InflaRx N.V. · NASDAQ:IFRX
InflaRx — Investor Presentation (March 2024)
49 slides from InflaRx's investor presentation, March 2024
Slide 1: Corporate Presentation March 2024
CORPORATE PRESENTATION MARCH 2024
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 the I&I Space
Harnessing C5a/C5aR for Controlling Inflammation in the I&I Space 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-
Slide 5: 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 6: Focus INF904 on Immuno-Dermatology: I&I Pipeline-in-a-Drug Potential
Focus INF904 on Immuno-Dermatology: I&I Pipeline-in-a-Drug Potential • Chronic spontaneous urticaria (CSU) Key initial development focus Immuno- • Hidradenitis suppurativa (HS) and area to demonstrate dermatology • others potential of INF904 • Chronic inflammatory demyelinating polyneuropathy (CIDP)
Slide 7: Late-Stage Pipeline Targets Multiple Sizable Markets
Late-Stage Pipeline Targets Multiple Sizable Markets INDICATIONS PRECLIN PHASE I PHASE II PHASE III MARKET STATUS & MILESTONES Enrollment ongoing vilobelimab pyoderma Interim analysis for adaptation and futility C5a Inhibitor gangrenosum anticipated in 2025 IMMUNO-DERMATOLOGY chronic spontaneous Pha
Slide 8: C5a/C5aR: A Strategic Position in the Inflammatory Cascade
C5a/C5aR: A Strategic Position in the Inflammatory Cascade Vilobelimab [C5a monoclonal antibody] INF904 [oral C5aR inhibitor]
Slide 9: 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 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 Need
PG: An Autoimmune Condition With High Unmet 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 colitis, rheum
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 IIa Showed No Safety Concerns and Dose-Dependent Drug Activity
PG Phase IIa Showed No Safety or Tolerability Concerns and Dose-Dependent Drug 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
Slide 15: PG Study Phase IIa – Treatment Examples
PG Study Phase IIa – 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 on
Slide 16: PG Phase III Study Design: Interim Analysis Expected in 2025
PG Phase III Study Design: Interim Analysis Expected in 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
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 INF904 Key Features Focusing on Immuno-Derm, Other Options Possible ✓ Favorable drug profile supported by preclinical studies and data reported from InflaRx’s Phase I SAD and MAD trials As a small molecule orally ✓ Phase I PK/PD profile that
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: C5a-Mediated CD11b Upregulation on Neutrophils Ex Vivo up to 14-day Dosing
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: Investing Into INF904 Development
Investing Into INF904 Development Phase IIa Expected to Begin by EOY 2024 Initial Phase IIa – 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 establishe
Slide 23: INF904 for Chronic Spontaneous Urticaria (CSU)
INF904 for Chronic Spontaneous Urticaria (CSU)
Slide 24: 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 25: 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 26: CSU Endotypes - Type 1 Auto-Allergens and Type IIb Autoimmunity
CSU Endotypes - Type 1 Auto-Allergens and Type IIb Autoimmunity Two major endotypes of CSU described as activation of mast 1 cells include: 1 Type I autoallergens (IgE mediated) 2 Type IIb autoimmunity (IgG mediated; ~30% of CSU) • C5a is activated by the binding of IgG-anti-FcεRI or IgG-anti-IgE to
Slide 27: 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 28: C5a/C5aR Contributes to Histamine Release in an IgE Independent Manner
C5a/C5aR Contributes to Histamine Release in an IgE Independent Manner C5a-Induced Histamine Release is Important for Both, IgE Dependent Pathway and IgE Independent Pathway Anti-IgE Stimulus pos. (>20% HR) Anti-IgE Stimulus neg. Basophils isolated from CSU patients Basophils isolated from CSU patie
Slide 29: 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 mechan
Slide 30: INF904 for Hidradenitis Suppurativa (HS)
INF904 for Hidradenitis Suppurativa (HS)
Slide 31: 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 – E.g. moderate to severe patients with active draining disease currently have limited approved treatment options which have proven to be effective for them – a
Slide 32: 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 33: 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 devel
Slide 34: 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 35: Enhanced C5aR Staining in Biopsies From HS Patients at All Disease Stages
Enhanced C5aR Staining in Biopsies From HS Patients at All Disease Stages H&E Staining HF: Hair follicles T: Tunnel T: Tunnel C5aR1 Staining S: Suppurative R: Tunnel rupture G: Granuloma PEH: Psoriasiform F: Fibrosis epidermal hyperplasia Hurley stage I patient with extensive deep Hurley stage II pa
Slide 36: 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 IIb 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 reductio
Slide 37: Avacopan Data in Phase II Trial Shows Efficacy Emerging Only at W12
Avacopan Data in Phase II Clinical Trial Shows Efficacy Emerging Only at W12 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.
Slide 38: Avacopan Data in ANCA Patients Shows Steady State Reached by 13 Weeks
Avacopan Data in ANCA Patients Shows 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 39: Vilobelimab and Avacopan Provide Evidence for Efficacy in HS Patients
Vilobelimab* and Avacopan** Provide Evidence for Efficacy in HS Patients Conclusion: • There is a strong scientific rationale for the role of C5aR in HS • C5a/C5aR signaling inhibition has resulted in signals of efficacy in HS patients • Tight control over C5aR signaling is required to achieve optim
Slide 40: Gohibic (vilobelimab) Critical COVID-19 & ARDS
Gohibic (vilobelimab) Critical COVID-19 & ARDS
Slide 41: 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 42: 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 43: INF904 Appendix
INF904 Appendix www.inflarx.com
Slide 44: INF904: Pre-Clinical Summary
INF904: Pre-Clinical Summary INF904 Facts C5a-binding site • INF904 binds to the well-defined allosteric site in C5aR transmembrane domain • INF904 has a novel and proprietary molecular structure • US patent issued in October 2021; pending in other countries (PCT) Trp213 (human, Pre-clinical Finding
Slide 45: Targeted Improvement of C5aR-Inhibition
Targeted Improvement of C5aR-Inhibition Properties of a Best-in-Class C5aR Antagonist • Improved PK properties with higher plasma trough level (>> 36 ng/mL) to achieve: • Improved blocking activity in vivo in humans (>> 50% blocking at 10 nM C5a) = significantly stronger inhibition of neutrophil act
Slide 46: INF904: Phase I Study Design
INF904: Phase I Study Design Single ascending dose (SAD) Multiple ascending dose (MAD): 14 days 3mg Safety evaluation SAD (N=8, in 6:2 ratio) 10mg Safety evaluation SAD (N=8, in 6:2 ratio) 30mg QD Safety evaluation MAD 30mg Safety evaluation N=8 (in 6:2 ratio) SAD (N=8, in 6:2 ratio) 30mg BID Safety
Slide 47: INF904 Phase I Study: PD Results From SAD Part
INF904 Phase I Study: PD Results From SAD Part C5a-Mediated CD11b Upregulation on Neutrophils Ex Vivo at 24h Post Dosing rh C 5 a -C D 1 1 b R e s p o n s e , T = 2 4 h • INF904: In response to 12.64 nM of C5a, ≥ 90% blocking activity was observed in 120 the PD analysis in the dose range of 30- 240
Slide 48: INF904: PK Results From Multiple Ascending Dose (MAD) Phase I
INF904: PK Results From Multiple Ascending Dose (MAD) Phase I Dose (Regimen) Day Cmax (ng/mL) ±SD AUC0-12hr (ng x hr/mL) ± SD 1 233 ± 79 1,615 ± 427 30 mg QD 14 284 ± 60 2,609 ± 792 1 236 ± 97 1,742 ± 648 30 mg BID 14 356 ± 84 3,331 ± 821 1 653 ± 217 4,815 ± 1,993 90 mg BID 14 1,028 ± 431 8,962 ± 4,
Slide 49: INF904: Oral C5aR Antagonist With Best-in-Class Potential
INF904: Oral C5aR Antagonist With Best-in-Class Potential MAD SAD • Well tolerated and with no signals of safety concern in • Well tolerated and with no signals of safety concern in single multiple ascending doses involving 30 mg QD, 30 mg BID and ascending doses ranging from 3 mg to 240 mg 90 mg BI