Inflarx N.v. · NASDAQ:IFRX
Inflarx — Investor Presentation (January 2025)
55 slides from Inflarx's investor presentation, Jan 15, 2025
Slide 1: Corporate Presentation January 2025
CORPORATE PRESENTATION JANUARY 2025
Slide 2: Important Notice and Disclaimer
IMPORTANT NOTICE AND DISCLAIMER This presentation has been prepared by InflaRx N.V. (“InflaRx” or the “Company”). 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. This presentation may not be relied up
Slide 3: Important Notice and Disclaimer
IMPORTANT NOTICE AND DISCLAIMER Information and Sources Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and InflaRx’s own internal estimates and research. While InflaRx believes these third-p
Slide 4: Harnessing C5a/C5aR for controlling inflammation in I&I
Harnessing C5a/C5aR for controlling inflammation in I&I InflaRx Highlights Uniquely targeting complement C5a/C5aR, a validated mechanism and critical part of the inflammation cascade with: • First-in-class and highly potent anti-C5a monoclonal antibody (vilobelimab + second generation IFX-2) • Best-
Slide 5: C5a/C5aR are validated targets promoting inflammation
C5a/C5aR are validated targets promoting inflammation Targeting strong pro-inflammatory mechanisms vilobelimab INF904 intravenous mAB oral small molecule C5 C5a C5aR expressed on many immune cells strong amplifier and upregulated in many tissues under disease of inflammation conditions Targeting C5
Slide 6: C5a/C5aR1 signaling inhibition: The importance of a targeted approach
C5a/C5aR1 signaling inhibition: The importance of a targeted approach Complement Pathways Classical Lectin Alternative Antibody binding Mannose binding Foreign surfaces 1.) through C5 convertases C3 activation MG7 (complement mediated) C5-convertases domain 2.) through enzymatic cleavage at scissile
Slide 7: Late-stage pipeline targets multiple sizable markets
Late-stage pipeline targets multiple sizable markets INDICATIONS PRECLIN PHASE 1 PHASE 2 PHASE 3 MARKET STATUS & MILESTONES critical COVID-19 US EUA granted vilobelimab C5a Inhibitor SARS-CoV-2-induced ARDS Approved by European Commission* broader ARDS Phase 2 “Just Breathe” ASPR/BARDA clinical plat
Slide 8: Significant opportunity in immuno-dermatology
Significant opportunity in immuno-dermatology Why Immuno-Dermatology • Potential to target several attractive, billion-dollar+ commercial markets • InflaRx has identified unmet medical needs that INF904 could strongly address • Strong rationale for the role of C5a/C5aR based on mechanism of action,
Slide 9: C5a & C5aR inhibition: Suggested medical utility in broader I&I
C5a & C5aR inhibition: Suggested medical utility in broader I&I by underlying pre- clinical and clinical research Infectious Autoimmune Immuno-derm • Initial focus on immuno-dermatology Cardiovascular • Vilobelimab with proven life-saving anti- inflammatory effect in critically ill COVID- C5a 19 pat
Slide 10: Vilobelimab for Ulcerative Pyoderma Gangrenosum (PG)
Vilobelimab for Ulcerative Pyoderma Gangrenosum (PG)
Slide 11: Vilobelimab: A first-in-class anti-C5a monoclonal antibody
Vilobelimab: A first-in-class anti-C5a monoclonal antibody Vilobelimab Key Features Development Areas in Acute and Sub-Acute Inflammation Highly selective anti-C5a mAb Blocks C5a biological effects up to 100% in human blood Leaves MAC formation intact Fast binding / high affinity to the newly discov
Slide 12: PG: An autoimmune condition with high unmet medical need
PG: An autoimmune condition with high unmet medical need PG Overview and Unmet Need Clinical features • PG is a rare but potentially life-threatening skin disorder that can lead to chronic, difficult-to-treat wounds • Patients frequently suffer from other autoimmune disorders, e.g. ulcerative coliti
Slide 13: PG Pathogenesis: Potential role of the C5a/C5aR axis
PG Pathogenesis: Potential role of the C5a/C5aR axis • The etiology of PG is believed to be linked C5a Induces NETosis in Control Neutrophils to the dysregulation of the immune system, specifically, altered neutrophil function Con C5a (20 nM; 1hr) Extracellular DNA Staining • Evidence suggest that c
Slide 14: PG Phase 2a showed no safety or tolerability concerns and dose-dependent activity
PG Phase 2a showed no safety or tolerability concerns and dose-dependent activity Clinical Response • High-dose group showed highest rate of target ulcer closure and clinical remission (86%) • Out of 17 evaluable patients at end of treatment visit or day of last drug administration – Clinical remiss
Slide 15: PG Phase 2a treatment examples - Patient case studies
PG Phase 2a treatment examples - Patient case studies Target Ulcer Developed While on Adalimumab Target Ulcer Reappeared • MH: PG since August 2020, Psoriasis since 2017 • MH: PG since 2019, Hypertension since 1998 • Previous PG medication: None • Previous PG medication: Methylprednisolone only in J
Slide 16: PG Phase 3 design: Interim analysis expected in 2Q 2025
PG Phase 3 design: Interim analysis expected in 2Q 2025 Screening Treatment: 26 Weeks Follow up: 12 Weeks Randomization Patient Level Stopping Criteria EOT (W 26) progression (any time) or no improvement at defined time points vilobelimab 2400 mg Q2W (13 doses) Safety Follow Up Arm 1 Prednisone tape
Slide 17: INF904: An Oral Highly Selective C5aR Inhibitor With Best-in-Class Potential
INF904: An Oral Highly Selective C5aR Inhibitor With Best-in-Class Potential
Slide 18: INF904: Oral C5aR antagonist with best-in-class potential
INF904: Oral C5aR antagonist with best-in-class potential 1,400 Avacopan 30mg ✓ Superior PK/PD profile in Phase 1 SAD and MAD studies compared to reported INF904 3mg 1,200 INF904 10mg data from marketed comparator avacopan: INF904 30mg INF904 60mg 1,000 INF904 120mg o ~3-fold higher Cmax and ~10-fol
Slide 19: INF904 has double the inhibitory effect in vivo compared to avacopan
INF904: Oral C5aR antagonist with best-in-class potential INF904 has double the inhibitory effect in vivo in a pre-clinical model compared to avacopan Inhibition of in vivo neutrophil activation by INF904 compared to avacopan-like molecule* ✱✱ Avacopan-like 120 (10mg/kg oral) 100 INF904 INF904 doubl
Slide 20: PK results from single ascending dose (SAD) Phase 1
INF904: Oral C5aR antagonist with best-in-class potential PK results from single ascending dose (SAD) Phase 1 1,400 Parameter Unit Dose INF904 Avacopan* Avacopan 30mg INF904 3mg AUCinf h.ng/ml 3 mg 285 25 1,200 INF904 10mg INF904 30mg 10 mg 1264 130 INF904 60mg 1,000 INF904 120mg 30 mg 5956 628 INF9
Slide 21: INF904: C5a-mediated CD11b upregulation on neutrophils ex vivo
INF904: Oral C5aR antagonist with best-in-class potential C5a-mediated CD11b upregulation on neutrophils ex vivo up to 14-day dosing INF904: 30 MG QD INF904: 30 MG BID INF904: 90 MG BID rh C 5 a -C D 1 1 b R e s p o n s e , 3 0 m g q .d ., 1 4 d o s e s r h C 5 a - C D 1 1 b R e s p o n s e , 3 0 m
Slide 22: INF904 development in the immuno-dermatology field
INF904 development in the immuno-dermatology field Phase 2a Study Ongoing Initial Phase 2a – demonstrating pipeline-in-a-drug potential of INF904 • Open-label PK / PD “basket study” to explore initial efficacy signals • 4-week treatment period in 2 immuno-derm indications CSU and HS with established
Slide 23: Phase 2a open-label basket study concept
Phase 2a open-label basket study concept Primary and Secondary Endpoints Include Safety and PK CSU [n = 45] HS [n = 30] • 4-week treatment period • 4-week treatment period • 4-week follow-up • 4-week follow-up • 3 study arms with 15 patients per arm • 3 study arms with 10 patients per arm • 45 patie
Slide 24: Strong commercial potential based on differentiated profile of INF904
Strong commercial potential based on differentiated profile of INF904 • Oral availability provides for ease of administration and patient acceptance • Favorable drug metabolism, PK and toxicology profile positions INF904 as a potential strong alternative to other drug classes • INF904 could address
Slide 25: INF904 for Chronic Spontaneous Urticaria (CSU)
INF904 for Chronic Spontaneous Urticaria (CSU)
Slide 26: A strong rationale for developing INF904 in CSU
A strong rationale for developing INF904 in CSU C5aR Signaling is Involved in Histamine Release in an IgE Independent Manner • Increasing scientific evidence suggests that C5aR signaling is involved in histamine release from mast cells and basophils in CSU in an IgE independent manner. This mechanis
Slide 27: Chronic spontaneous urticaria (CSU)
Chronic spontaneous urticaria (CSU) CSU Overview and Unmet Need Clinical features • An immune-mediated chronic inflammatory skin disorder, with dysregulated inflammatory cascades that leave patients predisposed to symptom development: debilitating and intensely itchy hives / wheals for > 6 weeks and
Slide 28: CSU endotypes: Type I auto-allergens and type IIb autoimmunity
CSU endotypes: Type I auto-allergens and type IIb autoimmunity C5aR Signaling is Suggested to be Involved in Both Type I and Type IIb Endotypes Activated Coagulation Factors II and X generate C5a from C5 1 Type I autoallergens (IgE mediated) Close contact of two Fc regions of the IgG anti-FcERI or I
Slide 29: C5a in CSU and its role in IgE-independent histamine release
C5a in CSU and its role in IgE-independent histamine release CSU patients have elevated C5a levels C5a induces histamine release from basophils C5a mediated histamine release is in a dose-dependent manner independent of the IgE pathway 46.9 ng/ml p = 0.004 20.1 ng/ml N=95 N=42 CSU patients show evid
Slide 30: C5a drives mast cell attraction, activation and degranulation
C5a drives mast cell attraction, activation and degranulation ▪ The chemoattractant nature of C5a for mast cells explains their accumulation at inflammation sites ▪ Mast cells amplify this cross talk by producing complement proteins and activating them via their released tryptase ▪ C5a is also produ
Slide 31: C5aR1-mediated induction of anaphylaxis via mast cell activation
C5aR1-mediated induction of anaphylaxis via mast cell activation 3 2 1 Kordowski et al. Allergy 2019 Activation of the C5a/C5aR1 axis drives the development of anaphylaxis at several levels 1. The regulation of the B cell response in male mice that leads to the production of antigen-specific IgE. 2.
Slide 32: Opportunity for a novel MoA such as anti-C5aR
Opportunity for a novel MoA such as anti-C5aR Opportunities Ease of administration to address patient preference and adherence ▪ Oral capsules (BD or QD dosing) New mechanism of action to treat all affected CSU patient populations ▪ Type I IgE mediated and Type IIb autoimmune non-IgE mediated ▪ Anti
Slide 33: INF904 development in CSU
INF904 development in CSU Conclusion • C5aR signaling is involved in histamine release from mast cells / basophils in CSU • This C5a-mediated histamine release is independent of the IgE pathway and has been suggested to play a role in both subtypes of CSU • C5aR inhibition represents a novel mechani
Slide 34: INF904 for Hidradenitis Suppurativa (HS)
INF904 for Hidradenitis Suppurativa (HS)
Slide 35: A strong rationale for developing INF904 in HS
A strong rationale for developing INF904 in HS New Mechanisms are Needed • New mechanisms are needed to address the disease more completely – Moderate to severe patients with active draining disease have limited approved treatment options proven to be effective – Response to treatment with approved
Slide 36: Hidradenitis suppurativa (HS)
Hidradenitis suppurativa (HS) HS Overview and Unmet Need Clinical features • A chronic, recurring, debilitating neutrophil-driven inflammatory disease, that can persist for years • Characterized by abscesses, nodules and draining tunnels (dTs) with purulent or bloodstained discharge, that can flare
Slide 37: An important role for C5a/C5aR is recognized in HS pathogenesis
An important role for C5a/C5aR is recognized in HS pathogenesis Mechanism in HS development Follicular occlusion of the folliculo-pilosebaceous unit, followed by follicular rupture, leading to immune responses which involve complement activation including C5a/C5aR engagement, resulting in the develo
Slide 38: Strong rationale for developing an anti-C5a/C5aR in HS
Strong rationale for developing an anti-C5a/C5aR in HS HS Patients Have Elevated C5a, a Major Neutrophil Activator That Can Be Blocked by an Anti-C5a/C5aR HS patients have significant complement C5a/C5aR activation is a key neutrophil activator in HS patient activation with elevated C5a levels plasm
Slide 39: Neutrophils play a critical role in HS pathogenesis
Neutrophils play a critical role in HS pathogenesis especially in draining tunnels (DTs) Hurley stage III patient with tunnel formation T: Tunnel and surrounding granulomatous G: Granuloma F: Fibrosis inflammation with foreign body giant cells. C5aR1 staining positive – neutrophils, histiocytes and
Slide 40: Clinical evidence for the role of C5a/C5aR signaling in HS
Clinical evidence for the role of C5a/C5aR signaling in HS Vilobelimab (anti-C5a mAb) • SHINE Phase 2b study in moderate-severe HS patients resulted in various signals of efficacy for high dose treatment group (1200mg EOW) including an overall inflammatory lesion reduction * • In SHINE, dT reduction
Slide 41: Evidence for efficacy of C5aR inhibition in HS: Avacopan data
Evidence for efficacy of C5aR inhibition in HS: Avacopan data Efficacy Evidence in Total Data Set* AN count reduction (w12)* 0 Primary outcome** Absolute change -2 -4 -3,1 -3,4 -6 -5,1 -8 Spalte4 IHS-4 count change (w12)* 0 Absolute change -2 -4 -6 -8 -6,4 -7,9 -10 -9,4 -12 placebo Spalte4 Avacopan
Slide 42: Avacopan data in Phase 2 showed efficacy emerging only at week 12
Avacopan data in Phase 2 showed efficacy emerging only at week 12 Results From Avacopan in HS Patients (Hurley III)* • Avacopan’s efficacy (separation from placebo group) in HS only starts to emerge at W12 – please note: steady state reported from ANCA patients was only reached at approx. 3 months d
Slide 43: Avacopan data in ANCA patients show steady state reached by 13 weeks
Avacopan data in ANCA patients show steady state reached by 13 weeks • Steady state plasma levels of avacopan 30mg BID are reached by 13 weeks and the accumulation is approximately 4-fold • Mean steady state plasma exposure estimates of Avacopan reported plasma trough avacopan are: 3466 h*ng/mL for
Slide 44: Vilobelimab - SHINE study: ANdT count and IHS4 score (week 16)
Vilobelimab - SHINE STUDY: outcome of ANdT count and IHS4 score (week 16) ANdT Count Change (LS means)* IHS-4 Score Change (LS means)* 0 0 -10 -10 placebo Relative Change % Relative Change % -20 minimum -20 -19,8 low -25,3 -24,6 medium -30 -30 -29,4 high -40 -40 -38,4 -41,0 -41,1 -50 -50 -48,3 -50,4
Slide 45: Vilobelimab - SHINE study: Evidence of inflammatory lesion reduction
Vilobelimab - SHINE STUDY: Evidence of inflammatory lesion reduction under C5a inhibition DT Count Change Week 16 (LS means)* Complete resolution of DT (DT100) ** Placebo 400 Q4W 800 Q4W 800 Q2W 1200 Q2W % Reduction in Number of Draining Tunnels 0 45 40,9 % patients with DT 100 response -10 40 absol
Slide 46: Vilobelimab – SHINE study patients who completed OLE phase (w 40)
Vilobelimab – SHINE study patients who completed OLE phase (w 40) Substantial inflammatory lesion reductions when compared to placebo from the double-blind main period (w 16) Relative reduction (% mean) of counts / scores compared to respective baseline (Day1)* Placebo patients on week 16 All OLE pa
Slide 47: Summary and rationale for developing INF904 in HS
Summary and rationale for developing INF904 as a potent oral C5aR inhibitor in HS Learnings • Both C5a as well as C5aR signaling inhibition have resulted in clear signals of efficacy (reduction of inflammatory lesions + established scores) in moderate to severe HS patients • Both treatment attempts
Slide 48: Gohibic (vilobelimab) Critical COVID-19 & ARDS
Gohibic (vilobelimab) Critical COVID-19 & ARDS
Slide 49: Emergency Use Authorization (EUA) granted for Gohibic
Emergency Use Authorization (EUA) granted for Gohibic (vilobelimab) Gohibic (vilobelimab) has not been approved, but has been authorized for emergency use by FDA under an EUA*, for the treatment of COVID-19 in hospitalized adults when initiated within 48 hours of receiving IMV**, or ECMO** Authoriza
Slide 50: COVID-19: Disease progression and therapeutic interventions
COVID-19: Disease progression and therapeutic interventions Vaccines Antiviral Treatments Anti-inflammatorische Anti-inflammatory Behandlung Treatments Versterben oder Death Heilung or Recovery Healthy Early Stage Intermediate to Severe Stage Critical Stage Recovery (pre- Incubation / asymptomatic o
Slide 51: PANAMO Phase 3 primary endpoint: 28-day all-cause mortality
PANAMO Phase 3 primary endpoint: 28-day all-cause mortality Placebo + SOC PANAMO Phase 3 trial 1:1 randomized, double-blind, placebo-controlled, multi-national trial in (n=369) invasive mechanically ventilated COVID-19 patients Day 28: 23.9 % relative reduction Kaplan-Meier point estimate: Placebo:
Slide 52: InflaRx N.V. contact details
InflaRx N.V. Winzerlaer Str. 2 07745 Jena, Germany Email: IR@inflarx.com Tel: +49-3641-508180 Fax: +49-3641-508181 www.inflarx.com
Slide 53: Appendix
APPENDIX
Slide 54: Main inclusion criteria for CSU
Main inclusion criteria for CSU Patients diagnosed with moderate to severe CSU and inadequately controlled by second generation H1-antihistamines at the time of randomization as defined in the following: 1. The presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of
Slide 55: Main inclusion criteria for HS
Main inclusion criteria for HS Moderate or severe hidradenitis suppurativa (with Hurley Stage II or III), and an Abscess and Nodule (AN) count ≥ 5. Inflammatory lesions should affect at least 2 distinct anatomic areas Diagnosis of HS based on clinical history and physical examination for at least 6