Inflarx N.v. · NASDAQ:IFRX
Inflarx — Technical Presentation (November 2019)
32 slides from Inflarx's technical presentation, Nov 14, 2019
Slide 1: IFX-1: Lessons Learned from Clinical Trials
IFX-1 C5a Controlling inflammation Developing the First in Class Anti-C5a Antibody IFX-1: Lessons Learned from Clinical Trials Niels C. Riedemann
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: The anti-inflammatory and tissue saving potential of IFX-1
The anti-inflammatory and tissue saving potential of IFX-1 Discussing the potential IFX-1 holds for various inflammatory disease indications
Slide 4: The Complement Pathways
The Complement Pathways 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-convertases
Slide 5: The Terminal Complement Pathway
The Terminal Complement Pathway Membrane Attack Complex (MAC)triggers lysis of pathogens strong amplifierof inflammation C5aR C5b-9 = MAC C5L2 C5b C5a C5 cell activationcytokine generation Inflammation PKC-signalling HMGB-1 induction* (Inflammasome) C5a concentration in blood: 10 ~ 30 ng/ml (~1-2.5
Slide 6: The InflaRx anti-C5a Technology
The InflaRx anti-C5a Technology 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:Complement pathway activation, orD
Slide 7: The C5a Blocking Potential of IFX-1 in Plasma of Patients suffering from Hidradenitis Suppurativa
The C5a Blocking Potential of IFX-1 in Plasma of Patients suffering from Hidradenitis Suppurativa 5 nM IFX-1 highly effectively blocks HS-plasma / C5a-induced neutrophil activation in human blood Data source: InflaRx GmbH in-house data
Slide 8: IFX-1 Specificity in Vitro and In Vivo
IFX-1 Specificity in Vitro and In Vivo * Riedemann NC et. Al., Clin. Immunol. 2017 Mar 30;180:25-32 IFX-1 does not influence the hemolytic activity and leaves C5 cleavage and formation of C5b-9 (MAC) intact. Plasma (1:10 dilution) [µl] OD (542 nm) 50% Iysis IFX-1 impact on Hemolytic Activity (CH50)*
Slide 9: Neutrophil Activation Potential of C5a
Neutrophil Activation Potential of C5a 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)pro
Slide 10: Potential of IFX-1 to Prevent Tissue damage in H7N9 induced Lung Inflammation
Potential of IFX-1 to Prevent Tissue damage in H7N9 induced Lung Inflammation non-treated monkey lung - H7N9 infection IFX-1-treated monkey lung - H7N9 infection IFX-1 treatment markedly improved the lung injury score in H7N9 infected lungsIFX-1 treatment strongly decreased viral load in H7N9 infect
Slide 11: The tissue damaging effect of C5a
The tissue damaging effect of C5a
Slide 12: C5a as Key Player in Inflammation
C5a as Key Player in Inflammation C5a Neutrophils & Monocytes proinflam. Cytokines > 5000 publications since the 1970th Endothelials/vascular Macrophages Epithelial cells Strong Amplifier Chemotaxis & ActivationAdhesionO2 RadicalsEnzyme release Upregulation of C5aRANGIOGENESISIncreased vascular perm
Slide 13: Summary IFX anti-C5a Technology: IFX-1
Summary IFX anti-C5a Technology: IFX-1 Strong IP on discovered conformational epitope on C5a with protection until late in 2030 and with potential extension until late in 2035IFX-1 shows a superior performance:up to 100% biological blocking activity towards its target C5a in a 1:1 ratioleaves MAC fo
Slide 14: Hearing clinical trials results and examining lessons learned
Hearing clinical trials results and examining lessons learned
Slide 15: Hidradenitis Suppurativa
Hidradenitis Suppurativa Clinical features Chronic, inflammatory, recurrent, debilitating skin disease of the hair follicles Most commonly in the armpit, groin and genital regionsExtremely painful inflammatory nodules, boils or abscessesDraining fistulas leading to considerable scarring and function
Slide 16: The HiSCR as Endpoint Used for Approval in HS
The HiSCR as Endpoint Used for Approval in HS 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
Slide 17: IFX-1 Open Label Phase IIa Study in Hidradenitis Suppurativa
IFX-1 Open Label Phase IIa Study in Hidradenitis Suppurativa 1 dose groupWeekly i.v. 800 mg until week 8 (plus one additional loading dose on day 4) Open labelSingle-center12 patients Assessing safety and efficacy of IFX-1 in HSPrimary endpoint: safetySecondary endpoint:HiSCR response at different t
Slide 18: IFX-1 Open Label Phase IIa Study in HS: HiSCR Response
IFX-1 Open Label Phase IIa Study in Hidradenitis Suppurativa: HiSCR Response 83% HiSCR response rate in a severe patient population – with long effect durationStrong effect on draining fistula reduction detected (not captured with the HiSCR) – data not shown HiSCR response: Treatment period day 1 –
Slide 19: Efficacy of IFX-1: Skin Response Example, Phase IIa Trial in HS
Efficacy of IFX-1: Skin Response Example, Phase IIa Trial in HS DAY 1 DAY 134 Peri-rectal IFX-1 demonstrated a long lasting effect on the inflammatory lesions after only 8 weeks of 800mg qw dosing
Slide 20: IFX-1 in HS: SHINE Study Details
IFX-1 in HD: SHINE Study Details Important Note: Patients entering the OLE were not unblinded to their initial therapy Test a dose dependent effect of IFX-1 on HiSCR responds at week 16 (primary endpoint) Assess long term safety of IFX-1Test durability of response with lower maintenance therapy in o
Slide 21: SHINE Study Patient Disposition for Open Label Extension (OLE)
SHINE Study Patient Disposition for Open Label Extension (OLE) Completed OLEn = 122 (69%) Discontinuedn = 34 (19%) visit at EOT at wk 40n = 116 completed wk 44n = 122 Patients Enrolledn = 179 Patients Dosed n = 177 (100%) Entered Extensionn =156 (88%) MAIN PERIOD OLE Period week 16 week 40 + 4 End o
Slide 22: SHINE STUDY: Primary Outcome HiSCR at Week 16 versus AN Count Reduction
SHINE STUDY: Primary Outcome HiSCR at Week 16 versus AN Count Reduction Primary Endpoint: HiSCR dose response signal not met but signal towards improved AN count n = approx. 35/ group * Full analysis set Treatment Group
Slide 23: SHINE STUDY: Outcome on Draining Fistula and IHS-4 Score Reduction
SHINE STUDY: Outcome on Draining Fistula and IHS-4 Score Reduction – week 16 stat. significant change in DF and in IHS-4 scores detected * Full analysis set Treatment Group ** Full analysis set – baseline adjusted p= 0.0202
Slide 24: IHS-4 Score: Includes and Weights All Inflammatory Lesions
IHS-4 Score: Includes and Weights All Inflammatory Lesions number of inflammatory nodules IHS-4 points = sum of number of abscesses number of draining fistulas x 1 x 2 x 4 Developed by KOL´s / Physicians to establish a new severity scoring system, suitable for tracking treatment response Captures re
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Slide 26: Inflammatory Lesion Reductions in all OLE Patients at End of Treatment (week 40)
Inflammatory Lesion Reductions in all OLE Patients at End of Treatment (week 40) Compared to Placebo Group Performance in Main Period Marked improvement of all inflammatory lesions over time – not explainable by placebo effect Relative Reduction (% mean) of Counts / Scores compared to Respective Bas
Slide 27: IHS-4 Scores Over Time in OLE: Non-responders versus Responders
IHS-4 Scores Over Time in OLE: Non-responders versus Responders Non-responders improve under medium dose IFX-1 treatment during OLE Responders are relatively “stable” with their IHS-4 scores on low dose IFX-1 Change in IHS-4 scores between week 16 and week 40 in week 16 HiSCR responders versus non-r
Slide 28: IHS-4 Scores in OLE Patients: HiSCR Non-responder Group
IHS-4 Scores in OLE Patients: Relative Change from Baseline (Day 1) HiSCR Non-responder Group (week 16) IFX-1 800 mg q2w Treatment Group in Main period: IHS-4 scores: Relative change from baseline (mean) in OLE patients at week 16 and week 40 in HiSCR non-responder patients (week 16) – displayed per
Slide 29: IHS-4 Scores in OLE Patients: HiSCR Responder Group
IHS-4 Scores in OLE Patients: Relative Change from Baseline (Day 1) HiSCR Responder Group (week 16) IHS-4 Scores relative change to baseline (mean) in OLE patients at week 16 and week 40 in week 16 HiSCR responders - displayed per Main Period Treatment group* IFX-1 800 mg q4w Treatment Group in Main
Slide 30: SHINE Study – Insights into Pharmacokinetics/Pharmacodynamics
SHINE Study – Insights into Pharmacokinetics/Pharmacodynamics LEARNINGS from SHINE study PK/PD and Related modeling Results indicate that IFX-1 consumption in HS is much higher than in other diseases (trough levels are a multiple lower at same dose) Results further indicate that this consumption in
Slide 31: Key Takeaways of SHINE Study
Key Takeaways of SHINE Study: HiSCR is burdened by high variability (driven by AN count variability) and by a lack of capturing reduction of draining fistula Evidence for a very high C5a turnover rate in HS, leading to IFX-1 consumption IFX-1 leads to a market reduction of all inflammatory lesions i
Slide 32: InflaRx N.V. contact details
InflaRx N.V.Winzerlaer Str. 207745 Jena, GermanyEmail: info@inflarx.comTel: +49-3641-508180Fax: +49-3641-508181www.inflarx.com Thank you for your attention