, which we believe is important in a broad range of MDS patients. Moreover, in anemia of CKD, roxadustat has demonstrated the ability in clinical trials to increase and maintain hemoglobin levels in the presence of inflammation as measured by CRP, where ESAs have shown limited effect. We believe that roxadustat has the potential to replicate this result in MDS anemia patients, where it is not uncommon for patients to present with autoimmune and inflammatory conditions.

Clinical Development of Roxadustat in Myelodysplastic Syndromes

We are continuing to enroll MATTERHORN, our Phase 3 placebo controlled, double-blind clinical trial to evaluate the safety and efficacy of roxadustat for treatment of anemia in MDS in the U.S. and Europe. This 160-patient trial is studying roxadustat in transfusion-dependent, lower-risk MDS patients, in which subjects are randomized 3:2 to receive roxadustat or placebo three-times-weekly. The primary endpoint is the proportion of patients who achieve transfusion independence by 28 weeks with secondary endpoints and safety evaluated at 52 weeks. We expect topline data from this study in the first half of 2022.

In the open-label dose-finding component of this study, 24 lower-risk, transfusion dependent MDS patients with anemia were enrolled in three sequential starting dose cohorts (1.5 mg/kg, 2.0 mg/kg, and 2.5 mg/kg), with roxadustat doses adjusted every eight weeks per a pre-defined algorithm based on hemoglobin response. Best supporting care including red blood cell transfusion was allowed, as needed, per investigator’s discretion. Patients treated with roxadustat achieved a greater than or equal to 8-week transfusion independence rate of 38% in the first 28 weeks and 54% of patients had greater than or equal to 50% reduction in red blood cell transfusion over any eight weeks, from baseline. Roxadustat was generally well tolerated in each dose cohort. The dose level of 2.5 mg/kg was selected as the starting dose for the double-blind component of the study.

In China, we are preparing to enroll the Phase 3 double-blind, placebo-controlled portion of our Phase 2/3 clinical trial to evaluate the safety and efficacy of roxadustat in non-transfusion dependent, lower-risk MDS patients with anemia. One hundred thirty-five subjects will be randomized 2:1 to receive roxadustat or placebo three-times weekly for 26 weeks. The primary endpoint for this study is percentage of patients achieving a hemoglobin response.

PAMREVLUMAB FOR THE TREATMENT OF FIBROSIS AND CANCER

We were founded to discover and develop therapeutics for fibrosis and began studying CTGF shortly after its discovery. Our accumulated discovery research efforts indicate that CTGF is a critical common element in the progression of serious diseases associated with fibrosis.

From our library of human monoclonal antibodies that bind to different parts of the CTGF protein and block various aspects of CTGF biological activity, we selected pamrevlumab, for which we have exclusive worldwide rights. We believe that pamrevlumab blocks CTGF and inhibits its central role in causing diseases associated with fibrosis. Our data to date indicate that pamrevlumab is a promising and highly differentiated product candidate with broad potential to treat a number of fibrotic diseases and cancers.

We are currently conducting Phase 3 studies in pancreatic cancer, IPF and DMD. In the U.S., the FDA has granted Orphan Drug Designation to pamrevlumab for the treatment of IPF, LAPC, and DMD. In addition, the EMA has granted Orphan Medicinal Product Designation to pamrevlumab for the treatment of DMD. Pamrevlumab has also received Fast Track designation from the FDA for the treatment of both IPF and LAPC.

18


 

Overview of Fibrosis

Fibrosis is an aberrant response of the body to tissue injury that may be caused by trauma, inflammation, infection, cell injury, or cancer. The normal response to injury involves the activation of cells that produce collagen and other components of the extracellular matrix (“ECM”) that are part of the healing process. This healing process helps to fill in tissue voids created by the injury or damage, segregate infections or cancer, and provide strength to the recovering tissue. Under normal circumstances, where the cause of the tissue injury is limited, the scarring process is self-limited and the scar resolves to approximate normal tissue architecture. However, in certain disease states, this process is prolonged and excessive and results in progressive tissue scarring, or fibrosis, which can cause organ dysfunction and failure as well as, in the case of certain cancers, promote cancer progression.

Excess CTGF levels are associated with fibrosis. CTGF increases the abundance of myofibroblasts, a cell type that drives wound healing, and stimulates them to deposit ECM proteins such as collagen at the site of tissue injury. In the case of normal healing of a limited tissue injury, myofibroblasts eventually die by programmed cell death, or apoptosis, and the fibrous scarring process recedes.

Multiple biological agents and pathways have been implicated in the fibrotic process, many of which converge on CTGF, a central mediator of fibrosis. In the case of cancer, the sustained tumor-associated fibrotic tissue promotes tumor cell survival and metastasis. CTGF is a secreted glycoprotein produced by fibroblasts, endothelium, mesangial cells and other cell types, including cancers, and is induced by a variety of regulatory modulators, including TGF-ß and VEGF. CTGF expression has been demonstrated to be up-regulated in fibrotic tissues. Thus, we believe that targeting CTGF to block or inhibit its activity could mitigate, stop or reverse tissue fibrosis. In addition, since CTGF is implicated in nearly all forms of fibrosis, we believe pamrevlumab has the potential to provide clinical benefit in a wide range of clinical indications that are characterized by fibrosis.

Until recently, it was believed that fibrosis was an irreversible process. It is now generally understood that the process is dynamic and potentially amenable to reversal. Based on studies in animal models of fibrosis of the liver, kidney, muscle and cardiovascular system, it has been shown that fibrosis can be reversed. It has also been demonstrated in humans that fibrosis caused by hepatitis virus can be reversed (Chang et al. Hepatology (2010)). Additionally, we have generated data in human and animal studies that lung fibrosis progression can be slowed, arrested, or possibly reversed in some instances upon treatment with pamrevlumab.

Clinical Development of Pamrevlumab — Overview

We have performed clinical trials of pamrevlumab in IPF, pancreatic cancer, liver fibrosis and diabetic kidney disease. In eleven Phase 1 and Phase 2 clinical studies involving pamrevlumab to date, including more than 600 patients who were treated with pamrevlumab (about half of patients dosed for more than six months), pamrevlumab has been well-tolerated across the range of doses studied, and there have been no dose-limiting toxicities seen thus far.

 

Idiopathic Pulmonary Fibrosis

Understanding IPF and Current Therapies

IPF is a form of progressive pulmonary fibrosis, or abnormal scarring, which destroys the structure and function of the lungs. As tissue scarring progresses in the lungs, transfer of oxygen into the bloodstream is increasingly impaired. Average life expectancy at the time of confirmed diagnosis of IPF is estimated to be between three to five years, with approximately two-thirds of patients dying within five years of diagnosis. Thus, the survival rates are comparable to some of the most deadly cancers. The cause of IPF is unknown but is believed to be related to unregulated cycles of injury, inflammation and fibrosis.

Patients with IPF experience debilitating symptoms, including shortness of breath and difficulty performing routine functions, such as walking and talking. Other symptoms include chronic dry, hacking cough, fatigue, weakness, discomfort in the chest, loss of appetite, and weight loss. Over the last decade, refinements in diagnosis criteria and enhancements in high-resolution computed tomography imaging technology (“quantitative HRCT”) have enabled more reliable diagnosis of IPF without the need for a lung biopsy.

The U.S. prevalence and incidence of IPF are estimated to be 44,000 to 135,000 cases, and 21,000 new cases per year, respectively, based on Raghu et al. (Am J Respir Crit Care Med (2006)) and on data from the United Nations Population Division. We believe that with the availability of technology to enable more accurate diagnoses, the number of individuals diagnosed per year with IPF will continue to increase.

19


 

There are currently two therapies approved to treat IPF in Europe and the U.S., pirfenidone and nintedanib. The approvals and subsequent launches of Esbriet (pirfenidone) and Ofev (nintedanib) have clearly shown the commercial potential in IPF. Hoffmann-La Roche (“Roche”) reported worldwide sales of approximately $1.1 billion for 2019 and $1.2 billion for 2020 for Esbriet® (pirfenidone). Similarly, Boehringer Ingelheim Pharma GmbH & Co. KG (“Boehringer Ingelheim”) reported total sales of approximately $1.3 billion for Ofev® (nintedanib) in 2018, and approximately $1.7 billion in 2019.

Phase 3 Clinical Development – Randomized, Double-Blind, Placebo-Controlled Trials of Pamrevlumab in IPF

We are conducting ZEPHYRUS-1, our Phase 3 trial of pamrevlumab in IPF patients, as well as our newly initiated ZEPHYRUS-2, a second IPF Phase 3 study. Both studies are double-blind, placebo-controlled Phase 3 trials targeting approximately 340 patients, each with a primary U.S. efficacy endpoint of change from baseline in forced vital capacity.

The primary efficacy endpoint in Europe for each study is disease progression (defined by a decline in forced vital capacity (“FVC”) percent predicted of greater than or equal to 10% or death). Secondary endpoints will include clinical outcomes of disease progression, patient reported outcomes, and quantitative changes in lung fibrosis volume from baseline.

The COVID-19 pandemic has affected enrollment in these IPF trials, more so than our other studies due to the vulnerability of this patient population. In addition to efforts we are making in ensuring patient safety, we are also working to expand enrollment through a number of methods, including expanding the number of clinical sites in China.

PRAISE – Study 067 – Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Pamrevlumab in IPF

In September 2019, positive results from PRAISE, our randomized, double-blind, placebo-controlled Phase 2 clinical trial (Study 067), were published in The Lancet Respiratory Medicine. PRAISE was designed to evaluate the safety and efficacy of pamrevlumab in patients with mild-to-moderate IPF (baseline FVC percentage predicted of 55%), as well as topline results from two sub-studies that were added to evaluate the safety of combining pamrevlumab with approved IPF therapies.

In the double-blind, placebo-controlled 48-week portion of this study, 103 patients were randomized (1:1) to receive either 30mg/kg of pamrevlumab or placebo intravenously every three weeks. Lung function assessments were conducted at baseline and at Weeks 12, 24, 36 and 48. Quantitative HRCT assessments were performed at baseline and at Weeks 24 and 48.

Pamrevlumab met the primary efficacy endpoint of change of FVC percent predicted, a measure of a patient’s lung volume as a percentage of what would be expected for such patient’s age, race, sex and height. The average decline (least squares mean) in FVC percent predicted from baseline to Week 48 was 2.9 in the pamrevlumab arm (n=50) as compared to an average decline of 7.2 in the placebo arm (n=51), a statistically significant difference of 4.33 (p=0.033).

FVC Change by Visit

20


 

 

Pamrevlumab-treated patients had an average decrease (least squares mean) in FVC of 129 ml at Week 48 compared to an average decrease of 308 ml in patients receiving placebo, a statistically significant difference of 178 ml (p=0.0249, using a linear slope analysis in the intent-to-treat population). This represents a 57.9% relative difference. In addition, the pamrevlumab-treated arm had a lower proportion of patients (10%) who experienced disease progression (defined by a decline in FVC percent predicted of greater than or equal to 10% or death), than did the placebo arm (31.4%) at Week 48 (p=0.0103).

Proportion of Patients with Decline in Percentage of Predicted FVC of 10% or Greater, or Death, by Visit

In this study, we measured change in quantitative lung fibrosis (“QLF”) from baseline to Week 24 and Week 48 using quantitative HRCT. The pamrevlumab arm achieved a statistically significant reduction in the rate of progression of lung fibrosis compared to placebo using HRCT to measure QLF. The change in QLF volume from baseline to Week 24 for pamrevlumab-treated patients was 24.8 ml vs. 86.4 ml for placebo, with a treatment difference of -61.6 ml, p=0.009. The change in QLF volume from baseline to 48 weeks was 75.4 ml in pamrevlumab-treated patients vs. 151.5 ml in patients on placebo, with a treatment difference of -76.2 ml, p=0.038.

Change from Baseline in Volume of Quantitative Lung Fibrosis (mL) in the Intention-to-Treat Population

As in our previous open label Phase 2 study, a correlation between FVC percent predicted and QLF was confirmed at both Week 24 and 48 in this study.

We are not aware of any other IPF therapies that have shown a statistically significant effect on lung fibrosis as measured by quantitative HRCT analysis.

21


 

The treatment effects of pamrevlumab were demonstrated not only on change in FVC, a measure of pulmonary function and IPF disease progression, and change in fibrosis using quantitative HRCT, but pamrevlumab-treated patients also showed a trend of clinically meaningful improvement in a measure of health-related quality of life using the St. George’s Respiratory Questionnaire (SGRQ) vs. a reduction in quality of life seen in placebo patients over the 48 weeks of treatment. The SGRQ quality of life measurement has been validated in chronic obstructive pulmonary disease. In the patients that were evaluated by the UCSD Shortness of Breath Questionnaire, pamrevlumab-treated patients had a significant attenuation of their worsening dyspnea in comparison to placebo patients.

Pamrevlumab was well-tolerated in the placebo-controlled study. The treatment-emergent adverse events were comparable between the pamrevlumab and placebo arms and the adverse events in the pamrevlumab arm were consistent with the known safety profile of pamrevlumab. In this study, as compared with the placebo group, fewer pamrevlumab patients were hospitalized, following an IPF-related or respiratory treatment-emergent adverse event, or died for any reason.

The double-blind, active-controlled combination sub-studies were designed to assess the safety of combining pamrevlumab with standard of care medication in IPF patients. Study subjects were on stable doses of pirfenidone or nintedanib for at least three months and were randomized 2:1 to receive 30 mg/kg of pamrevlumab or placebo every three weeks for 24 weeks. Thirty-six patients were enrolled in the pirfenidone sub-study and 21 patients were enrolled in the nintedanib sub-study. Pamrevlumab appeared to be well-tolerated when given in combination with either pirfenidone or nintedanib.

Study 049 – Open-Label Phase 2 Trial of Pamrevlumab in IPF

Our completed open-label extension of Study 049, a Phase 2 open-label, dose-escalation study to evaluate the safety, tolerability, and efficacy of pamrevlumab in 89 patients with IPF, was consistent with our results from our randomized, double-blind, placebo-controlled Phase 2 clinical trial PRAISE. We presented data from our open-label Phase 2 IPF extension study (049) at the International Colloquium on Lung and Airway Fibrosis in November 2016, reporting that no safety issues were observed during prolonged treatment with pamrevlumab. Some of the 37 patients who enrolled in the extension study were treated with pamrevlumab for up to five years. Trends regarding improved or stable pulmonary function and stable fibrosis observed during the initial one-year study were also observed in the extension study.

Pancreatic Cancer

Understanding Pancreatic Cancer and the Limitations of Current Therapies

Certain solid malignant tumors have a prominent fibrosis component consisting mostly of ECM that contributes to metastasis and progressive disease. ECM is the connective tissue framework of an organ or tissue.

Pancreatic ductal adenocarcinoma, or pancreatic cancer, is the third leading cause of cancer deaths in the U.S. According to the European Commission’s European Cancer Information System, there were 100,005 new cases of pancreatic cancer and 95,373 deaths from pancreatic cancer in Europe projected for 2018. The National Cancer Center of Japan estimated that there were 36,239 new cases of pancreatic cancer in 2014, increased from 24,442 cases in 2004. In its report of December 2017, Decision Resources Group estimated that the major market sales (U.S., Europe and Japan) of pancreatic cancer drugs will grow from $1.3 billion in 2016 to approximately $3.7 billion in 2026. According to the U.S. National Cancer Institute, there were an estimated 57,000 new cases of pancreatic cancer in the U.S. in 2019. Fifty percent of new cases are metastatic. Another 15-20% have localized resectable tumors. The remaining 30-35% have localized but unresectable tumors.

For those with non-resectable tumors, median survival is eight to 12 months post-diagnosis, and about 8% realize five years of survival; similar to metastatic cases. For those with resectable tumors, 50% survive 17 to 27 months post-diagnosis and ~20% report five-year survival.

Pancreatic cancer is aggressive and typically not diagnosed until it is largely incurable. Most patients are diagnosed after the age of 45, and according to the American Cancer Society, 94% of patients die within five years from diagnosis. The majority of patients are treated with chemotherapy, but pancreatic cancer is highly resistant to chemotherapy. Approximately 15% to 20% of patients are treated with surgery; however, even for those with successful surgical resection, the median survival is approximately two years, with a five-year survival rate of 15% to 20% (Neesse et al. Gut (2011)). Radiation treatment may be used for locally advanced diseases, but it is not curative.

22


 

The duration of effect of approved anti-cancer agents to treat pancreatic cancer is limited. Gemcitabine demonstrated improvement in median overall survival from approximately four to six months, and erlotinib in combination with gemcitabine demonstrated an additional ten days of survival. Nab-paclitaxel in combination with gemcitabine was approved by the FDA in 2013 for the treatment of pancreatic cancer, having demonstrated median survival of 8.5 months. The combination of folinic acid, 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) was reported to increase survival to 11.1 months from 6.8 months with gemcitabine. These drugs illustrate that progress in treatment for pancreatic cancer has been modest, and there remains a need for substantial improvement in patient survival and quality of life.

The approved chemotherapeutic treatments for pancreatic cancer target the cancer cells themselves. Tumors are composed of cancer cells and associated non-cancer tissue, or stroma, of which ECM is a major component. In certain cancers such as pancreatic cancer, both the stroma and tumor cells produce CTGF which in turn promotes the proliferation and survival of stromal and tumor cells. CTGF also induces ECM deposition that provides advantageous conditions for tumor cell adherence and proliferation, promotes blood vessel formation, or angiogenesis, and promotes metastasis, or tumor cell migration, to other parts of the body.

Pancreatic cancers are generally resistant to powerful chemotherapeutic agents, and there is now growing interest in the use of an anti-fibrotic agent to diminish the supportive role of stroma in tumor cell growth and metastasis. The anti-tumor effects observed with pamrevlumab in preclinical models indicate that it has the potential to inhibit tumor expansion through effects on tumor cell proliferation and apoptosis as well as reduce metastasis.

Phase 3 Clinical Development – Randomized, Double-Blind, Placebo-Controlled Trial of Pamrevlumab in Locally Advanced, Unresectable Pancreatic Cancer

We continue to enroll LAPIS, our double-blind placebo controlled Phase 3 clinical program for pamrevlumab as a neoadjuvant therapy for LAPC. We intend to enroll approximately 260 patients, randomized at a 1:1 ratio to receive either pamrevlumab or placebo, in each case in combination with gemcitabine and nab-paclitaxel. We expect topline resection data from this study in the second half of 2022.

Study 069 – Randomized, Open-Label, Active-Controlled Phase 1/2 Trial of Pamrevlumab in Locally Advanced Pancreatic Cancer

We continue to follow patients in our ongoing open-label, randomized (2:1) Phase 1/2 trial (FGC004C-3019-069) of pamrevlumab combined with gemcitabine plus nab-paclitaxel chemotherapy vs. the chemotherapy regimen alone in patients with inoperable locally advanced pancreatic cancer that has not been previously treated. We enrolled 37 patients in this study and completed the six-month treatment period and surgical assessment at the end of 2017. The overall goal of the trial is to determine whether the pamrevlumab combination can convert inoperable pancreatic cancer to operable, or resectable, cancer. Tumor removal is the only chance for cure of pancreatic cancer, but only approximately 15% to 20% of patients are eligible for surgery.

We reported updated results from this ongoing study at the American Society of Clinical Oncology Annual Meeting in June 2018. A higher proportion (70.8%) of pamrevlumab-treated patients whose tumors were previously considered unresectable became eligible for surgical exploration than patients who received chemotherapy alone (15.4%), based on pre-specified eligibility criteria at the end of 6 months of treatment. Furthermore, a higher proportion of pamrevlumab-treated patients (33.3%) achieved surgical resection than those who received chemotherapy alone (7.7%).  

In addition, this data showed improved overall survival among patients whose tumors were resected vs. not resected (NE vs. 18.56 months, p-value=0.0141) and a trend toward improved overall survival in patients eligible for surgery vs. patients who were not (27.73 vs. 18.40 months, p-value=0.0766). All of the patients on study at the time of the results reported in June 2018 continue to remain on study. No increase in serious adverse events was observed in the pamrevlumab arm and no delay in wound healing was observed post-surgery.

Patients with LAPC have median survival of less than 12 months, only slightly better than patients with metastatic pancreatic cancer, whereas patients with resectable pancreatic cancer have a much better prognosis with median survival of approximately 23 months and some patients being cured. If pamrevlumab in combination with chemotherapy continues to demonstrate an enhanced rate of conversion from unresectable cancer to resectable cancer, it may support the possibility that pamrevlumab could provide a substantial survival benefit for locally advanced pancreatic cancer patients.

23


 

Completed Clinical Trials of Pamrevlumab in Pancreatic Cancer

We completed an open-label Phase 1/2 (FGCL-MC3019-028) dose finding trial of pamrevlumab combined with gemcitabine plus erlotinib in patients with previously untreated locally advanced (Stage 3) or metastatic (Stage 4) pancreatic cancer. These study results were published in the Journal of Cancer Clinical Trials (Picozzi et al., J Cancer Clin Trials 2017, 2:123). Treatment continued until progression of the cancer or the patient withdrew for other reasons. Patients were then followed until death.

Seventy-five patients were enrolled in this study with 66 (88%) having Stage 4 metastatic cancer. The study demonstrated a dose-related increase in survival. At the lowest doses, no patients survived for even one year while at the highest doses up to 31% of patients survived one year.

A post-hoc analysis found that there was a significant relationship between survival and trough levels of plasma pamrevlumab measured immediately before the second dose (Cmin), as illustrated below. Cmin greater than or equal to 150 µg/mL was associated with significantly improved progression-free survival (p=0.01) and overall survival (p=0.03) vs. those patients with Cmin less than 150 µg/mL. For patients with Cmin >150 µg/mL median survival was 9.0 months compared to median survival of 4.4 months for patients with Cmin <150 µg/mL. Similarly, 34.2% of patients with Cmin >150 µg/mL survived for longer than one year compared to 10.8% for patients with Cmin <150 µg/mL. These data suggest that sufficient blockade of CTGF requires pamrevlumab threshold blood levels of approximately 150 µg/mL in order to improve survival in patients with advanced pancreatic cancer.

Increased Pancreatic Cancer Survival Associated with Increased Plasma Levels of Pamrevlumab

The Kaplan-Meier plot provides a representation of survival of all patients in the clinical trial. Each vertical drop in the curve represents a recorded event (death) of one or more patients. When a patient’s event cannot be determined either because he or she has withdrawn from the study or because the analysis is completed before the event has occurred, that patient is “censored” and denoted by a symbol (●) on the curve at the time of the last reliable assessment of that patient.

In the study, the majority of adverse events were mild to moderate, and were consistent with those observed for erlotinib plus gemcitabine treatment without pamrevlumab. There were 99 treatment-emergent serious adverse events; six of which were assessed as possibly related to the investigational drug by the principal investigator, and 93 as not related to study treatment. After investigation, it is our belief that there is no causal relationship between pamrevlumab and the treatment-emergent serious adverse events deemed possibly related by the principal investigator. We did not identify any evolving dose-dependent pattern, and higher doses of pamrevlumab were not associated with higher numbers of serious adverse events or greater severity of the serious adverse events observed.

24


 

Pamrevlumab for Duchenne Muscular Dystrophy

Understanding DMD and the Limitations of Current Therapies

In the U.S., approximately one in every 5,000 boys have DMD, and approximately 20,000 children are diagnosed with DMD globally each year. There are currently no approved disease-modifying treatments. Despite taking steroids to mitigate progressive muscle loss, a majority of children with DMD are non-ambulatory by adolescence and median survival is age 25.

DMD is an inherited disorder of one of the dystrophin genes resulting in absence of the dystrophin protein and abnormal muscle structure and function, leading to progressively diminished mobility as well as pulmonary function and cardiac function, which result in early death. Constant myofiber breakdown results in persistent activation of myofibroblasts and altered production of ECM resulting in extensive fibrosis in skeletal muscles of DMD patients. Desguerre et al. (2009) showed that muscle fibrosis was the only myo-pathologic parameter that significantly correlated with poor motor outcome as assessed by quadriceps muscle strength, manual muscle testing of upper and lower limbs, and age at ambulation loss. Numerous pre-clinical studies including those in the mdx model of DMD suggest that CTGF contributes to the process by which muscle is replaced by fibrosis and fat and that CTGF may also impair muscle cell differentiation during muscle repair after injury.

Phase 3 Clinical Development – LELANTOS, a double-blind, placebo-controlled trial in non-ambulatory DMD patients

In the third quarter of 2020, we initiated a Phase 3 clinical trial, LELANTOS 1, evaluating pamrevlumab as a treatment for DMD. LELANTOS 1 is a double-blind, placebo-controlled trial in approximately 90 non-ambulatory DMD patients. Patients will be randomized at a 1:1 ratio to pamrevlumab or placebo and have a treatment period of 52 weeks. The primary endpoint will assess change in upper limb strength and additional endpoints will include pulmonary, performance, cardiac, and fibrosis assessments.

We also plan to initiate a Phase 3 clinical trial, LELANTOS 2, evaluating pamrevlumab in 70 ambulatory DMD patients.

We expect topline data from these studies in the second half of 2022.  

Phase 2 Open-Label Trial of Pamrevlumab in DMD

In June 2019 at the Parent Project Muscular Dystrophy meeting, we reported topline results from this 21 patient open-label single-arm trial in non-ambulatory DMD patients. This one-year administrative analysis compared our Phase 2 data to previously published natural disease history studies of DMD patients. While we cannot make direct comparisons between our trial and previously published data due to, among other things, differences in subject numbers, baseline characteristics, inclusion/exclusion criteria, treatment protocols, and analysis methods, we are encouraged by the data obtained so far. Pamrevlumab was well tolerated in this study.   

In pulmonary function tests, the results from our study indicate a potential reduction in the 1-year decline in FVC percent predicted from baseline for pamrevlumab-treated patients when compared to FVC data of DMD patients (whether such patients were taking steroids or not) published in 2019 by Ricotti. In the 2019 Ricotti study, the DMD patients were treated with steroids only. Similarly, all of the patients in our Phase 2 pamrevlumab trial were on steroids. In addition, pamrevlumab showed less decline in both percent predicted forced expiratory volume as compared to previously published study results of Meier in 2016, and in percent predicted peak expiratory flow rate, compared to what was observed in the study by Ricotti in 2019.

Our data showed an increase in cardiac function, measured by mean change of left ventricular ejection fraction (“LVEF”), of 0.29% from baseline for pamrevlumab-treated patients. Whereas, data published in 2018 by McDonald of DMD patients only on steroids showed a mean LVEF decline of 0.82% from baseline in one year.

In muscle function tests, the majority of the results of this Phase 2 study showed the mean change from baseline in pamrevlumab-treated patients were more favorable than previously published data. Our results showed a positive increase in grip-strength score in both dominant and non-dominant hands at one year of treatment with pamrevlumab, while earlier results from a 2015 study by Seferian showed a decline at one year as expected. In the performance of the upper limb (“PUL”) test specifically developed for DMD patients, pamrevlumab-treated patients had a mean change from baseline of -1.53. In the 2019 study by Ricotti of DMD patients taking either nothing or only steroids, the annual mean change in the PUL test was -4.13. Furthermore, in our study a strong correlation between change in biceps brachii T2-mapping and change in PUL score was observed, demonstrating stabilization and even possible improvement in the muscle fibrosis burden.  

25


 

Commercialization Strategy for Pamrevlumab

Our goal, if pamrevlumab is successful, is to be a leader in the development and commercialization of novel approaches for inhibiting fibrosis and treating certain forms of cancer and muscular dystrophy diseases. To date, we have retained exclusive worldwide rights for pamrevlumab. We have commenced brand development activities for pamrevlumab and will be advancing these efforts in preparation for potential launches in IPF, LAPC and DMD, consistent with the approaches of companies with a product in late-stage clinical development.

Research at FibroGen

Our research programs at FibroGen are grounded in our three areas of expertise: HIF biology, 2-oxoglutarate enzymology, and CTGF biology.

We have applied our expertise in the field of HIF-PH inhibition to develop an understanding of other areas of HIF biology with important therapeutic implications. This consistent progression of discovery has led to findings relating to HIF-mediated effects associated with inflammatory pathways, various aspects of iron metabolism, insulin sensitivity and glucose and fat metabolism, neurological disease, and ischemic injury. There are at least three different HIF-PH enzymes that are known to regulate the stability of HIF — these enzymes are commonly referred to in the scientific literature as PHD1, PHD2 and PHD3. Studies of genetically modified mice, in which the individual HIF-PH enzymes have been deleted, have revealed that PHD2 plays a major role in the regulation of erythropoiesis by HIF. In contrast, PHD1 and PHD3 appear to play less important roles in HIF-mediated erythropoiesis, but instead have been implicated in other important biological pathways. We believe that both pan-PHD and PHD-selective inhibitors could have important therapeutic applications beyond anemia.  

The HIF-PH enzymes that are the targets of roxadustat belong to a broader family of enzymes known as 2-oxoglutarate (2OG)-dependent oxygenases. In humans, this family comprises more than 60 members that play important roles in a diverse range of biological processes including collagen biosynthesis, oxygen sensing, epigenetic regulation, nucleic acid modification/repair, and lipid metabolism. The first members of this enzyme family to be characterized were the collagen prolyl hydroxylases, which play a critical role in the biosynthesis of collagen and as a result, are potential targets for the treatment of fibrotic disease. Other members of the 2OG-dependent oxygenase family with relevance to human disease include the Jumonji domain-containing histone demethylases, which are emerging cancer targets.

The fact that all members of the 2OG-dependent oxygenase enzyme family use 2OG as a co-substrate makes them viable targets for small molecule inhibitors that compete with 2OG. FibroGen has been a leader in inhibition of enzymes belonging to this family, and our internal medicinal chemistry efforts have generated a library of novel compounds designed to target the 2OG-dependent oxygenase family.

Finally, we have applied our knowledge of CTGF to investigate additional applications of agents that interfere with the role of this protein in disease. In some instances, we are exploring direct engagement of CTGF itself.  In other instances, we are studying the regulation of CTGF.

COLLABORATIONS

Our revenue to date has been generated primarily from our collaboration agreements with Astellas and AstraZeneca for the development and commercialization of roxadustat. In addition, we started roxadustat commercial sales in China in the third quarter of 2019. For fiscal year ended December 31, 2020, 58% of our revenue was related to our collaboration agreements, and 42% of our revenue was from roxadustat commercial sales in China. For the fiscal years ended December 31, 2019 and 2018, substantially all of our revenue was related to our collaboration agreements.

Astellas

We have two agreements with Astellas for the development and commercialization of roxadustat, one for Japan, and one for Europe, the Commonwealth of Independent States, the Middle East and South Africa. Under these agreements, we provided Astellas the right to develop and commercialize roxadustat for anemia in these territories.

26


 

We share responsibility with Astellas for clinical development activities required for U.S. and Europe regulatory approval of roxadustat, and share equally those development costs under the agreed development plan for such activities. Astellas will be responsible for clinical development activities and all associated costs required for regulatory approval in all other countries in the Astellas territories. Astellas will hold and have responsibility for regulatory filings in its territories. We are responsible, either directly or through our contract manufacturers, for the manufacture and supply of all quantities of roxadustat to be used in development and commercialization under the agreements, other than roxadustat drug product for Japan. Astellas is responsible for roxadustat commercialization activities in the Astellas territories.

AstraZeneca

We also have two agreements with AstraZeneca for the development and commercialization of roxadustat for anemia, one for China (the “China Agreement”), and one for the U.S. and all other countries not previously licensed to Astellas (the “U.S./RoW Agreement”). Under these agreements, we provided AstraZeneca the right to develop and commercialize roxadustat for anemia in these territories. We share responsibility with AstraZeneca for clinical development activities required for U.S. regulatory approval of roxadustat, and FibroGen will transfer the U.S. NDA to AstraZeneca upon approval. AstraZeneca will hold the equivalent regulatory filings in the other licensed countries.

In China, our subsidiary FibroGen (China) Medical Technology Development Co., Ltd. (“FibroGen Beijing”) has conducted the development work for CKD anemia and will continue to hold all of the regulatory licenses issued by China regulatory authorities and be primarily responsible for regulatory, clinical and manufacturing. China development costs are shared 50/50. AstraZeneca is also responsible for 100% of development expenses in all other licensed territories outside of China. We are responsible, ourselves and through our contract manufacturers, for the manufacture and supply of all quantities of roxadustat to be used in development and commercialization under the AstraZeneca agreements.

Under the China Agreement, which is conducted through FibroGen China Anemia Holdings, Ltd. (“FibroGen Cayman”), FibroGen Beijing, and FibroGen International (Hong Kong) Limited (collectively, “FibroGen China”), the commercial collaboration is structured as a 50/50 profit share, which was restructured in the third quarter of 2020. Pursuant to an Amendment to the China Agreement, the parties agreed to establish a jointly owned entity to conduct distribution. FibroGen Beijing will manufacture and transfer commercial product to the distribution entity in exchange for a transfer price at a percentage of net sales. AstraZeneca will conduct sales and marketing activities in China for roxadustat, which will be billed to the distribution entity, subject to a cap of a percentage of roxadustat net sales until AstraZeneca has recouped its sales and marketing expenses, at which time it will bill actual expenses, subject to the cap.

Additional Information Related to Collaboration Agreements

Additional information related to our collaboration agreements is set forth in Item 7 of this Annual Report on Form 10-K, and Note 4, Collaboration Agreements and Revenues, to our consolidated financial statements under Item 8 of this Annual Report. Information about collaboration partners that accounted for more than 10% of our total revenue or accounts receivable for the last three fiscal years is set forth in Note 15, Segment and Geographic Information, to our consolidated financial statements under Item 8 of this Annual Report.

COMPETITION

The pharmaceutical and biotechnology industries are highly competitive, particularly in some of the indications we are developing drug candidates, including anemia in CKD, IPF, pancreatic cancer, and DMD. We face competition from multiple other pharmaceutical and biotechnology companies, many of which have significantly greater financial, technical and human resources and experience in product development, manufacturing and marketing. These potential advantages of our competitors are particularly a risk in IPF, pancreatic cancer, and DMD, where we do not currently have a development or commercialization partner.

We expect any products that we develop and commercialize to compete based on, among other things, efficacy, safety, convenience of administration and delivery, price, the level of generic competition, and the availability of reimbursement from government and other third-party payors.

When any of our product candidates are approved, they will compete with currently marketed products, and product candidates that may be approved for marketing in the future, for treatment of the indications described below.

27


 

In addition, we will likely face competition from other companies developing treatments of other anemia indications that we may also seek to pursue in the future or that may be sold in indications we are pursuing but for which they are not yet approved. We may face competition for patient recruitment, enrollment for clinical trials, and potentially in commercial sales. There may also be new therapies for renal-related diseases that could limit the market or level of reimbursement available for roxadustat.

Roxadustat

Approved Medicines

Drugs that will compete with roxadustat are expected to include ESAs, particularly in those patient segments where ESAs are used. Some of the available ESAs include epoetin alfa (EPOGEN® marketed by Amgen Inc. in the U.S., Procrit® and Erypo®/Eprex®, marketed by Johnson & Johnson, Inc. and Espo® marketed by Kyowa Hakko Kirin in Japan and China), darbepoetin (Amgen/Kyowa Hakko Kirin’s Aranesp® and NESP®) and Mircera® marketed by Roche outside the U.S. and by Vifor Pharma, a Roche licensee, in the U.S. and Puerto Rico, as well as biosimilar versions of these currently marketed ESA products. ESAs have been used in the treatment of anemia in CKD for more than 30 years, serving a significant majority of dialysis patients. While non-dialysis CKD anemia patients who are not under the care of nephrologists, including those with diabetes and hypertension, do not typically receive ESAs and are often left untreated, some patients under nephrology or hematology care may be receiving ESA therapy. It may be difficult to encourage healthcare providers and patients to switch to roxadustat from products with which they have become familiar.

Biosimilars

The first biosimilar ESA, Pfizer’s Retacrit® (epoetin zeta), entered the U.S. market in November 2018. Market penetration of Retacrit and the potential addition of other biosimilar ESAs currently under development may alter the competitive and pricing landscape of anemia therapy in CKD patients on dialysis under the end-stage renal disease bundle. The patents for Amgen’s EPOGEN® (epoetin alfa) expired in 2004 in Europe, and the final material patents in the U.S. expired in May 2015. Several biosimilar versions of currently marketed ESAs are available for sale in Europe, China and other territories. In the U.S., a few ESA biosimilars are currently under development. Sandoz, a division of Novartis, markets Binocrit® (epoetin alfa) in Europe and may file a biosimilar Biologics License Application in the U.S.

Product Candidates in Development

We may also face competition from potential new anemia therapies currently in clinical development, including in those patient segments not adequately addressed by ESAs. Companies that are currently developing HIF-PH inhibitors for anemia in CKD indications include GlaxoSmithKline plc (“GSK”), Bayer Corporation (“Bayer”), Akebia Therapeutics, Inc. (“Akebia”), Otsuka Pharmaceutical (“Otsuka”), Akebia’s partner in the U.S. and Europe, Japan Tobacco, and Zydus Cadila (India) (“Zydus”). Akebia has completed Phase 3 studies in CKD patients on dialysis and not on dialysis in the U.S., as well as a Phase 3b, randomized, open-label, active-controlled trial evaluating the efficacy and safety of oral vadadustat once daily and three times weekly for the maintenance treatment of anemia in hemodialysis subjects converting from erythropoiesis stimulating agents. The study completion date is estimated to be May 2022. Akebia announced an additional Phase 3 study evaluating the efficacy and safety of dose conversion from a long-acting erythropoiesis stimulating agent (Mircera®) to three times weekly oral vadadustat for the maintenance treatment of anemia in hemodialysis subjects. The estimated study start date is February 2021. Akebia has publicly stated their intent to file the vadadustat NDA in the U.S. in the second quarter of 2021.

Japan

In Japan, Mitsubishi Tanabe Pharmaceutical Corporation, Akebia’s collaboration partner, received approval for vadadustat on June 29, 2020 for the treatment of anemia of CKD patients on and not on dialysis. GSK received approval for daprodustat in Japan on June 29, 2020 for the treatment of anemia of CKD patients on and not on dialysis. Price listing for the launch in Japan of both vadadustat and daprodustat occurred in the third quarter of 2020, with pricing in line with roxadustat pricing. GSK is also conducting global Phase 3 studies in CKD patients on dialysis and not on dialysis, and expects to complete those studies by March 2022. GSK and Kyowa Hakko Kirin announced in November 2018 that the two companies signed a strategic commercialization deal in Japan for daprodustat. Bayer has completed global Phase 2 studies and its HIF-PH inhibitor is now in Phase 3 development in CKD populations on dialysis and not on dialysis in Japan. Japan Tobacco received approval in Japan for enarodustat for the treatment of anemia in CKD patients on dialysis and not on dialysis, to be sold by Torii Pharmaceuticals Ltd as ENAROY®. Japan Tobacco and its partner JW Pharmaceuticals started a Phase 3 study in dialysis patients in Korea in 2019. Zydus started Phase 3 studies in dialysis and non-dialysis CKD patients in India in 2019.

28


 

China

In China, biosimilars of epoetin alfa are offered by Chinese pharmaceutical companies such as EPIAO marketed by 3SBio Inc. as well as more than 15 other local manufacturers. We may also face competition by HIF-PH inhibitors from other companies such as Akebia, Bayer, and GSK, which was authorized by the National Medical Products Administration (“NMPA”) to conduct trials in China to support its ex-China regulatory filings. Two domestic companies, Jiangsu Hengrui Medicine Co., Ltd. and Guandong Sunshine Health Investment Co., Ltd, have been permitted by the NMPA to conduct clinical trials for CKD anemia patients both on dialysis and not on dialysis, and 3SBio Inc. has submitted a clinical trial application to the NMPA to initiate trials for their HIF-PH inhibitor. Another domestic company, China Medical System Holdings Ltd., in-licensed desidustat, a compound that is currently in Phase 3 trials in India, from Zydus for greater China in January 2020. In January 2021, China Medical System Holdings Ltd. was granted approval by the NMPA in China to begin trials for desidustat in patients with anemia of CKD, including dialysis and non-dialysis patients. Shenzhen Salubris Pharmaceutical Co., Ltd., a domestic company in China, has in-licensed enarodustat from Japan Tobacco and received NMPA approval in the third quarter of 2020 to initiate Phase 3 studies. Akebia announced in April 2017 an expansion of their U.S. collaboration with Otsuka to add markets, including China. 3SBio Inc. announced in 2016 its plan to begin a Phase 1 clinical trial of a HIF-PH inhibitor for the China market.

CIA and MDS

In July 2020, Zydus received approval from the FDA to begin a Phase 1 study of desidustat for the treatment of CIA, which could potentially be competitive with roxadustat within this indication.  

Reblozyl® (luspatercept) was approved by the FDA in April 2020 for the treatment of anemia in adults with MDS with ring sideroblasts or myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis who need regular red blood cell transfusions and have not responded well to or cannot receive an ESA. It is the first and only erythroid maturation agent approved in the U.S., Europe, and Canada and is part of a global collaboration between Acceleron Pharma, Inc. and Bristol Myers Squibb. In 2020, Reblozyl net revenue was $274 million, including $115 million in Q4 2020.

Large Dialysis Organizations

The majority of the current CKD anemia market focuses on dialysis patients, who visit dialysis centers on a regular basis, typically three times a week, and anemia therapies are administered as part of the visit. Two of the largest operators of dialysis clinics in the U.S., DaVita Healthcare Partners Inc. (“DaVita”), and Fresenius Medical Care AG & Co. KGaA (“Fresenius”), collectively provide dialysis care to more than 80% of U.S. dialysis patients, and therefore have historically secured long-term contracts including rebate terms with Amgen. DaVita has a six-year sourcing and supply agreement with Amgen effective through 2022. Fresenius’ contract with Amgen expired in 2015, following which Fresenius is providing Roche’s ESA Mircera® to a significant portion of its U.S. dialysis patients. Successful penetration in this market may require our partner AstraZeneca to enter into an agreement with Fresenius, DaVita, or other dialysis organizations, on favorable pricing terms to each party.

Pamrevlumab

We are currently in Phase 3 development of pamrevlumab in IPF, locally advanced pancreatic cancer, and DMD. Most of our competitors have significantly more resources and expertise in development, commercialization and manufacturing, particularly due to the fact that we have not yet established a partnership for pamrevlumab. For example, both Roche and Boehringer Ingelheim, which market products for the treatment of IPF in the U.S., have successfully developed and commercialized drugs in various indications and have built sales organizations that we do not currently have; both have more resources and more established relationships when competing with us for patient recruitment and enrollment for clinical trials or, if we are approved, in the market.

29


 

Idiopathic Pulmonary Fibrosis

If approved and launched commercially to treat IPF, pamrevlumab is expected to compete with Roche’s Esbriet® (pirfenidone), and Boehringer Ingelheim’s Ofev® (nintedanib). We believe that if pamrevlumab can be shown to safely stabilize or reverse lung fibrosis, and thus stabilize or improve lung function in IPF patients, it can compete with pirfenidone and nintedanib for market share in IPF. However, it may be difficult to encourage treatment providers and patients to switch to pamrevlumab from a product with which they are already familiar. We may also face competition from potential new IPF therapies in recruitment and enrollment in our clinical trials and potentially in commercialization.

Pamrevlumab is administered via infusion, which may be more expensive and less convenient than small molecules such as nintedanib and pirfenidone. Other potential competitive product candidates in various stages of development for IPF include Kadmon Holdings, Inc.’s KD025, Liminal BioSciences’ PBI-4050, and Roche/Promedior, Inc.’s PRM-151.

Pancreatic Cancer

We are developing pamrevlumab to be used in combination with Abraxane® (nab-paclitaxel) and gemcitabine in pancreatic cancer. Celgene’s Abraxane was launched in the U.S. and Europe in 2013 and 2014, respectively, and was the first drug approved in this disease in nearly a decade. In 2015, Merrimack Pharmaceuticals Inc. (“Merrimack”) received FDA approval for the use of ONIVYDE (irinotecan liposome injection, now licensed to Ipsen) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy, and the combination therapy with Abraxane and gemcitabine became the first-line standard of care in these patients. As treatments for pancreatic cancer have shown limited success to date, combination therapies are expected, but the incremental cost may slow a new product adoption in the market, at least until the generic versions of Abraxane becomes available. In addition, we may also face competition from other products seeking approval in conjunction with gemcitabine and Abraxane including FOLFRINOX, a combination chemotherapy regimen of folic acid, 5-fluouracil, oxaliplatin and irinotecan, Rafael Pharma’s defactinib/CPI-613, and Merrimack’s istiratumab.

Duchenne Muscular Dystrophy

If approved and launched commercially to treat DMD, pamrevlumab is expected to face competition from drugs that have been approved in major markets such as the U.S., European Union, and Japan.

On September 19, 2016, the FDA approved Sarepta Therapeutics Inc.’s (“Sarepta”) Exondys 51TM (eteplirsen). Exondys 51 is approved to treat patients who have a mutation of the dystrophin gene amenable to exon 51 skipping, representing approximately 13% of patients with DMD. In Europe, Sarepta received a negative opinion for its marketing application for eteplirsen from the EMA in September 2018. Sarepta has reported a full year Exondys 51 revenue of $380 million in 2019. Sarepta’s Vyondys 53TM (golodirsen) was approved by the FDA in December 2019 for patients with a confirmed genetic mutation that is amenable to exon 53 skipping, which accounts for approximately 8% of the DMD population. Sarepta’s Amondys 45™ (casimersen) was approved by the FDA in February 2021 for patients with a confirmed genetic mutation that is amenable to exon 45 skipping, which accounts for approximately 8% of the DMD population.

PTC Therapeutics’ product Translarna TM received a conditional approval in Europe in 2014, which was renewed in November 2016 with a request for a new randomized placebo-controlled 18-month study by the Committee for Medicinal Products for Human Use of the EMA; however, the FDA informed the sponsor in a complete response letter in October 2017, as well as in its response to PTC Therapeutics’ appeal, that the FDA is unable to approve the application in its current form. While Translarna TM targets a different set of DMD patients from those targeted by Sarepta’s Exondys 51®, it is also limited to a subset of patients who carry a specific mutation. Conversely, pamrevlumab is intended to treat DMD patients without limitation to type of mutation.

Pamrevlumab may also face competition from other drugs currently in clinical development in patient recruiting and enrollment in clinical trials, and, if approved, in commercialization. Examples of those compounds currently under clinical development are the drug candidates from Catabasis Pharmaceuticals, Santhera Pharmaceuticals, and Sarepta.   

30


 

MANUFACTURE AND SUPPLY

We have historically and in the future plan to continue to enter into contractual arrangements with qualified third-party manufacturers to manufacture and package our products and product candidates. We believe that this manufacturing strategy enables us to more efficiently direct financial resources to the research, development and commercialization of product candidates rather than diverting resources to establishing a significant internal manufacturing infrastructure, unless there is additional strategic value for establishing manufacturing capabilities, such as in China. As our product candidates proceed through development, we explore or enter into longer term commercial supply agreements with key suppliers and manufacturers in order to meet the ongoing and planned clinical and commercial supply needs for ourselves and our partners. Our timing of entry into these agreements is based on the current development and commercialization plans.

Roxadustat

Roxadustat is a small-molecule drug manufactured from generally available commercial starting materials and chemical technologies and multi-purpose equipment available from many third party contract manufacturers. We have entered into commercial supply arrangements with Shanghai SynTheAll Pharmaceutical Co., Ltd. (“WuXi STA”) and Catalent, Inc. (“Catalent”) as our primary manufacturers of roxadustat drug substance (also known as active pharmaceutical ingredient or “API”) and roxadustat drug product, respectively. WuXi STA is located in China and currently supplies our API globally except for China, for which it manufactures an intermediate to be further manufactured by FibroGen Beijing. WuXi STA has passed inspections by several regulatory agencies, including the FDA and NMPA, and is Current Good Manufacturing Practice (“cGMP”) compliant. Catalent is located in the U.S. and supplies our drug product tablets globally except for Japan, where they are manufactured by Astellas, and China, where they are manufactured by FibroGen Beijing. Catalent has passed several regulatory inspections, including by the FDA, and manufactures commercial products for other clients.

In China, our Beijing facility received the Good Manufacturing Practice (“GMP”) license for API and drug product. We are manufacturing drug product at our FibroGen Beijing manufacturing facility for commercial supply, but we are not currently manufacturing API at this facility. We are manufacturing API at our Cangzhou manufacturing facility, which has been fully qualified and licensed. We may also qualify a third party manufacturer to produce commercial API under the Marketing Authorization Holder System program.

Irix Pharmaceuticals, Inc.

In July 2002, we and IRIX Pharmaceuticals, Inc. (“IRIX”), a third party manufacturer, entered into a Letter of Agreement for IRIX Pharmaceuticals Single Source Manufacturing Agreement (the “Letter of Agreement”), in connection with a contract manufacturing arrangement for clinical supplies of HIF-PH inhibitors, including roxadustat. The Letter of Agreement contained a service agreement that included terms and schedule for the delivery of clinical materials and also included a term sheet for a single source agreement for the cGMP manufacture of HIF-PH inhibitors, including roxadustat. Specifically, pursuant to the Letter of Agreement, we and IRIX agreed to negotiate a single source manufacturing agreement that included a first right to negotiate a manufacturing contract for HIF-PH inhibitors, including roxadustat, provided that IRIX is able to match any third party bids within 5%, and the exclusive right to manufacture extends for five years after approval of an NDA. Any agreement would provide that no minimum amounts would be specified until appropriate by forecast, that we and our commercialization partner would have the rights to contract with independent third parties that exceed IRIX’s internal capabilities or in the event that we or our commercialization partner determines for reasons of continuity and security that such a need exists, provided that IRIX would supply a majority of the product if it is able to meet the requirements and the schedule required by us and our partner. Subsequent to the Letter of Agreement, IRIX and we have entered into several additional service agreements. IRIX has requested in writing that we honor the Letter of Agreement with respect to the single source manufacturing agreement. To date, we have offered to IRIX opportunities to bid for the manufacture of HIF-PH inhibitors, including roxadustat. In 2015, Patheon Pharmaceuticals Inc., a business unit of DPx Holdings B.V., acquired IRIX, and in 2017 ThermoFisher Scientific Inc. acquired Patheon Pharmaceuticals Inc.

Pamrevlumab

To date, pamrevlumab has been manufactured using specialized biopharmaceutical process techniques under a clinical supply agreement with a qualified third party contract manufacturer, Boehringer Ingelheim. We have entered into a clinical and commercial supply agreement for the manufacture of pamrevlumab with Samsung Biologics Co., Ltd., which has passed several regulatory inspections, including by the FDA, and manufactures commercial products for other clients.

31


 

GOVERNMENT REGULATION

Our business activities and operations, including the clinical testing, manufacturing, labeling, storage, distribution, record keeping, advertising, promotion, import, export and marketing of our product candidates, among other things, are subject to extensive regulation by governmental authorities in the U.S., China, and other countries. The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations, including in Europe and China, requires the expenditure of substantial time and financial resources. Compliance with environmental laws, rules, and regulations has not had, and is not expected to have, a material effect on our capital expenditures, results of operations, or competitive position, and we do not currently anticipate material capital expenditures for environmental control facilities.

Failure to comply with the applicable requirements at any time during the product development process, approval process or after approval may subject an applicant and/or sponsor to a variety of administrative or judicial sanctions, including refusal by the applicable regulatory authority to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by FDA and the Department of Justice, or other governmental entities.

We cannot predict with certainty whether future costs of compliance with government regulations, including any changes thereto or reinterpretations thereof, will have a material impact on capital expenditures, earnings or the company’s competitive position. Refer to the section of this Annual Report captioned “Item 1A. Risk Factors” for a discussion of these potential impacts.

U.S. Product Approval Process

In the U.S., the FDA regulates drugs and biological products, or biologics, under the Public Health Service Act, as well as the FDCA, which is the primary law for regulation of drug products. Both drugs and biologics are subject to the regulations and guidance implementing these laws. Pharmaceutical products are also subject to regulation by other governmental agencies, such as the Federal Trade Commission, the Office of Inspector General of the U.S. Department of Health and Human Services, the Consumer Product Safety Commission and the Environmental Protection Agency. The clinical testing, manufacturing, labeling, storage, distribution, record keeping, advertising, promotion, import, export and marketing, among other things, of our product candidates are subject to extensive regulation by governmental authorities in the U.S. and other countries. The steps required before a drug or biologic may be approved for marketing in the U.S. generally include:

 

Preclinical laboratory tests and animal tests conducted under Good Laboratory Practices.

 

The submission to the FDA of an IND for human clinical testing, which must become effective before each human clinical trial commence.

 

Adequate and well-controlled human clinical trials to establish the safety and efficacy of the product and conducted in accordance with good clinical practices (“GCP”).

 

The submission to the FDA of an NDA, in the case of a small molecule drug product, or a BLA, in the case of a biologic product.

 

FDA acceptance, review and approval of the NDA or BLA, as applicable.

 

Satisfactory completion of an FDA inspection of the manufacturing facilities at which the product is made to assess compliance with cGMPs.

The testing and approval process requires substantial time, effort and financial resources, and the receipt and timing of any approval is uncertain. The FDA may suspend clinical trials at any time on various grounds, including a finding that the subjects or patients are being exposed to a potentially unacceptable health risk.

32


 

Preclinical studies include laboratory evaluations of the product candidate, as well as animal studies to assess the potential safety and efficacy of the product candidate. Preclinical studies must be conducted in compliance with FDA regulations regarding GLPs. The results of the preclinical studies, together with manufacturing information and analytical data, are submitted to the FDA as part of the IND, which includes the results of preclinical testing and a protocol detailing, among other things, the objectives of the clinical trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated if the first phase or phases of the clinical trial lends themselves to an efficacy determination. The IND will become effective automatically 30 days after receipt by the FDA, unless the FDA raises concerns or questions about the conduct of the trials as outlined in the IND prior to that time. In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can proceed. The IND must become effective before clinical trials may be commenced.

Clinical trials involve the administration of the product candidates to healthy volunteers, or subjects, or patients with the disease to be treated under the supervision of a qualified principal investigator. Clinical trials must be conducted under the supervision of one or more qualified principal investigators in accordance with GCPs and in accordance with protocols detailing the objectives of the applicable phase of the trial, dosing procedures, research subject selection and exclusion criteria and the safety and effectiveness criteria to be evaluated. Progress reports detailing the status of clinical trials must be submitted to the FDA annually. Sponsors must also timely report to the FDA serious and unexpected adverse events, any clinically important increase in the rate of a serious suspected adverse event over that listed in the protocol or investigator’s brochure, or any findings from other studies or tests that suggest a significant risk in humans exposed to the product candidate. Further, the protocol for each clinical trial must be reviewed and approved by an independent institutional review board (“IRB”), either centrally or individually at each institution at which the clinical trial will be conducted. The IRB will consider, among other things, ethical factors, and the safety of human subjects and the possible liability of the institution.

Clinical trials are typically conducted in three sequential phases prior to approval, but the phases may overlap and different trials may be initiated with the same drug candidate within the same phase of development in similar or different patient populations. These phases generally include the following:

Phase 1. Phase 1 clinical trials represent the initial introduction of a product candidate into human subjects, frequently healthy volunteers. In Phase 1, the product candidate is usually tested for pharmacodynamic and pharmacokinetic properties such as safety, including adverse effects, dosage tolerance, absorption, distribution, metabolism and excretion.

Phase 2. Phase 2 clinical trials usually involve studies in a limited patient population to (1) evaluate the efficacy of the product candidate for specific indications, (2) determine dosage tolerance and optimal dosage and (3) identify possible adverse effects and safety risks.

Phase 3. If a product candidate is found to be potentially effective and to have an acceptable safety profile in Phase 2 studies, the clinical trial program will be expanded to Phase 3 clinical trials to further evaluate clinical efficacy, optimal dosage and safety within an expanded patient population at geographically dispersed clinical study sites.

Phase 4. Phase 4 clinical trials are conducted after approval to gain additional experience from the treatment of patients in the intended therapeutic indication and to document a clinical benefit in the case of drugs approved under accelerated approval regulations, or when otherwise requested by the FDA in the form of post-market requirements or commitments. Failure to promptly conduct any required Phase 4 clinical trials could result in withdrawal of approval.

The results of preclinical studies and clinical trials, together with detailed information on the manufacture, composition and quality of the product candidate, are submitted to the FDA in the form of an NDA (for a drug) or BLA (for a biologic), requesting approval to market the product. The application must be accompanied by a significant user fee payment. The FDA has substantial discretion in the approval process and may refuse to accept any application or decide that the data is insufficient for approval and require additional preclinical, clinical or other studies.

33


 

Review of Application

Once the NDA or BLA submission has been accepted for filing, which occurs, if at all, 60 days after submission, the FDA informs the applicant of the specific date by which the FDA intends to complete its review. This is typically 12 months from the date of submission. The review process is often extended by FDA requests for additional information or clarification. The FDA reviews NDAs and BLAs to determine, among other things, whether the proposed product is safe and effective for its intended use, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, strength, quality and purity. Before approving an NDA or BLA, the FDA may inspect the facilities at which the product is manufactured and will not approve the product unless the manufacturing facility complies with cGMPs and will also inspect clinical trial sites for integrity of data supporting safety and efficacy. During the approval process, the FDA also will determine whether a REMS, is necessary to assure the safe use of the product. If the FDA concludes a REMS is needed, the sponsor of the application must submit a proposed REMS; the FDA will not approve the application without an approved REMS, if required. A REMS can substantially increase the costs of obtaining approval. The FDA may also convene an advisory committee of external experts to provide input on certain review issues relating to risk, benefit and interpretation of clinical trial data. The FDA may delay approval of an NDA if applicable regulatory criteria are not satisfied and/or the FDA requires additional testing or information. The FDA may require post-marketing testing and surveillance to monitor safety or efficacy of a product. FDA will issue either an approval of the NDA or BLA or a complete response letter detailing the deficiencies and information required in order for reconsideration of the application.

Pediatric Exclusivity and Pediatric Use

Under the Best Pharmaceuticals for Children Act, certain drugs or biologics may obtain an additional six months of exclusivity in an indication, if the sponsor submits information requested in writing by the FDA (“Written Request”), relating to the use of the active moiety of the drug or biologic in children. The FDA may not issue a Written Request for studies on unapproved or approved indications or where it determines that information relating to the use of a drug or biologic in a pediatric population, or part of the pediatric population, may not produce health benefits in that population.

We have not received a Written Request for such pediatric studies with respect to our product candidates, although we may ask the FDA to issue a Written Request for studies in the future. To receive the six-month pediatric market exclusivity, we would have to receive a Written Request from the FDA, conduct the requested studies in accordance with a written agreement with the FDA or, if there is no written agreement, in accordance with commonly accepted scientific principles, and submit reports of the studies. A Written Request may include studies for indications that are not currently in the labeling if the FDA determines that such information will benefit the public health. The FDA will accept the reports upon its determination that the studies were conducted in accordance with and are responsive to the original Written Request, agreement, or commonly accepted scientific principles, as appropriate, and that the reports comply with the FDA’s filing requirements.

In addition, the Pediatric Research Equity Act (“PREA”) requires a sponsor to conduct pediatric studies for most drugs and biologicals, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, original NDAs, BLAs and supplements thereto must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must include the evaluation of the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA, on its own initiative or at the request of the sponsor, may request a deferral of pediatric studies for some or all of the pediatric subpopulations. A deferral may be granted by FDA if they believe that additional safety or effectiveness data in the adult population needs to be collected before the pediatric studies begin. After April 2013, the FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Post-Approval Requirements

Even after approval, drugs and biologics manufactured or distributed pursuant to FDA approvals are subject to continuous regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to prior FDA review and approval. There also are continuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured, as well as new application fees for supplemental applications with clinical data.

The FDA may impose a number of post-approval requirements as a condition of approval of an NDA or BLA. For example, the FDA may require post-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

34


 

In addition, entities involved in the manufacture and distribution of approved drugs and biologics are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may also result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other things:

 

Restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls.

 

Fines, warning letters or holds on post-approval clinical trials.

 

Refusal of the FDA to approve pending NDAs or BLAs or supplements to approved NDAs or BLAs, or suspension or revocation of product license approvals.

 

Product seizure or detention, or refusal to permit the import or export of products.

 

Injunctions or the imposition of civil or criminal penalties.

The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

Prescription Drug Marketing Act

The distribution of pharmaceutical products is subject to the Prescription Drug Marketing Act (“PDMA”), which regulates the distribution of drugs and drug samples at the federal level and sets minimum standards for the registration and regulation of drug distributors at the state level. Under the PDMA and state law, states require the registration of manufacturers and distributors who provide pharmaceuticals in that state, including in certain states manufacturers and distributors who ship pharmaceuticals into the state even if such manufacturers or distributors have no place of business within the state. The PDMA and state laws impose requirements and limitations upon drug sampling to ensure accountability in the distribution of samples. The PDMA sets forth civil and criminal penalties for violations of these and other provisions.

Federal and State Fraud and Abuse and Data Privacy and Security and Transparency Laws and Regulations

In addition to FDA restrictions on marketing of pharmaceutical products, federal and state healthcare laws restrict certain business practices in the biopharmaceutical industry. These laws include, but are not limited to, anti-kickback, false claims, data privacy and security, and transparency statutes and regulations.

35


 

The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration, directly or indirectly, to induce, or in return for, purchasing, leasing, ordering or arranging for the purchase, lease or order of any good, facility, item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term “remuneration” has been broadly interpreted to include anything of value, including for example, gifts, discounts, the furnishing of supplies or equipment, credit arrangements, payments of cash, waivers of payment, ownership interests and providing anything at less than its fair market value. The Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers and formulary managers on the other. Although there are a number of statutory exemptions and regulatory safe harbors protecting certain common activities from prosecution, the exemptions and safe harbors are drawn narrowly, and our practices may not in all cases meet all of the criteria for a statutory exception or safe harbor protection. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances. Several courts have interpreted the statute’s intent requirement to mean that if any one purpose of an arrangement involving remuneration is to induce referrals of federal healthcare covered business, the statute has been violated. The intent standard under the Anti-Kickback Statute was amended by the Patient Protection and Affordable Care Act as amended by the Health Care and Education Reconciliation Act of 2010 (collectively “PPACA”), to a stricter intent standard such that a person or entity no longer needs to have actual knowledge of this statute or the specific intent to violate it in order to have committed a violation. In addition, PPACA codified case law that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act (discussed below). Further, civil monetary penalties statute imposes penalties against any person or entity who, among other things, is determined to have presented or caused to be presented a claim to a federal health program that the person knows or should know is for an item or service that was not provided as claimed or is false or fraudulent.

The federal false claims laws prohibit, among other things, any person or entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment or approval to the federal government or knowingly making, using or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government. As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the U.S. government. Recently, several pharmaceutical and other healthcare companies have been prosecuted under these laws for, among other things, allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses. The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of, or payment for, healthcare benefits, items or services.

In addition, we may be subject to data privacy and security regulation by both the federal government and the states in which we conduct our business. HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and its implementing regulations, imposes certain requirements relating to the privacy, security and transmission of individually identifiable health information. Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to business associates — independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity. HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Additionally, the federal Physician Payments Sunshine Act within the PPACA, and its implementing regulations, require that certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report information related to certain payments or other transfers of value made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals and to report annually certain ownership and investment interests held by physicians and their immediate family members.

36


 

Also, many states have similar healthcare statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. Some states require the posting of information relating to clinical studies. In addition, California requires pharmaceutical companies to implement a comprehensive compliance program that includes a limit on expenditures for, or payments to, individual medical or health professionals. If our operations are found to be in violation of any of the health regulatory laws described above or any other laws that apply to us, we may be subject to penalties, including potentially significant criminal, civil and/or administrative penalties, damages, fines, disgorgement, individual imprisonment, exclusion of products from reimbursement under government programs, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations. To the extent that any of our products will be sold in a foreign country, we may be subject to similar foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals.

Pharmaceutical Coverage, Pricing and Reimbursement

In both domestic and foreign markets, our sales of any approved products will depend in part on the availability of coverage and adequate reimbursement from third-party payors. Third-party payors include government health administrative authorities, managed care providers, private health insurers and other organizations. Patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Patients are unlikely to use our products unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our products. Sales of our products will therefore depend substantially, both domestically and abroad, on the extent to which the costs of our products will be paid by third-party payors. These third-party payors are increasingly focused on containing healthcare costs by challenging the price and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the coverage and reimbursement status of newly approved healthcare product candidates. The market for our products and product candidates for which we may receive regulatory approval will depend significantly on access to third-party payors’ drug formularies, or lists of medications for which third-party payors provide coverage and reimbursement. The industry competition to be included in such formularies often leads to downward pricing pressures on pharmaceutical companies. Also, third-party payors may refuse to include a particular branded drug in their formularies or otherwise restrict patient access to a branded drug when a less costly generic equivalent or other alternative is available.

Because each third-party payor individually approves coverage and reimbursement levels, obtaining coverage and adequate reimbursement is a time-consuming, costly and sometimes unpredictable process. We may be required to provide scientific and clinical support for the use of any product to each third-party payor separately with no assurance that approval would be obtained, and we may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. This process could delay the market acceptance of any product and could have a negative effect on our future revenues and operating results. We cannot be certain that our products and our product candidates will be considered cost-effective. Because coverage and reimbursement determinations are made on a payor-by-payor basis, obtaining acceptable coverage and reimbursement from one payor does not guarantee that we will obtain similar acceptable coverage or reimbursement from another payor. If we are unable to obtain coverage of, and adequate reimbursement and payment levels for, our product candidates from third-party payors, physicians may limit how much or under what circumstances they will prescribe or administer them and patients may decline to purchase them. This in turn could affect our ability to successfully commercialize our products and impact our profitability, results of operations, financial condition and future success.

In addition, in many foreign countries, particularly the countries of the European Union and China, the pricing of prescription drugs is subject to government control. In some non-U.S. jurisdictions, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing vary widely from country to country. For example, the European Union provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use. A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of a company placing the medicinal product on the market. We may face competition for our product candidates from lower-priced products in foreign countries that have placed price controls on pharmaceutical products. In addition, there may be importation of foreign products that compete with our own products, which could negatively impact our profitability.

37


 

Healthcare Reform

In the U.S. and foreign jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes to the healthcare system that could affect our future results of operations as we begin to directly commercialize our products. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state level that seek to reduce healthcare costs. If a drug product is reimbursed by Medicare or Medicaid, pricing and rebate programs must comply with, as applicable, the Medicaid rebate requirements of the Omnibus Budget Reconciliation Act of 1990, as amended, and the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (“MMA”). The MMA imposed new requirements for the distribution and pricing of prescription drugs for Medicare beneficiaries. Under Part D, Medicare beneficiaries may enroll in prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Part D plans include both stand-alone prescription drug benefit plans and prescription drug coverage as a supplement to Medicare Advantage plans. Unlike Medicare Part A and B, Part D coverage is not standardized. Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level. However, Part D prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and reviewed by a pharmacy and therapeutic committee. Government payment for some of the costs of prescription drugs may increase demand for our products for which we receive marketing approval. However, any negotiated prices for our future products covered by a Part D prescription drug plan will likely be lower than the prices we might otherwise obtain from non-governmental payors. Moreover, while the MMA applies only to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. Any reduction in payment that results from Medicare Part D may result in a similar reduction in payments from non-governmental payors.

Moreover, on November 27, 2013, the federal Drug Supply Chain Security Act was signed into law, which imposes new obligations on manufacturers of pharmaceutical products, among others, related to product tracking and tracing. Among the requirements of this new federal legislation, manufacturers will be required to provide certain information regarding the drug product to individuals and entities to which product ownership is transferred, label drug product with a product identifier, and keep certain records regarding the drug product. Further, under this new legislation, manufacturers will have drug product investigation, quarantine, disposition, and notification responsibilities related to counterfeit, diverted, stolen, and intentionally adulterated products, as well as products that are the subject of fraudulent transactions or which are otherwise unfit for distribution such that they would be reasonably likely to result in serious health consequences or death.

Furthermore, political, economic and regulatory influences are subjecting the healthcare industry in the U.S. to fundamental change. Initiatives to reduce the federal budget and debt and to reform healthcare coverage are increasing cost-containment efforts. We anticipate that Congress, state legislatures and the private sector will continue to review and assess alternative healthcare benefits, controls on healthcare spending through limitations on the growth of private health insurance premiums and Medicare and Medicaid spending, the creation of large insurance purchasing groups, price controls on pharmaceuticals and other fundamental changes to the healthcare delivery system. Any proposed or actual changes could limit or eliminate our spending on development projects and affect our ultimate profitability.

Under the Medicare Improvements for Patients and Providers Act (“MIPPA”), a basic case-mix adjusted composite, or bundled, payment system commenced in January 2011 and transitioned fully by January 2014 to a single reimbursement rate for drugs and all services furnished by renal dialysis centers for Medicare beneficiaries with end-stage renal disease. Specifically, under MIPPA the End-Stage Renal Disease Prospective Payment System (the “ESRD PPS”) bundle now covers drugs, services, lab tests and supplies under a single treatment base rate for reimbursement by the CMS based on the average cost per treatment, including the cost of ESAs and IV iron doses, typically without adjustment for usage. It is unknown whether roxadustat, if approved in the U.S., will be included in the payment bundle or the timing of inclusion. Under MIPPA, agents that have no IV equivalent in the bundle are currently expected to be excluded from the bundle until 2025. If roxadustat were included in the bundle, it may reduce the price that could be charged for roxadustat, and therefore potentially limit our profitability. Based on roxadustat’s differentiated mechanism of action and therapeutic effects, and discussions with our collaboration partner, we currently believe that roxadustat might not initially be included in the bundle and would instead be eligible for a Transitional Drug Add-on Payment Adjustment (“TDAPA”) for a 24-month period. At the 24-month mark, CMS would determine if the TDAPA period should be extended for roxadustat or ended. When the TDAPA period ends, CMS will determine if roxadustat should be included in the bundle and, if so, what changes to the ESRD PPS reimbursement should be made. If roxadustat is included in the ESRD PPS bundle, it may have an impact on roxadustat pricing within Dialysis Organizations. If roxadustat is not included in the bundle after the TDAPA period, and would therefore be reimbursed outside of the bundle, it may potentially limit further market penetration of roxadustat.

38


 

In March 2010, PPACA was signed into law. PPACA has the potential to substantially change the way healthcare is financed by both governmental and private insurers. Among other cost containment measures, PPACA established: an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and biologic agents; revised the methodology by which rebates owed by manufacturers to the state and federal government for covered outpatient drugs under the Medicaid Drug Rebate Program are calculated; increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program; and extended the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care organizations. There remain judicial and Congressional challenges to certain aspects of the PPACA. The U.S. Supreme Court is currently reviewing the constitutionality of the PPACA, but it is unknown when a decision will be reached. It is unclear how the U.S. Supreme Court ruling, other such litigation, and the healthcare reform measures of the Biden administration will impact the PPACA. In the future, there may continue to be additional proposals relating to the reform of the U.S. healthcare system, some of which could further limit the prices we are able to charge for our products, or the amounts of reimbursement available for our products. If future legislation were to impose direct governmental price controls and access restrictions, it could have a significant adverse impact on our business. Managed care organizations, as well as Medicaid and other government agencies, continue to seek price discounts.

Further, in the U.S. there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under government payor programs, and review the relationship between pricing and manufacturer patient programs. At the federal level, the Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives. For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that attempt to implement several of the administration’s proposals. The FDA also released a final rule, effective November 30, 2020, implementing a portion of the importation executive order providing guidance for states to build and submit importation plans for drugs from Canada. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law. The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed pending review by the Biden administration until March 22, 2021. On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021. On December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule. However, it is unclear whether the Biden administration will work to reverse these measures or pursue similar policy initiatives.

Some states have implemented, and other states are considering, price controls or patient access constraints under the Medicaid program, and some states are considering price-control regimes that would apply to broader segments of their populations that are not Medicaid-eligible. Due to the volatility in the current economic and market dynamics, we are unable to predict the impact of any unforeseen or unknown legislative, regulatory, payor or policy actions, which may include cost containment and healthcare reform measures. Such policy actions could have a material adverse impact on our profitability.

Approval Process and Other Regulation in China

The pharmaceutical industry in China is highly regulated. The primary regulatory authority is the NMPA, including its provincial and local branches. As a developer, manufacturer and supplier of drugs, we are subject to regulation and oversight by the NMPA and its provincial and local branches. The Drug Administration Law of China provides the basic legal framework for the administration of the production and sale of pharmaceuticals in China and covers the manufacturing, distributing, packaging, pricing and advertising of pharmaceutical products. Its implementing regulations set forth detailed rules with respect to the administration of pharmaceuticals in China. In addition, we are, and we will be, subject to other Chinese laws and regulations that are applicable to business operators, manufacturers and distributors in general.

39


 

Pharmaceutical Clinical Development

A new drug must be approved by the NMPA before it can be manufactured and marketed for sale. To obtain NMPA approval, the applicant must conduct clinical trials, which must be approved by the NMPA and are subject to the NMPA’s supervision and inspection. There are four phases of clinical trials. Application for registration of new drugs requires completion of Phase 1, 2 and 3 of clinical trials, similar to the U.S. In addition, the NMPA may require the conduct of Phase 4 studies as a condition to approval.

Phase 4 studies are post-marketing studies to assess the therapeutic effectiveness of and adverse reactions to the new drug, including an evaluation of the benefits and risks, when used among the general population or specific groups, with findings used to inform adjustments to dosage, among other things.

NDA and Approval to Market

China requires approval of the NDA as well as the manufacturing facility before a drug can be marketed in China. Approval and oversight are performed at national and provincial levels of the NMPA, involve multiple agencies and consist of various stages of approval.

Under the applicable drug registration regulations, drug registration applications are divided into three different types, namely Domestic NDA, Domestic Generic Drug Application, and Imported Drug Application. Drugs fall into one of three categories, namely chemical medicine, biological product or traditional Chinese or natural medicine.

Our roxadustat NDA for treatment of CKD anemia was submitted by FibroGen Beijing as a domestic entity under the Domestic Class 1 designation, which refers to a new drug that has never been marketed in any country.

Our NDA package in China contained information similar to what is necessary for a U.S. NDA, including preclinical data, clinical data, technical data on API and drug product, and related stability data. We are currently performing a safety study of 2,000 patients who will be treated for 52 weeks as part of our post-approval commitment to the NMPA.

Shortly before NDA approval, FibroGen Beijing conducted a three-batch validation campaign, one of which was observed onsite by the NMPA. Following the successful completion of the validation campaign and associated inspection, FibroGen Beijing was granted a cGMP certification for the commercial production of roxadustat at our Beijing manufacturing facility. We are using our FibroGen Beijing manufacturing facility for commercial supply of drug product.  Our Cangzhou manufacturing facility has been fully qualified and licensed for manufacture of roxadustat API for the China market, and we will continue to use this facility for commercial supply. We may also qualify a third party manufacturer to produce commercial API under the Marketing Authorization Holder System program.

Pricing, Reimbursement, Hospital Listing, and Tendering

Please see the discussion above in the section Roxadustat for the Treatment of Anemia in Chronic Kidney Disease in China.

Foreign Regulation Outside of China

In order to market any product outside of the U.S., we would need to comply with numerous and varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, manufacturing, marketing authorization, commercial sales and distribution of our products. Whether or not we obtain FDA approval for a product, we would need to obtain the necessary approvals by the comparable foreign regulatory authorities before we can commence clinical trials or marketing of the product in foreign countries and jurisdictions. Although many of the issues discussed above with respect to the U.S. apply similarly in the context of other countries we are seeking approval in, including Europe and China, the approval process varies between countries and jurisdictions and can involve different amounts of product testing and additional administrative review periods. For example, in Europe and in China, a sponsor must submit a clinical trial application (“CTA”), much like an IND prior to the commencement of human clinical trials. A CTA must be submitted to each national health authority and an independent ethics committee.

40


 

For other countries outside of the European Union, such as China and the countries in Eastern Europe, Latin America or Asia, the requirements governing the conduct of clinical trials, product licensing, pricing, and reimbursement vary from country to country. The time required to obtain approval in other countries and jurisdictions might differ from or be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory approval process in other countries.

Regulatory Exclusivity for Approved Products

U.S. Patent Term Restoration

Depending upon the timing, duration, and specifics of the FDA approval of our product candidates, some of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process. The patent term restoration period is generally one-half the time between the effective date of an initial IND and the submission date of an NDA or BLA, plus the time between the submission date of the NDA or BLA and the approval of that product candidate application. Patent term restoration cannot, however, extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. In addition, only one patent applicable to an approved product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The U.S. Patent and Trademark Office, in consultation with the FDA, reviews and approves applications for any patent term extension or restoration. In the future, we expect to apply for restoration of patent term for patents relating to each of our product candidates in order to add patent life beyond the current expiration date of such patents, depending on the length of the clinical trials and other factors involved in the filing of the relevant NDA or BLA.

Market exclusivity provisions under the FDCA can also delay the submission or the approval of certain applications of companies seeking to reference another company’s NDA or BLA. The Hatch-Waxman Act provides a 5-year period of exclusivity to any approved NDA for a product containing a NCE never previously approved by FDA either alone or in combination with another active moiety. No application or abbreviated NDA directed to the same NCE may be submitted during the 5-year exclusivity period, except that such applications may be submitted after four years if they contain a certification of patent invalidity or non-infringement of the patents listed with the FDA by the innovator NDA.

Biologic Price Competition and Innovation Act

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), established an abbreviated pathway for the approval of biosimilar and interchangeable biological products. The abbreviated regulatory approval pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on similarity to an existing branded product. Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the original branded product was approved under a BLA. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator BLA holder. The BPCIA is complex and is only beginning to be interpreted and implemented by the FDA. As a result, its ultimate impact, implementation, and interpretation are subject to uncertainty.

Orphan Drug Act

Pamrevlumab has received orphan drug designation in IPF, LAPC, and DMD in the U.S. Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S., or if it affects more than 200,000 individuals in the U.S. there is no reasonable expectation that the cost of developing and making a drug product available in the U.S. for this type of disease or condition will be recovered from sales of the product. Orphan product designation must be requested before submitting an NDA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

41


 

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity. The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval of the same drug or biological product as defined by the FDA or if our drug candidate is determined to be contained within the competitor’s product for the same indication or disease. If a drug product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity in any indication.

The EMA has granted Orphan Medicinal Product Designation to pamrevlumab for the treatment of DMD. Orphan Medicinal Product Designation status in Europe has similar but not identical benefits in that jurisdiction.

Products receiving orphan designation in Europe can receive ten years of market exclusivity, during which time no similar medicinal product for the same indication may be placed on the market. The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation; for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity. Additionally, marketing authorization may be granted to a similar product for the same indication at any time if the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior; the initial applicant consents to a second orphan medicinal product application; or the initial applicant cannot supply enough orphan medicinal product. An orphan product can also obtain an additional two years of market exclusivity in Europe for pediatric studies. No extension to any supplementary protection certificate can be granted on the basis of pediatric studies for orphan indications.

Foreign Country Data Exclusivity

Europe also provides opportunities for additional market exclusivity. For example, in Europe, upon receiving marketing authorization, an NCE generally receives eight years of data exclusivity and an additional two years of market exclusivity. If granted, data exclusivity prevents regulatory authorities in Europe from referencing the innovator’s data to assess a generic application. During the additional two-year period of market exclusivity, a generic marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic product can be marketed until the expiration of the market exclusivity.

In China, there is also an opportunity for data exclusivity for a period of six years for data included in an NDA applicable to a NCE. According to the Implementing Regulations of the PRC Drug Administration Law, the Chinese government protects undisclosed data from drug studies and prevents the approval of an application made by another company that uses the undisclosed data for the approved drug. In practice, the NMPA has not established an effective mechanism to enforce data exclusivity. The NMPA issued a draft regulation on regulatory data protection on April 25, 2018 for public comments but this draft regulation has yet to be finalized and implemented.

In addition, if an approved drug manufactured in China qualifies as an innovative drug or an improved new drug before December 1, 2019, such drugs will be eligible for a monitoring surveillance period for up to five years. During this post-marketing observation period, the NMPA will not accept marketing authorization applications filed by another company for the same product. Nor will the NMPA approve marketing authorization applications filed by another company to produce, change dosage form of or import the drug while the innovative or improved new drug is under observation for the purpose of protecting public health. The approved manufacturer is required to provide an annual report to the regulatory department of the province, autonomous region or municipality directly under the central government where it is located.

Each of the data exclusivity period and the observation period runs from the date of approval for production of the NCE or innovative or improved new drug, as the case may be.

42


 

INTELLECTUAL PROPERTY

Our success depends in part upon our ability to obtain and maintain patent and other intellectual property protection for our product candidates including compositions-of-matter, dosages, and formulations, manufacturing methods, and novel applications, uses and technological innovations related to our product candidates and core technologies. We also rely on trade secrets, know-how and continuing technological innovation to further develop and maintain our competitive position.

Our policy is to seek to protect our proprietary position by, among other methods, filing U.S. and foreign patent applications related to our proprietary technologies, inventions and any improvements that we consider important to the development and implementation of our business and strategy. Our ability to maintain and solidify our proprietary position for our products and technologies will depend, in part, on our success in obtaining and enforcing valid patent claims. Additionally, we may benefit from a variety of regulatory frameworks in the U.S., Europe, China, and other territories that provide periods of non-patent-based exclusivity for qualifying drug products. Refer to “Government Regulation — Regulatory Exclusivity for Approved Products.”

We cannot ensure that patents will be granted with respect to any of our pending patent applications or with respect to any patent applications that may be filed by us in the future, nor can we ensure that any of our existing or subsequently granted patents will be useful in protecting our drug candidates, technological innovations, and processes. Additionally, any existing or subsequently granted patents may be challenged, invalidated, circumvented or infringed. We cannot guarantee that our intellectual property rights or proprietary position will be sufficient to permit us to take advantage of current market trends or otherwise to provide or protect competitive advantages. Furthermore, our competitors may be able to independently develop and commercialize similar products, or may be able to duplicate our technologies, business model, or strategy, without infringing our patents or otherwise using our intellectual property.

Our extensive worldwide patent portfolio includes multiple granted and pending patent applications relating to roxadustat and pamrevlumab. Currently granted patents relating to composition-of-matter for roxadustat and for pamrevlumab are expected, for each product candidate, to expire in 2024 or 2025, in each case exclusive of any patent term extension that may be available. U.S. and foreign patents relating to crystalline forms of roxadustat are expected to expire in 2033, exclusive of any extension. Additional patents and patent applications relating to manufacturing processes, formulations, and various therapeutic uses, including treatment of specific indications and improvement of clinical parameters, provide further protection for product candidates.

The protection afforded by any particular patent depends upon many factors, including the type of patent, scope of coverage encompassed by the granted claim