argenx (ARGX) 2024年年度報告「NASDAQ」.pdf

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1、Annual Report 2024Disclaimer PDF print this document is only a“printed version”and is not the original annual financial reporting including the audited financial statements pursuant to Article 361 of Book 2 of the Dutch Civil Code.These original annual financial reporting included in the audited fin

2、ancial statements and the auditors report thereto,are included in the single report package which can be found athttps:/ Annual Report including the Annual Financial Statements for the year ended December31,2024This Annual Report is filed with the Dutch Authority for the Financial Markets(Stichting

3、Autoriteit Financile Markten,AFM).The following main items included in our annual report on Form 20-F for the year ended December31,2024(2024 20-F)filed with the United States Securities and Exchange Commission(SEC)on or about the date of this Annual Report have not been included in this Annual Repo

4、rt:Form 20-F cover page;Item 7 Major Shareholders and Related Party Transactions;Item 10E Taxation;Item 16E Purchases of Equity Securities by the Issuer and Affiliated Purchasers;Item 16G Corporate Governance;Report of Independent Registered Public Accounting Firm in respect of Internal Control over

5、 Financial Reporting for the SEC filing;Report of Independent Registered Public Accounting Firm in respect of the PCAOB audits of the 2024 financial statements for the SEC filing;Exhibits;andSignatures.The following main sections of our Annual Report have not been included in our 2024 20-F:Sharehold

6、er Letter;Outlook 2025;Statement of the Board of Directors;Risk Appetite and Control;Share Classes and Principal Shareholders;Non-Financial Information(including Sustainability Statement);The Company Financial Statements under Section Financial Statements(prepared pursuant to Dutch law);Independent

7、auditors report-Report on the audit of the financial statements 2024 included in the Annual Report with respect to the AFM Filing;Limited Assurance Report of the Independent Auditor on the Sustainability Statement;andGlossary.Certain defined termsUnless otherwise indicated,“argenx,”“argenx SE,”“the

8、Company,”“our company,”“we,”“us”,“our”our“Group”refer to argenx SE and its consolidated subsidiaries.argenx SE is a European public company(Societas Europaea)incorporated under the laws of the Netherlands with its statutory seat in Amsterdam,the Netherlands.It is publicly listed in Belgium and the U

9、nited States of America(the U.S.)The applicable regulations with respect to public information and protection of investors,as well as the commitments we make to securities and market authorities,are described in this Annual Report.We own various trademark registrations and applications,and unregiste

10、red trademarks,including but not limited to VYVGART,VYVGART HYTRULO,VYVDURA,ARGENX,ABDEG,NHANCE,SIMPLE argenx Annual Report 20242ANTIBODY,ARGENXMEDHUB,MG UNITED,SHINING THROUGH CIDP and our corporate logo.Trade names,trademarks and service marks of other companies appearing in this Annual Report are

11、 the property of their respective holders.Solely for convenience,the trademarks and trade names in this Annual Report may be referred to without the and symbols,but such references should not be construed as any indicator that their respective owners will not assert,to the fullest extent under appli

12、cable law,their rights thereto.We do not intend to use or display other companies trademarks and trade names to imply a relationship with,or endorsement or sponsorship,any other companies.VYVGART(efgartigimod alfa)(VYVGART)has been approved in the U.S.,Japan,the European Union(the EU),the United Kin

13、gdom(UK),Switzerland,Israel,mainland China(Mainland China),Canada,South Korea and United Arab Emirates for the intravenous treatment of generalized myasthenia gravis(gMG).We have now commercialized VYVGART in the U.S.,several countries in the EU,Japan,Mainland China(through our partner Zai Lab Ltd(Z

14、ai Lab),Israel(through our Medison Pharma Ltd.(Medison)and Canada.VYVGART is now also approved and launched in Japan for the treatment of ITP.VYVGART subcutaneous(SC)(efgartigimod alfa+hyaluronidase qvfc)(VYVGART SC)has been approved in the U.S.and China as VYVGART HYTRULO(VYVGART HYTRULO),in Japan

15、as VYVDURA(VYVDURA)and in the EU and the UK as VYVGART for the treatment of gMG.VYVGART SC has also been approved in Israel for the treatment of gMG.We have now commercialized VYVGART SC for gMG in the U.S.and China(as VYVGART HYTRULO),in Japan(as VYVDURA)and in several countries in the EU(as VYVGAR

16、T).Pricing and reimbursement discussions for VYVGART SC remain ongoing in multiple other countries,including more countries in the EU.VYVGART SC has now also been approved in the U.S.,China and Japan for the treatment of chronic inflammatory demyelinating polyneuropathy(CIDP).We have now commerciali

17、zed VYVGART SC for CIDP in the U.S.and China(as VYVGART HYTRULO)and in Japan(as VYVDURA).For both VYVGART and VYVGART SC,we are aiming for further approvals and we are working to expand commercialization in other jurisdictions.Unless otherwise specified,references in this Annual Report to VYVGART sh

18、ould be read as references to VYVGART and/or VYVGART SC,including VYVGART HYTRULO in relation to the U.S.and China,VYVGART in relation to the EU and the UK and VYVDURA in relation to Japan,depending on the context.Basis of preparation of our audited consolidated financial statementsOur consolidated

19、financial statements are prepared in accordance with the IFRS Accounting Standards(IFRS)as issued by the International Accounting Standards Board(IASB)as adopted by the EU(EU-IFRS)and in accordance with the legal requirements of Part 9 of Book 2 of the Dutch Civil Code.Our consolidated financial sta

20、tements are presented in this Annual Report in U.S.dollars.All references in this Annual Report to“$,”“US$,”“U.S.$,”“U.S.dollars,”“dollars”and“USD”mean U.S.dollars and all references to“,”“EUR,”and“euros”mean euros,unless otherwise noted.Throughout this Annual Report,references to ADSs mean American

21、 depositary shares(ADSs)or ordinary shares represented by ADSs,as the case may be.Forward-looking StatementsThis Annual Report contains certain forward-looking statements.A forward-looking statement is any statement that does not relate to historical facts or events or to facts or events as of the d

22、ate of this Annual Report or that are derived from our managements beliefs and assumptions based on information currently available to our management.Forward-looking statements are generally identified by the use of forward-looking words,such as“anticipate”,“aspire”,“believe”,“can”,“continue”,“could

23、”,“estimate”,“expect”,“entail”,“hope”,“intend”,“is designed to”,“look forward to”,“may”,“might”,“objective”,“plan”,“potential”,“pursue”,“project”,“predict”,“seek”,“should”,“target”,“will”or other or comparable variations or the negative of such argenx Annual Report 20243terms,or by discussion of str

24、ategy,plans,objectives,goals,future events or intentions,although not all forward-looking statements contain these identifying words.These statements relate to our future results of operations and financial positions,prospects,developments,growth,business strategies,plans and our objectives for futu

25、re operations,results of clinical trials and regulatory approvals,and are based on analyses or forecasts of future developments and estimates of amounts not yet determinable.These forward-looking statements represent the view of management only as of the date of this Annual Report,and we expressly d

26、isclaim any obligation or undertaking to update,review or revise forward-looking statements(whether as a result of new information,future developments or otherwise),except as may be otherwise required by applicable law.The forward-looking statements in this Annual Report involve known and unknown ri

27、sks,future events,assumptions,uncertainties and other factors that could cause our actual future results of operations and financial positions,prospects,developments,growth,business strategies,plans and our objectives for future operations,results of clinical trials and regulatory approvals to diffe

28、r materially from those forecasted or suggested herein.Forward-looking statements include,but are not limited to,statements about:the initiation,timing,progress,development and results of clinical trials of our product candidates,including new indications,alternative dosing regimens,treatment modali

29、ties,and methods of administration,including statements regarding when results or interim analysis of the clinical trials will be available or made public;the expansion of our business,including the further development of our sales and marketing abilities and our IIP,and the value of our pipeline;th

30、e potential attributes,benefits,and side effects of our products and product candidates,including new indications,alternative dosing regimens and treatment modalities,and their competitive position with respect to other alternative treatments;our ability to advance product candidates into,and succes

31、sfully complete,clinical trials;our estimates of the number of patients who suffer from the diseases we are targeting and the number of patients that will enroll in our clinical trials;the demand and commercialization of our products and product candidates,including new indications,alternative dosin

32、g regimens,treatment modalities,and methods of administration,if approved;the anticipated timing or likelihood of market or regulatory decisions relating to or of our products,including new indications,alternative dosing regimens,treatment modalities,and methods of administration;the anticipated pri

33、cing and reimbursement of our products and product candidates,if approved;our plans to have various programs to help patients afford our products,including patient assistance and co-pay coupon programs for eligible patients;our ability to establish sales,marketing and distribution capabilities for a

34、ny of our products and product candidates that achieve regulatory approval;our regulatory strategy and our ability to establish and maintain manufacturing arrangements for our products and product candidates;the scope and duration of protection,including any exclusivity period,we are able to establi

35、sh and maintain for intellectual property rights covering our products and product candidates,platform and technology,including our intention to seek patent term extensions where available;our estimates regarding expenses,future revenues,cash flow,capital requirements and our needs for additional fi

36、nancing;our expectation that we will benefit from the Belgian innovation income deduction;our financial performance,including potential volatility in the price of our ordinary shares and ADSs;the competition we face in our drug discovery,development,and commercialization efforts;the rate and degree

37、of market acceptance of our products and product candidates,if approved;the potential benefits of our current collaborations,including the possibility to access partner technology platforms or capabilities;argenx Annual Report 20244our plans and ability to enter into or maintain current collaboratio

38、ns for additional programs or product candidates;our plans and ability to enter into or maintain current new distribution partnerships;our long-term growth strategy to develop and market additional products and product candidates,including efgartigimod for new indications,empasibrubart and ARGX-119;

39、the impact of government laws and regulations on our business;our expectations with respect to the timing and amount of any dividends(if any);our plans regarding our supply chain,including our reliance on third parties,including contract manufacturing organizations(CMOs);andour business strategies,p

40、lans,projects,goals and targets and the timing,outcomes and benefits thereof.These include changes in general economic and business conditions.You should refer to Section 2”RiskFactors”of this Annual Report for a discussion of important factors that may cause our actual results to differ materially

41、from those expressed or implied by our forward-looking statements.As a result of these factors,we cannot assure you that the forward-looking statements in this Annual Report will prove to be accurate.Furthermore,if our forward-looking statements prove to be inaccurate,the inaccuracy may be material.

42、In light of the significant uncertainties in these forward-looking statements,you should not regard these statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame or at all.We undertake no obligation to publicly up

43、date any forward-looking statements,whether as a result of new information,future events or otherwise,except as required by law.You should read this Annual Report and the documents that we reference in this Annual Report and have filed as exhibits to the Annual Report completely and with the underst

44、anding that our actual future results may be materially different from what we expect.We qualify all of our forward-looking statements by these cautionary statements.Information regarding market and industry statistics contained in this Annual Report is included based on information available to us

45、that we believe is accurate.Forecasts and other forward-looking information obtained from this available information is subject to the same qualifications and the additional uncertainties accompanying any estimates of future market size,revenue and market acceptance of products and services.In addit

46、ion,statements that include“we believe”and similar statements reflect our beliefs and opinions on the relevant subject.These statements are based upon information available to us as of the date of this Annual Report,and while we believe such information forms a reasonable basis for such statements,s

47、uch information may be limited or incomplete,and our statements should not be read to indicate that we have conducted an exhaustive inquiry into,or review of,all potentially available relevant information.These statements are inherently uncertain and you are cautioned not to unduly rely upon these s

48、tatements.argenx Annual Report 20245Table of ContentsTo our ShareholdersShareholder Letter102024 In Brief112025 Outlook231 Presentation of the Group1.1Company Profile251.2Strategy and Objectives291.3Our Products and Products Candidates311.4Collaborations and licenses491.5Manufacturing and Supply561.

49、6Intellectual Property561.7Regulation591.8Documents on display802 Risk Factors2.1Summary Risk Factors822.2Risk Factors Related to Commercialization of argenxs Products and Product Candidates,Including for New Indications842.3Risk Factors Related to the Development and Clinical Testing of argenxs Pro

50、ducts and Product Candidates912.4Risk Factors Related to argenxs Dependence on Third Parties942.5Risk Factors Related to Other Government Regulations982.6Risk Factors Related to argenxs Financial Position1032.7Risk Factors Related to argenxs Business and Industry1042.8Risk Factors Related to argenxs

51、 Intellectual Property1072.9Risk Factors Related to argenxs Organization and Operations1112.10 Risk Factors Related to the ADSs1142.11 Risk Factors Related to being a Foreign Private Issuer or a Dutch Company116argenx Annual Report 202463 Corporate Governance3.1Dutch Corporate Governance Code1203.2M

52、anagement Structure1213.3Report of the Non-Executive Directors1403.4Remuneration Report and Compensation Statement1433.5Corporate Governance Nasdaq Listing Rules1833.6Share Ownership1833.7Insider Trading1833.8Cybersecurity1843.9Risk Appetite&Control1854 General Description of the Company and its Sha

53、re Capital4.1Legal Information on the Company1904.2Share Capital1904.3Share Classes and Principal Shareholders1944.4Limitations on the right to hold securities1964.5General Meeting,Voting Rights and Admission1974.6Anti-Takeover Provisions1994.7Change of Control1994.8Exchange Controls1994.9Amendments

54、 of Articles of Association1994.10 Transparency Directive1994.11 Dutch Financial Reporting Supervision Act2004.12 Dividends and Other Distributions2004.13 Right to a surplus in the event of a liquidation2014.14 Material Modifications to the Rights of Security Holders and Use of Proceeds2014.15 Enfor

55、cement of civil liabilities2024.16 Controls and Procedures2034.17 Financial Calendar 2025204argenx Annual Report 202475 Operating and Financial Review and Prospects5.1Overview2065.2Basis of presentation2085.3Critical Accounting Judgements and Major Sources of Estimation Uncertainty2105.4Results of O

56、peration2125.5Liquidity and Capital Resources2155.6Research and development,patents and licenses2185.7Trend information2185.8Off-Balance Sheet Arrangements2195.9Contractual Obligations2195.10 Information Regarding the Independent Auditor2195.11 Material Contracts and Related Party Transactions2195.1

57、2 Employees2225.13 Insurance2225.14 Legal and Arbitration Proceedings2225.15 Taxation2236 Financial Statements6.1Consolidated Financial Statements2426.2Notes to the Consolidated Financial Statements2496.3Company Financial Statements of argenx SE for the Year ended December 31,20242856.4Other informa

58、tion2917 Non-Financial Information7.1Sustainability Statement3057.2Sustainability Strategy3127.3Environment3277.4Social3447.5Industry Specific Disclosures3567.6Governance3617.7Other Considerations3657.8Appendix3678 Glossary8.1Cross Reference table for annual reporting requirements3758.2Management Co

59、nfirmations3768.3Definitions377argenx Annual Report 20248To our ShareholdersShareholder Letter102024 In Brief112025 Outlook23argenx Annual Report 20249Shareholder LetterDear Shareholder,As we reflect on 2024,we are filled with pride and gratitude for the remarkable progress and achievements that hav

60、e defined this year for argenx.We are more committed than ever to transforming the treatment of severe autoimmune diseases and the milestones we have reached are a testament to the dedication and resilience of our entire team.This year,we made significant steps in expanding the reach and impact of V

61、YVGART(efgartigimod alfa-fcab),our first-in-class antibody fragment targeting FcRn.With approvals for both intravenous and subcutaneous formulations in multiple indications,including gMG,primary immune thrombocytopenia(ITP),and CIDP,we are now able to offer life-changing treatments to more than 10,0

62、00 patients globally.Our financial performance has been robust,with global product net sales reaching$2.2bn in 2024.With our continued commercial execution,we expect to reach sustainable profitability during 2025,giving us the financial flexibility to fuel the next generation of groundbreaking thera

63、pies.This growth reflects the strong demand for our innovative therapies and the successful execution of our strategic initiatives.We are particularly proud of the initial success of our CIDP launch,with approximately 1,000 patients on therapy in first two quarters of launch.Looking ahead,we remain

64、focused on our Vision 2030,which aims to transform the treatment landscape for autoimmune diseases.Our goals include reaching at least 50,000 patients globally,advancing our pipeline to achieve 10 labelled indications,and bringing five new molecules into Phase 3 by 2030.This vision has already start

65、ed to take shape as we continue to innovate on the patient experience with our pre-filled syringe(VYVGART SC)(with an expected Prescription Drug User Fee Act target action date(PDUFA Date)of April 10,2025)and the auto-injector approval expected in 2027.We are also advancing our clinical programs bri

66、nging us to 10 Phase 3 clinical trials and 10 Phase 2 clinical trials across our 3 clinical assets(efgartigimod,empasiprubart,ARGX-119).We continue investing in our growing pipeline by progressing 4 INDs into Phase 1 in 2025.We are confident that our continued investment in innovation leading to dif

67、ferentiated antibody candidates will drive transformative outcomes for patients.None of this would be possible without the relentless commitment of all argonauts i.e.,all employees,management and our board of directors(Board of Directors)to our mission and in particular the unwavering support of our

68、 shareholders.Your belief in our mission and your trust in our vision have been instrumental in our success.As we move forward,we remain committed to delivering value to our shareholders while making a meaningful difference in the lives of patients.Thank you for your continued support.Sincerely,Tim

69、Van Hauwermeiren&Peter Verhaegheargenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Shareholder Letter10Peter VerhaegheTim vanHauwermeiren2024 In BriefIn 2024,we established our Vision 2030 outlining our long-

70、term commitment to transform the treatment of severe autoimmune disease with VYVGART,empasiprubart and our expanding pipeline of antibody-based therapeutics.With our eyes set on 2030,we are targeting the treatment of 50,000 patients globally,securing 10 labeled indications across all approved medici

71、nes,and advancing five pipeline candidates into Phase 3 development.In 2024,we made important progress to reach this goal.We grew our global commercial footprint in gMG to reach more than 10,000 patients and we remain on track to expand into additional regions throughout 2025.We received FDA approva

72、l for VYVGART HYTRULO for the treatment of CIDP and have been working hard to bring VYVGART HYTRULO to CIDP patients,reaching approximately 1,000 patients by the end of 2024.This,together with our continued growth in MG,translated in$2.2 billion in product net sales in 2024.We look forward to contin

73、ued commercial execution as we expand our patient reach through label enabling studies in seronegative gMG and ocular MG patient populations and we continue to innovate on the patient experience with our pre-filled syringe(PFS)with VYVGART SC,with an PDUFA Date of April 10,2025.We made significant p

74、rogress in evaluating efgartigimod across additional autoimmune diseases.We announced the GO-decisions for primary Sjgrens disease(SjD)and three subsets of myositis(immune-mediated necrotizing myopathy(IMNM),anti-synthetase syndrome(ASyS),dermatomyositis(DM),for which we are currently running Phase

75、3 clinical trials.We continue to evaluate efgartigimod in more than 10 additional indications,and this year,we added autoimmune encephalitis to the line-up.We are excited to add another indication in 2025.In 2024 we made significant progress with our second asset,empasiprubart(ARGX-117)targeting com

76、plement component 2(C2).empasiprubart has now shown proof-of-concept in multifocal motor neuropathy(MMN)and has started its first Phase 3 in this indication.We additionally announced CIDP as the 4th indication for which we go straight to a Phase 3 clinical trial,expected to start in 2025.Beyond our

77、first two assets,efgartigimod and empasiprubart,we worked to further advance our third clinical pipeline asset,ARGX-119,targeting muscle-specific kinase(MuSK).ARGX-119 has started its first proof-of-concept clinical trial in congenital myasthenic syndrome(CMS)and amyotrophic lateral sclerosis(ALS)th

78、is year and we have announced a 3rd indication,spinal muscular atrophy(SMA).We believe ARGX-119 has potential as a novel treatment modality in multiple serious indications.Our immunology innovation program(IIP)is a key driver for our future sustainable growth.This is reflected in 4 new investigation

79、al new drugs(INDs)that will start Phase 1 clinical trials in 2025 to continue to deliver immunology innovations to the patients who need them.argenx Annual Report 20242024 In Brief11Operational HighlightsReach More Patients Globally with VYVGARTVYVGART is now approved in the U.S.,Japan,the EU,the UK

80、,Switzerland,Israel,Mainland China,Canada,South Korea,United Arab Emirates,Australia and Kuwait(through Genpharm Services FZ-LLC(Genpharm)for the treatment of gMG.VYVGART is now also approved and launched in Japan for the treatment of ITP.VYVGART SC is now approved in the U.S.,the EU,the UK,Japan,Ch

81、ina(through Zai Lab),Australia and Kuwait(through Genpharm)for the treatment of gMG and in the U.S.,Japan,and China for the treatment of CIDP.VYVGART is the only gMG treatment available as both an intravenous(IV)and a simple SC injection,providing choice to patients in how and where they are treated

82、.In 2024,we generated product net sales of$2.2 billion.Pricing and reimbursement discussions for VYVGART and VYVGART SC remain ongoing in multiple jurisdictions,including in several countries in the EU,with new agreements in place in France,Luxembourg,Belgium,the Netherlands,Poland,Slovakia and Aust

83、ria.We filed for approval of VYVGART for gMG in Saudi Arabia and are expecting a decision on approval in 2025.We filed for approval of VYVGART SC for CIDP in the EU and are expecting a decision on approval in 2025.We received approval of the PFS for gMG in Europe on February 13,2025.We filed for app

84、roval of the PFS for gMG and CIDP in the U.S.with a PDUFA Date of April 10,2025.We also filed for approval in Canada and Japan with expected decisions on approval in 2025.argenx Annual Report 20242024 In Brief12The science of co-creation drives our quest to engineer life-changing immunology solution

85、s,the resilient spirit of patients fuels our urgency to deliver them.The infinity sign symbolizes our commitment to science and patients;it has no bounds.Our potential is infinite.Our purpose is immunology innovation.Advance Extensive PipelineWe continue to demonstrate breadth and depth within our i

86、mmunology pipeline and have advanced multiple pipeline-in-a-product candidates.With efgartigimod,we are furthering our leadership in neonatal Fc receptor(FcRn)and we are continuing its development in more than 10 indications today.Beyond efgartigimod,we are advancing our other clinical pipeline prog

87、rams,including empasiprubart(C2 inhibitor)which has now shown proof-of-concept in MMN and initiated its first Phase 3 clinical trial,and is in Phase 2 POC clinical trials in delayed graft function(DGF)and DM.We also announced CIDP as the 4th indication for empasiprubart during our R&D Day on July 16

88、,2024 and plan to start a registrational study in CIDP evaluating empasiprubart head-to-head versus intravenous IgG(IVIg)in first half of 2025.In addition,we have initiated Phase 1b/2a clinical trials of ARGX-119,a MuSK agonist,in CMS congenital myasthenic syndromes and ALS.Four new pipeline candida

89、tes were nominated in 2024 from our immunology innovation program(IIP),including:ARGX-213,ARGX-121 and ARGX-220 and ARGX-109.Phase 1 results expected for ARGX-109 in second half of 2025 and for ARGX-213 and ARGX-121 in first half of 2026.argenx Annual Report 20242024 In Brief13Pioneer the FcRn Pathw

90、ay with efgartigimodNeurology indications:CIDP(ADHERE):following the positive topline results from the ADHERE clinical trial in CIDP,a supplemental biologics license application(sBLA)for efgartigimod SC was approved for the treatment of CIDP and launched in July 2024 in the U.S.We also received appr

91、oval in Japan and China for the treatment of CIDP.Myositis(ALKIVIA):In November 2024,we announced the GO decision to continue Phase 3 of the ALKIVIA clinical trial.The decision to continue clinical development of efgartigimod SC in each of the three myositis subtypes,including IMNM,ASyS and DM,is su

92、pported by the efficacy and safety results from the Phase 2 portion of the seamless Phase 2/3 ALKIVIA clinical trial.Overall,the clinical trial met its primary endpoint,demonstrating a statistically significant treatment effect in mean total improvement score(TIS)at week 24,and showed improvement ac

93、ross all six core set measures of the TIS in favor of efgartigimod SC compared to placebo.The observed safety and tolerability profile was consistent to that demonstrated with other clinical trials.Topline results expected 2H 2026.TED(UplighTED):registrational clinical trials in thyroid eye disease(

94、TED)ongoing with efgartigimod PFS.Topline results expected 2H 2026.Seronegative gMG(ADAPT-SERON):registrational clinical trial in seronegative gMG patients ongoing with efgartigimod IV.Topline results expected 2H 2025.Ocular MG(ADAPT-OCULUS):registrational clinical trial in ocular MG patients ongoin

95、g with efgartigimod PFS.Topline results expected 1H 2026.argenx Annual Report 20242024 In Brief14efgartigimodHematology/rheumatology indications:ITP(ADVANCE-IV):positive clinical trial results formed the basis of approval in Japan for ITP,received on March 26,2024.ITP(ADVANCE-NXT):confirmatory clini

96、cal trial in ITP ongoing with efgartigimod IV in the U.S.Topline results expected in 2H 2026.Primary SjD(RHO):following the analysis of topline data from the Phase 2 POC clinical trial through our partnership with IQVIA Ltd(IQVIA)in SjD we decided to continue the development of efgartigimod PFS to P

97、hase 3(UNITY),which was initiated at the end of 2024.Topline results expected in 2027.Systemic Sclerosis(SSc):Phase 2 POC clinical trial ongoing.Topline results expected in 2H 2026.Nephrology indications:Lupus Nephritis:Phase 2 POC clinical trial ongoing through our partnership with Zai Lab.Topline

98、results expected in 2H 2025.Antibody-mediated rejection:shAMRock Phase 2 POC clinical trial in antibody-mediated rejection(AMR)has been initiated.In 2024 we made the decision to stop development in PC-POTS(ALPHA),Bullous Pemphigoid(BALLAD)and membranous nephrology based on review of the Phase 2 data

99、.argenx Annual Report 20242024 In Brief15Broaden Immunology Pipeline with empasiprubart and ARGX-119empasiprubart(C2 inhibitor):MMN(ARDA):based on the positive Phase 2 POC data of empasiprubart in MMN we have advanced empasiprubart into Phase 3(EMPASSION).Topline results expected in 2H 2026.In Janua

100、ry 2024,we reported positive clinical data from the first cohort of the Phase 2 POC ARDA clinical trial establishing POC in MMN.empasiprubart demonstrated a 91%reduction in the need for IVIg rescue compared to placebo HR(95%CI)=0.09(0.2:0.44).In July 2024,we reported positive clinical data from the

101、second cohort of the Phase 2 POC ARDA clinical trial confirming POC in MMN.empasiprubart demonstrated a 84%reduction in the need for IVIg rescue compared to placebo HR:(95%CI)=0.16(0.02:1.54).Safety profile was consistent with Phase 1 data in both cohorts.We are also conducting a natural history stu

102、dy(IMMERSION)in MMN.DGF(VARVARA)and DM(EMPACIFIC)Phase 2 POC clinical trials ongoing in DGF and DM.Topline results expected 2H 2025 and 1H 2026,respectively.CIDP(EMVIGORATE):Phase 3 clinical trial in CIDP expected to start in 1H 2025.ARGX-119(MuSK agonist):Phase 1 dose-escalation clinical trial in h

103、ealthy volunteers completed;data supports advancement in POC studies.CMS:Phase 1b clinical trial started to assess early signal detection in patients with CMS.Topline results expected in 2H 2025.ALS(reALiSe):Phase2a clinical trial started to assess early signal detection in patients with ALS.Topline

104、 results expected 1H 2026.argenx Annual Report 20242024 In Brief16empasiprubartARGX-119Build out the Innovation EcosystemIn January 2024,we announced the nomination of four new pipeline candidates,including:ARGX-213 targeting FcRn,furthering argenxs leadership in this new class of medicine;ARGX-121

105、targeting Immunoglobulin A(IgA)and ARGX-220,which are first-in-class targets broadening argenxs focus across the immune system;and ARGX-109,targeting IL-6,which plays an important role in inflammation.Preclinical work is ongoing in each candidate and the first healthy volunteer studies are expected

106、to start in 2025.argenx Annual Report 20242024 In Brief17Corporate AchievementsDr.Brian KotzinDr.Brian Kotzin joined the Board of Directors in May 2024 as a non-executive director and chairperson of the research and development committeeMr.Peter VerhaegheMr.Peter Verhaeghe,who has served as a non-ex

107、ecutive director since July 2014,was reappointed as a non-executive director and chairperson of the Board of Directors for a term of 2 yearsDr.Pamela KleinDr.Pamela Klein,who has served as a non-executive director since April 2016,was reappointed as a non-executive director for a term of 2 years1,59

108、9Expansion to 1,599 full-time employees(as of December31,2024)to support further growth of our business,including fully staffed commercial teams in the U.S.,Europe,Japan and CanadaEmployeesargenx Annual Report 20242024 In Brief18Financial Highlights$2.2$1.0billionbillionProduct net salesResearch&dev

109、elopmentTransition to sustainable operating profitability in 2025 enables continued investment in innovation.argenx Annual Report 20242024 In Brief19argenx Annual Report 2024This is the story of Nicola20The future belongs to those who dare to do more.Nicola“I think its really important that people w

110、ith MG are able to feel like theyre still in control of their health.”Living with an autoimmune disease can come with many unknowns.And trying to navigate the ups and downs may make you feel like youre not in control of your own life.Nicola,who is living with myasthenia gravis(MG),says,“MG,as a dise

111、ase,can take so much away from you.In terms of the symptoms themselves,it can feel like a loss of power in your own self in some ways.”But this didnt sit well with Nicola.“Myasthenia gravis is such an unpredictable disease because everyones symptoms are so different.On top of that,our symptoms will

112、fluctuate day to day,week to week and sometimes even hour to hour.”She goes on to say,“Because of this,I think being able to have a sense of agency is so important,and you can have a say to help direct your treatment path.”Meet Nicola as she shares her journey with self-advocacy,why she uses the Mya

113、sthenia Gravis Activities of Daily Living(MG-ADL)scale and more.Being a self-advocate was something that Nicola herself had to practice.One of Nicolas favorite instances of self-advocacy was when she was told that despite her diagnosis,she wasnt the typical age to have MG.But because of the thorough

114、 research she did on her own,she knew that while MG can happen at any time,it commonly impacts young adult women under the age of 40.Looking back on that moment,Nicola thinks it may seem small,but it really wasnt.Because she had been so hesitant to stand up for herself in the past and was frustrated

115、 by feeling that she lacked power in managing her MG,not only was it a win,but it was also a stepping stone for other opportunities in the future.She says,“I really like having agency over my healthcare and feeling like Im in control.”What fuels her confidence with self-advocacy is her drive to keep

116、 learning.When she was first experiencing MG symptoms,she took it upon herself to read medical textbooks and join multiple MG support groups online.Not only were the groups good for emotional support,but she says the group members would also compare notes and share tips.She also has a“Myasthenia Gra

117、vis”alert set up on her internet browser so she can get notified whenever theres new information and then talk about it with her healthcare provider.“I think it is so important to take a proactive approach to your health,”she says.Nicolas advice on how to be your own best advocate?“Know the facts an

118、d the most current research about MG so you can properly articulate any questions or concerns.”She goes on to say,“Its important you have the confidence to stand firm when it comes to your experiences.And its especially helpful when you know that information to be true,whether thats through your own

119、 medical research or shared anecdotal evidence from other people living with MG.”But she acknowledges its not always easy and its perfectly OK to lean on your support system,“I always bring my boyfriend with me to appointments.Its so helpful to have someone else there to take notes and advocate for

120、me,especially if Im too short of breath to get out everything I need to say.”“I think its really important that people with MG are able to feel like theyre still in control of their health.”NicolaIn step with her knowledge-is-power approach,Nicola embraces tools like the Myasthenia Gravis Activities

121、 of Daily Living scale(or MG-ADL).“Its so important for us to find resources that can help us be equipped with the best knowledge,”says Nicola.The MG-ADL scale is a tool that helps identify the impact MG has on a persons daily life by providing an assessment of the severity of some common symptoms a

122、ssociated with MG.Its made up of eight questions,six of which are about daily activities like breathing,brushing teeth and getting up out of a chair.argenx Annual Report 2024This is the story of Nicola21The last two questions are eye-related(eyelid droop and double vision),because,as you may know,oc

123、ular symptoms are common in MG.To use the scale,you simply review each activity or item and give it a score from zero to three.A zero means you experienced normal function and a three means you experienced the greatest severity of symptoms.“I think the MG-ADL scale makes you stop and think about wha

124、ts really happening,”says Nicola.Sometimes there are symptoms Nicola has grown accustomed to,and she doesnt recognize their impact on her day-to-day life until she sees the number written out on the scale.“Sitting and looking at the MG-ADL makes you realize either,OK,I did have a few episodes this w

125、eek and maybe I didnt notice it,or,Hey,I havent actually had a choking episode in a while!Its really good to be able to see it in front of you.”Staying consistent with the scale may also be helpful when noticing changes.“I think the MG-ADL scale is really good for measuring your symptoms,so you can

126、reflect back on where you were before,and compare it to where you are now,”reflects Nicola.I think all people living with MG could benefit from using the MG-ADL scale.Nicolas self-advocacy and her MG-ADL score come together at her healthcare appointments.“I think the MG-ADL scale is a really good to

127、ol to start a conversation with your provider.You can write down the list of symptoms and discuss how they might be affecting you.”She adds,“I think its a good starting point to be able to bring up certain issues with your physician and start that dialogue.”In fact,regularly tracking your symptoms m

128、ay lead to more productive conversations with your healthcare team.It can also help you aim for improved daily abilities and,if possible,minimal or no symptoms(MSE).MSE means a person is experiencing minimal or almost no symptoms.“Minimal symptoms would be amazing,”Nicola says.“I couldnt think of an

129、ything better.I light up just thinking about it.”As a professional actor,dancer and singer,Nicola shares another aspiration:“I would also like to write,direct and act in a film about MG based on my experiences.”Her love of advocacy for herself and others comes with its own set of goals,too.“Some oth

130、er goals of mine would be to improve MG awareness and ensure healthcare providers have access to critical information about MG patients in crisis.”“When living with an unpredictable disease,”she says,“Things are going to beunpredictable!”Goal setting is important but so is giving yourself grace.“I t

131、hink its important to be patient with yourself when setting and achieving goals,”she advises.“Dont be discouraged when things dont happen the way youd like or in the time that you planned,some things take longer than expected and thats OK!”argenx Annual Report 2024This is the story of Nicola222025 O

132、utlookargenx Annual Report 20242025 Outlook23Presentation of the Group1.1 Company Profile251.2 Strategy and Objectives291.3 Our Products and Product Candidates311.4 Collaborations and licenses491.5 Manufacturing and Supply561.6 Intellectual Property561.7 Regulation591.8 Documents on display80argenx

133、Annual Report 20242411Presentation of the Group1.1Company Profile1.1.1GeneralWe are a commercial-stage,global,fully-integrated biopharma company developing a deep pipeline of differentiated therapies for the treatment of severe autoimmune diseases.By combining our suite of antibody engineering techn

134、ologies with the disease biology expertise of our research collaborators,we aim to translate immunology breakthroughs into a pipeline of novel antibody-based medicines through our discovery engine,the IIP.We developed and are commercializing the first approved FcRn blocker in more than 30 countries

135、and we are evaluating efgartigimod in multiple serious autoimmune diseases.We are also advancing our second asset,empasiprubart,a C2 inhibitor,now in Phase 3.Several earlier stage experimental medicines,including ARGX-119,a MuSK agonist,are now in its first patient proof-of-concept studies.Our legal

136、 and commercial name is argenx SE.We were incorporated under the laws of the Netherlands on April 25,2008,as a private company with limited liability(besloten vennootschap met beperkte aansprakelijkheid).From incorporation until August 28,2009,our research and development activities were initially p

137、erformed in the Netherlands,then Belgium,by argenx N.V.and its legal predecessors.Since August 28,2009,all our research and development activities have been performed by our wholly-owned subsidiary,argenx BV,under a license provided by argenx N.V.Throughout this time,argenx BV assigned all resulting

138、 intellectual property to argenx N.V.On May 28,2014,we converted to a Dutch public company with limited liability(naamloze vennootschap).On April 26,2017,we converted to a Dutch European public company with limited liability(Societas Europaea or SE).On May 5,2017,we transferred the legal ownership o

139、f all intellectual property rights of argenx SE to argenx BV,effective retroactively as of January 1,2017.As a result,since January 1,2017,(i)argenx BV holds all legal and economic ownership of our intellectual property rights,and(ii)the research and development agreement between argenx SE and argen

140、x BV has been terminated.Our official seat is in Amsterdam,the Netherlands,and our registered office is at Laarderhoogtweg 25,1101 EB Amsterdam,the Netherlands.We are registered with the trade register of the Dutch Chamber of Commerce under number 24435214.Our European legal entity identifier number

141、(LEI)is 7245009C5FZE6G9ODQ71.Our telephone number is+31(0)10 70 38 441.Our website address is .This website is not incorporated by reference in this Annual Report.The SEC maintains an Internet site that contains reports,proxy and information statements,and other information regarding issuers that fi

142、le electronically with the SEC at www.sec.gov.The registered agent for service of process in the U.S.is CT Corporation System,with an address at 111 8th Avenue,New York,NY 10011.Our ordinary shares are listed on the regulated market of Euronext Brussels in Belgium under ISIN NL0010832176 under the s

143、ymbol“ARGX”since 2014 and ADSs,each representing one ordinary share in argenx(or a right to receive such share),are listed on the Nasdaq Global Select Market(Nasdaq)under the symbol“ARGX”since 2017.argenx SE is the parent entity of the Group and the sole shareholder of:argenx B.V.,a private company

144、with limited liability(besloten vennootschap/socit responsabilit limite)incorporated under the laws of Belgium,having its registered seat in Zwijnaarde,Belgium and its address at Industriepark-Zwijnaarde 7,9052 Zwijnaarde,Belgium.argenx B.V.is the sole shareholder of:argenx US,Inc.,incorporated unde

145、r the laws of the state of Delaware,U.S.,having its registered office in Wilmington,Delaware and its address at 33 Arch Street,Boston,Massachusetts 02110;argenx Japan KK.,incorporated under the laws of Japan,having its registered office in Tokyo,Japan and its address at HULIC JP Akasaka Building 2-5

146、-8,Akasaka,Minato-ku,Tokyo,107-0052,Japan;argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Company Profile25argenx Benelux B.V.(prior to October 31,2022 known as argenx IIP BV),incorporated under the laws o

147、f Belgium,having its registered seat in Zwijnaarde,Belgium and its address at Industriepark-Zwijnaarde 7,9052 Zwijnaarde,Belgium;argenx Switzerland,S.A.,incorporated under the laws of Switzerland,having its registered office in Geneva,Switzerland,and its address at Rue du Pr-de-la-Bichette 1,1202 Ge

148、neva,Switzerland;argenx France SAS,incorporated under the laws of France,having its registered office in Paris,France,and its address at Rue Camille Desmoulins 13,92130 Issy-Les-Moulineaux,France;argenx UK Ltd.,incorporated under the laws of the UK,having its registered office in Gerrards Cross,UK,a

149、nd its address at Spaces Gerrards Cross Chalfont Park,Building 1 Gerrards Cross,SL9 0BG,UK;argenx Netherlands Services B.V.,incorporated under the laws of the Netherlands,having its registered office in Laarderhoogteweg 25,1101 EB Amsterdam,the Netherlands;argenx Germany GmbH,incorporated under the

150、laws of Germany,having its registered office in Munich,Germany,and its address at Konrad-Zuse-Platz 8,81829 Munich,Germany;argenx Canada Inc.,incorporated under the laws of Ontario,having its registered office in Ontario,Canada and its address at 9131 Keele Street Suite A4,Vaughan,Ontario,Canada,L4K

151、 0G7;argenx Italy S.r.l.,incorporated under the laws of Italy,having its registered office in Milan,Italy and its address at Largo Francesco Richini 6 CAP,20122 Milan,Italy;argenx Spain S.L.,incorporated under the laws of Spain,having its registered office in Madrid,Spain and its address at Paseo de

152、la Castellana 200,Planta 8a,Oficina 819,28046 Madrid,Spain,with the branch office:argenx Spain S.L.-Sucursal em Portugal,organized under the laws of Portugal,having its registered office and address at Palcio Sottomayor,Rua Sousa Martins,n1,1 esquerdo 1050 217,Lisboa Portugal;argenx Australia Pty.Lt

153、d.,incorporated under the laws of Australia,having its registered office and address at Level 14,2 Riverside Quay,Melbourne VIC 3006,Australia(since January 12,2024);and,argenx Austria Services GmbH,incorporated under the laws of Austria,having its registered office and address at Graben 19,4th&5th

154、floor Vienna A-1010 Austria.The following chart provides an overview of the Group as of the date of this Annual Report.Percentages refer to both the share of capital and voting rights.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informati

155、onargenx Annual Report 2024Company Profile26argenx Corporate Legal Structure1.1.2OverviewOur MedicinesVYVGART is a first-in-class antibody fragment targeting FcRn.VYVGART is the only gMG treatment available as both an IV and a simple SC injection(VYVGART SC).VYVGART is approved in more than 30 count

156、ries and VYVGART SC is now approved in the U.S.,the EU,the UK,Japan,Israel,China and in Australia for the treatment of gMG.VYVGART SC is now also approved in the U.S.,China and Japan(as VYVDURA)for the treatment of CIDP.VYVDURA is also approved for the treatment of ITP in Japan.Our Pipelineefgartigi

157、mod is an IgG1 antibody Fc fragment that has been engineered for increased affinity to FcRn compared to endogenous IgG.efgartigimod selectively reduces IgG by blocking FcRn-mediated IgG recycling without impacting antibody production,or affecting other parts of the immune system.It is approved in th

158、ree indications,including gMG,CIDP and ITP,and is being evaluated in more than 10 additional serious autoimmune indications.empasiprubart(C2 inhibitor):empasiprubart is a novel complement inhibitor targeting C2,blocking the function of both the classical and lectin pathways while leaving the alterna

159、tive pathway intact.We believe empasiprubart has the potential to be a pipeline-in-a-product candidate and is being evaluated in 4 serious autoimmune diseases,of which 2 indications are in Phase 3.ARGX-119(MusK agonist):ARGX-119 is an agonist SIMPLE ANTIBODY to the MuSK receptor with potential in mu

160、ltiple neuromuscular indications.It is currently in proof-of-concept studies for CMS(Phase 1b clinical trial),ALS(Phase 2a)and will start in SMA in 2025.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Comp

161、any Profile27Preclinical Candidates:Four INDs to start Phase 1 studies in 2025:ARGX-213,targets FcRn,furthering argenxs leadership in this new class of medicineARGX-121 targeting IgA and ARGX-220 both broadening argenxs focus across the immune systemARGX-109,targets IL-6,which plays an important rol

162、e in inflammationIn addition to our wholly-owned pipeline,we have candidates that emerged from our IIP that we out-licensed to a partner for further development and for which we have milestone,royalty or profit-share agreements.These candidates include,amongst others:cusatuzumab(anti-CD70 antibody O

163、ncoVerity),ARGX-112(LP-0145 anti-IL-22R antibody LEO Pharma),ARGX-114(AGMB-101 agonistic anti-MET antibody Agomab)and ARGX-115(ABBV-151 anti-GARP antibody AbbVie).Immunology Innovation Program(IIP)Our IIP is central to our core business strategy of co-creation and innovation.The IIP also serves as o

164、ur discovery engine to identify novel targets and together,in collaboration with our scientific and academic partners,to build potential new pipeline candidates.Every current pipeline candidate from both our wholly-owned and partnered pipeline emerged from an IIP collaboration.The IIP enables us to

165、build our broad pipeline of products and product candidates and advance our long-term strategy to be a sustainable,integrated immunology company.Examples of our IIP programs include:efgartigimod emerged from a collaboration with Professor Sally Ward at the University of Texas Southwestern Medical Ce

166、nter and later became one of the blueprints for our IIP collaborations.Professor Wards research identified the crucial role that FcRn plays in maintaining and distributing IgGs throughout the body.efgartigimod is a human IgG1 Fc fragment that is equipped with ABDEG mutations,which we in-licensed fro

167、m the University of Texas Southwestern Medical Center.These proprietary mutations modified efgartigimod to increase its affinity for FcRn while retaining the pH-dependent binding that is characteristic of FcRn interactions with its natural ligand,endogenous IgG.empasiprubart was built in collaborati

168、on with Broteio Pharma B.V.(Broteio).Broteio was launched in 2017 with support from Professor Erik Hack and the University of Utrecht,to conduct research demonstrating preclinical POC of the mechanism of action of empasiprubart.Professor Hack is a renowned researcher in the role of inflammation in d

169、isease,specifically in the complement system,and has contributed research and expertise to the approval of two complement inhibitors.His understanding of the mild phenotype associated with a natural C2 deficiency and C2s unique positioning at the junction of the classical and lectin pathways led to

170、our interest in engineering empasiprubart with our proprietary NHANCE mutations and LALA mutations.ARGX-119 was built in collaboration with the Leiden University Medical Center(LUMC)and New York University(NYU)with support from teams led by Professor Verschuuren and Professor Steve Burden,respective

171、ly.Both groups have world-class expertise in unraveling the biological mechanism of neuromuscular disease and translating these insights from the lab to the patient.We bring to the collaboration our unique suite of antibody discovery and antibody engineering technologies and experience in clinical d

172、evelopment to complement our partners expertise in disease and target biology.Our suite of technologies include amongst others our SIMPLE ANTIBODY platform technology and NHANCE,ABDEG,POTELLIGENT,and DHS mutations that focus on engineering the Fc region of antibodies in order to augment their intrin

173、sic therapeutic properties.For more information,please see Section“1.3.7 IIP”.Our Suite of TechnologiesThrough our IIP,we collaborate with scientific and academic partners to identify immunology breakthroughs and build potential pipeline candidates.This is done through co-creation.We bring to the co

174、llaboration our unique suite of antibody engineering technologies and experience in clinical development to complement our partners expertise in disease and target biology.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Ann

175、ual Report 2024Company Profile28SIMPLE ANTIBODY platform technology:Our proprietary SIMPLE ANTIBODY platform technology,based on the powerful llama immune system,allows us to exploit novel and complex disease biology targets.The platform sources antibody variable regions(V-regions)from the immune sy

176、stem of outbred llamas,each of which has a different genetic background.The llama produces highly diverse panels of antibodies with a high human homology,or similarity,in their V-regions when immunized with targets of human disease.Our SIMPLE ANTIBODY platform technology allows us to access and expl

177、ore a broad target universe while potentially minimizing the long timelines associated with generating antibody candidates using traditional methods.NHANCE,ABDEG,POTELLIGENT,and DHS mutations focus on engineering the Fc region of antibodies in order to augment their intrinsic therapeutic properties.

178、In addition,we obtained a non-exclusive research license and option from Chugai Pharmaceutical Co.,Ltd.(Chugai)for the SMART-Ig(Recycling Antibody and part of Sweeping Antibody)and ACT-Ig(Antibody half-life extending)technologies.These technologies are designed to enable us to expand the therapeutic

179、 index of our product candidates,which is the ratio between toxic and therapeutic dose,by potentially modifying their half-life,tissue penetration,rate of disease target clearance and potency.In 2020,we also entered into a non-exclusive research agreement with the Clayton Foundation under which we m

180、ay access the Clayton Foundations proprietary DHS mutations to extend the serum half-life of therapeutic antibodies.1.2Strategy and Objectives1.2.1Companys StrategiesOur goal is to transform the lives of at least 50,000 patients and their communities before 2030 by providing them with life-changing

181、medicines built on scientific breakthroughs in immunology.To reach this goal,we plan to deliver a set of different strategies:Maximize the VYVGART opportunity:redefine treatment expectations for MG and CIDP,and deliver 6 additional labelled indications We plan to do this through our differentiated s

182、cientific and clinical activities and our commercial execution to drive VYVGART preference.Our PFS with PDUFA Date in April 2025 as a perfect example of our continued innovation for the patient experience.Beyond neurology,we plan to establish argenx and VYVGART in rheumatology as we prepare for data

183、 in Myositis and SjD,while also maximizing the therapeutic potential of VYVGART in other indications through the execution of multiple Phase 2 and Phase 3 studies.Maximize the empasiprubart opportunity:establish its potential as a pipeline-in-a-product We plan to develop argenx as scientific leader

184、in complement inhibitions and elevate the differentiation story.In particular,we have advanced the clinical development of empasiprubart in MMN,currently in Phase 3,DGF in the context of kidney transplants and DM,currently in Phase 2,and expect to start a registrational clinical trial for our fourth

185、 selected indication,CIDP in 2025.For both MMN and CIDP we will prepare for launches,building on key elements of the VYVGART playbook.Build a sustainable,diversified portfolio of breakthrough and differentiated antibody-based products We plan to further advance ARGX-119 to a differentiated first-in-

186、class MuSK agonist in multiple indications(CMS,ALS,SMA,1 new indication),maximize our leadership position in the FcRn space through multiple generations of projects(e.g.ARGX-213),substantially grow our clinical portfolio of differentiated pipeline-in-a-product opportunities(ARGX-109,ARGX-121,ARGX-22

187、0,ARGX-213,other),create an exciting portfolio of promising new assets(through our IIP)and advance our clinical trial designs and speed.Grow a unique,global biotech company by scaling the argenx Way:one company,one plan,on a mission to achieve the unthinkable We plan to embed the argenx Way througho

188、ut the organization,who we are through our cultural pillars and how we work through our operating principles.We want to demystify innovation and make it everyones business,strengthen the winning competencies to share the future of argenx and advance our partnership approach to access.To be able to c

189、ontinue in this way,we plan to remain a magnet for talent and create unlimited opportunities for growth and development of our people,an important driver of developing the business.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationa

190、rgenx Annual Report 2024Company Profile29Ensure long-term sustainability We plan to continue to seek out,listen to and prioritize on behalf of the patient in all what we do,accelerate the science of immunology by being an active and trusted partner in the global immunology ecosystem through high-qua

191、lity publications and patent applications,elevate and expand our relationships with regulatory,payors and policy stakeholders and create long-term shareholder value.In our 2030 vision,we aim to build on our strong strategic pillars to have a continuous pipeline of innovation,strengthen our FcRn lead

192、ership and scale in a disciplined way.Our goal is to have 5 new molecules in Phase 3 development,10 labelled indications and reaching 50,000 patients who are on treatment by 2030.1.2.2Competitive positionWe participate in a highly innovative industry characterized by a rapidly growing understanding

193、of disease biology,quickly changing technologies,strong intellectual property barriers to entry,and a multitude of companies involved in the creation,development and commercialization of novel therapeutics.Many of these companies are highly sophisticated and often strategically collaborate with each

194、 other.Competition in the autoimmune field is intense and involves multiple monoclonal antibodies(mAbs),other biologics and small molecules either already marketed or in development by many different companies,including large pharmaceutical companies.We compete with a wide range of biopharmaceutical

195、 companies,who are developing products for the treatment of gMG,CIDP,ITP and other autoimmune diseases,including products that are in the same class as VYVGART,as well as products that are similar to some of our product candidates.We are aware of several FcRn inhibitors that are in clinical developm

196、ent or marketed.Competitive product launches may erode future sales of our products,including our existing products and those currently under development,or result in unanticipated product obsolescence.Such launches continue to occur,and potentially competitive products are in various stages of deve

197、lopment.We could also face competition for use of limited international infusion sites,particularly in new markets as competitors launch new products.We cannot predict with accuracy the timing or impact of the introduction of competitive products that treat diseases and conditions like those treated

198、 by our products or product candidates.In addition,our competitors compete with us to recruit and retain qualified scientific and management personnel,establish clinical trial sites and patient registration for clinical trials,as well as in acquiring technologies complementary to,or necessary for,th

199、e development of our products.Please see the risk factor titled”We face significant competition for our drug discovery and development efforts.for further details on the competition we face.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Inf

200、ormationargenx Annual Report 2024Strategy and Objectives301.3Our Products and Product CandidatesThe following table summarizes key information on our portfolio of lead products and product candidates as of the date of this Annual Report.ProgramIndicationPreclinicalPhase 1Proof of ConceptRegistration

201、alCommercialVYVGARTVYVGART HYTRULOgMG ITP(Japan)CIDP efgartigimodSeronegative gMG Ocular gMG Thyroid Eye Disease ITP Myositis(IMNM,ASyS,DM)Sjgrens Disease Lupus Nephropathy Systemic Sclerosis Antibody-Mediated Rejection Autoimmune encephalitis NOT DISCLOSED empasiprubartMultifocal Motor Neuropathy C

202、IDP Delayed Graft Function Dermatomyositis ARGX-119Congenital Myasthenic Syndrome Amyotrophic Lateral Sclerosis Spinal Muscular Atrophy ARGX-109NOT DISCLOSED ARGX-121NOT DISCLOSED ARGX-213NOT DISCLOSED ARGX-220 NOT DISCLOSED NEUROLOGY HEMATOLOGY AND RHEUMATOLOGY DERMATOLOGY NEPHROLOGY INDICATION NOT

203、 DISCLOSEDargenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates311.3.1VYVGART Approvals and Regulatory PlanOur two approved medicines,VYVGART and VYVGART SC,are FcRn blockers.

204、VYVGART is approved in more than 30 countries for the treatment of adults with gMG who are anti-acetylcholine receptor(AChR)antibody positive(AChR-AB+)and for the treatment of adults with gMG who do not have sufficient response to steroids or non-steroidal immunosuppressive therapies(ISTs),including

205、 seronegative patients,in Japan.VYVGART is now also approved for the treatment of adult patients with ITP in Japan.Our second product,VYVGART SC,is a subcutaneous combination of efgartigimod alfa and recombinant human hyaluronidase PH20(rHuPH20),Halozyme Therapeutics,Inc.s(Halozyme)ENHANZE SC drug d

206、elivery technology.It has been approved for the treatment of adults with gMG who are AChR-AB+as VYVGART HYTRULO in the U.S.and China,as VYVGART in the EU,and as VYVGART SC in the UK,Israel.It has also been approved as VYVDURA in Japan for the treatment of adults with gMG who do not have sufficient r

207、esponse to steroids or non-steroidal ISTs,including seronegative patients.VYVGART SC has now also been approved for the treatment of adults with CIDP in the U.S.and China as VYVGART HYTRULO and in Japan as VYVDURA.More approvals and launches of both VYVGART and VYVGART SC in multiple jurisdictions a

208、nd countries are planned following pricing and reimbursement negotiations.The following table summarizes the status of regulatory approvals and commercialization efforts for VYVGART IV,VYVGART SC and PFS as March 17,2025:ProductProduct nameIndicationGeographySubmissionApprovalLaunchedVYVGART IVVYVGA

209、RT gMGUSDecember 17,2021December 17,2021VYVGART gMGEuropeAugust 10,2022Germany was the first European country to launch on September 1,2022VYVGART gMGCanada September 19,2023November 6,2023VYVGART gMGIsraelApril 24,2023Not marketedVYVGART gMGJapanJanuary 20,2022May 9,2022VYVGART gMGThe UK March 14,2

210、023Not marketedVYVGART gMGChina June 30,2023September 5,2023VYVGARTgMGAustralia February 24,2025Not availableVYVGARTgMGKuwait February 19,2025Not availableVYVGART gMGSaudi Arabia Submitted Not availableNot availableVYVGARTgMGKorea(the Republic of)January 20,2025Not availableVYVGART gMGUnited Arab Em

211、iratesOctober 30,2024Not marketedVYVGART gMGSwitzerlandOctober 3,2024Not marketedVYVGART ITPJapanMarch 26,2024On the market since launch of IV productNot availablegMGBrazilPlanned submission 2H 2025Not availableNot availableNot availablegMGSingaporeNot availableNot availableNot availableargenx Group

212、Risk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates32VYVGART SCVYVGART HYTRULOgMGUS June 20,2023June 20,2023VYVGART HYTRULO CIDP US June 21,2024On the market since launch of SC productV

213、YVGARTgMGAustralia February 24,2025Not available VYVGARTgMGEurope November 15,2023Germany was the first European country to launch on December 15,2023VYVGARTCIDPEuropeSubmitted Expected in 2H Not availableNot availablegMGSwitzerlandFebruary 10,2025Not availableVYVGARTgMGThe UKFebruary 6,2024Not mark

214、etedVYVGART SCgMGIsraelSeptember 23,2024Not marketedVYVGART HYTRULOgMGChina July 9,2024December 3,2024VYVGART HYTRULOCIDPChina November 5,2024On the market since launch of SC productVYVDURA gMGJapan January 18,2024April 17,2024VYVDURA CIDP Japan December 27,2024On the market since launch of SC produ

215、ctPFSVYVDURA gMG Japan SubmittedExpected in 2H 2025Not availableVYVDURA CIDP Japan SubmittedExpected in 2H 2025Not availableNot availablegMGU.S.Submitted Expected in 1H 2025Not availableNot availableCIDP U.S.Submitted Expected in 1H 2025Not availableVYVGARTgMGEuropeFebruary 13,2025February 13,2025VY

216、VGARTCIDPEuropeSubmitted Expected in 1H 2025Not availableNot availablegMGCanada Submitted Expected in 2H 2025Not availableNot availableCIDPCanada Submitted Expected in 2H 2025Not availableNot availablegMGThe UKSubmittedNot availableNot availableCommercialization We have established our own sales for

217、ce in the U.S.,Japan,Europe and Canada for VYVGART for the treatment of gMG and CIDP(where approved).We plan to expand our own sales and marketing capabilities and promote our products and product candidates in other regions if we decide there is a business case to do so after regulatory approval ha

218、s been obtained.Development and commercialization may also be done through collaborations with third parties.In January 2021,we entered into an exclusive out-license agreement with Zai Lab(Zai Lab Agreement),a commercial-stage biopharmaceutical company,for the development and commercialization of ef

219、gartigimod in Greater China,(which includes Mainland China,Hong Kong,Taiwan and Macau,Greater China).Zai Lab announced approval of VYVGART in Mainland China in June 2023 for the treatment of adult gMG patients and in 2024 Zai Lab also announced the approval of VYVGART SC for gMG and CIDP.Under the Z

220、ai Lab Agreement,we received and continue to be eligible for certain sales-based milestone payments and royalties based on annual product net sales of efgartigimod in Greater China.In October 2021,we announced an exclusive distribution agreement with Medison to commercialize efgartigimod for gMG in

221、Israel(Medison Agreement).Medison filed for and obtained approval for VYVGART in April 2023 and for VYVGART SC in September 2024.On June 6,2022 we announced an exclusive multi-regional agreement with Medison to commercialize efgartigimod in 14 countries,including Poland,Hungary,Slovenia,Czech Republ

222、ic,Romania,Bulgaria,Lithuania,Croatia,Slovakia,Estonia,Latvia,Greece,and Cyprus,for the treatment of adult patients with gMG(Medison Multi-Regional Agreement).argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 20

223、24Our Products and Product Candidates33In January 2022,we entered into a partnership agreement with Genpharm,under which Genpharm shall purchase VYVGART from us for the resale in the Gulf Cooperation Council(comprising Saudi Arabia,Kuwait,the United Arab Emirates,Qatar,Bahrain and Oman)on an exclusi

224、ve basis for Genpharms own account and own name(Genpharm Agreement).In 2023,we entered into the Handok Agreement for the distribution of VYVGART in South Korea and in 2024 we received approval for VYVGART in South Korea.We intend to sign additional distribution partnerships for other territories.In

225、the U.S.,argenx advertises certain products via digital and traditional media channels,including the internet and television.For a discussion of total revenues by geographic market,please see“Note17Segment Reporting”in our consolidated financial statements.Pre-Approval Access ProgramWe are committed

226、 to improving the lives of people suffering from rare diseases.We are driven to discover new treatment approaches fueled by the resilience of patients to urgently deliver them.We aim to do this in partnership;we listen to patients,supporters and advocacy communities,and we hear their stories.Their i

227、nsights guide us as we develop our investigational therapies and motivate us to advance the understanding of rare diseases.We have a Pre-Approval Access program(PAA)for patients with gMG which opened on February 21,2021 for patients who are unable to participate in an ongoing clinical trial.In 2024,

228、we approved access to this PAA for over 403 gMG patients in 14 countries.The PAA program remains open in countries where VYVGART is not yet launched or reimbursed.1.3.2efgartigimod(formerly ARGX-113)DevelopmentMechanism of ActionAs shown in Figure 1,efgartigimod is a human IgG1 Fc fragment equipped

229、with our ABDEG mutations that is designed to target the FcRn and reduce IgG.FcRn is foundational to the immune system and functions to recycle IgG,extending its serum half-life over other IgGs that are not recycled by FcRn.IgGs that bind to FcRn are rescued from lysosomal degradation.By binding to F

230、cRn,efgartigimod can reduce IgG recycling and increase IgG degradation.Compared to alternative immunosuppressive approaches,such as B-lymphocyte(B-cell)depleting agents,efgartigimod acts in a highly selective manner.For efgartigimod,we now have an estimated 8,000 patients years of safety follow-up b

231、etween clinical trials and real world experience.efgartigimod has been observed to significantly reduce concentrations of all IgG subtypes without decreasing levels of other IgGs or human serum albumin,which is also recycled by FcRn,discussed in more detail in the paragraph of this section on formul

232、ations below.Based on its mechanism of action in targeting FcRn to selectively reducing IgGs,efgartigimod has the potential to address a multitude of severe autoimmune diseases where pathogenic IgGs are believed to be mediators of disease.As of the end of 2024,we are evaluating efgartigimod in more

233、than 10 serious autoimmune indications and plan to continue to expand into new indications.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates34Figure 1:efgartigimods mechan

234、ism of action blocks the recycling of IgG antibodies and removes them from circulationIndication Selection StrategyWe utilize the following strategy to select indications for efgartigimod:We first start with a strong,unifying biological rationale.The indications in our pipeline are unified in that t

235、here exists a wide range of supportive evidence that demonstrates that each is IgG-mediated.This ranges from published literature,clinical trials with currently used therapies such as IVIg,PLEX,or rituximab,and other experiments,such as passive transfer models.We also look at indications where a sig

236、nificant clinical or commercial opportunity exists.These are disease areas where there is a significant unmet need for innovation as patients are often not well-managed by current therapies and their respective side effects.Furthermore,for each indication,there is a defined path forward with establi

237、shed precedent for how to run POC and registrational clinical trials with generally accepted clinical and regulatory endpoints.FormulationsOverviewWe are developing two formulations of efgartigimod to address the needs of patients,physicians,and payers across indications and geographies,including ef

238、gartigimod IV(VYVGART)and efgartigimod SC(VYVGART SC).Scientific PublicationsWe refer to our key scientific publications from our Phase 3 studies with either the IV or SC formulation in gMG,ITP and CIDP.Publication in The Lancet Neurology of Phase 3 ADAPT study data in generalized myasthenia gravis:

239、 GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates35Publication in The Lancet of Phase 3 ADVANCE-IV study data in primary immune thrombocytopenia: in The Lancet Neurology of Phas

240、e 3 ADHERE study data in chronic inflammatory demyelinating polyneuropathy: IndicationsClinical trial overviewClinical TrialStageIndicationPatientsPrimary EndpointStatusADAPTRegistrationalgMGThe proportion of responders based on the Myasthenia Gravis Activities of Daily Living(MG-ADL)scoreMarketedAD

241、APT-SCRegistrationalgMGThe proportion of responders based on the Myasthenia Gravis Activities of Daily Living(MG-ADL)scoreMarketedADAPT-SERONRegistrationalseronegative gMG 110MG-ADL total score change from baseline to day 29(w4)Ongoing clinical trial results expected 2H 2025 ADAPT-OCULUSRegistration

242、alocular MG92-124Change in MGII PRO ocular score from baseline to day 29(w4)Ongoing clinical trial results expected 1H 2026ADHERERegistrationalCIDP322The hazard ratio for the time to first adjusted INCAT deteriorationMarketed ADVANCE-IVRegistrationalITPThe proportion of patients that achieved sustai

243、ned platelet responseMarketed ADVANCE-NXTRegistrationalITP63Extent of disease control(cumulative number of weeks over the planned 24-week treatment period with platelet counts of 50109/LOngoing clinical trial results expected in 2H 2026 BALLADRegistrationalBP98The proportion of participants in compl

244、ete remission while off oral corticosteroids for at least eight weeks at week 36Clinical trial discontinued in 2024 ALKIVIARegistrationalMyositisTarget 240The total improvement score(TIS)at the end of treatment periodOngoing clinical trial results expected in 2H 2026RHOPoCPrimary SjDTarget 30The pro

245、portion of responders to the Composite of Relevant endpoints for SjD(CRESS;response on three out of five items)at week 24GO decision made in 2024 advanced in Phase 3 UNITYRegistrationalPrimary SjD Target 580The change from baseline on the ClinESSDAI score(w48)Ongoing clinical trial results expected

246、in 2027ALPHAPoCPOTS post-COVID1953The co-primary endpoints are 1)COMPASS-31 and 2)the Malm POTS Symptom score at the end of the 24-week treatment periodClinical trial discontinued in 2024 In partnership with Zai LabPoCLNTarget 60The change in urine protein creatinine ratio from baseline to end of th

247、e treatment periodOngoing clinical trial results expected in 2H 2025In partnership with Zai LabPoCMNTarget 70The change in urine protein creatinine ratio from baseline to end of the treatment period in the anti-PLA2R Ab seropositive populationClinical trial discontinued in 2024 argenx GroupRisk Fact

248、orsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates36uplighTED RegistrationalTEDTarget 108/trial Percentage of participants who were proptosis responders at week 24 Ongoing clinical trial result

249、s expected in 2H 2026 shAMRock PoCAMRTarget 30 Safety and tolerability.Efficacy measures such as estimated glomerular filtration rate,histology and urine protein creatinine ratio are captured in the secondary endpointsClinical trial has been initiated in 2024 ADAPT-JUNIOR IVPhase 2/3gMGTarget over 1

250、2To confirm an age-adjusted optimum dose of efgartigimod IV and provide(model-predicted)evidence for a treatment responseOngoing clinical trialADAPT-JUNIOR SCPhase 2/3gMGTarget over 12To confirm an appropriate dose of efgartigimod PH20 SC in pediatric participants with gMGOngoing clinical trialOther

251、 clinical trials PoCAAVClinical trial discontinued in 2024PoCSSc To be confirmedTo be confirmedOngoing clinical trial results expected in 2H 2026gMGOverviewgMG is a rare and chronic autoimmune disease where IgG autoantibodies disrupt communication between nerves and muscles,causing debilitating and

252、potentially life-threatening muscle weakness.In myasthenia gravis(MG),IgG autoantibodies either bind and occupy or cross-link and internalize the receptor on the muscle cells,thereby preventing the binding of acetylcholine,the signal sent by the nerve cell.In addition,these autoantibodies can cause

253、destruction of the neuromuscular junction by recruiting complement,a potent cell-destroying mechanism of the human immune system.The muscle weakness associated with MG usually presents initially in ocular muscles and can then spread into a generalized form affecting multiple muscles,known as gMG.App

254、roximately 85%of people with MG progress to gMG within 24 months(source:Behin et al.New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis.J Neuromusc Dis 5.2018.265-277).MG in the ocular form initially causes droopy eyelids and blurred or double vision due to partial paralysis of eye

255、 movements.As MG becomes generalized it affects muscles in the neck and jaw,causing problems in speaking,chewing and swallowing.MG can also cause weakness in skeletal muscles leading to problems in limb function.In the most severe cases,respiratory function can be weakened to the point where it beco

256、mes life-threatening.These respiratory crises occur at least once in the lives of approximately 15%to 20%of MG patients.The U.S.prevalence of MG is estimated at approximately 20 cases per 100,000(source:Philips et al,Ann NY Acad Sci.2003).Patients with confirmed AChR antibodies account for approxima

257、tely 85%of the total gMG population(Behin et al.New Pathways and Therapeutics Targets in Autoimmune Myasthenia Gravis.J Neuromusc Dis 5.2018.265-277).In May 2020,we announced positive topline results from the pivotal ADAPT clinical trial of efgartigimod for the treatment of gMG.The topline results f

258、rom the ADAPT clinical trial showed that efgartigimod was well-tolerated,demonstrated clinically meaningful improvements in strength and quality of life measures,and provided the option of an individualized dosing schedule for gMG patients.The full Phase 3 ADAPT results were published in The Lancet

259、Neurology in July 2021.The data from the ADAPT clinical trial and the subsequent OLE(ADAPT+)formed the basis for the regulatory approvals of VYVGART in the U.S.,Japan,the EU,Mainland China,Israel,the UK and Canada.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial Sta

260、tementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates37On March 22,2022,we announced positive topline results from the Phase 3 ADAPT-SC clinical trial,a registrational non-inferiority bridging clinical trial of efgartigimod SC for the treatment of gMG.efgartigi

261、mod SC achieved the primary endpoint of total IgG reduction from baseline at day 29,demonstrating statistical noninferiority to VYVGART IV formulation in gMG patients.Based on these results,we received regulatory approval in the U.S.,the EU,China,Japan,Switzerland,the UK,Israel and Australia.Other c

262、linical trialsIn 2024,we initiated registrational clinical trials to expand the VYVGART label into broader MG populations,including in seronegative gMG patients(ADAPT-SERON)and ocular MG patients(ADAPT-OCULUS).We also have clinical trials ongoing in pediatric gMG patients(ADAPT-JUNIOR)with efgartigi

263、mod IV and efgartigimod SC.CIDPOverviewCIDP is a chronic autoimmune disorder of peripheral nerves and nerve roots caused by an autoimmune-mediated destruction of the myelin sheath,or myelin producing cells,insulating the axon of the nerves and enabling speed of signal transduction.The cause of CIDP

264、is unknown,but abnormalities in both cellular and humoral immunity have been shown.CIDP is a chronic and progressive disease:onset and progression occur over at least eight weeks in contrast with the more acute Guillain-Barr-syndrome.Demyelination and axonal damage in CIDP lead to loss of sensory an

265、d/or motor neuron function,which can lead to weakness,sensory loss,imbalance and/or pain.U.S.prevalence for CIDP patients is 42,000 of whom 24,000 are treated patients.Most CIDP patients require treatment,the majority currently with IVIg.Glucocorticoids and plasma exchange are used to a lesser exten

266、t as they are either limited by side effects upon chronic use,in the case of glucocorticoids,or invasiveness of the procedure and access,which is restricted to specialized centers in case of plasma exchange.Alternative immunosuppressant agents are typically reserved for patients ineligible for or re

267、fractory to IVIg,glucocorticoids or plasma exchange.In July 2023,we announced positive topline results from the ADHERE clinical trial evaluating VYVGART SC(efgartigimod alfa and hyaluronidase-qvfc)in adults with CIDP.The clinical trial met its primary endpoint(p=0.000039),demonstrating a significant

268、ly lower risk of relapse with VYVGART SC compared to placebo(HR:0.39 95%CI:0.25;0.61).67%of patients in open-label Stage A demonstrated evidence of clinical improvement,indicating that IgG autoantibodies play a significant role in the underlying biology of CIDP.VYVGART SC was well-tolerated with a s

269、afety profile that is consistent with prior clinical trials and the known profile of VYVGART.The most frequent treatment-related adverse event was ISRs,which occurred in a lower percentage of patients than previous VYVGART SC clinical trials(20%in Stage A;10%in Stage B).All ISRs were mild to moderat

270、e and resolved over time.99%(226/249)of eligible patients continued to the ADHERE-Plus OLE clinical trial.Based on these results,we received regulatory approval in the U.S.in June 2024,in China in November 2024 and in Japan in December 2024.Regulatory review is currently ongoing in other jurisdictio

271、ns including in the EU.Primary ITPOverviewPrimary ITP is an acquired autoimmune bleeding disorder,characterized by a low platelet count(100109/L)in the absence of other causes associated with thrombocytopenia.In most patients,IgG autoantibodies directed against platelet receptors can be detected.The

272、y accelerate platelet clearance and destruction,inhibit platelet production,and impair platelet function,resulting in increased risk of bleeding and impaired quality of life.Primary ITP is differentiated from secondary ITP,which is associated with other illnesses,such as infections or autoimmune dis

273、eases,or which occurs after transfusion or taking other drugs,such as cancer drugs.Platelet deficiency,or thrombocytopenia,can cause bleeding in tissues,bruising and slow blood clotting after injury.Patients may suffer from depression and fatigue as well as side effects of existing therapies,impairi

274、ng their quality of life.Current therapeutic approaches include non-specific immunosuppression(e.g.,steroids and rituximab),inhibition of platelet clearance(e.g.,splenectomy,IVIg,argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationarg

275、enx Annual Report 2024Our Products and Product Candidates38anti-D globulin,and spleen tyrosine kinase inhibitor fostamatinib13)or stimulation of platelet production(e.g.,thrombopoietin receptor agonist TPO-RA).Splenectomy remains the only treatment that provides sustained remission off therapy for o

276、ne year or longer for a high proportion of patients.ITP affects approximately 72,000 patients in the U.S.(sources:Current Medical Research and Opinion,25:12,2961-2969;Am J Hematol.2012 Sep;87(9):848852;Pediatr Blood Cancer.2012 Feb;58(2):216220).Phase 3 ADVANCE Clinical TrialsIn 2019,the first of tw

277、o registrational clinical trials,the ADVANCE clinical trial,was initiated to evaluate efgartigimod IV(VYVGART)for the treatment of primary ITP.The second registrational ADVANCE-SC clinical trial of efgartigimod SC for the treatment of primary ITP was initiated in 2020.In May 2022,we announced positi

278、ve Phase 3 data from the ADVANCE clinical trial.Primary endpoint was met,demonstrating that a significantly higher proportion of patients with chronic ITP receiving VYVGART(17/78;21.8%)compared to placebo(2/40;5%)achieved a sustained platelet response(p=0.0316),defined as having platelet counts grea

279、ter than or equal to 50 x109/L on at least four of the last six scheduled visits between weeks 19 and 24 of treatment.There was also a statistically significant separation from placebo in key platelet-derived secondary endpoints.Additional secondary endpoint data from the ADVANCE clinical trial are

280、consistent with primary and secondary platelet-derived endpoints and provide additional context on metrics that often drive treatment decisions,including on International Working Group responder status.VYVGART was well-tolerated in this 24-week clinical trial and the observed safety and tolerability

281、 profile was consistent with previous clinical trials.Results from ADVANCE-IV clinical trial were published in The Lancet in September 2023.In November 2023,results of the second registrational clinical trial as part of the ongoing ITP development program for VYVGART in adult patients with chronic a

282、nd persistent ITP were announced.Patients were heavily pre-treated and 75%of patients had received three or more prior ITP therapies.The clinical trial did not meet the primary endpoint of a sustained platelet count response in chronic ITP patients.Secondary endpoints were also not met,including add

283、itional endpoints on International Working Group responder status and mean platelet count change from baseline.VYVGART SC was well-tolerated in ADVANCE-SC;the observed safety and tolerability profile was consistent with ADVANCE-IV and the confirmed safety profile of VYVGART and VYVGART SC.Based on t

284、he results of the ADVANCE-IV clinical trial we received regulatory approval for VYVGART for the treatment of adults with ITP in Japan in March 2024.We have initiated ADVANCE-NEXT in the U.S.with efgartigimod IV in ITP in 2024.MyositisOverviewMyositis are a rare group of autoimmune diseases that can

285、be muscle specific or affect multiple organs including the skin,joints,lung,gastrointestinal tract and heart.Myositis can be very severe and disabling and have a material impact on quality of life.Initially these Myositis were classified as either DM or polymyositis,but as the underlying pathophysio

286、logy of Myositis has become better understood,including through the identification of characteristic autoantibodies,new polymyositis subgroups have emerged.Two of these subtypes are IMNM and ASyS.Proximal muscle weakness is a unifying feature of each Myositis subset.IMNM is characterized by skeletal

287、 muscle weakness due to muscle cell necrosis.The muscle weakness is typically symmetrical on both sides of the body and affects proximal muscles including hips,thighs,upper arms,shoulder and neck.The muscle weakness can be severe and lead to difficulty in completing daily tasks.Characteristic autoan

288、tibodies of IMNM,include anti-signal recognition particle and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies.ASyS is characterized by muscle inflammation,inflammatory arthritis,interstitial lung disease,thickening and cracking of the hands(mechanics hands)and Raynaud phenomenon.

289、Autoantibodies associated with ASyS attack tRNA synthetase enzymes and include anti-Jo-1 and anti-PL1 and PL-12 most commonly.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candid

290、ates39DM is characterized by muscle inflammation and degeneration and skin abnormalities,including heliotrope rash,Gottron papules,erythematous,calcinosis and edema.DM is associated with Myositis-specific autoantibodies,including anti-Mi-2,anti-MDA-5,anti-TIF-1 and others.There are no current FDA-ap

291、proved therapies for IMNM or ASyS.IVIg(Octagam 10%)was approved by the FDA for the treatment of DM in July 2021.Myositis patients are most often treated with high-dose steroids.ALKIVIA Clinical TrialWe initiated the registrational ALKIVIA clinical trial of efgartigimod SC for the treatment of Myosit

292、is in 2022.The clinical trial will enroll approximately 240 patients in three Myositis subtypes,IMNM,ASyS and DM.The clinical trial is being conducted in two Phases,with an analysis of the Phase 2 portion of the clinical trial,including 30 patients of each subtype,followed by conduct of the Phase 3

293、portion of the clinical trial only if a signal is observed in the Phase 2 portion of the clinical trial.The primary endpoint is the total improvement score(TIS)at the end of the treatment period.Key secondary endpoints include response rates at the end of treatment,time to response,and duration of r

294、esponse in TIS,as well as change from baseline in individual TIS components.Other secondary endpoints include quality of life and other functional scores.In November 2024,argenx announced our GO decision to continue clinical development of efgartigimod SC in the seamless phase2/3 ALKIVIA clinical tr

295、ial(ongoing)in all three Myositis subtypes following analysis of topline data from the Phase 2 portion of the clinical trial.The decision is supported by the efficacy and safety results from the Phase 2 portion of the seamless Phase 2/3 ALKIVIA clinical trial.Overall,the clinical trial met its prima

296、ry endpoint,demonstrating a statistically significant treatment effect in mean TIS at Week 24,and showed improvement across all six core set measures of the TIS in favor of efgartigimod SC compared to placebo.The observed safety and tolerability profile was consistent to that demonstrated with other

297、 clinical trials.TEDOverview TED is an autoimmune orbital disease associated with Graves disease and other autoimmune thyroid pathologies such as Hashimotos thyroiditis.TED is characterized by extraocular muscle enlargement,orbital adipose tissue expansion,and orbital inflammation,which can lead to

298、proptosis,diplopia,or vision loss in severe cases.Persistent orbital symptoms often impair patient QoL long-term.Substantial nonclinical and clinical evidence supports thyrotropin receptor autoantibodies as causative in the pathology of TED.Clinical evidence supports the removal of autoantibodies as

299、 a mechanism for the treatment of TED.By reducing IgGs,including TED-associated pathogenic IgG autoantibodies,efgartigimod is expected to ease disease manifestations.Additionally,IgG reduction could address the underlying hyperthyroidism.Side effects and tolerability issues with current therapies,in

300、cluding steroids and teprotumumab(only FDA-approved biologic),are treatment limiting for many patients based on comorbidities and a significant unmet need remains for safe and convenient therapies.UplighTED Clinical Trials The UplighTED program aims to evaluate the efficacy and safety of weekly efga

301、rtigimod for SC administration in pre-filled syringe,coformulated with rHuPH20(efgartigimod PH20 SC)in two randomized,placebo-controlled,double-blinded studies.Adult participants with moderate-to-severe active TED,with controlled baseline autoimmune thyroid pathology are dosed with 1000mg efgartigim

302、od PH20 SC or placebo PH20 SC for 24 weeks and evaluated for proptosis response.At the end of the treatment period,participants will enter a follow-up observational period to assess safety,tolerability,and durability of efgartigimod PH20 SC treatment while off therapy or an open-label treatment peri

303、od depending on their response to study treatment.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Products and Product Candidates40SjDOverviewSjD is a chronic,progressive autoimmune disease,characteriz

304、ed by lymphocytic infiltration and progressive destruction of exocrine glands.B-cells play a pivotal role in the development of the disease and this results amongst others in production of IgG autoantibodies,especially those which target SSA/Ro,SSB/La ribonuclear complexes.In addition to symptoms of

305、 dry eyes,dry mouth,chronic pain and fatigue,a substantial subset of patients suffer from extraglandular systemic disease.There are no FDA-approved treatments currently registered for the treatment of SjD.Phase 2 RHO Clinical Trial(in partnership with IQVIA)In March 2024,argenx announced its plan to

306、 continue the development of efgartigimod to Phase 3 in adults with primary SjD,following the analysis of topline data from the Phase 2 RHO clinical trial.The decision to advance the clinical development of efgartigimod in SjD was supported by the safety,efficacy and biomarker results from the clini

307、cal trial.The observed safety and tolerability profile was consistent with other clinical trials.Efficacy assessments showed a treatment effect across multiple clinical endpoints,which were also consistent with biomarker data.In the RHO clinical trial,efgartigimod demonstrated increased response on

308、composite endpoints(CRESS,STAR,ESSDAI(22-34%).A response was observed in four out of five items of CRESS.The IgG reduction and biomarker data correlated to clinical benefit and efgartigimod was well tolerated and safe similar to other clinical trials.Phase 3 UNITY Clinical Trial(in partnership with

309、IQVIA)In 2024,we initiated a Phase 3 clinical trial evaluating efgartigimod PH20 SC for the treatment of SjD.The Unity clinical trial is a randomized,placebo-controlled,double-blind clinical trial evaluating safety and efficacy of efgartigimod PH20 SC.The clinical trial plans to enroll 480 patients

310、with at least moderate systemic disease(ClinESSDAI 6).Patients have to be on stable background treatment and positive for anti-SSA/Ro.At the end of the 48-week treatment period,participants who complete the clinical trial may roll over into an OLE.The primary endpoint is change from baseline in the

311、clinESSDAI(Clinical ESSDAI).Key secondary endpoints will focus on patient-reported outcomes,ESSDAI(EULAR Sjgrens Syndrome Disease Activity Index),and STAR(Sjgrens Tool for Assessing Response,composite endpoint).LNOverviewLN is an inflammatory autoimmune disease of the kidney and one of the most seve

312、re and common organ manifestations of the autoimmune disease systemic lupus erythematosus(SLE).In patients with SLE,approximately 25%to 50%have signs or symptoms of kidney disease at SLE onset.Approximately 40%to 60%of patients with SLE will develop renal involvement during the course of disease,wit

313、h substantial morbidity or mortality.Pathogenic autoantibodies and complement deposits are critically involved in SLE pathogenesis and particularly LN,where renal deposition of immune complexes is a hallmark of the disease.Autoantibodies associated with LN include anti-dsDNA,anti-C1q,anti-cardiolipi

314、n,anti-Smith and anti-nuclear antibodies.10-30%of LN patients progress to end-stage renal disease.Oral corticosteroids and broad immunosuppressants are current standards of care but are not uniformly effective.Belimumab(Benlysta)and voclosporin(Lupkynis)are approved by the FDA for the treatment of L

315、N.Phase 2 POC Clinical Trial(in partnership with Zai Lab)In 2023,we initiated a POC clinical trial to evaluate the efficacy and safety of efgartigimod IV in Chinese patients with active LN.The clinical trial plans to enroll approximately 60 patients with LN class III or IV(with or without class V).T

316、he primary endpoint is the change in urine protein creatinine ratio from baseline to end of the treatment period.Key secondary endpoints include proportion of patients achieving complete and partial renal response at the end of treatment period and time to complete renal response and partial renal r

317、esponse.Other secondary endpoints include additional efficacy measurements,PK,PD,immunogenicity,biomarkers,safety,and quality of life assessments.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our Product

318、s and Product Candidates41Other efgartigimod Indications AMRAMR is an autoimmune disease that affects transplanted organs and can contribute to allograft loss.AMR in kidney allografts is driven by donor specific antibodies,which often target HLA antigens expressed by endothelial allograft cells.Thro

319、ugh different mechanism,donor specific antibodies can induce microvascular inflammation,a histopathological hallmark of AMR.Microvascular inflammation leads to loss in organ function which,if continued,can result in allograft loss.The unmet need for an efficacious treatment is very high,as evidenced

320、 by AMR being the leading cause of kidney transplant failure.There are currently no approved therapies for treating AMR.Phase 2 shAMRock Clinical Trial Design In the end of 2024,we initiated a Phase 2 POC study to evaluate efgartigimod PFS in kidney transplant recipients with AMR.The clinical trial

321、will enroll 30 participants,randomized 1x1x1 across 2 treatment arms and placebo.Primary endpoint is safety and tolerability and secondary endpoints include efficacy endpoints around estimated glomerular filtration rate,kidney biopsy,urine protein creatinine ratio and survival.Partnerships for efgar

322、tigimod indicationsZai Lab LimitedPursuant to the Zai Lab Agreement,Zai Lab obtained the exclusive right to develop and commercialize efgartigimod in Greater China.Zai Lab will also contribute patients to our global Phase 3 clinical trials of efgartigimod.Our Zai Lab strategic collaboration allows u

323、s to accelerate development of efgartigimod into new autoimmune indications with Zai Lab taking operational leadership of selected Phase 2 POC clinical trials.In 2022 Zai Lab initiated the Phase 2 POC clinical trials in MN and LN,which both fall within the emerging nephrology indications.Zai Lab als

324、o completed a Phase 1 PK/PD clinical trial to support the approval of efgartigimod for gMG in Mainland China and to obtain regulatory approvals to enroll Chinese patient into our global Phase 3 clinical trials.IQVIAOn December 2,2021 we entered into a strategic asset development agreement(Asset Deve

325、lopment Agreement)with IQVIA.Pursuant to the Asset Development Agreement,IQVIA shall perform asset and indication development services for efgartigimod through an advanced outsourcing model.Such services include,but are not limited to,overall product indication development strategy,design of clinica

326、l trial protocol,set-up,execution and management of clinical development plans for an indication for efgartigimod selected by us.To enable and encourage fast and innovative delivery of the services by IQVIA,the Asset Development Agreement contains an innovative earn-back and bonus plan based upon th

327、e performance of IQVIA.Clinical trials that have been discontinued:In May 2024,the decision was made to discontinue planned development of efgartigimod in AAV following the risk assessment of all ongoing clinical trials based on learnings from ADDRESS(PV)and ADVANCE SC(ITP)clinical trials.We determi

328、ned the risk did not outweigh the benefit in AAV given the potentially unmanageable interference of background medications.In June 2024,we announced results from the Phase 2 ALPHA clinical trial of efgartigimod in PC-POTS.Based on the results,we decided not to move forward development of efgartigimo

329、d in PC-POTS.In October 2024,we announced the discontinuation of development of efgartigimod in MN.This decision was based on the observation that no clear signal was seen in the blinded data,which was part of an interim review by the executive data review team and the data and safety monitoring boa

330、rd.Early January 2025,we announced our decision to discontinue development in BP based on results from 98 patients in the Phase 2 BALLAD clinical trial.argenx GroupRisk FactorsCorporate GovernanceShare CapitalFinancial ReviewFinancial StatementsNon-Financial Informationargenx Annual Report 2024Our P

331、roducts and Product Candidates421.3.4empasiprubart(ARGX-117)DevelopmentMechanism of Actionempasiprubart is a differentiated therapeutic mAb targeting C2 equipped with our proprietary NHANCE mutations.By addressing a novel target at the intersection of the complement and lectin pathways of the comple

332、ment cascade,we believe empasiprubart represents a broad pipeline opportunity across several severe autoimmune indications.Activation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction in a number of autoimmune inflammatory diseases and ischemia-r

333、eperfusion conditions.Targeting C2 also leaves the alternative pathway of the complement system intact,which is an important component of the innate defense system.empasiprubart exhibits both pH-and calcium dependent binding.These unique characteristics enable empasiprubart to capture free C2 in circulation and release it in the endosome to be sorted for degradation in the lysosome.empasiprubart i