#1R&D DAY July 20, 2021 GONGE argenx#2Welcome & Introductions Beth DelGiacco Vice President, Corporate Communications & Investor Relations argenx#3Forward Looking Statements Safe Harbor: 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. Examples of such forward-looking statements include those regarding the therapeutic and commercial potential of our product candidates; our clinical development and regulatory plans, including the timing, design and outcome of ongoing and planned clinical trials and preclinical activities; the timing, progress and benefits of commercialization activities; our plans to start registrational trials this year; our statements regarding new assets yearly from IIP; our statements regarding potential and effect of efgartigimod; our expectation to have IND filing this year; our plan to start Phase 2 trial in MMN this year; and the expected size of the markets for our product candidates. When used in this presentation, the words "anticipate," "believe," "can," "could," "estimate," "expect," "intend," "is designed to," "may," "might," "will," "plan," "potential," "predict," "objective," "should," or the negative of these and similar expressions identify forward-looking statements. Such statements, based as they are on the current analysis and expectations of management, inherently involve numerous risks and uncertainties, known and unknown, many of which are beyond the Company's control. Such risks include, but are not limited to: the impact of COVID-19 pandemic on our business, the impact of general economic conditions, general conditions in the biopharmaceutical industries, changes in the global and regional regulatory environments in the jurisdictions in which the Company does or plans to do business, market volatility, fluctuations in costs and argenx changes to the competitive environment. Consequently, actual future results may differ materially from the anticipated results expressed in the forward-looking statements. In the case of forward- looking statements regarding investigational product candidates and continuing further development efforts, specific risks which could cause actual results to differ materially from the Company's current analysis and expectations include: failure to demonstrate the safety, tolerability and efficacy of our product candidates; final and quality controlled verification of data and the related analyses; the expense and uncertainty of obtaining regulatory approval, including from the U.S. Food and Drug Administration and European Medicines Agency; the possibility of having to conduct additional clinical trials; our ability to obtain and maintain intellectual property protection for our product candidates; and our reliance on third parties such as our licensors and collaboration partners regarding our suite of technologies and product candidates. Further, even if regulatory approval is obtained, biopharmaceutical products are generally subject to stringent on- going governmental regulation, challenges in gaining market acceptance and competition. These statements are also subject to a number of material risks and uncertainties that are described in the Company's filings with the U.S. Securities and Exchange Commission ("SEC"), 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. The reader should not place undue reliance on any forward-looking statements included in this presentation. These statements speak only as of the date made and the Company is under no obligation and disavows any obligation to update or revise such statements as a result of any event, circumstances or otherwise, unless required by applicable legislation.#4Today's Agenda Advancing Towards argenx 2025 | Tim Van Hauwermeiren, Chief Executive Officer and Co-Founder Efgartigimod: Differentiation of our Anti-FcRn Fc Fragment | Hans de Haard, Chief Scientific Officer and Co-Founder Fifth Efgartigimod Indication: Myositis | Bas van der Woning, Research Fellow Sixth Efgartigimod Indication: Bullous Pemphigoid | Peter Verheesen, Research Fellow KOL Panel: Myositis and Bullous Pemphigoid | Moderated by Albert Kovera, Global Marketing Rohit Aggarwal, MD, MS, University of Pittsburgh Medical Center Russell Hall, MD, Duke University Medical Center ● ● ARGX-117 Phase 1 Data | New Biology Insights for Multifocal Motor Neuropathy Olivier Van de Steen, Medical Director | Inge Van de Walle, Principal Scientist Q+A argenx 4#5Visit the argenx R&D Day Microsite to View Additional Resources Myositis and Bullous Pemphigoid Disease Overview argenx Discussion on FcRn and Albumin Patient Stories Relevant Publications MG Experience in China 5#6Advancing Towards argenx 2025 Tim Van Hauwermeiren Co-Founder and CEO argenx#7Where critical patient need meets breakthrough science PATIENT SCIENCE That is where we redefine immunology argenx ☆#82021: Reaching Myasthenia Gravis Patients with Efgartigimod New modality nature biotechnology FcRn. Only Fc fragment targeting FcRn Designed ADAPT with patient input adapt myasthenia gravis study MG-ADL Change from Baseline 0 -1 -5 -6 Defined disease biology -80 Correlation of total IgG and MG ADL Engaging MG community -70 -60 SP -50 -40 -30 IgG Percent Change from Baseline -20 -10 0 8#9Efgartigimod: A Precision Tool to Revolutionize Autoimmunity Membranous Nephropathy Thyroid Eye Disease Bullous Pemphigoid ITP O Myositis IgG pom IgG AMR Sjogren's Syndrome GBS IgG Pemphigus 104 POST IgG Lupus Nephritis Neuromyelitis Optica Myasthenia Gravis CIDP O 9#10Myositis: IgG-Mediated Biology Neuromuscular Disease Neuromuscular Disease Neuromuscular Disease argenx Myasthenia Gravis Chronic Inflammatory Demyelinating Polyneuropathy Myositis ACHR, MUSK, LRP4 autoantibodies comprise + ~90% of MG patients 40% anti-myelinated peripheral nerve IgGs + Autoantibodies characterized in 70% of patients across + IMNM, ASYS and DM IND filing by end of 2021 pending interactions with FDA ADAPT Data ADHERE GO/NO-GO Next Opportunity IMNM: Immune-Mediated Necrotizing Myopathy ASyS: Anti-Synthetase Syndrome DM: Dermatomyositis Gilhus et al., Nature Rev/Disease Primers. 2019; Gilhus et al., NEJM, 2016; Querol et al., Nat Rev Neurol. 2017; Schmidt, Journal Neuromusc Diseases. 2018; Aquilar-Vazquez et al., Frontiers in Immunology. 2021; McHugh, Managing Myositis. 2019 10#11Bullous Pemphigoid: Expanding the Skin Franchise argenx Autoimmune Blistering Diseases Autoantibody Driven Convincing Rationale Unmet Patient Needs Primary Endpoint Pemphigus DSG1 and DSG3 Pemphigoid BP180 and BP230 IVlg, PLEX, Immunoadsorption demonstrate role of IgG Fast-acting, tolerable therapies; ability to taper corticosteroids Complete or partial remission off corticosteroids Registrational trial to start by end of year in parallel to ongoing pemphigus trial 11#12Our Pipeline Starts with our Immunology Innovation Program CLINICAL DEVELOPMENT S argenx ANTIBODY ENGINEERING argenx Internal Value Creation First in Class | Unique Design | Multiple Indications Efgartigimod ARGX-117 ARGX-119 ARGX-118 Cusatuzumab LEADING TRANSLATIONAL BIOLOGY LABS External Value Creation Staten (ARGX-116) Genor (ARGX-109) AgoMAb (ARGX-114) LEO (ARGX-112) Dualyx AbbVie (ARGX-115) 12#13Neuromuscular Franchise: A Company within a Company IIP Programs argenx ARGX-119 SIMPLE AntibodyTM aimed to boost the neuromuscular junction in disease ARGX-117 C2 inhibitor Efgartigimod FcRn antagonist Leveraging infrastructure across multiple indications and molecules ALS MG 2021 SMA MMN Myositis CIDP MG MUSK MG MG-SC 2022 Congenital MG MMN Myositis CIDP 2023 - 2026 13#14Building a Leading Immunology Company argenx Committed to our Patients and their Communities Rooted in Science through our IIP Enviable Immunology Pipeline Global autoimmune market has surpassed $150B Efgartigimod available globally Vibrant neuromuscular, hematology and skin franchises Efgartigimod in 15 indications (commercial or development) ARGX-117 in multiple late-stage trials Proof-of-concept demonstrated with ARGX-119 New asset each year from IIP We believe the future belongs to those who collaborate best 14#15Building a Leading Immunology Company Committed to our Patients and their Communities Rooted in Science through our IIP argenx Enviable Immunology Pipeline Global autoimmune market has surpassed $150B Efgartigimod available globally Vibrant neuromuscular, hematology and skin franchises Efgartigimod in 15 indications (commercial or development) ARGX-117 in multiple late-stage trials Proof-of-concept demonstrated with ARGX-119 New asset each year from IIP We believe the future belongs to those who collaborate best argenx 2025 15#16Efgartigimod: Differentiation of our Anti-FcRn Fragment Hans de Haard Chief Scientific Officer and Co-Founder argenx#17FcRn Plays a Key Role in IgG and Albumin Homeostasis Studies have shown: 1 2 3 Circulating antibodies are taken up in the cell via pinocytosis. In the endosome, IgG antibodies bind to FcRn¹,2 argenx Unbound IgGs enter the lysosomal degradation pathway, while FcRn-bound IgGs are rescued from degradation ¹,2 The IgG antibodies bound by FcRn are then released back into circulation, thereby extending their half-life ¹,2 Albumin is recycled by FcRn, independently of IgG FcRn, neonatal fragment crystallizable receptor; IgG, immunoglobulin G. (1) Sesarman et al., Cell Mol Life Sci. 2010; (2) Habib et al., Supp Neuro Review. 2020. 1 Endothelial Cell 2 Lysosome 3 Endosome IgG Autoantibody IgG Antibody FcRn Albumin 17#18Efgartigimod Endogenous IgGs argenx 1 FcRn B2M Endogenous FcRn:IgG Interaction G Fc Fragment Binds to FcRn in Same Way as 2 Ulrichts et al, Clin Invest. 2018 tha Efgartigimod 3 P Efgartigimod binds to FcRn in the same formation as endogenous IgG Our hypothesis is that different binding properties of FcRn antagonists lead to different subcellular trafficking pathways Anti-FcRn mAb 18#19Efgartigimod Keeps FcRn in its Recycling Path FcRn over time 0 min No treatment argenx 0 min Efgartigimod 0 min Control anti-FcRn mAb Normalized Volume (%) 150- 100 50- Normalized Sum Volume (FcRn) -0 -09 120- 180- 240- 300- 360- 420- -087 540- -009 -099 Time (Min) ********* 720- 780- 840- No treatment → Efgartigimod → Control anti-FcRn mAb -006 096 19#20Albumin Serves a Crucial Role in Lipid Housekeeping Proposed Interactions Between Serum Albumin and CV Outcomes4 Underlying conditions argenx Inflammatory process Vasodilatory ability ↓ G Low serum albumin levels Vascular permeability ↑ Anticoagulation ↓ Cholesterol transport and LDL catabolism Adverse cardiovascular events Small molecule binding ↓ (toxins & medicines) Serum albumin is proposed to enhance cholesterol transport, facilitating steady state levels as cholesterol is metabolized (1) Law S, et al. Int J Mol Sci. 2019; (2) Packard CJ, et al. J Lipid Res. 2000; Noto D. et al., Kidney International. 1999; (4) Chien SC, et al. Biomark Res. 2017; (5) Sankaranarayanan S, et al. J Lipid Res. 2013 20#21Efgartigimod Blocks IgG Binding to FcRn Without Reducing Albumin Mean Percent Change (+/-SE) -20 0 4 -60 ● ● 0 IgG levels - 1st cycle argenx 60 63 63 161 2 4 61 16.3 62 13 Cycle 1 6 A 8 54 25 16 10 12 15 15 Phase 3 ADAPT Trial of Efgartigimod in Myasthenia Gravis Patients T 16 18 Albumin (g/L) Howard et al., The Lancet Neurology. 2021 LDL (mmol/L) 60- 50- 40- 10.0 7.5- 5.0- 2.5- Albumin and LDL Cholesterol levels - 1st & 2nd cycles 0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8 10 10 Week 12 14 16 12 14 16 18 20 18 20 60- 50- 40- 10.0- 7.5- 5.0- 2.5- 0 1 . 3 Potent reduction in IgG levels without decrease in albumin or increase in LDL levels No albumin decreases observed with chronic dosing out to 34 weeks in Phase 2 pemphigus trial (25mg/kg dose) Selective blockade of IgG recycling without affecting serum albumin levels is emerging as a key differentiator in the FcRn space Maintaining levels of human serum albumin is important for lipid housekeeping as well as other key physiological functions 4 5 6 7 . 8 10 12 0 1 2 3 4 5 6 7 8 10 Week 12 □ 14 16 18 20 H 14 16 18 20 TH T EFGARTIGIMOD PLACEBO THE LANCET Neurology 21#22Efgartigimod: Data Support Favorable Benefit to Risk Ratio 600+ subjects dosed 125+ patients on efgartigimod for over 12 months argenx 100 patients on efgartigimod for over 18 months Clinical proof-of-concept in four indications (MG, ITP, PV, CIDP) No evidence of dose-limiting toxicities in healthy volunteers or patients across trials Opportunity to dose efgartigimod to maximum PD effect 22#23Fifth Efgartigimod Indication: Myositis Bas van der Woning Research Fellow argenx#24Idiopathic Inflammatory Myopathy (IIM) or Myositis Rare, severe autoimmune disorders characterized by chronic muscle inflammation, pain and impaired quality of life; no FDA-approved therapies for myositis PREVALENCE 14 per 100,000 Mid-adult onset More common in females argenx MYOSITIS IS MEDIATED BY AUTOANTIBODIES HALLMARK Proximal muscle weakness is unifying feature of myositis subsets TREATMENT No consensus guidelines for management Treated primarily by rheumatologists and neurologists BURDEN (1) Meyer et al., Rheumatology. 2015; (2) Pinal-Fernandez et al., Curr Rheumatol Rep. 2018; (3) Schmidt, Journal of Neuromuscular Diseases. 2018 High impact on quality of life: muscle atrophy, pain, functional impairment, dysphagia, dyspnea High mortality rate: malignancy, interstitial lung disease and infections Myositis subsets mediated by autoantibodies: immune-mediated necrotizing myopathy (IMNM), anti-synthetase syndrome (ASyS), and dermatomyositis (DM) Significant market opportunity with ~33K eligible patients in the U.S. 24#25Many Myositis-Specific Autoantibodies Have Been Identified Polymyositis KS argenx IMNM HMGCR PL-7 ASYS OJ SRP PL-12 Jo-1 EJ U1RNP PM-Scl SAE TIF-1y Mi-2 Ku MDA-5 Overlap Myositis MJ DM Aggarwal; Lundberg, Ann Rheum Dis. 2017 *American College of Rheumatology European Alliance of Associations for Rheumatology Myositis classification is based on myositis-specific autoantibodies (IgG) and clinical symptoms EULAR/ACR* classification criteria for adult myositis Classification IMNM, ASYS and DM based on clinical symptoms 25#26IMNM Autoantibodies Trigger Muscle Damage and Impair Muscle Regeneration Classical complement activation →>> Myolysis (muscle enzymes e.g., CK) argenx 2 Anti-SRP/-HMGCR autoantibodies bind 1 muscle fiber Complement dependent Necrosis 3 Myofibre Allenbach, Nature Reviews Rheumathology. 2020 Macrophage recruitment and activation Membrane attack complex -C1q Complement activation Necrosis Induction by proinflammatory cytokines Atrophy IL-1 IL-6 . TNF Y Autoantibodies Myoblasts Muscle damage Impaired muscle regeneration 4 Low IL-4 IL-13 Macrophage recruitment and activation IL-1, IL-6, TNF atrophy Regeneration Myotube SRP antigen - HMGCR antigen 00 00 00 00 Young myofibre 5 Blocking myotube formation Complement independent 26#27DM and ASyS Autoantibodies Activate Complement and Type 1 Interferon Y Autoantibodies argenx Complement Activation Complement Activation Interferon Production Myolysis Disruption of capillaries 1 1 Dendritic cells produce Type 1 interferon from immune complexes ● 1 complement 6:5 2 2 2 Type 1 Interferon Impaired myotube formation Impaired angiogenesis: destruction of capillaries and hypoperfusion Necrosis Hypoperfusion Increased autoantibody production Necrosis Atrophy 27#28Autoantibodies are Central Mediators of Myositis Pathophysiologies Summary of Mode of Action of Autoantibodies Complement activation of muscle lysis Complement activation of endothelial cell lysis Interferon production alpha/beta induce atrophy argenx Inhibition of myotube formation myotube i Y autoantibody complement type 1 interferon 28#29Efgartigimod Designed to Clear IgG Autoantibodies Regardless of Target Antigen IMNM (70% MSA+) anti-SRP Anti-HMGCR MAA or Abs against unidentified targets argenx ASYS (100% MSA+) anti-Jo-1 anti-PL-12 anti-PL-7 other anti-synthetases DM (75% MSA+) anti-Mi-2 anti-NXP-2 anti-MDA5 anti-TIF-1y anti-SAE MAA or Abs against unidentified targets Defining new myositis biology Myositis patients can have myositis-specific autoantibodies (MSA+), myositis-associated autoantibodies (MAA+) or autoantibodies against yet unknown targets 29#30Biology Rationale is at the Core of our Indication Selection Preclinical Evidence Passive transfer model of IMNM autoantibodies from patient serum induce muscle weakness and loss of grip strength in mice argenx Y Clinical Evidence No approved targeted therapies for myositis but common immune therapies* show correlation of autoantibodies to disease progression ● ● ● Correlation of identity of autoantibodies to muscle damage across myositis subtypes Direct link between titer of autoantibody and disease activity Rituximab and IVlg evidence demonstrate autoantibodies are foundational drivers of disease *Plasmapheresis and immunoadsorption (commonly used as correlates for efgartigimod) are not used in the treatment of myositis 30#31● ● Autoantibody Levels Correlate to Indicators of Myositis: CK Levels and Muscle Strength Patients were treated with standard of care immunosuppressants CK (U/L) 8000 argenx 6000 4000 2000 7500 5000 2500 Patient 1 CK (U/L) -Anti-SRP54 level (AUJmL) 600 Patient 5 800 1600 1200 800 -400 1000 8000 4000 2000 +0 200 400 600 800 1000 1200 1400 Days 1500- 12000 100001 1000- 500- 7500- 5000 2500- 0 200 400 100 200 Patient 2 12000 Patient 6 9000 6000 3000 +0 600 800 1000 1200 400 300 200 100 0 300 400 500 600 Days 1200- 600- 300 10000 7500 5000 2500 0 200 Patient 3 400 600 Patient 7 200 Days 4000 3000 2000 1000 +0 800 1000 1200 12000 9000 6000 3000 40 600 4000 3000 2000 1000 8000 6000- 4000- 2000- 50 Patient 4 100 Patient 8 200 Days 150 400 Benveniste et al., Arthritis Rheumatol. 2011; Stone et al., Arthritis and Rheumatism 2007; Allenbach et al, Medicine (Baltimore). 2014; Muro et al., Rheumatology 2012 4000 3000 2000 1000 200 75 50 25 to 600 Similarly, anti-HMGCR, -Jo-1 and -Mi-2 titers correlate with CK levels and muscle strength Anti-MDA5, -Jo-1 and -Mi-2 titers correlate with extramuscular disease activities (e.g. interstitial lung disease, skin disease) Anti-SRP54 level (A.U./mL) 31#32ASyS and DM: Anti-Jo-1 and Anti-Mi-2 Patients Respond to Rituximab DOI-free Survival Probability 10 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 8 argenx 12 16 20 24 28 TIME (weeks) 32 Aggarwal et al, Arthritis Rheumatol. 2015 (Wilcoxon p<0.001) no AutoAb other AutoAb Mi-2 Jo-1 36 40 44 Shorter time to improvement in patients positive for anti-Jo-1 and anti-Mi-2 autoantibodies Anti-Jo-1 and anti-Mi-2 levels decreased after B-cell depletion Correlation of anti-Jo-1 and anti-Mi-2 titers with disease activity measures Endpoint based on 6 measures: PhGA, PTGA, HAQ, MMT-8, muscle enzymes, extramuscular disease activity score Anti-Jo-1 and anti-Mi-2 autoantibodies are predictive biomarkers for response 32#33DM Patients Respond to IVlg Total Improvement Score (TIS, 0-100) 100- 8 60 40 20- 0- Octagam 45 Placebo 48 argenx O Placebo-controlled, First period Open Label, Extension Period A A 45 47 Week 4 Week 8 G A 45 46 45 43 Week 12 Week 16 Octagam 37 40 Week 28 Placebo 2g/kg IVlg/Placebo Aggarwal et al., Arthritis Rheumatol. 2020 34 35 Week 40 43 44 EOS ProDERM study: % of patients with increase of ≥20 points on Total Improvement Score (TIS) at week 16 TIS220 TIS240 IVIg 78.7% 68.1% Placebo 43.8% 22.9% 33#34IMNM Autoantibodies Weakness and Loss of Grip Strength IgG purified from plasma from anti-SRP and anti-HMGCR IMNM patients causes loss of grip strength and muscle weakness in recipient mice A Grip strength (g) -20- 40- -60- argenx 아이에 n 0 100 dod *** Control IgG IgG-depleted plasma (P3) Anti-SRP* IgG (P3) Muscle strength (g) 120- 100- 80- 60- Bergua et al., Ann Rheum Dis. 2018 from Patient Serum Induce Muscle 0 H Control IgG • Anti-HMGCR* IgG (P4) Necrosis and complement deposition are observed similarly in recipient mice as in IMNM patients NECROSIS C5b-9 COMPLEMENT DEPOSITION x400 x400 34#35Significant Market Opportunity Across Myositis Subsets REACHING PATIENTS + 33K Estimated eligible myositis patients in U.S. argenx DEFINING NEW BIOLOGY Building a Basket Trial Concept 1 IMNM: 4K pts U.S. Role of autoantibody is best-characterized in IMNM IMNM anchors market opportunity 2 ASYS: 8K pts U.S. Basket trial approach to include ASYS and DM as well Reaching more patients with high unmet need 3 DM: 21K pts U.S. Efgartigimod may allow us to redefine all three myositis subsets as being truly IgG- mediated 35#36Adaptive Phase 2/3 Enrichment Design Independent adjudication committee Stratified for IMNM ASYS DM ● ● ● 180 patients ● ● Severity of muscle weakness (MMT) Eligibility criteria • Minimal muscle weakness No malignancies ili argenx Adults IMNM ASYS DM Total Duration: 26 weeks 1000mg efgartigimod SC (+ SOC) Placebo SC (+ SOC) 1000mg efgartigimod SC (+ SOC) Placebo SC (+ SOC) 1000mg efgartigimod SC (+ SOC) Placebo SC (+ SOC) Adaptive enrichment Interim analysis Independent DSMB Subpopulation adjustment Sample size re-estimation IND filing by end of 2021 pending interaction with DCOA and CID division of FDA Primary Response based on Total Improvement Score (TIS) ACR/EULAR endorsed Key Secondary Mean change and duration in TIS Quality of Life Individual Core Set Measures TIS ● Proposed Endpoints ● ● ● ● ● ● ● ● MMT-8 score Physician Global Assessment Patient Global Assessment HAQ-Disability Index score Extramuscular Global Assessment Muscle enzyme serum level 36#37Conclusions >30,000 IMNM, ASyS and DM patients in the U.S. Clinical evidence links IgG levels to disease activity Adaptive enrichment trial enables enrollment of broader patient population argenx Diverse panel of IgG autoantibodies emerge as key driver of muscle inflammation Efgartigimod is designed to reduce all IgGs regardless of target antigen and can further elucidate myositis biology First basket trial design based on unifying biology 37#38Sixth Efgartigimod Indication: Bullous Pemphigoid Peter Verheesen Research Fellow argenx#39Bullous Pemphigoid: Most Common Autoimmune Blistering Disease Severe, rare, chronic and recurrent autoimmune disorder characterized by fluid-filled blisters, itching and skin redness PREVALENCE argenx BULLOUS PEMPHIGOID IS MEDIATED BY AUTOANTIBODIES 12 per 100,000¹ Increasing with aging population Median age of onset is 81 years BURDEN Severe blistering disease Strong impact on quality of life High mortality rate 2.40 (U.S.)² No approved treatments Topical/systemic corticosteroids, steroid-sparing agents, rituximab, IVlg TREATMENT Significant market opportunity with ~41K patients in the U.S. (1) Wertenteil et al., J Am Acad Dermatol. 2019; (2) Tedbirt et al., JAMA Dermatol. 2021; argenx market research UNMET NEED Time to remission High relapse rate Side effects from corticosteroids 39#40Bullous Pemphigoid Autoantibodies are Origin of Blister Formation EPIDERMIS DERMIS IL-6, IL-8 Efgartigimod argenx MECHANICAL DISRUPTION Autoantibodies B Cells сссс COMPLEMENT ACTIVATION Chemokines & proteases Mast cells 3 Macrophages 4 Chemokines INFLAMMATORY REACTION Neutrophils T cell Proteases ROS 5 Eosinophils Drawn after Schmidt E, Zillikens D. Lancet. 2013; Fang H, Li Q, Wang G. Autoimmun Rev. 2020 6 BLISTER FORMATION • BP180 and BP230: key pathogenic hemidesmosomal antigens driving blistering between epidermis and dermis • Autoantibody actions: • Mechanical disruption of keratinocyte adhesion IgG autoantibody deposition triggers complement activation • Recruitment and activation of immune cells (inflammatory cell recruitment, release of proteolytic enzymes) 40#41Passive Transfer Model Highlights Toxicity of Bullous Pemphigoid Autoantibodies argenx WT FcRn Mice injected with BP180 Ab e d HDIG: High-dose human lgG Li et al., J Clin Invest. 2005 HDIG lowers BP180 Ab levels and improves disease scores =+IgM + HDIG e Serum R530 IgG level (relative OD reading) 2.8 2.4 2.0 1.6 1.2 0.8 0.4 0.0 li 1 2 HDIG dose (mg/g body wt) 3 4 5 0 0 0.5 1.0 2.0 WT FcRn Clinical disease score (mean ± SEM) Anti-mBP180 Control IgG 0.0 2.5 2.0 1.5 1.0 0.5 Pathogenic autoantibodies induce typical skin lesions in murine passive transfer model of bullous pemphigoid Mice injected with BP180 Ab FcRn -/-: Degradation of BP180 Ab 0.0 HDIG dose (mg/g body wt) 0.4 0.8 1.2 1.6 2.0 2.4 Serum anti-mBP180 lgG level (relative OD reading) FcRn-knockout mice show fast elimination of pathogenic autoantibodies and are resistant to disease 1 0 2 0 +IgM + HDIG ** 4 5 3 0.5 1.0 2.0 41#42Bullous Pemphigoid Disease Activity Improves with Increasingly Selective IgG Therapies argenx Selectivity for IgG IVlg PLEX Immuno adsorption (Protein A) Trial Phase 3 double-blind randomized trial 56 patients High dose IVlg (5 days) + oral corticosteroids Case series 5 patients PLEX (7-14 cycles) in 4-8 weeks Two case series 27 patients* Immunoadsorption (most 1 cycle) * 4 recalcitrant BP, 3 first line with high disease activity, 20 severe or refractory (1) Kasperkiewicz et al., J Am Acad Dermatol. 2014; (2) Hübner et al., J Dtsch Dermatol Ges. 2018 (3) Mazzi, Transfusion and Apheresis Science. 2003; (4) Amagai et al., J. Dermatol. Sci. 2017 ● ● Response Clear therapeutic benefit Stronger response in severe disease Fast improvement 100% complete remission 70% prednisone dose reduction Strong antibody reductions 68% complete remission 37% off oral corticosteroids No need for second cycle in most patients Clinical evidence for the role of pathogenic autoantibodies in bullous pemphigoid 42#43IgG-Targeted Therapies Drive Fast Remissions IVIg¹ Disease activity b 100 90 80 70 60 50 40 30 20 10 0 -21 to -7 1 (SG) 2 (CG) 3 (BG) 4 (PM) Plasmapheresis details, therapy and outcome Patient Blistering Therapy before disease ТРЕ 5 (EG) ***** IMIG 1 argenx BP BP BP PV 8 BP 15 22 Observation period (day) S (125 mg/day) I (150 mg/day) S (120 mg/day) I (175 mg/day) S (110 mg/day) I (150 mg/day) S (150 mg/day) I (150 mg/day) S (60 mg/day) I (150 mg/day) 29 14ª 8º No. of TPE Side effects procedures 9d 43 7⁰ Placebo (n=16) 3 TPE/first week, 2 TPE/week x 2 weeks, 1 TPE/week. 3 TPE/first week, 2 TPE/week x 3 weeks. 2 TPE/first week, 2 TPE/week x 2 weeks, 1 TPE/week. IVIG (n=17) S: prednisone, I: azathioprine, IVIg: intravenous immunoglobulin. * 3 TPE/first week, 2 TPE/week x 4 weeks, I TPE/week x 3 weeks. bIVIg 0.4 mg/kg/day x 5 days x 2 cycles. 57 Change in erosions/blisters Outcome Plasma Exchange (PLEX) ² -10 Remission 20 -20 Remission 10 -30 Hypotension at the Remission end of TPE 0 -40 Remission Remission IVIG 1 8 15 Therapy after TPE S (40 mg/day) I (100 mg/day) IVIg S (35 mg/day) I (175 mg/day) IVIgb S (75 mg/day) S (22.5 mg/day) I (150 mg/day) S (37.5 mg/day) I (125 mg/day) 22 29 Observation period (day) Therapy 3 months post- ТРЕ S (30 mg/day) I (75 mg/day) S (22.5 mg/day) I (75 mg/day) S (35 mg/day) S (15 mg/day) I (100 mg/day) S (20 mg/day) 1 (75 mg/day) 43 Therapy 6 months post- TPE S (20 mg/day) I (50 mg/day) S (15 mg/day) I (50 mg/day) S (25 mg/day) S (10 mg/day) I (75 mg/day) Not applicable Placebo (n=27) -IVIG (n=29) Relapse after TPE 15 months 57 BP180 NC16A ELISA (U/ml)¹ Protein A Immunoadsorption³ 100.000- 50.000- 10.000- 5.000- 1.000- 800 600- 400- 200- 0 ■ Before IA After 1 month G After Last testing 3 months (3-39 months) Active disease Clinical remission on therapy Median Partial remission Clinical remission off therapy (1) Amagai et al., J. Dermatol. Sci. 2017 (2) Mazzi, Transfusion and Apheresis Science. 2013 (3) Kasperkiewicz et al., J Am Acad Dermatol. 2014 43#44Pemphigus Serves as Proof of Concept for Autoimmune Blistering Diseases Proof of Concept in Initial Indication... Fast onset of action SKIN BLISTERING DISEASES – AUTOANTIBODY DRIVEN 90% disease control after median time of 17 days argenx PEMPHIGUS Significant responses 64% complete clinical remission after median 92 days Corticosteroid sparing potential by using lower initial doses of corticosteroids and rapid tapering Favorable tolerability seen in data to date BULLOUS PEMPHIGOID ...Before Expansion into Adjacent Indications Autoantibodies initiate disease Pathophysiology of blister formation more heterogeneous Larger yet more elderly, fragile population Important to confirm efgartigimod profile in pemphigus before expanding into other skin indications 44#45Registrational Study of Bullous Pemphigoid to Start in 2021 Study Population Bullous Pemphigoid Moderate-to-severe disease (BPDAI activity score ≥ 20) Newly diagnosed and relapsing within 1 year of diagnosis ili argenx IIII III Total Duration: 36 weeks Randomization (1:1) III Efgartigimod weekly SC Placebo weekly SC ||||| Concomitant Oral Corticosteroids (OCS) OCS starting dose 0.5 mg/kg/day with ability to adjust Active tapering to start from sustained control of disease activity (CDA) Proposed primary endpoint proportion of participants in complete or partial remission while off OCS ● Endpoints Secondary endpoints • cumulative dose of OCS • time to complete remission on minimal OCS ● proportion of participants with CDA and remain free of relapse quality of life Followed by Open Label Extension study 45#46Conclusions ~41K bullous pemphigoid patients in U.S. IgG autoantibodies against BP180/BP230 are hallmark of bullous pemphigoid argenx Preclinical and clinical evidence links IgG autoantibody level to disease activity Robust Phase 2 PoC data for efgartigimod in pemphigus lead to bullous pemphigoid Phase 3 trial design Second registrational trial in skin franchise to start in parallel to ongoing pemphigus trial 46#47KOL Panel: Myositis and Bullous Pemphigoid argenx#48argenx Russell P. Hall III, MD J. Lamar Callaway Professor, Department of Dermatology, Duke University Medical Center Rohit Aggarwal, MD, MS Rheumatology, Professor of Medicine, Medical Director, Arthritis and Autoimmunity Center, Co-Director UPMC Myositis Center, Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh 48#49ARGX-117 Phase 1 Data | New Biology Insights for Multifocal Motor Neuropathy Olivier Van de Steen, Medical Director Inge Van de Walle, Principal Scientist argenx#50ARGX-117 is First in Class Targeting C2 argenx IgG (Auto)antibodies Classical C1 qrs IgM Clearance by macrophages Membrane damage C4 C2 C3b Lectin Mannose sugar MBL MASPS C3 convertase C3 C5 convertase C5 C5b-C9 MAC C3a C5a ▬▬▬I C3a-R C5a-R Sublytic MAC Microorganisms Alternative Foreign surface CFB C3 CFD Inflammation 50#51C2 is Ideal Point of Intervention within Complement Cascade IgG argenx (Auto)antibodies Classical C1 qrs IgM 3 Crossroad of classical & lectin pathways Manageable C2 levels in circulation Benign C2-deficiency phenotype Clearance by macrophages Membrane damage C4 C2 C3b Lectin Mannose sugar MBL MASPS C3 convertase C3 C5 convertase C5 C5b-C9 MAC C3a C5a ▬▬▬I C3a-R C5a-R Sublytic MAC Microorganisms Alternative Foreign surface C3 CFB CFD 2 Intact alternative pathway to reduce infection risk 1 Target upstream of C5 to shut down all effector functions Inflammation 51#52C2 is Ideal Point of Intervention within Complement Cascade IgG argenx (Auto)antibodies Classical C1 qrs 3 Crossroad classical & lectin pathway Manageable C2 levels in circulation Benign C2-deficiency phenotype IgM Clearance by macrophages Membrane damage C4 C2 C3b Lectin Mannose sugar MBL MASPS C3 convertase C5 convertase C5 C5b-C9 MAC C3a C5a C3a-R C5a-R Sublytic MAC Microorganisms Alternative Foreign surface C3 CFB CFD 2 Intact alternative pathway to reduce infection risk 1 Target upstream of C5 to shut down all effector functions Inflammation 52#53C2 is Ideal Point of Intervention within Complement Cascade IgG argenx (Auto)antibodies Classical C1 qrs 3 Crossroad classical & lectin pathway Manageable C2 levels in circulation Benign C2-deficiency phenotype IgM Clearance by macrophages Membrane damage C4 C2 C3b Lectin Mannose sugar MBL MASPS C3 convertase C5 convertase C5 C5b-C9 MAC C3a C5a C3a-R C5a-R Sublytic MAC Microorganisms Alternative Foreign surface CFB C3 CFD 2 Intact alternative pathway to reduce infection risk 1 Target upstream of C5 to shut down all effector functions Inflammation 53#54C2 is Ideal Point of Intervention within Complement Cascade IgG argenx (Auto)antibodies Classical C1 qrs IgM 3 Crossroad of classical & lectin pathways Manageable C2 levels in circulation Benign C2-deficiency phenotype Clearance by macrophages Membrane damage C4 C2 C3b Lectin Mannose sugar MBL MASPS C3 convertase C5 convertase C5 C5b-C9 MAC C3a C5a C3a-R C5a-R Sublytic MAC Microorganisms Alternative Foreign surface C3 CFB CFD 2 Intact alternative pathway to reduce infection risk 1 Target upstream of C5 to shut down all effector functions Inflammation 54#55ARGX-117 Blocks and Actively Removes C2 from Circulation Features of ARGX-117 pH and Ca2+ switch No effector function argenx Optimal recycling 2 Uptake & drop off C2 FcRn ARGX-117 C2 Sweeping Antibody 1 pH: 7.4 Ca²+: 1.5 mM 1 Cell 3 Bind & block C2 3 Endosome *********** Lysosome Degradation of C2 4 Recycling of ARGX-117 55#56Ongoing Robust Phase 1 First-in-Human Study 0.1 mg/kg IV N=8 argenx ● ● ● 0.5 mg/kg IV N=8 10 mg/kg IV N=7 30 mg/kg IV N=7 Single Ascending Dose (SAD): IV and SC Halozyme 2.5 mg/kg IV N=8 60 mg/kg IV N=8 10-10-10-10* mg/kg IV N=8 60 mg/kg SC N=8 60-10-10# mg/kg IV N=8 80 mg/kg IV N=8 10-50-20# mg/kg IV N=8 15 mg/kg SC N=8 Broad dose range investigated with both IV and SC formulations (up to 80 mg/kg and 60 mg/kg respectively) 102 subjects dosed (70 in SAD, 32 in MAD) yielding comprehensive clinical, PK/PD and biomarker dataset 75 subjects exposed to ARGX-117 15-15-15-15* mg/kg SC N=8 Multiple Ascending Dose (MAD): IV and SC Halozyme IMP= Investigational Medicinal Product *IMP administered on Days 1, 8, 15 & 22 #IMP administered on Days 1, 8 & 22 56#57Phase 1 Safety Results Support Proof of Concept Studies in Patients Any Grade 2 Grade 3 or higher Serious argenx ● ● 0.1 mg/kg ● 6 (75.0) 1 (12.5) 0.5 mg/kg 5 (62.5) 1 (12.5) 2.5 mg/kg Treatment-Emergent Adverse Events (TEAE) 5 (62.5) 1 (12.5) 1 (12.5) 10 mg/kg 5 (71.4) *Safety data still blinded in Phase 1 study 30 mg/kg 7 (100) 60 mg/kg 5 (62.5) 1 (12.5) TEAEs primarily Grade 1 and not dose-related Serious TEAE determined to be unrelated to drug No increased risk of infection N (%) 60 mg/kg SC 5 (62.5) 2 (25.0) 80 mg/kg 6 (75.0) 15 mg/kg SC 6 (75.0) 10-10-10-10 mg/kg 6 (75.0) 60-10-10 mg/kg Single and multiple administrations of ARGX-117 or placebo show favorable safety and tolerability profile to date* 8 (100) 10-50-20 mg/kg 8 (100) 15-15-15-15 mg/kg SC 8 (100) TEAE = treatment emergent adverse event n = number of subjects that experienced at least one TEAE % = number of subjects (n) as percentage Data Cut-off for Interim Analysis: May 20th 2021 57#58ARGX-117 SAD: Long Half-life and Sustained PD Profile Mean ARGX117 Concentration µg/ml (log scale) 1 E7- 1E6- 1E5 1E4- 1E3 1 E2- 1 E1- 14+ Beeeee 0 argenx 7 Pharmacokinetics 14 21 28 35 42 49 Conclusions 56 63 70 77 days Days 84 T 91 98 105 112 119 126 133 140 147 ● ● ● Mean Free C2 µg/ml(log scale) 100 10- 0.1- 0.01- 0 7 Free C2 levels 21 28 35 42 49 56 63 A Placebo IV/SC 0.1 mg/kg ARGX-117 IV 0.5 mg/kg ARGX-117 IV 2.5 mg/kg ARGX-117 IV 10 mg/kg ARGX-117 IV 70 77 Days -4 84 91 98 105 112 119 Estimated half-life~ 65-70 days Dose proportional increase of Cmax Sustained reduction in free C2 levels by 95% for > 100 days as of 30 mg/kg dose 95% reduction 99% reduction 30 mg/kg ARGX-117 IV 60 mg/kg ARGX-117 IV 60 mg/kg ARGX-117 SC 80 mg/kg ARGX-117 IV 126 133 140 147 58#59ARGX-117 MAD: Consistent Activity Mean ARGX117 Concentration µg/ml (log scale) 1E7 1 E6- 1E5- 1E4 0 argenx 7 Pharmacokinetics 14 Conclusions 21 Days 28 ● ● 35 42 49 Mean Free C2 µg/ml(log scale) 100 10- 0.1- 0.01- 0 7 14 21 Free C2 levels 28 35 42 49 Days 56 63 Placebo IV/SC on days 1, 8, 15, 22, and/or 29 60, 10, 10 mg/kg ARGX-117 IV on days 1, 8, and 22 10, 50, 20 mg/kg ARGX-117 IV on days 1, 8, and 22 10 mg/kg ARGX-117 IV on days 1, 8, 15, and 22 70 77 Induction dose followed by maintenance dosing concept established Resulting robust PK/PD model informing dosing strategy for Phase 2 studies 1.0 μg/ml T 84 0.2 µg/ml 91 98 59#60Model Predicts Potential for Infrequent Dosing argenx Free C2, mg/L 20.00 1.00 0.10 0.01 0 Free C2 levels Free C2 concentration-time plot 60 mg/kg LD + 10 mg/kg Q2W from Week 1 onwards 40 mg/kg Q4W 60 mg/kg Q8W 4 Time, weeks 10 99% reduction 12 14 1 16 Model assumes full complement blockage as of free C2 levels < 0.2 µg/mL or >99% reduction of free C2 levels 60#61Phase 1 Data Support Path Forward and Potential for Individualized Dosing Schedule in Patients Favorable safety & tolerability profile supports advancing to Phase 2 patient trials Consistent PK/PD profile across IV and SC dosing that may enable infrequent dosing Phase 2 trial in multifocal motor neuropathy (MMN) to start by end of year argenx 61#62Multifocal Motor Neuropathy: A Serious, Debilitating Autoimmune Disease Need for new therapies that slow progression of disease and reduce reliance on IVlg UNMET NEED PREVALENCE ~13,000 patients in the U.S. - increasing Often underdiagnosed Predominantly men argenx Median age 40 years HALLMARK Slowly progressive muscle weakness due to motor neuron degeneration Mainly affects hands and forearms - patients become dependent DIAGNOSIS Often misdiagnosed as ALS Takes ~1.5 years for correct diagnosis Nerve conduction blocks Anti-GM1 IgM antibody presence >$0.5B IVlg sales and growing Persson et al., Br J Dermatol. 2021; Tedbirt et al., JAMA Dermatol. 2021; Wertenteil et al., J Am Acad Dermatol. 2019; argenx market research Steroids ineffective First line and only approved therapy is frequent, high doses of IVlg over 2-5 days 62#63Anti-GM1 Antibodies Activate Classical Complement Pathway 1 IgM autoantibodies bind to GM1 located on motor neurons and Schwann cells 3 Complement activity correlates with disease severity argenx IgM muscle CP activity (%) Schwann cell 110 100 90 80 axon motor endplate Minor myelin node of Ranvier + GM1 Vlam et al, Neurol Neuroimmunol Neuroinflamm. 2015 Yuki et al, J Peripheral Nervous System. 2011 cell body Į Mild Moderate Severe Muscle weakness 2 IgM autoantibodies are potent activators of the complement cascade IgM titer is correlated with classical pathway complement deposition 4 SOC IVlg reduces C3b deposition A C3b deposition (OD) Complement depositon (OD) تن 2 - 0 0 2.5 XO O -------.. 5 -- C1q -* C4b → C3b 2 Anti-GM1 antibody titer (OD) OHSA 10 Concentration (mg/ml) 3 IVIG IgM autoantibodies cannot be addressed by efgartigimod 63#64ARGX-117 Inhibits Complement Deposition on Motor Neurons and Schwann Cells Motor neurons Schwann cells argenx C3 DEPOSITION C3 DEPOSITION U UMC Utrecht Isotype control IVIg Serum MMN Patient C2 depleted serum C2 depleted serum + 100% C2 ARGX-117 64#65ARGX-117 Blocks C3 Deposition in Dose-Dependent Manner Motor neurons Schwann cells argenx C3 DEPOSITION C3 DEPOSITION U UMC Utrecht Isotype control C2 depleted serum ARGX-117 (200 µg/mL-3,1 µg/mL) Reconstitution with hC2 (1,97 µg/mL - 30 µg/mL) 65#66ARGX-117 Protects Axon Integrity While Blocking C3 Deposition in ex vivo Model ARGX-117 prevents loss of neurofilament staining at the nerve terminal and thereby preserves the integrity of the axon by blocking C3 deposition and downstream complement activation argenx C3 deposition Neurofilament Isotype control GalNACT-/-(neuronal mice) - Yao et al., Journal of Neuroscience. 2014; Mouse model - McGonigal et al., Acta Neuropathologica Communications. 2016 ARGX-117 66#67Phase 2 Multifocal Motor Neuropathy Trial Design Patient Population Trial to enroll approximately 45 MMN patients ● ● ● ● Probable or definite MMN (per EFNS/PNS 2010) Independent adjudication committee Stable IVlg regimen IVlg treatment dependent ili argenx 4-10 weeks IVIg Monitoring Period Randomization (1:1:1) Total Duration: 16 weeks ARGX-117 Dose Regimen 1 (N=15) ARGX-117 Dose Regimen 2 (N=15) Placebo (N=15) ARGX-117 Open-label Extension Trial on track to start by end of 2021 Key Outcome Measures Safety and tolerability Time to IVlg re-treatment Measures of peripheral muscle strength: grip strength, mMRC sum score, 9-HPT, MMN-RODS Patient-reported outcomes PK, PD, biomarkers 67#68ARGX-117: Pipeline-in-a- Product Opportunity fitting our franchises argenx Indications IgAN Therapeutic Franchises Kidney Classical Lectin Pathway Pathway IRI LN C4GN Skin MN Heme Neuro BP HS ALS MG CAD ITP MGUS anti-MAG GBS MMN 68#69Q&A Tim Van Hauwermeiren Chief Executive Officer and Co-Founder, argenx Hans de Haard, PhD Chief Scientific Officer and Co-Founder, argenx Wim Parys, MD Chief Medical Officer, argenx Keith Woods Chief Operating Officer, argenx Karl Gubitz Chief Financial Officer, argenx Bas van der Woning, PhD Research Fellow, argenx Peter Verheesen, PhD Research Fellow, argenx Rohit Aggarwal, MD, MS University of Pittsburgh Russell P. Hall III, MD Duke University Olivier Van de Steen, MD Medical Director, argenx Inge Van de Walle, PhD Principal Scientist, argenx argenx