Inflarx N.v. · NASDAQ:IFRX
Inflarx — Investor Presentation (May 2019)
37 slides from Inflarx's investor presentation, May 8, 2019
Slide 1: C5a Controlling inflammation Corporate Presentation May 2019
IFX-1 C5a Controlling inflammation Corporate Presentation May 2019
Slide 2: Important Notice and Disclaimer
Important Notice and Disclaimer THIS PRESENTATION HAS BEEN PREPARED BY INFLARX n.v. (“INFLARX”), a US-Nasdaq publicly listed Dutch company having its principle place of business in germany. THIS PRESENTATION IS MADE FOR INFORMATIONAL PURPOSES ONLY AND DOES NOT CONSTITUTE AN OFFER TO SELL OR A SOLICI
Slide 3: About InflaRx
About Inflarx: 3 Founded in Germany in 2008 Offices/Subsidiaries: JENA + Munich (Ger) & Ann Arbor + New York (USA) IPO on Nasdaq in November 2017 with GROSS proceeds of $106m strong balance sheet:$176 million as of Dec 31st 2018 Follow-on Financing round April 2018 with Gross proceeds of $117m
Slide 4: Investment highlights
Investment highlights Leading anti-c5a ANTIBODY TECHNOLOGY Full and selective blockade of the biological activity of C5aStrong global IP protection Leading PROPRIETARY anti-c5a ANTIBODY TECHNOLOGY Leading anti-c5a ANTIBODY TECHNOLOGY Highly statistically significant C5a inhibition leaving MAC format
Slide 5: Pipeline with multiple opportunities
pipeline with multiple opportunitieswe are planning to begin multiple Phase ii studies with potential to expand into further indications 5 IFX-1 IFX-2 Current status Prevalence Pre-clinical Program Phase III Market Phase II Phase I Hidradenitis Suppurativa (HS) ANCA associated vasculitis (AAV) Pyode
Slide 6: C5a as target & our proprietary anti-C5a technology
C5a as target & our PROPRIETARY anti-c5a TECHNOLOGY
Slide 7: Biological activity of C5a: booster of inflammation
Biological activity of C5a: booster of inflammation 7 C5a Neutrophils & Monocytes proinflam. Cytokines > 5000 publications since the 1970th Endothelials/vascular Macrophages Epithelial cells Strong Amplifier Chemotaxis & ActivationAdhesionO2 RadicalsEnzyme release Upregulation of C5aRANGIOGENESISInc
Slide 8: C5a activation of neutrophils
C5a activation of neutrophils 8 Data Source: Prof. Peter Ward, University of Michigan Neutrophils , (4’600x enlarged) + C5a control C5a Mode of Action on Neutrophils:Chemotaxis of neutrophils (Shin et al 1968, Science 162,361-3)Enzyme release (Goldstein et al 1974, J. Immunol. 113, 1583-8)Production
Slide 9: Routes to Terminal C5 activation
9 Routes to Terminal C5 activation Classical Lectin Alternative Complement Pathways Extrinsic “Pathway” Enzymatic C5 Cleavage Membrane Attack Complex (MAC)triggers lysis of pathogens strong amplifierof inflammation Antibody binding Mannose binding Foreign surfaces C3 activation C5aR C5b-9 = MAC C5-c
Slide 10: Terminal complement activation: model
10 Terminal complement activation: model C5a C5 activation through the Complement Pathways results in functional C5a and C5b (MAC)C5 cleavage through the Extrinsic Pathway generates functional C5a (not C5b!) C5b C5 Classical Lectin Alternative Complement Pathways C5-convertases Extrinsic “Pathway” E
Slide 11: Terminal complement activation: competitive clinical landscape
11 Terminal complement activationCompetitive clinical landscape Previous programmes targeting C5a Complement Pathways Extrinsic Pathway C5b-9 = MAC InflaRx’s approach is to ensure complete blockade of C5a regardless of activating pathway or receptor signaling while preserving MAC formation C5 C5a C5
Slide 12: IFX-1 is a first-in-class anti-C5a monoclonal antibody
IFX-1 is a first-in-class anti-C5a monoclonal antibody 12 MAC lysis invading microorganisms C5b-9 = MAC C5b KEY FEATURES Blocks C5a biological effects up to 100% in human blood Leaves MAC formation intactBinds with high affinity to the discovered epitope C5 newepitope Cleavage of C5 through:Compleme
Slide 13: Preclinical studies have established IFX-1 mechanism of action
13 A number of preclinical studies have established ifx-1 mechanism of action Riedemann NC et. Al., Clin. Immunol. 2017 Mar 30;180:25-32 ò 101% ò 96% IFX-1 can block C5a induced neutrophil activation as measured by CD11b IFX-1 does not influence the hemolytic activity curves and leaves C5 cleavage a
Slide 14: IFX-1 for hidradenitis suppurativa
ifx-1 for hidradenitis Suppurativa
Slide 15: Hidradenitis Suppurativa: high unmet need
hidradenitis Suppurativaa chronic severely debilitating C5a-driven inflammatory skin condition with high unmet need 15 Clinical features Chronic, inflammatory, recurrent, debilitating skin disease of the hair follicles Most commonly in the armpit, groin and genital regionsExtremely painful inflammat
Slide 16: HiSCR – a validated endpoint
IFX-1 in Hidradenitis Suppurativa 16 HISCR – a validated endpoint Humira was approved based on HiSCR response – providing a potential pathway to approvalHiSCR defines 3 types of lesions:AbscessesInflammatory nodules Draining fistulasHiSCR response defined as:At least 50% reduction in total abscess a
Slide 17: Rationale for targeting C5a in HS
IFX-1 in Hidradenitis Suppurativa 17 InflaRx established that HS patients have significant complement activation with elevated C5a levels C5a is involved in several key pathophysiological mechanisms in HSNeutrophil activation is driven by C5aVarious C5a dependent players potentially involved (TNFa,
Slide 18: C5a as key neutrophil activator in HS patient plasma
IFX-1 in Hidradenitis Suppurativa - rational C5a as key neutrophil activator in HS patient plasma 18 Presented in more detail also in Abstract by Guo et. al., European Meeting on Complement in Human Disease, Copenhagen 2017, Manuscript in preparation by Prof. Giamarellos-Bourboulis, E.J., Athens, Gr
Slide 19: Overview of IFX-1 Phase IIa study in HS
19 Overview of IFX-1 Phase Iia study in HSStudy design and Patient characteristics 1 dose groupWeekly i.v., total of 8 doses Open labelSingle-center12 patientsKey inclusion: patients with moderate to severe HS with either primary or secondary failure to respond to biological treatment or not eligibl
Slide 20: Phase IIa promising results in HS: clinical efficacy
IFX-1 Phase Iia PROMISING Results in Hsclinical efficacy 20 HISCR response rate in HS patients HiSCR response in HS patients Efficacy: In these late-stage patients who previously failed to respond to SOC including TNF-alpha blockade, 75% of patients were HISCR responders following 8 weeks treatment
Slide 21: Phase IIa results: pharmacodynamics and C5a blocking activity
21 IFX-1 Phase Iia Results in HsPHARMACODYNAMICS & C5A blocking activity of ifx-1 Mean c5a PLASMA LEVELS Data displayed in the F1 prospectus: Mean C5a levels (ng / ml) in HS patients at day 1 (pre-dosing), day 22 and day 50 (end of treatment) as well as on day 134 (at the end of the trial observatio
Slide 22: Phase IIa results in HS: skin response examples
IFX-1 Phase Iia Results in HsSKIN REsPONSE EXAMPLES from treated patients 22 Day 1 Day 134 Visible improvement at the end of the trial Gluteal fold Right inguinal Day 1 Day 134
Slide 23: Phase IIb study in HS: SHINE study design
IFX-1 Phase Iib study in HS: SHINEStudy design 23 Responders Non Responders Placebo IFX-1 minimum dose IFX-1 low dose IFX-1 medium dose IFX-1 high dose IFX-1 low dose IFX-1 medium dose Screening Open Label Extension Period 28 Weeks Main Period (double blind)16 weeks 179 patients with moderate or sev
Slide 24: Phase IIb SHINE statistical model MCP-mod
IFX-1 Phase Iib study in HS: SHINE statistical Model MCP-mod 24 The Multiple comparison Procedure – Modelling (MCP-mod) What is this? novel and now more frequently used design for dose findingtests whether a new drug has a dose-response effect on an endpoint = MCP stepcalculates the dose-response re
Slide 25: Phase IIb SHINE statistical analysis plan
IFX-1 Phase Iib study in HS: SHINEstatistical analysis plan 25 SHINE Study MCP-mod set up dose placebo min dose low dose med dose high dose response ca. 25-30% 55% - 60% increasing response Main set up and assumptions dose groups: 4 + placeboplacebo HiSCR rate: 25% - 30%effective dose HiSCR rate: 55
Slide 26: Phase IIb in HS: MCP-mod outcome
IFX-1 Phase Iib study in HS:mCP-mod outcome Simulated examples for illustration purposes only 26 26,7% 63,3% 56,7% 60% 66,7% Emax: p = 0.00256 logistic: p = 0.01994 36,7% 30% 43,3% 56,7% 73,3% Emax: p = 0.00608 logistic: p = 0.00172 30% 43,3% 43,3% 46,7% 33,3% Emax: p = 0.0787 logistic: p = 0.0719 E
Slide 27: IFX-1 for ANCA associated vasculitis
ifx-1 for ANCA associated vasculitis
Slide 28: ANCA associated vasculitis (AAV): a life-threatening autoimmune condition
Anca associated vasculitis (AAV)A LIFE-THREATENING AUTOIMMUNE CONDITION 28 Rare, life-threatening autoimmune disease, characterized by necrotizing vasculitisLife-threatening flare phases affect organs leading to potentially fatal organ dysfunction and failure Predominantly affecting small vessels as
Slide 29: Clinical PoC established for role of C5a/C5aR pathway in AAV
IFX-1 in AAVClinical Poc established for role of C5a / C5aR pathway in AAV 29 rationale C5a/C5aR interaction is essential for development of MPA-ANCA crescentic glomerulonephritis in a mouse modelComplement activation in active AAV patients is significantChemocentryx’ CCX168 (small molecule, C5aR an
Slide 30: Complement activation in AAV
IFX-1 in AAVComplement activation in AAV 30 Guo SI, 2012, Kid intl 83:127 C5a is significantly increased in patients with active AAV – but not in remission
Slide 31: C5a plays a key role in AAV
IFX-1 in AAVC5a plays a key role in AAV 31 Van Timmeren, Curr. Opinion Rheumatol. 2012; 24:8 Role of c5a in AAV Chemotaxis of PMNsEnhancing IC effectsActivation of PMNsCytokine inductionEndothelial injury (enzymes & oxidative stress)Tissue factor releaseThrombo-inflammation & prolonged PMN life-span
Slide 32: Phase II study in AAV in the US (IXPLORE)
32 IFX-1 – P2.6 Phase Ii study in AAV in the US (IXPLore)Study design Assessing safety and efficacy of IFX-1 in AAVPrimary endpoint: SafetySecondary endpoint: Response rate based on the Birmingham Vasculitis Score (BVAS), various other secondary endpoints Study objective Placebo + SOCGroup C (N=12)
Slide 33: Phase II study in AAV in Europe (IXCHANGE)
group C: IFX-1 + no GC (N=33) group A: IFX-1 + reduced GC(N=15) Screening Remission Induction Phase:RTX/CYC group B: placebo + standard GC (N=15) Randomization 1:1 End of Study W 24 Treatment: 16 Weeks Follow up: 8 Weeks Remission Maintenance Phase: AZA/MTX/MMF/MPS; or can remain RTX/CYC W 16 W 8 W
Slide 34: Financials & Strategic long term goals
FiNancials & Strategic long term goals
Slide 35: Strong balance sheet to support clinical development
Strong balance sheet to support clinical development 35 Financings $ Series D: $55m in Oct 2017NASDAQ IPO: $106m in Nov 2017 $15.00 per shareFollow-on: $117m in May 2018 $34.00 per share$63m gross proceeds for InflaRx$54m for selling shareholders J.P.Morgan Anupam RamaLeerink Joseph P. SchwartzBank
Slide 36: Our strategy
Our strategy 36 goal and strategy Advance our lead program IFX-1 for HS to commercialization and extent with additional IFX-1 s.c. development Our goal is to maintain and advance our leadership position within the anti-C5a complement space by leveraging full potential of our proprietary technology C
Slide 37: InflaRx N.V. contact and Investor Relations
InflaRx N.V.Winzerlaer Str. 207745 Jena, GermanyEmail: info@inflarx.comTel: +49-3641-508180Fax: +49-3641-508181www.inflarx.com Investor Relations InflaRx N.V.Jordan Silverstein Head of Corporate Development and Strategyjordan.silverstein[at]inflarx.de Page 37