Argenx Se · EURONEXT:ARGX
Argenx — Investor Day (September 2025)
50 slides from Argenx's investor day presentation, September 2025
Slide 1: R&D Spotlight: Pioneering Biology with argenx
A R&D Spotlight “ ~~ = = Pioneering ‘a Bioloay | with ARGIG 1 tS ~ bar a Ss
Slide 2: Welcome & Opening Remarks
Welcome & Opening Remarks Beth DelGiacco /// Vice President, Corporate Communications & Investor Relations 2
Slide 3: Forward Looking Statements
Forward Looking Statements This presentation has been prepared by argenx se (“argenx” or the “company”) for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter or
Slide 4: argenx Leadership Here Today
argenx Tim Van Hauwermeiren Chief Executive Officer Luc Truyen M.D., Ph.D. Chief Medical Officer Beth DelGiacco Vice President, Corporate Peter Ulrichts, Ph.D. Chief Scientific Officer Leadership Communications & Investor Relations Here Today Rebecca Shilling, M.D. Roeland Vanhauwaert, Jeff Guptill,
Slide 5: Key Opinion Leaders Here Today
Key Opinion Leaders Here Today Steve Burden, Ph.D. Ricardo Maselli, M.D. Senior Lecturer, Neurology Professor, Neurology Massachusetts General Hospital University of California, Davis 5
Slide 6: Agenda
Agenda Welcome and Opening Remarks Beth DelGiacco Roeland Vanhauwaert MuSK Biology and Designing ARGX-119 Panel with Dr. Steve Burden, Moderated by Peter Ulrichts Luc Truyen, Rebecca Shilling Proof of Biology for ARGX-119 in CMS Panel with Dr. Ricardo Maselli, Moderated by Jeff Guptill ARGX-119: Pip
Slide 7: Vision 2030
Vision 2030 COMMITMENT TO OUR INNOVATION MISSION 5 New Molecules in Phase 3 10 Labeled Indications 50k Patients on Treatment 7
Slide 8: Key Take Aways For Today
Key Take Aways For Today 01 Pioneering innovation MuSK plays dual role at NMJ 02 Structurally at skeletal muscle and signaling to motor neuron 03 CMS is severe with no precision treatment options 04 Data-rich, bold approach to CMS development Maximizing opportunity of ARGX-119 05 CMS playbook into A
Slide 9: Our Innovation Playbook
Our OurInnovation InnovationPlaybook Playbook Best-in-Field Pipeline-in- Novel Disease Antibody a-Product Biology Insights Engineering Development Foundational First-in-Class Differentiated Immune Antibodies Patient Targets Outcomes 9
Slide 10: Bringing Together the Experts on MuSK Biology
Bringing Together the Experts on MuSK Biology WORLD CLASS ANTIBODY DISEASE BIOLOGY INSIGHTS ENGINEERING CAPABILITY Steven Burden Collaborators SIMPLE Maartje Jan Antibody™ Huijbers Verschuuren 10
Slide 11: Understanding MuSK at the Neuromuscular Junction & ARGX-119
Understanding MuSK at the Neuromuscular Junction & ARGX-119 Roeland Vanhauwaert // ARGX-119 Scientific Lead 11
Slide 12: The Neuromuscular Junction
The Neuromuscular Junction A Gateway to a New Class of Neuromuscular Diseases Advancing treatments for neuromuscular conditions Cell body ARGX-119 CMS, ALS, SMA MuSK Agonist Neuromuscular Nerve Junction v Empasiprubart MMN, CIDP C2 inhibitor Efgartigimod Myositis, MG, CIDP FcRn blocker Muscle tissue
Slide 13: Uncovering Multiple Mechanisms to Target Diseases of the NMJ
Uncovering Multiple Mechanisms to Target Diseases of the NMJ RAPSYN AGRIN MUSK LRP4 DOK-7 ARGX-119 Binds directly to AChRs Synthesized by motor Receptor tyrosine Muscle receptor for Facilitates in the postsynaptic neurons; stimulates kinase transduces agrin that forms a dimerization of MuSK; membran
Slide 14: MuSK Activation for NMJ Formation, Maturation and Maintenance
MuSK Activation for NMJ Formation, Maturation and Maintenance Muscle Motor neuron Maturation v Funtional Ω Diffuse NMJ Clustered AChRs Clustered AChRs AChRs 14
Slide 15: ARGX-119 Mechanism of Action
ARGX-119 Mechanism of Action 15
Slide 16: MuSK Plays a Critical Role in Neuromuscular Junction Signaling
1 MuSK Plays a Critical Role in Neuromuscular 3 Junction 2 Signaling 1 2 3 AGRIN is secreted from Recruitment of DOK7 furthers RAPSYN causes AChRs to neurons and binds LRP4, MuSK phosphorylation, resulting anchor and cluster on the which in turn activates MuSK in binding of RAPSYN to AChRs postsynap
Slide 17: ARGX-119 Engineered by Innovation, Empowered by Collaboration
ARGX-119 Engineered by Innovation, Empowered by Collaboration MuSK-MG patient derived Synthetic MuSK Antibody ARGX-119 Agrin Adjust binding SIMPLE LRP4 domain AntibodyTM platform MuSK MuSK MuSK MuSK Fz domain Fz domain Fz domain Muscle Patient-derived sequences Synthetic-derived antibody Llama-deriv
Slide 18: ARGX-119 Boosts Functioning of NMJs by Improving AChR Clustering
ARGX-119 Boosts Functioning of NMJs by Improving AChR Clustering Motor nerve terminal SIMPLE Antibody™ 100 % human Activation of MuSK identity agonistic binding to MuSK by ARGX-119 hIgG1-LALA to diminish effector functions Acetylcholine Agrin LRP4 MuSK AChR Rapsyn DOK7 ARGX-119 18
Slide 19: Critical Milestones in the Development of ARGX-119 in CMS
Critical Milestones in the Development of ARGX-119 in CMS Natural History Study initiated CMS First dosing Phase 1b data registrational in humans – in CMS study on track Phase 1 study Start Phase 1b to begin in DOK7 CMS 2023 2024 2025 2026 19
Slide 20: Strong Biologic Rationale of CMS
Strong Biologic Rationale of CMS Presynaptic Genetic testing exists to diagnose CMS CMS CMS Subtypes AGRIN ACh COLQ AGRN CHAT Synaptic CMS AChR gene MUSK RAPSN family Postsynaptic CMS RAPSYN DOK7 DOK7 LRP4 GFPT1 Ubiquitous (glycosylation) 20
Slide 21: ARGX-119 Improves Motor Function of DOK7 CMS Mice
ARGX-119 Improves Motor Function of DOK7 CMS Mice Early Neonatal Lethality and Disease ARGX-119 Rescues Motor Deficits Relapse are Rescued by ARGX-119 within the Month Mice running on a rotating wheel ARGX-119 mAb Dose 2 ARGX-119 ARGX-119 Dose 1 control animals sacrificed Dose 2 21
Slide 22: Panel Discussion
Panel Discussion Dr. Steve Burden, Roeland Vanhauwaert, moderated by Peter Ulrichts 22
Slide 23: Moderator Panelists
Moderator Panelists Peter Ulrichts, Ph.D. Steve Burden, Ph.D. Roeland Vanhauwaert , Ph.D. Chief Scientific Officer Senior Lecturer, Harvard ARGX-119 Scientific Lead University, Neurology, MGH 23
Slide 24: Clinical Development of ARGX-119 in CMS
Clinical Development of ARGX-119 in CMS Luc Truyen /// Chief Medical Officer 24
Slide 25: Congenital Myasthenic Syndromes (CMS)
Congenital Myasthenic Syndromes (CMS) Rare, inherited, mutations affecting components of the NMJ Can present at any age – birth to adulthood Fatigable Muscle Weakness May require feeding tubes, use of a wheelchair, or ventilatory support No FDA Approved Treatments Taal, Living with CMS Refs: Guimarã
Slide 26: Applying Our Innovation Approach to Clinical Development
Applying Our Innovation Approach to Clinical Development Innovation Co-Creation Execution Evidence Empowering Speed Generation Patients Build broadest data Patient engagement Bring medicines to to guide treatment in trial design and patients as quickly decisions for patients execution as possible 27
Slide 27: Applying Innovation to CMS Clinical Trial
Applying Innovation to CMS Clinical Trial CMS Trial Features Digital Sensors, Evidence Broad Set of Generation Measures Natural History Study, Empowering Patient-Focused Patients Development Trial Intra-Patient Efficiency Dose Escalation 28
Slide 28: Natural History Study: Foundation for Clinical Development in CMS
Natural History Study: Foundation for Clinical Development in CMS Study Overview Outcomes ~40 adult patients Patients chronically disabled with DOK7-CMS 58% requiring assistive devices, eg canes, wheelchair, nocturnal noninvasive ventilation Understanding Patient-centered patient journey and outcome
Slide 29: Phase 1b Clinical Trial in CMS
Phase 1b Clinical Trial in CMS Study population: ~16 participants with DOK7-CMS SCREENING TREATMENT PERIOD FOLLOW-UP PERIOD Up to 4 wk 12 wk 30 wk ARGX-119 IV R 4:1 Placebo IV STUDY VISITS WEEK -4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 ARGX-119 or placebo dosing Primary Endp
Slide 30: CMS Phase 1b Study Results
CMS Phase 1b Study Results Rebecca Shilling /// ARGX-119 Clinical Development Lead 31 31
Slide 31: Proof of Biology of ARGX-119 in CMS
Proof of Biology of ARGX-119 in CMS First dedicated DOK7 CMS Clinically meaningful study, observing 16 patients increase in 6MWT distance; improvements in cadence/leg Favorable safety and function in line with MoA at tolerability profile neuromuscular junction Proof of biology established Confidence
Slide 32: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics ARGX-119 IV Placebo IV ARGX-119 IV Placebo IV (N=13) (N=3) Baseline Characteristics (N=13) (N=3) Age, years, mean (SD) 45.2 (14.0) 49.7 (10.4) MG-ADL PRO total score, mean (SD) 7.6 (3.3) 9.3 (2.5) Sex at birth, n (%) QMG total score, mean (SD) 17.5 (
Slide 33: QMG Components Most Affected at Baseline
QMG Components Most Affected at Baseline n 16 16 16 16 16 16 16 16 16 16 16 16 16 Sum of item score 33 33 26 30 27 39 24 16 10 15 10 8 3 100 1 (6.3) 1 (6.3) 1 (6.3) 1 (6.3) 2 1 (6.3) 2 (12.5) 3 (18.8) 3 (18.8) (12.5) 1 (6.3) 90 6 2 80 (37.5) (12.5) 70 10 6 10 5 11 (62.5) (37.5) (62.5) (31.3) (68.8)
Slide 34: ARGX-119 Demonstrated Improvements in QMG Key Components
ARGX-119 Demonstrated Improvements in QMG Key Components Both Legs Outstretched Both Arms Outstretched Composite Leg Outstretched (45° Supine; Raw Value, s) Composite Arm Outstretched (90° Sitting; Raw Value, s) 240 100 100 80 80 60 60 40 40 20 20 0 0 0 2 4 6 8 10 12 0 2 4 6 8 10 12 Time (Weeks) Tim
Slide 35: Clinically Meaningful Increase Observed in Median 6MWT Distance
Clinically Meaningful Increase Observed in Median 6MWT Distance in Ambulatory Patients Total Distance Walked* Cadence 75 10 Median Change From Baseline Median Change From Baseline 6MWT‡ Cadence (Steps/Min) 6MWT‡ Total Distance (m) 50 5 Clinically Meaningful2 Clinically Meaningful1 25 0 0 –5 0 2 4 6
Slide 36: Correlation Between Endpoints Measuring Leg Function in Ambulatory Patients
100 Correlation Between 75 Corr: 0.8 Endpoints (Change From Baseline) 6MWT Total Distance* Measuring Leg 50 Function in Ambulatory 25 Corr: -1 Patients 0 20 40 60 80 Composite Leg Outstretched (Change From Baseline) 37
Slide 37: Increased Activity Parameters at Home in ARGX-119 Treated Patients
Increased Activity Parameters at Home in ARGX-119 Treated Patients Long term activity parameters Short term activity parameters Increased Treated patients showed increase in measurable activity at home; placebo did not Decreased A A A P A A A A A A A A P A P Patients Reported Wheelchair Use Ambulato
Slide 38: ARGX-119: Favorable Safety & Tolerability Profile
ARGX-119: Favorable Safety & Tolerability Profile ARGX-119 IV was No grade ≥3 No discontinuation No SAEs well tolerated AEs reported due to AEs ARGX-119 IV Placebo IV (N=13) (N=3) AEs n (%) n (%) Most common AEs (occurring in >10% of participants treated with ARGX-119 IV) Nasopharyngitis 5 (38.5) 0
Slide 39: Qualitative Analysis of Patient Exit Interviews
Qualitative Analysis of Patient Exit Interviews Summary of Participant Responses 30-minute semi-structured exit interview* Positive reception Overall Improvements Increase in of study satisfaction with in symptoms mobility clinical measures “I couldn’t walk from the bathroom “…I was able to go for a
Slide 40: Plan Forward in CMS
Plan Forward in CMS Engage with regulators on Phase 3 CMS • Target population DOK7-CMS age 12 and up and additional subtypes (MuSK, LRP4, AGRN) Phase 3 • Proposed primary endpoint – 6MWT to start • Digital health technology-derived endpoints in 2026 Amended natural history study Proof of Biology Est
Slide 41: CMS Panel Discussion
CMS Panel Discussion Dr. Ricardo Maselli, Rebecca Shilling, Luc Truyen, moderated by Jeff Guptill 42
Slide 42: Moderator Panelists
Moderator Panelists Jeff Guptill Ricardo Maselli, M.D. Rebecca Shilling, M.D. Luc Truyen, M.D., Ph.D Neuromuscular Franchise Lead, Professor, Neurology ARGX-119 Chief Medical Officer Clinical Development University of California, Davis Clinical Development Lead 43
Slide 43: ARGX-119 Opportunity
ARGX-119 Opportunity Roeland Vanhauwaert // ARGX-119 Scientific Lead 44
Slide 44: ALS: Activation of MuSK Signaling Slows Muscle Denervation
ALS: Activation of MuSK Signaling Slows Muscle Denervation and Improves Motor Function Disease Characterization Progressive and fatal neurodegenerative disorder caused by motor neuron death ARGX-119 preserves NMJ numbers and restores muscle Deteriorating muscle function, weakness, and atrophy contra
Slide 45: reALiSe Phase 2a Clinical Trial Design in ALS
reALiSe Phase 2a Clinical Trial Design in ALS ACTIVE TREATMENT SAFETY SCREENING TREATMENT PERIOD EXTENSION PERIOD FOLLOW-UP (≤4 weeks) 24 wk 48 wk Low dose N=15 Mid dose N=15 24 weeks of High dose no treatment N=60 High dose N=15 R 1:1:1:1 Placebo N=15 WEEK 0 1 2 4 24 26 28 72 104 Q4W Q4W ARGX-119 o
Slide 46: MScan: A Precision Tool for Quantifying Motor Unit Loss in ALS
MScan: A Precision Tool for Quantifying Motor Unit Loss in ALS MScan set-up MScan visual changes during disease progression. Stimulation electrode (reference) Stimulation electrode (active) Quantifies changes in motor unit number Recording electrode (active) (MUNE) Recording electrode (reference) Co
Slide 47: SMA: Activation of MuSK by ARGX-119 Can Mature NMJs
SMA: Activation of MuSK by ARGX-119 Can Mature NMJs, Improve NMJ Transmission and Motor Function On Top of DMTs Increase in muscle force without corresponding Disease Characterization increases in weight, suggests muscle function may Characterized by neuromuscular weakness and be more important than
Slide 48: ARGX-119 Pipeline-in-a-Product Potential
ARGX-119 Pipeline-in-a-Product Potential NMJ Diseases CMS – MG Agrin Acetylcholine LRP4 ARGX-119 Muscle Diseases AChR Muscular Dystrophies and Myopathies MuSK DOK7 Clustering Rapsyn Motor Neuron Diseases ALS – SMA Peripheral Neuropathies 49
Slide 49: Path Forward for ARGX-119
Path Forward for ARGX-119 CMS ALS SMA Phase 3 Phase 2a reALiSe Phase 2 Sparkle to start in 2026 data 1H26 study to initiate Proof of Biology Innovative Endpoint First Time Pediatric Established Using MScan Dosing 50
Slide 50: Closing Remarks
Closing Remarks Tim Van Hauwermeiren, CEO 51 51