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Welcome & Opening RemarksBeth DelGiacco /// Vice President, Corporate Communications & Investor Relations 2
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Forward Looking StatementsThis presentation has been prepared by argenx se (“argenx” or the “company”) for informational purposes only and not for any other purpose. Nothingcontained in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter or the company or any director, employee, agent, or adviser of the company. This presentation does not purport to be all-inclusive or to contain all of the information you may desire. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the company’s own internal estimates and research. While argenx believes these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of argenx’s internal estimates or research, and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research.Certain statements contained in this presentation, other than present and historical facts and conditions independently verifiable at the date hereof, may constitute forward-looking statements. These forward-looking statements can be identified by the use of forward-looking terminology, including the terms “advance,” “bring,” “can,” “engage,” “expand,” “may,” “plan,” and “potential,” and include statements argenx makes regarding its Vision 2030, including its commitment to reach 50,000 patients across 10 labeled indications and to advance five molecules in Phase 3 indications; its goal to advance treatments for neuromuscular conditions, including with ARGX-119 for CMS, ALS and SMA, empasiprubart for MMN and CIDP, efgartigimod for myositis, MG and CIDP and with its IIP; the development of ARGX-119 and the timing and outcome of decisions on potential regulatory approvals and of clinical trials, including (i) its plan to advance ARGX-119 in CMS to registrational study with the Phase 3 to start in 2026, (ii) the start of clinical development in SMA with the Phase 2 set to start in 2025 and (iii) the Phase 2a reALiSe in ALS expected in the first half of 2026; the application of its innovation approach to clinical development through (i) evidence generation to build broadest data to guide treatment decisions for patients, (ii) patient empowerment through patient engagement in trial design and execution, and (iii) speed to bring medicines to patients as quickly as possible; its plan to expand the clinical study for ARGX-119’s development in CMS to include more patients, including pediatrics and other genotypes; its plan to engage with regulators on Phase 3; and ARGX-119’s potential pipeline for NMJ diseases, motor neuron diseases, muscle diseases and peripheral neuropathies. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. argenx’s actual results may differ materially from those predicted by the forward-looking statements as a result of various important factors, including the results of argenx's clinical trials; expectations regarding the inherent uncertainties associated with the development of novel drug therapies; preclinical and clinical trial and product development activities and regulatory approval requirements in products and product candidates; the acceptance of argenx's products and product candidates by patients as safe, effective and cost-effective; the impact of governmental laws and regulations on our business, including tariffs, export controls, sanctions and other regulations on its business; its reliance of third-party suppliers, service providers and manufacturers; inflation and deflation and the corresponding fluctuations in interest rates; and regional instability and conflicts. A further list and description of these risks, uncertainties and other risks can be found in argenx’s U.S. Securities and Exchange Commission (the “SEC”) filings and reports, including in argenx’s most recent annual report on Form 20-F filed with the SEC as well as subsequent filings and reports filed by argenx with the SEC. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. argenx undertakes no obligation to publicly update or revise the information in this presentation, including any forward-looking statements, except as may be required by law.This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners.3 3
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argenx Leadership Here TodayTim Van HauwermeirenChief Executive OfficerLuc Truyen M.D., Ph.D.Chief Medical OfficerBeth DelGiacco Vice President, Corporate Communications & Investor RelationsPeter Ulrichts, Ph.D.Chief Scientific Officer Rebecca Shilling, M.D. ARGX-119 Clinical Development LeadJeff Guptill, M.D. Neuromuscular Franchise Lead, Clinical Development Roeland Vanhauwaert, Ph.D.ARGX-119 Scientific Lead 4
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Key Opinion Leaders Here TodaySteve Burden, Ph.D.Senior Lecturer, Neurology Massachusetts General HospitalRicardo Maselli, M.D.Professor, Neurology University of California, Davis 5
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Agenda Welcome and Opening RemarksBeth DelGiaccoMuSK Biology and Designing ARGX-119Roeland VanhauwaertPanel with Dr. Steve Burden, Moderated by Peter UlrichtsProof of Biology for ARGX-119 in CMSLuc Truyen, Rebecca ShillingPanel with Dr. Ricardo Maselli, Moderated by Jeff Guptill ARGX-119: Pipeline in a Product PotentialRoeland VanhauwaertClosing Remarks Tim Van HauwermeirenQ&A Sessionargenx Management Team 6
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Vision 2030 COMMITMENT TO OUR INNOVATION MISSION 5New Moleculesin Phase 310Labeled Indications50kPatients on Treatment 7
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Key Take Aways For TodayPioneering innovationMuSK plays dual role at NMJ Structurally at skeletal muscle and signaling to motor neuronCMS is severe with no precision treatment options Data-rich, bold approach to CMS developmentMaximizing opportunity of ARGX-119 CMS playbook into ALS, SMA - and more broadly 01 02 03 04 05 8
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Our Innovation Playbook Best-in-Field Antibody EngineeringPipeline-in-a-Product Development First-in-Class AntibodiesDifferentiated Patient Outcomes Novel Disease Biology Insights Foundational Immune Targets Our Innovation Playbook 9
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SIMPLE Antibody™ Collaborators DISEASE BIOLOGY INSIGHTSWORLD CLASS ANTIBODY ENGINEERING CAPABILITY Bringing Together the Experts on MuSK Biology Jan VerschuurenMaartje Huijbers Steven Burden 10
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Understanding MuSK at the Neuromuscular Junction & ARGX-119 Roeland Vanhauwaert // ARGX-119 Scientific Lead 11
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The Neuromuscular JunctionA Gateway to a New Class of Neuromuscular Diseases v EfgartigimodFcRn blocker EmpasiprubartC2 inhibitor ARGX-119MuSK Agonist IIP ProgramsUndisclosed Advancing treatments for neuromuscular conditions MMN, CIDP Myositis, MG, CIDP CMS, ALS, SMANeuromuscular JunctionCell bodyNerve Muscle tissue 12
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Uncovering Multiple Mechanisms to Target Diseases of the NMJ RAPSYNBinds directly to AChRs in the postsynaptic membrane AGRINSynthesized by motor neurons; stimulates formation and maintenance of synapses MUSKReceptor tyrosine kinase transduces agrin signal LRP4Muscle receptor for agrin that forms a complex with MuSK; essential for activating MuSK DOK-7Facilitates dimerization of MuSK; stabilizes MuSK kinase ARGX-119 Muscle Nerve Terminal Ach Receptor1980s1990s2000s20191970s 13
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MuSK Activation for NMJ Formation, Maturation and Maintenance v ΩDiffuse AChRsClustered AChRs Maturation Muscle Clustered AChRs Motor neuron Funtional NMJ 14
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ARGX-119Mechanism of Action15
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MuSK Plays a Critical Role in Neuromuscular Junction SignalingAGRIN is secreted from neurons and binds LRP4, which in turn activates MuSKRecruitment of DOK7 furthers MuSK phosphorylation, resulting in binding of RAPSYN to AChRs 1 2RAPSYN causes AChRs to anchor and cluster on the postsynaptic membrane 3 1 2 3 16
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ARGX-119 Engineered by Innovation, Empowered by Collaboration Adjust binding domainSIMPLEAntibodyTM platformMuSKFz domain MuSKFz domain MuSK-MG patient derived Synthetic MuSK AntibodyARGX-119 MuSKFz domain Unexpected male mice lethalityBinding at Ig-like 1 domainXPatient-derived sequences X Binding at Fz domainBehaves like agrin Llama-derived antibodyBinding at Fz domainCMC concernsXOff-target bindingX Synthetic-derived antibody Agrin MuSK LRP4 Muscle 17
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ARGX-119 Boosts Functioning of NMJs by Improving AChR Clustering Activation of MuSK by ARGX-119 MuSK LRP4 AChR RapsynDOK7 Agrin Motor nerve terminal Acetylcholine SIMPLE Antibody™100 % human identity agonistic binding to MuSKhIgG1-LALA to diminish effector functions ARGX-119 18
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Critical Milestones in the Development of ARGX-119 in CMS First dosing in humans – Phase 1 study Phase 1b data in CMS CMS registrational study on track to begin 2023202420252026 Natural History Study initiatedStart Phase 1b in DOK7 CMS 19
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Strong Biologic Rationale of CMS Presynaptic CMS Synaptic CMSPostsynaptic CMS Ubiquitous (glycosylation) DOK7 RAPSYN AGRIN ACh Genetic testing exists to diagnose CMSCMS Subtypes GFPT1LRP4 MUSK DOK7 RAPSN AGRNCOLQCHAT AChR gene family 20
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ARGX-119 Improves Motor Function of DOK7 CMS Mice mAb control animals sacrificedARGX-119 Dose 1 ARGX-119 Dose 2 Early Neonatal Lethality and Disease Relapse are Rescued by ARGX-119 ARGX-119 Rescues Motor Deficits within the Month Mice running ona rotating wheel ARGX-119 Dose 2 21
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Panel DiscussionDr. Steve Burden, Roeland Vanhauwaert, moderated by Peter Ulrichts 22
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Peter Ulrichts, Ph.D.Chief Scientific OfficerSteve Burden, Ph.D.Senior Lecturer, Harvard University, Neurology, MGHRoeland Vanhauwaert , Ph.D.ARGX-119 Scientific Lead PanelistsModerator 23
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Clinical Development of ARGX-119 in CMSLuc Truyen /// Chief Medical Officer 24
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Congenital Myasthenic Syndromes (CMS) Refs: Guimarães-Costa R et al. Presse Med. 2013. Beadon K et al. Curr Opin Neurol. 2018; Bozovic et al. J Neurol Sci.2019. Allen J et al, 2024 MayoClin ProcInnovQual Outcomes Rare, inherited, mutations affecting components of the NMJ Fatigable Muscle WeaknessMay require feeding tubes, use of a wheelchair, or ventilatory support Can present at any age – birth to adulthood No FDA Approved Treatments Taal, Living with CMS25
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Applying Our Innovation Approach to Clinical Development Evidence GenerationEmpowering PatientsSpeed InnovationCo-CreationExecution Bring medicines to patients as quickly as possiblePatient engagement in trial design and executionBuild broadest data to guide treatment decisions for patients 27
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Applying Innovation to CMS Clinical Trial Empowering Patients Evidence Generation Trial Efficiency CMS Trial Features Natural History Study, Patient-Focused Development Digital Sensors, Broad Set of Measures Intra-Patient Dose Escalation 28
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Natural History Study: Foundation for Clinical Development in CMSStudy Overview Understanding patient journey and disease burden Patients chronically disabled58% requiring assistive devices, eg canes, wheelchair, nocturnal noninvasive ventilation Plan to expand to include more patients, including pediatrics and other genotypes ~40 adult patients with DOK7-CMS Outcomes Patient-centered outcome measure development 29
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Phase1b Clinical Trial in CMS Study population: ~16 participants with DOK7-CMS Up to 4 wk 12 wk 30 wkSCREENINGTREATMENT PERIODFOLLOW-UP PERIOD R 4:1ARGX-119 IVPlacebo IV ARGX-119 or placebo dosingWEEK-2 426810121416202428 42 STUDY VISITS -4 182226 Primary EndpointSecondary EndpointsPK and immunogenicity•PK parameters •Incidence/ prevalence of ADA against ARGX-119 •Muscle weakness and fatigability•Mobility, QoL and dyspnea•Home physical activity•Patient/physician assessments of disease activity•Exit interviews (qualitative) Safety and tolerability of ARGX-119• AEs•Clinical laboratory tests•ECGs and vital signs Exploratory EndpointsEfficacy measures •QMG score key components, MG-ADL score, and PROMIS Global Health score 3034383236400 30
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CMS Phase 1b Study ResultsRebecca Shilling /// ARGX-119 Clinical Development Lead 31 31
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First dedicated DOK7 CMS study, observing 16 patients Favorable safety and tolerability profile Proof of biology established Proof of Biology of ARGX-119 in CMS Clinically meaningful increase in 6MWT distance; improvements in cadence/leg function in line with MoA at neuromuscular junction Confidence to advance ARGX-119 in CMS to registrational study 32
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Patient Demographics and Baseline Characteristics 6MWT, Six-Minute Walk Test; BMI, body mass index; CMS, congenital myasthenic syndromes; IV, intravenous; MG-ADL PRO, Myasthenia Gravis –Activities of Daily Living Patient-Reported Outcome; PROMIS-GPH, Patient-Reported Outcomes Measurement Information System –Global Physical Health; QMG, Quantitative Myasthenia Gravis; s, seconds.*n=12 participants. †6MWT measured the distance (meters) a participant walked in 6 minutes. ARGX-119 IV(N=13)Placebo IV(N=3)Age, years, mean (SD)45.2 (14.0)49.7 (10.4)Sex at birth, n (%)Female 6 (46.2)1 (33.3)Male 7 (53.8)2 (66.7)BMI, kg/m2, mean (SD)22.1 (6.8)*34.8 (3.9)CMS-related therapy, n (%)12 (92.3)3 (100)Beta-agonists (salbutamol, albuterol, ephedrine) 11 (91.7)3 (100)Medical assistive devices currently being used, n (%)Wheelchair6 (46.2)1 (33.3)Nocturnal noninvasive ventilation6 (46.2)3 (100) Baseline CharacteristicsARGX-119 IV(N=13)Placebo IV(N=3)MG-ADL PRO total score, mean (SD)7.6 (3.3)9.3 (2.5) QMG total score, mean (SD)17.5 (4.2)15.3 (1.5)Composite arm outstretched (90° sitting), s, mean (SD)28.6 (14.5)27.0 (9.5) Head lifted (45° supine), s, mean (SD)35.7 (34.7)22.0 (18.3)Composite leg outstretched (45° supine), s, mean (SD)28.0 (13.9)15.3 (15.6) Distance of 6MWT†, m, mean (SD)246.6 (222.2)282.7 (245.0) PROMIS-GPH T-score, mean (SD)38.1 (5.9)31.5 (1.6) 33
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QMG Components Most Affected at Baseline FVC, forced vital capacity; QMG, Quantitative Myasthenia Gravis. Right arm outstretched Percent 90100 10 70 20 0 80 5060 3040 Left arm outstretchedHead liftedRight leg outstretchedLeft leg outstretchedFVCPtosisRight-hand grip, kgDouble visionFacial musclesLeft-hand grip, kgSpeechSwallowing ScoreNoneMildModerateSevere 15(93.8)15 (93.8) 5 (31.3) 7 (43.8) 1 (6.3) 1 (6.3)1 (6.3)3 (18.8)1 (6.3) 12 (75.0) 3(18.8)5 (31.3) 11 (68.8) 4 (25.0) 10 (62.5) 1 (6.3)1 (6.3)1 (6.3) 1 (6.3) 14 (87.5) 1 (6.3)1 (6.3) 14(87.5) 2 (12.5)2 (12.5) 12(75.0) 6 (37.5) 2 (12.5)2 (12.5) 6 (37.5)6 (37.5) 10 (62.5)6 (37.5) 2 (12.5) 4 (25.0) 3 (18.8) 9 (56.3) 8 (50.0) nSum of item score16331633162616301627163916241616161016151610168163 34
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ARGX-119 Demonstrated Improvements in QMG Key Components Actual (raw) values for median change are reported. Composite Leg Outstretched (45° Supine; Raw Value, s) Both Legs Outstretched Time (Weeks) 80 100 60 40 20 0 024681012 ARGX-119 IVPlacebo IV Both Arms Outstretched Time (Weeks) Composite Arm Outstretched (90° Sitting; Raw Value, s) 240 024681012 133133133133133113133 80 100 60 40 20 0 133133133133133133133No of participants 35
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Clinically Meaningful Increase Observed in Median 6MWT Distance in Ambulatory Patients 1.McIlroy S, et al. Eur Spine J. 2025. Epub ahead of print. doi: 10.1007/s00586-025-09085-4. 6MWT, Six-Minute Walk Test *A change of 15–50 m has been reported to be clinically meaningful in analogous neuromuscular populations.1 †Ambulatory patients were defined as patients who did not report wheelchair use at baseline. ‡6MWT measured the distance (meters) a patient walked in 6 minutes. 2 Baudendistel ST, Haussler AM, Rawson KS, Earhart GM. Minimal clinically important differences of spatiotemporal gait variables in Parkinson disease. Gait Posture. 2024 Feb;108:257-263. doi: 10.1016/j.gaitpost.2023.11.016. Epub 2023 Nov 25. PMID: 38150946; PMCID: PMC10878409. Coca-Tapia M, Cuesta-Gómez A, Molina-Rueda F, Carratalá-Tejada M. Gait Pattern in People with Multiple Sclerosis: A Systematic Review. Diagnostics (Basel). 2021 Mar 24;11(4):584. doi: 10.3390/diagnostics11040584. PMID: 33805095; PMCID: PMC8064080. Time (Weeks) 6MWT‡ Total Distance (m)Median Change From Baseline Total Distance Walked* 024681012 0 25 50 75 Clinically Meaningful1 72 62 72 72ARGX-119 IVPlacebo IVNo of ambulatory patients† Time (Weeks) 6MWT‡ Cadence (Steps/Min) Median Change From Baseline Cadence 024681012 –5 0 5 10 72 62 72 71 Clinically Meaningful2 *Study was not designed or powered to demonstrate clinical efficacy 36
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Correlation Between Endpoints Measuring Leg Function in Ambulatory PatientsComposite Leg Outstretched (Change From Baseline) 6MWT Total Distance*(Change From Baseline) 100 20406080 75 50 25 0 Corr: 0.8 Corr: -1 37
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Increased Activity Parameters at Home in ARGX-119 Treated Patients Long term activity parameters Short term activity parameters A Treated patients showed increase in measurable activity at home; placebo did not Reported Wheelchair UseAmbulatory Increased Decreased Patients AAPAAAAAAAAAPP A = ActiveP = Placebo 38
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AE, adverse event; IV, intravenous; m, number of events; SAE, serious AE. No grade ≥3 AEs reportedNo discontinuation due to AEs AEs ARGX-119 IV(N=13)Placebo IV(N=3)n (%) n (%)Most common AEs (occurring in >10% of participants treated with ARGX-119 IV)Nasopharyngitis 5 (38.5) 0Arthralgia 3 (23.1)0Muscle spasms 3 (23.1)0Toothache 2 (15.4)0Fatigue 2 (15.4)0Headache 2 (15.4)1 (33.3) No SAEs ARGX-119 IV was well tolerated ARGX-119: Favorable Safety & Tolerability Profile 39
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“…I was able to go for a short walk arm in arm with my husband, my daughter, which are things that are very dear to me.” Qualitative Analysis of Patient Exit Interviews *Within 14 days after the treatment period; if participants discontinued treatment early, then interviews were conducted after the early discontinuation visit. 30-minute semi-structured exit interview*Positive reception of study Increase in mobility Overall satisfaction with clinical measuresImprovementsin symptoms Summary of Participant Responses “I couldn’t walk from the bathroom to the sofa. I had to stop. Now, I can tell I have more energy in the legs, and I don’t stop.” 40
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Plan Forward in CMS Engage with regulators on Phase 3 •Target population DOK7-CMS age 12 and up and additional subtypes (MuSK, LRP4, AGRN)•Proposed primary endpoint – 6MWT •Digital health technology-derived endpoints Amended natural history study •Include expansion of genotypes and ages 2+ Phase 3 to start in 2026Proof of Biology Established CMS 41
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CMS Panel DiscussionDr. Ricardo Maselli, Rebecca Shilling, Luc Truyen, moderated by Jeff Guptill 42
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Panelists Ricardo Maselli, M.D.Professor, Neurology University of California, DavisRebecca Shilling, M.D.ARGX-119 Clinical Development Lead Luc Truyen, M.D., Ph.DChief Medical Officer Jeff GuptillNeuromuscular Franchise Lead, Clinical Development Moderator 43
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ARGX-119 OpportunityRoeland Vanhauwaert // ARGX-119 Scientific Lead 44
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ALS: Activation of MuSK Signaling Slows Muscle Denervation and Improves Motor Function Fidelity (%) ALSALS + ARGX-119Healthy ARGX-119 preserves NMJ numbers and restores muscle contraction in ALS patient derived NMJs on-a-chip Disease Characterization In Partnership with Disease Characterization Progressive and fatal neurodegenerative disorder caused by motor neuron deathDeteriorating muscle function, weakness, and atrophy Loss of motor neurons from the muscle Variable disease burden Unmet need remains for more efficacious treatments on top of SoC Phase 2a TLR expected 1H 2026 45
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reALiSe Phase 2a Clinical Trial Design in ALS SCREENING ACTIVE TREATMENT EXTENSION PERIODTREATMENT PERIOD24 wk(≤4 weeks) 48 wk 24 weeks of no treatment Low dose N=15 Placebo N=15 Mid dose N=15High dose N=15High dose WEEK0124 242628Q4W 72Q4W104 Additional electrophysiological markers of disease progression, clinical outcomes (ALSFRS-R, SVC), biomarkers (NfL), quality of life (ALSAQ-5), home physical activity, and survival ARGX-119 or placebo dosing SAFETY FOLLOW-UP Key Secondary EndpointsRate of change from baseline to week 24 in MScan-derived MU number PK parameters and incidence/prevalence of ADA against ARGX-119 in serum over time Exploratory EndpointsPrimary EndpointSafety and tolerability of ARGX-119• AEs•Clinical laboratory tests•ECGs and vital signs R 1:1:1:1 N=60 46
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MScan: A Precision Tool for Quantifying Motor Unit Loss in ALS Sleutjes et al. Advancing disease monitoring of amyotrophic lateral sclerosis with the compound muscle action potential scan. Clin Neurophys 2021 Quantifies changes in motor unit number (MUNE) Correlates strongly with functional outcomes (eg ALSFRS-R) Easy to apply Stimulation electrode (reference)Stimulation electrode (active)Recording electrode (active)Recording electrode (reference) MScan set-upMScan visual changes during disease progression. MUNE progression rate Correlation MUNE and ALSFRS-R 47
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SMA: Activation of MuSK by ARGX-119 Can Mature NMJs, Improve NMJ Transmission and Motor Function On Top of DMTs Next Milestone: Initiate Phase 2 Study Increase in muscle force without corresponding increases in weight, suggests muscle function may be more important than size Disease Characterization In Partnership with Characterized by neuromuscular weakness and motor function impairment Unmet need remains despite significant progress inSMA carePatients want improved muscle function Reduced NMJ maturity and transmission defects remain even after DMTs 48
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ARGX-119 Pipeline-in-a-Product Potential Motor Neuron Diseases ALS – SMA Muscle Diseases Muscular Dystrophies and Myopathies NMJ Diseases CMS – MG Peripheral Neuropathies Acetylcholine Clustering AChR Rapsyn ARGX-119Agrin MuSK DOK7 LRP4 49
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Path Forward for ARGX-119 Phase 3 to start in 2026 Phase 2a reALiSedata 1H26 Innovative EndpointUsing MScanProof of Biology Established CMSALS Phase 2 Sparkle study to initiate SMA First Time Pediatric Dosing 50
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Closing Remarks Tim Van Hauwermeiren, CEO 51 51