Delving into the Latest Updates on Icanomab Gmbh with Synapse

Overview

Tags

Skin and Musculoskeletal Diseases

Neoplasms

Infectious Diseases

Monoclonal antibody

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Neoplasms	2
Infectious Diseases	2
Endocrinology and Metabolic Disease	1
Hemic and Lymphatic Diseases	1
Immune System Diseases	1

Top 5 Drug Type	Count

Monoclonal antibody	3

Top 5 Target	Count

HER2(Receptor tyrosine-protein kinase erbB-2)	1
IL18RAP(interleukin 18 receptor accessory protein)	1
CD40(Tumor necrosis factor receptor superfamily member 5)	1

Author: Jiang, Liqiong ; Wegmann, Michael ; Dinarello, Charles A ; Webber, William S ; Amo-Aparicio, Jesus ; Li, Suzhao ; Orlicky, David J ; Falkesgaard Højen, Jesper ; Dinarello, Alberto ; Fischer, Stephan ; Parera, Daniel ; Lunding, Lars P ; Beckmann, Karsten ; Azam, Tania ; Nguyen, Tom T ; Pessara, Ulrich

IntroductionInterleukin-18 (IL-18), a pro-inflammatory cytokine belonging to the IL-1 Family, is a key mediator ofautoinflammatory diseases associated with the development of macrophage activation syndrome (MAS).High levels of IL-18 correlate with MAS and COVID-19 severity and mortality, particularly in COVID-19patients with MAS. As an inflammation inducer, IL-18 binds its receptor IL-1 Receptor 5 (IL-1R5), leadingto the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7). This heterotrimeric complex subsequentlyinitiates downstream signaling, resulting in local and systemic inflammation.MethodsWe reported earlier the development of a novel humanized monoclonal anti-human IL-1R7 antibody whichspecifically blocks the activity of human IL-18 and its inflammatory signaling in human cell and wholeblood cultures. In the current study, we further explored the strategy of blocking IL-1R7 inhyperinflammation in vivo using animal models.ResultsWe first identified an anti-mouse IL-1R7 antibody that significantly suppressed mouse IL-18 andlipopolysaccharide (LPS)-induced IFNg production in mouse splenocyte and peritoneal cell cultures. Whenapplied in vivo, the antibody reduced Propionibacterium acnes and LPS-induced liver injury and protectedmice from tissue and systemic hyperinflammation. Importantly, anti-IL-1R7 significantly inhibited plasma,liver cell and spleen cell IFNg production. Also, anti-IL-1R7 downregulated plasma TNFa, IL-6, IL-1b,MIP-2 production and the production of the liver enzyme ALT. In parallel, anti-IL-1R7 suppressed LPSinducedinflammatory cell infiltration in lungs and inhibited the subsequent IFNg production andinflammation in mice when assessed using an acute lung injury model.DiscussionAltogether, our data suggest that blocking IL-1R7 represents a potential therapeutic strategy to specificallymodulate IL-18-mediated hyperinflammation, warranting further investigation of its clinical application intreating IL-18-mediated diseases, including MAS and COVID-19.

100 Deals associated with Icanomab Gmbh

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100 Translational Medicine associated with Icanomab Gmbh

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Pipeline

Pipeline Snapshot as of 23 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

IL-1R7 antagonist (Icanomab) ( IL18RAP )	Inflammation More	Preclinical
HER2newC apoptosis inducer (Icanomab) ( HER2 )	Early Stage Breast Carcinoma More	Preclinical
CD40 agonist (Icanomab) ( CD40 )	Neoplasms More	Preclinical