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Capital Markets DayNovember 3, 2026
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•InflaRx N.V . Important notice and disclaimerThis presentation has been prepared by InflaRx N.V. (“InflaRx” or “we”). This presentation is made for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy securities in any jurisdiction in which such offer or solicitation would be unlawful prior to the registration or qualification of such securities under the securities law of any such jurisdiction.This presentation contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “estimate,” “believe,” “predict,” “potential” or “continue,” among others. Forward-looking statements appear in a number of places throughout this presentation and may include statements regarding our intentions, beliefs, projections, outlook, analyses and current expectations concerning, among other things, the therapeutic potential of izicopan in renal and other complement-mediated diseases; the success of our future clinical trials for izicopan’s treatment of AAV and other renal diseases, including aHUS, IgAN and C3G, as well as our assessment of a broader development and registrational strategy in Europe following the revocation of the marketing authorization for Tavneos (avacopan) in the European Union, the United Kingdom and other jurisdictions, and our ability to establish proof of concept for izicopan across such indications; the timing of initiation, enrollment and data readouts of our planned Phase 2 trials of izicopan in AAV, the investigator-initiated trial in aHUS, our planned pilot study in IgAN and our PK bridging study in China; the timing, progress and results of the Phase 3 trial of BDB-001 being conducted by our collaborator Staidson in China; the timing, progress and results of preclinical studies and clinical trials of vilobelimab, izicopan and any other of our product candidates; our interactions with regulators regarding the results of clinical trials and potential regulatory approval pathways, including potential regulatory paths in AAV for vilobelimab and izicopan and related discussions with the FDA and EMA; the timing and outcome of any discussions or submission of filings for regulatory approval of vilobelimab, izicopan or any other product candidate, and the timing of and our ability to obtain and maintain full regulatory approval and/or marketing authorization for any indication; potential strategic transactions or collaborations, including a potential partnership of izicopan or vilobelimab for PG, HS, CSU or any other indications; our expectations regarding the size of the patient populations for, the market opportunity for and the potential peak sales of izicopan, if approved; whether the FDA, EMA or any comparable foreign regulatory authority will accept or agree with the number, design, size, conduct or implementation of our clinical trials, including any proposed primary or secondary endpoints for such trials; whether the results of our future clinical trials will reflect results seen in previously conducted preclinical studies and clinical trials, and the limitations of cross-study comparisons of izicopan to other product candidates or approved products, including avacopan; our ability to leverage our proprietary anti-C5a and anti-C5aR technologies to discover and develop therapies to treat complement-mediated immunological and inflammatory diseases; our ability to protect, maintain and enforce our intellectual property protection for vilobelimab, izicopan and any other product candidates, and the scope of such protection; our manufacturing capabilities and strategy, including the scalability and cost of our manufacturing methods and processes, the optimization of our manufacturing methods and processes, and our ability to rely on existing third-party manufacturers or engage additional third-party manufacturers for planned future clinical trials and commercial supply; our estimates of our expenses, ongoing losses, future revenue, capital requirements and our needs for or ability to obtain additional financing, and the period through which our existing cash, cash equivalents and marketable securities will be sufficient to fund our operations; our ability to defend against liability claims resulting from the testing of our product candidates in the clinic or, if approved or authorized, any commercial sales; if any of our product candidates obtain regulatory approval or authorization, our ability to comply with and satisfy ongoing drug regulatory obligations and continued regulatory oversight; our ability to comply with enacted and future legislation in seeking marketing approval, authorization or commercialization; our future growth and ability to compete, which depends on our retaining key personnel and recruiting additional qualified personnel; our competitive position and the development of and projections relating to our competitors in the development of C5a and C5aR inhibitors (including avacopan) and other therapeutic products being developed in similar medical conditions in which vilobelimab, izicopan or any other of our product candidates is being developed or our industry; risks related to our reliance on foreign third-party manufacturers and suppliers, including those located in China; and the risks, uncertainties and other factors described under the heading “Risk Factors” in our periodic filings with the SEC. These statements speak only as of the date of this presentation and involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and we assume no obligation to update these forward-looking statements, even if new information becomes available in the future, except as required by law.Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources, as well as InflaRx’s own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. All market data and other information from third-party sources involve a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Further, while we believe our own internal research is reliable, such research has not been verified by any independent source.InflaRx (Nasdaq: IFRX) is a biopharmaceutical company pioneering anti-inflammatory therapeutics by applying its proprietary anti-C5a and anti-C5aR technologies to discover, develop and commercialize highly potent and specific inhibitors of the complement activation factor C5a and its receptor, C5aR. C5a is a powerful inflammatory mediator involved in the progression of a wide variety of inflammatory diseases. InflaRx‘s lead program is izicopan, an orally administered small molecule inhibitor of C5a-induced signaling via the C5a receptor, which has shown promising PK/PD characteristics as well as therapeutic potential in Phase 1 and Phase 2a clinical studies. The Company is developing izicopan for the treatment of ANCA-associated vasculitis and additional renal diseases. InflaRx also has developed vilobelimab, a novel, intravenously delivered, first-in-class, anti-C5a monoclonal antibody that selectively binds to free C5a and has demonstrated disease-modifying clinical activity and tolerability in multiple clinical studies. InflaRx and the group has offices and subsidiaries in Jena and Munich, Germany, as well as Ann Arbor, MI, USA. For further information, please visit www.inflarx.de. InflaRx GmbH (Germany) and InflaRx Pharmaceuticals Inc. (USA) are wholly owned subsidiaries of InflaRx N.V. (together, InflaRx). Comparisons to avacopan in this presentation are not based on head-to-head clinical trials, are derived from cross-study comparisons and preclinical and in vitro data, and may not be predictive of clinical results.
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Today’s agenda01WelcomeNiels Riedemann 04AAV clinical development and commercial opportunityNiels Riedemann, Thomas Taapken05Closing remarks06Q&A sessionInflaRx team, Jörg Köhl, Peter Merkel PROF . DR. NIELS RIEDEMANNChief Executive Officer & Founder DR. THOMAS TAAPKENChief Financial Officer GABRIELA ALPEROVICH,MD, PHDSVP, Global Head of Clinical Development JAN MEDINA, CFAVice President, Head of IR 3 02Targeting C5a/C5aR in ANCA-associated vasculitis (AAV)PROF . DR. JÖRG KÖHL Director of the Institute for Systemic Inflammation Research, University of Lübeck 03The evolving treatment landscape and unmet need in AAVPETER MERKEL, MD, MPHChief, Division of Rheumatology; Professor of Medicine (Rheumatology); Professor of Epidemiology in Biostatistics and Epidemiology; University of Pennsylvania InflaRxParticipants
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•InflaRx N.V . IzicopanNext-generation oral C5aR inhibitor
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Izicopan’s “triple threat” for a potential best-in-class agent 5Sources: InflaRx data on file; for TAVNEOS (avacopan) US prescribing information, EU SmPC, NDA filing documents for ANCA-associated vasculitis. No head-to-head clinical studies performed with izicopan vs avacopan. Abbreviations: AUC [Area under curve]. CYP [cytochrome]. DDI [drug-drug-interaction]. GSH [glutathione]. h [hour]. min [minutes]. mg [milligram]. FAST ONSET + HIGH EXPOSUREPOTENTIAL FOR BETTER EFFICACY ≤1 weekto target therapeutic exposure (vs avacopan at ~3 months) •~10× AUC, ~3× Cmax at equal doses•≥90% C5a blockade within 24 h•~2× in vivo inhibition, head-to-head NO SAFETY SIGNALS OF CONCERN >100x lowerreactive-metabolite signal(GSH trapping assay 5-10 min) •No time-dependent CYP3A4/5 inhibition•Very high metabolic stability•197 subjects dosed, no safety signals of concern, no liver enzyme elevations BETTER CONVENIENCE pill burden3 x drug strength per capsule30 mg vs. 10 mg •Expected lower pill no. intake•Once-daily dosing potential•Fewer co-medication restrictions expected (less DDI concern)
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Today’s takeaways§Izicopan has potential to expand the AAV market, with multiple differentiating features that could drive a $1.5B – $2B peak sales potential§Izicopan AAV development program is primed for generating differentiated efficacy and safety data -placebo-controlled study in patients with renal vasculitis (i.e., renal involvement)assessing izicopan’s ability to drive signals of efficacy over the standard of care-open-label study in “all-comers” to demonstrate the ability to replace corticosteroids§Additional studies in rare renal disease targeted for initiation in 2027 include aHUS, with initial data targeted for 2H 2027; and IgAN / rapidly progressiveIgAN/ others, with expected initial data readouts in 2028§Phase 3 data from BDB-001 (vilobelimab cell-line derived anti-C5a antibody licensed to partner in China) expected 2H 2028§Strong IP position and balance sheet (€153.3M at end of 3Q26), with cash runway through 2029 61: Independent commercial assessment (Oct 2026); Evaluate Pharma 2026. Izicopan is investigational; third-party forward-looking estimates, not company guidance // I&I [immunology & inflammation]. AAV [ANCA-associated vasculitis]. aHUS [atypical hemolytic uremic syndrome]. IgAN [immunoglobulin-A nephropathy]. RPGN [rapidly progressive glomerulonephritis]
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Prof. Dr. Jörg KöhlTargeting C5aR1-driven inflammation in ANCA vasculitis and beyond
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ANCA-associated vasculitisA group of rare, systemic small-vessel vasculitides AAV WHAT IT ISNecrotizing inflammation damages predominantly small blood vessels, with few or no immune deposits.Antineutrophil cytoplasmic antibodies usually target proteinase 3 (PR3) or myeloperoxidase (MPO). Some patients are ANCA-negative. ANCA neutrophilsmall-vessel injuryANCA can activate primed neutrophils, promoting endothelial injury and organ inflammation. THREE CLINICAL TYPES GPAGranulomatosis with polyangiitisGranulomatous disease of the upper and lower airways; kidneys commonly involvedPR3-ANCA often predominates MPAMicroscopic polyangiitisNon-granulomatous vasculitis; rapidly progressive glomerulonephritis and lung capillaritis are typicalMPO-ANCA often predominates EGPAEosinophilic granulomatosis with polyangiitisAsthma and eosinophilia with eosinophil-rich inflammation; nerves, lungs, skin, heart or kidneys may be affectedANCA present in only a subset Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 8
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Nakazawaet al NatRevRheumatol2019 Pathwaysdrivingthe pathogenesisof ANCA-associatedvasculitis •InfectiousstimuliactiveDCs to driveTh17 àTNF/IL-1ß •TNF/IL-1ß prime neutrophilsàMPO/PR3 surfacetransition •ComplementAP activationàC5a –> neutrophil priming •ANCAs bind and activateFcgRson neutrophilsàROS •Infectionand ANCA-inducedNET formationon neutrophils •Antigen presentationand B cellstimulationof CD4+ T cell-derivedIL-21 and neutrophil-derivedBAFF enhanceANCAgeneration Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 9
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A Nakazawaet al NatRevRheumatol2019 Activationof complementand importanceof the C5/C5a/C5aR1 axisin PMN priming Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 10
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C5-deficient miceareprotectedfromanti-MPO-inducedcrescentGN Xiao et al. AJP 2007Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 11 Gou et al. ClinJ Am Soc Nephrol2013
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Schreiber et al. JASN 2009 C5aR1-deficient miceareprotectedfromanti-MPO-inducedcrescentGN C5ar1-/-Wildtype WildtypeC5ar1-/- Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 12 Brillandet al. Kidney IntRep 2026
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Xiao et al. JASN 2014 C5aR1-deficientbut not C6-deficient miceareprotectedfromanti-MPO-inducedGN Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 13
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B Falk et al. ProcNatlAcadSci1990 Activationof FcgRson neutrophilsby ANCA-speficicIgGdrivesROS release fromneutrophils Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 14
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The C5a/C5aR1 axissynergizeswithFcgRsto promote a pro-inflammatoryenvironment SynergisticeffectsonInflammation Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 15
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Amplificationof neutrophil activationthroughcross-talk betweenC5aR1 and activatingFcgRs Heller et al. JI 1999Shushakova et al. JCI 2002Godau et al. JI 2004Skokowa et al. JI 2005Kumar et al. JCI 2006 Karsten and Köhl Immunobiol 2012 Schreiber et al. JASN 2009Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 16
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C Activationof FcgRson neutrophilsdrivesNET formation Kessenbrocket al. NatMed2009 HealthyCtrlSerum MPO AAV Serum Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 17
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C C5aR1 drivesNETosis Neutrophil Critical driverofofinflammationinNeutrophilsSilva et al J ClinInvest2023 /Byrd et al. Sci. Immunol.2019 C5aR1 on neutrophilsdrivesNETosis Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 18
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C Kessenbrocket al Nat Med 2009 Huang et al. ArthrRheumatol2015 HealthyCtrlSerum MPO AAV Serum MPO AAV SerumAnti-C5ar1 mAb+ Cross-talk betweenFcgRsand C5aR1 on neutrophilsdrivesNET formation Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 19
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Nakazawaet al NatRevRheumatol2019 Pathwaysdrivingthe pathogenesisof ANCA-associatedvasculitis Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis D Page 20
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An autocrineC5/C5a/C5aR1 loop controlsGerminal Center B celldifferentiationand IgG1/IgE classswitch WTC5ar1-/- Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisCreated in Page 21 Einwohltet al (unpublished)
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KeyMessages Why targetingC5aR1 in ANCA-associatedvasculitis? Key Message 2C5aR1 primes and activatesneutrophilsas the keyeffectorcell. It isintertwinedwithFcgR-mediatedneutrophil activationby ANCA Key Message 4Tailored targeting effect:Blocking C5aR1 leaves upstream and downstream complement pathways intact Key Message 1Genetic or pharmacological C5aR1 targeting strongly reduces disease development in preclinical AAV disease models Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis Key Message 3Evidencefor an intrarenal complement-relatedtranscriptionalprogramin AAV patientswithincreasedC5AR1geneexpressionBrillandet al. Kidney IntRep 2026, JASN 2026 Page 22
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Outlook – role of the C5a/C5aR1axis in the AKI to CKD transition Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis
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Ma. et al.Nephrol. Dial. Transplant.2026Created in C5aR1 signalingin tubularepithelial cellsdrivesAKI-CKD transitionby enhancingautophagyin ischemiareperfusioninjury Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 24
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Sahu et al.Am. J. Physiol. Renal Physiol.2022 Created in Myeloid and pericyteC5aR1 signalingdrivesAKI-CKD transitionina folic-acidinjurymodel Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitisPage 25
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Page 26 1.Schreiber, A. et al.J. Am. Soc. Nephrol.2009.2.Ma, J. et al.Nephrol. Dial. Transplant.2026. 3.Sahu, R. K. et al.Am. J. Physiol. Renal Physiol.2022. 4.Yu, S. M.-W. et al.Am. J. Pathol.2025. 5.McGraw, M. et al.Physiol. 2026. 6.Brilland, B. et al.J. Am. Soc. 2026. 7.Brilland, B. et al.Kidney Int. 2026. 8.Almaani, S. et al.Kidney Int. 2023. Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis Created in
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Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis https://isef-luebeck.de/ Page 27 Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis Thankyoufor yourattention
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Appendix
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Page 29 Prof. Dr. Jörg Köhl – Role of C5aR1 in ANCA-associated vasculitis
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Peter Merkel, MD, MPHChief, Division of Rheumatology; Professor of Medicine (Rheumatology); Professor of Epidemiology in Biostatistics and Epidemiology; University of Pennsylvania
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 1 Standard of Care and Unmet Medical Needs in ANCA-Associated Vasculitis Peter A. Merkel, M.D., M.P.H. Chief, Division of Rheumatology PI, Vasculitis Clinical Research Consortium Director, Penn Vasculitis Center Professor of Medicine and Epidemiology University of Pennsylvania Philadelphia, PA, USA pmerkel@upenn.edu; 1-215-614-4401 November 3, 2026 All content © Peter A. Merkel, MD, MPH
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 2 Presentation Outline Brief introduction to the clinical spectrum of ANCA-associated vasculitis (AAV), specifically, granulomatosis with polyangiitis (GPA) / microscopic polyangiitis (MPA) Outline unmet needs for the treatment of AAV Based on current sets of consensus guidelines and key clinical trials, review the standard of care for the treatment of AAV Discuss the results of the ADVOCATE trial of avacopan, a C5aR inhibitor
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 3 Adapted from A&R 2013 Variable Vessel Vasculitis Behçet's Disease Cogan’s Syndrome Single-Organ Vasculitis CNS Vasculitis Other Organs Drug-Induced Vasculitis Relapsing Polychondritis IgG4-Related Disease Vasculitis in CTD SLE, SSc, SjS, RA, etc.
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 4 Clinical Features of ANCA-Associated Vasculitis: GPA/MPA Upper airway disease - Nasal septum - Sinuses - Subglottic stenosis - Mastoiditis/OM/ - Conductive hearing loss Pulmonary disease - Nodules - Alveolitis/capillaritis - ILD-fibrosis - Other Glomerulonephritis Neuropathy - Sensory - Motor - CNS - Sensorineural hearing loss Arthritis/arthralgias Malaise/Fatigue Eye disease - Scleritis/episcleritis - Pseudotumor Skin/Mucosa - Oral ulcers - Purpura - Nodules Vascular - Gangrene - Venous thrombosis Cardiac Disease GI Disease Laboratory Findings - ANCA - Proteinemia - Hematuria - Elevated ESR/CRP - Anemia Other Upper airway disease - Nasal septum - Sinuses - Subglottic stenosis - Mastoiditis/OM/ - Conductive hearing loss Pulmonary disease - Nodules - Alveolitis/capillaritis - ILD-fibrosis - Other Glomerulonephritis Neuropathy - Sensory - Motor - CNS - Sensorineural hearing loss Arthritis/arthralgias Malaise/Fatigue
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 5 Treatment of AAV: Unmet Needs Less toxic regimens -Glucocorticoid-sparing -CYC-sparing/avoiding -Non-sterilizing & non-teratogenic drugs -Reduction in infections More rapid induction of remission Prevention of relapse/remission-maintenance -Relapse rates are still high, even on treatment Prevention/reversal of damage, especially kidney/neuro Treatment of exceptionally resistant disease Avoidance of chronic immunosuppression Treatment of mild-moderate disease Treatment of flares (short-term) Advances in non-drug therapies CURE New treatments are still needed!
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 6 Treatment of AAV: Unmet Needs Less toxic regimens -Glucocorticoid-sparing -CYC-sparing/avoiding -Non-sterilizing & non-teratogenic drugs -Reduction in infections More rapid induction of remission Prevention of relapse/remission-maintenance -Relapse rates are still high, even on treatment Prevention/reversal of damage, especially kidney/neuro Treatment of exceptionally resistant disease Avoidance of chronic immunosuppression Treatment of mild-moderate disease Treatment of flares (short-term) Advances in non-drug therapies CURE New treatments are still needed!
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 7 Glucocorticoid Toxicity Psychosis Insomnia Anxiety/depression Hyperactivity Cataracts Glaucoma Weight gain Cushingoid appearance Diabetes mellitus Adrenal suppression Myopathy Hypertension Heart failure Edema Skin fragility/ecchymoses Osteoporosis Osteonecrosis Infections Reduced vaccine response More…
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 8 Treatment of AAV: Unmet Needs Less toxic regimens -Glucocorticoid-sparing -CYC-sparing/avoiding -Non-sterilizing & non-teratogenic drugs -Reduction in infections More rapid induction of remission Prevention of relapse/remission-maintenance -Relapse rates are still high, even on treatment Prevention/reversal of damage, especially kidney/neuro Treatment of exceptionally resistant disease Avoidance of chronic immunosuppression Treatment of mild-moderate disease Treatment of flares (short-term) Advances in non-drug therapies CURE New treatments are still needed!
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 9 Renal (Kidney) Disease in AAV Major source of morbidity and mortality in AAV Residual kidney function after initial disease or a relapse is highly predictive of mortality Rates of end-stage kidney disease (ESKD, dialysis) in AAV remain high - ESKD is associated with marked reductions in function, HRQoL, and increases in disability, mortality, and costs Rapid effective treatment of kidney disease in AAV is a major goal of new treatment strategies Outcomes of kidney disease are easily measured: - Serum creatinine/estimated glomerular filtration rate (eGFR) - Urinary protein levels (measured as urine protein:creatinine ration (UPCR) - Urinary biomarkers of kidney physiology: helpful in Phase II trials
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 10 Standard of Care Treatment for AAV Based on data from >25 years of high-quality, large, multi-center, randomized, controlled, clinical trails
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 11 International Guidelines for Treatment of AAV
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 12 TREATMENT OF ANCA-ASSOCIATED VASCULITIS Remission Induction (3-6 Months) Remission Maintenance (6-48 Months-Indefinite) Severe Disease Azathioprine Methotrexate [Mycophenolate (3rd Choice)] or or Rituximab Rituximab Observe off Treatment Glucocorticoids ??? Cyclophosphamide Avacopan + Non- Severe Disease Methotrexate Methotrexate Rituximab Rituximab
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 13 Rituximab is the current mainstay of treatment for AAV Rituximab was a major advance in the treatment of AAV Repeated use (every 6 months) with continuous B cell depletion is now the usual treatment for AAV - Once rituximab is discontinued high rate of relapse However - Still only 70% of patients enter glucocorticoid-free remission on rituximab at 6 months - Relapses happen later, too - Rituximab leads to chronic immunosuppression and risk of infection We seek new treatments for AAV beyond B cell depletion
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 14
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 15 Post-ADVOCATE NEJM Retraction Actions Amgen sponsored an independent full readjudication of the primary outcome data for all study patients and re-analyzed the results using the original statistical analysis plan A new report focusing on primary outcome at 26 and 52 weeks was published on August 14, 2026 on the medRxiv preprint server A complete report incorporating the readjudicated data and more will be forthcoming in a standard publication
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 16 ADVOCATE Report with Readjudicated Data Note: This paper has not been peer-reviewed
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 17 ADVOCATE Report with Readjudicated Data: 26 Weeks
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 18 ADVOCATE Report with Readjudicated Data: 52 Weeks
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 19 ADVOCATE with Readjudicated Data Secondary Outcomes • None of the key secondary outcomes were impacted by the issue of adjudication or readjudication – The raw data was unaffected by the issue of readjudication, including eGFR, glucocorticoid toxicity, HRQoL • Avacopan vs. Prednisone Taper Less glucocorticoid-related toxicity in avacopan group Greater improvement in quality-of-life measures in avacopan group More recovery of kidney function in avacopan group
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 20 Detailed kidney outcomes in ADVOCATE These analyses are not impacted by the readjudication issues in ADVOCATE
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 21 Report of kidney outcomes among the 268/330 (81%) of patients in ADVOCATE with kidney disease at baseline
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 22 Change in UACR from baseline in patients with kidney involvement and baseline UACR > 300 mg/g. Kidney Int Rep 2025
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 23 Analysis of kidney outcome in ADVOCATE among patients with eGFR ≤20 ml/min per 1.73 m2 N=50 patients 2025
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 24 Change in kidney function among patients in the ADVOCATE trial with baseline eGFR ≤20 ml/min per 1.73 m2. *P < 0.05 **P < 0.01 Kidney Int Rep 2023
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 25 Treatment of AAV: Unmet Needs Less toxic regimens -Glucocorticoid-sparing -CYC-sparing/avoiding -Non-sterilizing & non-teratogenic drugs -Reduction in infections More rapid induction of remission Prevention of relapse/remission-maintenance -Relapse rates are still high, even on treatment Prevention/reversal of damage, especially kidney/neuro Treatment of exceptionally resistant disease Avoidance of chronic immunosuppression Treatment of mild-moderate disease Treatment of flares (short-term) Advances in non-drug therapies CURE New treatments are still needed!
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 26 Benefits of More Rapid Induction of Remission of AAV Prevent progression to organ- or life-threatening status Preserve kidney function predictor of long-term outcome Prevent damage to other organs; e.g. nerves, airways Allow for more rapid reduction or elimination of glucocorticoids Reduce hospitalization length of stay
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 27 Treatment of AAV: Unmet Needs Less toxic regimens -Glucocorticoid-sparing -CYC-sparing/avoiding -Non-sterilizing & non-teratogenic drugs -Reduction in infections More rapid induction of remission Prevention of relapse/remission-maintenance -Relapse rates are still high, even on treatment Prevention/reversal of damage, especially kidney/neuro Treatment of exceptionally resistant disease Avoidance of chronic immunosuppression Treatment of mild-moderate disease Treatment of flares (short-term) Advances in non-drug therapies CURE New treatments are still needed!
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 28 The Potential of Enhanced Complement Inhibition for the Treatment of AAV Stronger/better complement inhibition could result Overall better outcomes Faster remission Faster and greater recovery of kidney function Less permanent damage to kidneys and other organs An alternativee to rituximab for maintenance of remission Reduction or elimination of use of glucocorticoids
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Standard of Care and Unmet Needs in AAV Peter A. Merkel, MD, MPH November 3, 2026 ©Peter A Merkel MD MPH 2025 29 Summary Treatment of patients with AAV has improved markedly over the past 25 years However, the rates of remission, relapse-free remission, and prevention of organ damage, especially kidney function, remain unacceptably low Strong inhibition of complement C5a/C5aR offers the potential for substantially improving treatment of AAV and the lives of patients with this challenging disease
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•InflaRx N.V . IzicopanNext-generation oral C5aR inhibitor
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Potential for better efficacy: fast onset with deep C5aR blockade 61 FAST ONSET OF ACTION Week 1Izicopan exceeds avacopan’s steady state exposure within first week*Izicopan≤1 weekAvacopan~13 weeks IzicopanAvacopan ~10× higher exposureAUC (h·ng/mL) after a single 30 mg dose, Phase 1**5,197557 ≥90% C5a blockade in 24 hEx vivo CD11b; izicopan 30 mg BID at 24 h vs. avacopan day-7 trough, phase 1** 94%~50% ~2× in vivo C5aR inhibitionHead-to-head hamster C5a neutropenia model, 10 mg/kg oral** ~90%~50% Izicopan’s faster onset of action is supported by Ph1 SAD & MAD data, and a Ph2a basket study in HS & CSU, where improvements began by Week 1 and deepened to Week 4* Avacopan steady state reported from AAV approval filings, izicopan plasma exposure from phase 2 a studies in different disease setting (Hidradenitis suppurativa and Chronic spontaneous urticaria) – InflaRx data on file** Cross-study comparison: Avacopan was not a comparator in izicopan Ph1. CD11b challenge 12.6 vs 10 nM C5a. Sources: For InflaRx clinical phase 1 data Grippo JF et al. Clin Pharmacol Drug Dev. 2026 and preclinical data on file; For Avacopan Bekker et al., PLoS One 2016; TAVNEOS USPI., NDA filing of avacopan for ANCA-associated vasculitis. Abbreviations: AUC [Area under curve]. BID [twice daily]. CSU [Chronic spontaneous urticaria h [hour]. HS [Hidradenitis Suppurativa]. Kg [kilogram]. MAD [multiple ascending dose]. mg [milligram]. Ph [phase]. SAD [single ascending dose].
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Potential for better safety: lower liver and drug-drug interaction risk 62 REACTIVE METABOLITES* >100-fold lowerreactive-metabolite signal than avacopan in the early reaction phase (GSH trapping, 5–10 min) GSH-conjugate signal, avacopan relative to izicopan (log scale)5–10 min>100×20–40 min>10× Izicopan: no TDI in Ki/kinact assay; IC50 >100 µMAvacopan: TDI of CYP3A4/5; midazolam AUC up 1.8-fold Izicopan: very low clearance in human microsomes and hepatocytesAvacopan: high CYP-mediated turnover in the same assays Izicopan: 197 humans dosed, no safety signals of concernAvacopan: label warns of life-threatening liver injury 197 human subjects have been dosed with izicopan to-date - Ph1 SAD & MAD - Ph2a in HS & CSU - othersIzicopan’s cleaner metabolic profile suggests lower liver toxicity risk and a low risk of drug-drug interaction*In vitro data unless stated. Sources: InflaRx clinical and preclinical data on file, Izicopan phase 1 First-in-human data in Grippo JF et al. Clin Pharmacol Drug Dev. 2026; TAVNEOS USPI and EU SmPC; FDA/CDER, 2026 (as reported). Abbreviations: AUC [Area under curve]. CSU [Chronic spontaneous urticaria]. CYP [cytochrome]. DDI [drug-drug-interaction]. GSH [glutathione]. h [hour]. HS [Hidradenitis Suppurativa]. MAD [multiple ascending dose]. min [minutes]. mg [milligram]. Ph [phase]. SAD [single ascending dose. TDI [time-dependent inhibition]. No time-dependent CYP3A4/5 inhibition* Very high metabolic stability* Strong safety profile to date
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Better convenience: potential for simpler dosing and fewer drug-drug interactions 63 PILL BURDEN at equivalent dose, 1 pill twice per day vs 3 pills twice per day for avacopanCapsules per day, by regimenAvacopan 30 mg BID (label) – 6 pills total Izicopan 60 mg BID (Ph2a) – 4 pills totalIzicopan 30 mg QD (Ph1) – 1 pill per day Izicopan could provide a simpler dosing regimenIzicopan could be further differentiated from competitors given its lack of vaccine requirement*Izicopan Ph1 first-in-human trial published in Grippo JF et al. Clin Pharmacol Drug Dev. 2026 and InflaRx data on file; **InflaRx data on file. Clinical Drug-Drug interaction study not yet performed. AAV dose and regimen to be set in Phase 2. Sources: TAVNEOS USPI and EU SmPC.Abbreviations: AUC [Area under curve]. BID [twice daily]. CYP [cytochrome]. mg [milligram]. Ph [Phase]. PK [pharmacokinetic]. QD [once daily]. TDI [time-dependent inhibition]. pill countOnce-daily [QD] dosing potentialIzicopan: 30 mg QD reached ≥90% C5a blockade by day 6, phase 1* , supported by PK modeling of phase 2 dataAvacopan: twice daily, 3 capsules per dose No CYP time dependent inhibition concern**Izicopan: no CYP3A4 TDI, no CYP3A4 dose rules anticipatedAvacopan: CYP3A4 rules for inducers, inhibitors and statins High Drug StrengthIzicopan: amorphous solid, 30 mg per capsuleAvacopan: crystalline solid, 3x pill burden vs izicopan, 50% greater pill count at half the dose of izicopan
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Izicopan differentiation driven by optimized molecular structureModelling indicates that the additional trifluoromethyl group in izicopan introduces steric interactions (clashes) within the CYP3A4/5 binding pocket ...thereby providing a molecular basis for three key experimental findings:•absence of time-dependent inhibition (TDI) of CYP3A4/5•increased metabolic stability in vitro•reduced reactive metabolite formation in GSH-trapping assays Avacopan – CYP3A/4Izicopan – CYP3A/4 no trifluoromethylno clash Maestro 14.4.136 Docking Maestro 14.4.136 Docking Cyan cartoon: CYP3A4; Wheat sticks: HEMPurple sticks: Avacopan; Green sticks: IzicopanYellow dash lines: hydrogen bonds; Blue dash line: pi-pi stacking;Docking score: -8.19 (avacopan); -7.13 (izicopan) Avacopan: efficient CYP3A4/5 interaction supports high metabolic activation potentialIzicopan: weak CYP3A4/5 interaction lowers metabolic activation potential64Source: InflaRx data on file Abbreviations: CYP [cytochrome]. GSH [glutathione]. TDI [time-dependent inhibition].
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•InflaRx N.V . IzicopanAAV market considerations
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66 Market research: Physicians back izicopan as the next-generation C5aR inhibitorC5a/C5aR blockade remains a key target – physicians see izicopan’s profile as a potentially safer, more convenient successor with added potential kidney upside What drives appealComplement-class MoA 11Kidney / eGFR benefit11Oral administration11Lower hepatotoxicity10Lower pill burden10GC reduction 10Remission ≈ avacopan10Infection rate ≈ avacopan10 10/12retain confidence in C5a/C5aR inhibition despite the regulatory controversy 8/10likelihood to prescribe with GC-reduction data (7/10 without) 65-70%stated preference share in severe renal AAV if / once avacopan is withdrawn 7/12would use it routinely in most eligible severe renal patients Upside levers Source: Primary market research, Oct 2026 (draft): 12 AAV-focused nephrologists and rheumatologists (6 US, 5 EU4/UK, 1 Japan) rating an anonymized izicopan target product profile vs. avacopanAbbreviation: AAV [ANCA-associated vasculitis]. eGFR [estimated Glomerular Filtration Rate]. GC [glucocorticoids]. GPA [granulomatosis with polyangiitis. MoA [mode of action]. MPA [microscopic polyangiitis]. N [number]. GC-reduction: additional data would lead to higher prescribing likelihood 7 → 8/10; even if avacopan stays Safety benefit: after avacopan deaths in Asian patients, physicians seek strong safety evidence Wider patient pool: all GPA / MPA AAV patients become candidates; eGFR data puts kidney protection front of mind
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Izicopan in AAV: ~$1.5-2B global peak net sales potential1 67 Base-case izicopan global peak net sales $1.65bnUS $1.160MJapan $255MEU4 + UK $241M Sensitivity analysis: Peak izicopan sales by scenario, $M (ONLY in US + EU4/UK, excl. ROW) With additional GC data available 25.1keligible patients/yr50–54%net peak patient shareTailwind from increasing incidence Avacopan proven demand with $645M sales in 2025 and $1B+ peak sales potential2 before exiting key markets 1: Independent commercial assessment ( Oct 2026); Evaluate Pharma 2026. Net sales in $. Izicopan is investigational; third-party forward-looking estimates, not company guidance.2: March 2026: Guggenheim Securities, market research, Yatin Suneja – Figures and estimates by Guggenheim Securities, FactSet, Evaluate Pharma. Further upside from improved pricing power $1.4bn$1.8bn $1.3bn$1.5bn Broader label (i.e. all GPA / MPA AAV)Base case Base case(avacopan stays in US)
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•InflaRx N.V . AAV clinical development program
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Izicopan in AAV – capturing the opportunity 69 (A) Demonstrate superiority with focus on renal endpoints in randomized placebo-controlled Phase 2–Randomized, placebo-controlled Phase 2 trial optimized to increase signal delta to placebo by allowing severely ill AAV patients with renal vasculitis and dosing on top of SoC–Implementing a standard GC taper in all arms–Targeted enrollment of approximately 18 months anticipated (B) Demonstrate GC replacement opportunity with additional Phase 2 open-label study–Open-label trial to demonstrate ability to replace GC by rapid taper (stage 1) or stop at enrollment (stage 2), informed by recent positive Phase 1/2 data with BDB-001–Initial data anticipated in 2028 Development Goals Development strategy to focus on izicopan advantages in multiple clinical settingsStudies will utilize different enrollment criteria and selection of sites. Abbreviations: AAV [ANCA-associated vasculitis]. GC [glucocorticoids]. IZI [izicopan]. SOC [Standard of Care].
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Randomized, placebo-controlled Ph2 trial design Abbreviations: BID [twice daily]. BVAS [Birmingham Vasculitis Assessment Score]. eGFR [estimated Glomerular Filtration Rate]. FU [follow-up]. GC [glucocorticoids]. IZI [izicopan]. N [number]. Ph [Phase]. RTX [rituximab]. SOC [Standard of Care]. Wk [week]. Highlights•randomized, double-blind, placebo-controlled multicenter Phase 2 trial•key efficacy endpoint at wk 24•standard GC tapering (all arms)•n = ~35 per arm •randomization ratio: 1:1:1 Endpoint analysisPrimary•safetySecondary•BVAS-0 •eGFR change from baseline•proteinuria change from baseline•hematuria resolution 70 InductionScreening Wk 24MaintenanceWk 48 •Testing 2 doses on top of SOC (RTX plus standard GC tapering) in AAV patients with renal vasculitis•Designed to optimize potential benefits related to renal function and renal injury recovery and assess impact on disease activity Safety FUArm 3: IZI 60 mg BID + RTX IZI 60 mg BID + RTX Safety FUSafety FU Arm 1: Placebo BID + RTX Arm 2: IZI 30 mg BID + RTX Placebo BID + RTX Wk 52 IZI 30 mg BID + RTX Exploratory•other renal•others
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Open-label AAV Ph2 trial design planning Highlights•open-label two-stage Phase 2 trial •key safety / efficacy endpoints at wk 16 / 24 / 48 •safety assessment prior start of stage 2 •n ~ 30 patients•data in 2028 Endpoint analysisPrimary•safety including BVAS-0 assessmentSecondary•sustained remission wk 48•renal endpoints 71 •Design to demonstrate the ability of izicopan to replace GC during remission induction treatment•NewlydiagnosedormajorrelapseGPA orMPA patients in needof remissioninductiontherapy Exploratory•others IZI 60 mg BID + rapid GC taper + SOCMaintenanceInduction Safety FU Safety Assessment Wk 16Wk 24 Wk 48 IZI 60 mg BID + SOC (no GC)Safety FU Wk 16Wk 24 Wk 48IZI 60 mg BID + SOC maintenance Stage 1 Stage 2 Abbreviations: BID [twice daily]. BVAS [Birmingham Vasculitis Assessment Score]. FU [follow-up]. GC [glucocorticoids]. GPA [granulomatosis with polyangiitis]. IZI [izicopan]. MPA [microscopic polyangiitis]. N [number]. Ph [Phase]. RTX [rituximab]. SOC [Standard of Care]. Wk [week]. IZI 60 mg BID + SOC maintenance IZI 60 mg BID + SOC maintenance
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•InflaRx N.V . Development opportunities in additional renal disorders
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Planned izicopan pilot study in IgAN / RPGN in IgAN – signal searching 73 IZI 60 mg BID on top of SOCSafety FU •Open labelstudyto assesssafetyand exploreefficacyin patientswithIgANand IgANRPGN(rapidlyprogressive glomerulonephritis)•Cohortmaybeexpandedbasedon interimsignals Wk 12 Wk 24Wk 28 Signal searching study with focus on proteinuria in relation to well established placebo response rates in the field (IgAN)Exploration in IgAN RPGN as subgroup typically excluded from clinical studies (eGFR stabilization / improvement etc.) Highlights•open label Phase 2 trial•key efficacy endpoint at wks 12 / 24•n = ~20-30 total•early data readout in 2028 Endpoint analysis (exploratory)Primary•safety + proteinuria reduction (IgAN)•safety + eGFR (IgAN RPGN)Secondary•eGFR change from baseline•proteinuria change from baseline•others Abbreviations: BID [twice daily]. FU [follow-up]. GC [glucocorticoids]. eGFR [estimated Glomerular Filtration Rate]. IgAN [immunoglobulin-A nephropathy]. IZI [izicopan]. mg [milligram], N [number]. OL [open-label}.RPGN [rapidly progressive glomerulonephritis]. SOC [Standard of Care]. Wk [week]. Screening
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IIT in patientswithatypicalhemolyticuremicsyndrome(aHUS) 74 IZI 60mg BID Safety FU •Key efficacyfocusisTMA response(plateletcountnormalization, LDH normalization, kidneyfunctionimprovement≥ 25% creatininedropfrombaseline) untilweek24•Study participantsmayreceiveizicopanupto 12 mthat the discretionof the investigator Wk 1 Wk 12 Wk 24 Study to evaluate C5aR inhibition as alternative to C5 – or upstream complement inhibition in aHUS Initial responseassessmentEculizumab rescueat anytime pastweek1 -ifrescueoccurs, izicopanwill bestopped Wk 48 Highlights•open label Phase 2a pilot investigator-initiated trial •key efficacy endpoint will be TMA response•n = ~ 6 – 8•initial data in 2H 2027 Endpoint analysis (exploratory)Primary•safety + TMA responseSecondary•others Screening Abbreviations: aHUS [Atypical Hemolytic Uremic Syndrome]. BID [twice daily]. FU [follow-up]. IIT [investigator-initiated trial]. IZI [izicopan]. LDH [Lactate dehydrogenase]. mg [milligram]. Mth [month]. N [number]. OL [open-label}. RPGN [rapidly progressive glomerulonephritis]. SOC [Standard of Care]. TMA [Thrombotic Microangiopathy]. Wk [week].
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Today’s takeaways§Izicopan has potential to expand the AAV market, with multiple differentiating features that could drive a $1.5B – $2B peak sales potential§Izicopan AAV development program is primed for generating differentiated efficacy and safety data -placebo-controlled study in patients with renal vasculitis (i.e., renal involvement)assessing izicopan’s ability to drive signals of efficacy over the standard of care-open-label study in “all-comers” to demonstrate the ability to replace corticosteroids§Additional studies in rare renal disease targeted for initiation in 2027 include aHUS, with initial data targeted for 2H 2027; and IgAN /rapidly progressiveIgAN/ others, with expected initial data readouts in 2028§Phase 3 data from BDB-001 (vilobelimab cell-line derived anti-C5a antibody licensed to partner in China) expected 2H 2028§Strong IP position and balance sheet (€153.3M at end of 3Q26), with cash runway through 2029 751: Independent commercial assessment (Oct 2026); Evaluate Pharma 2026. Izicopan is investigational; third-party forward-looking estimates, not company guidance // I&I [immunology & inflammation]. AAV [ANCA-associated vasculitis]. aHUS [atypical hemolytic uremic syndrome]. IgAN [immunoglobulin-A nephropathy]. RPGN [rapidly progressive glomerulonephritis]
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•InflaRx N.V . WinzerlaerStr. 207745 Jena, GermanyEmail: ir@inflarx.comTel: +49-3641-508180Fax: +49-3641-508181 InflaRx N.V. (IFRX) www.inflarx.com