Delving into the Latest Updates on IFX002 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Target

C5a

Mechanism

C5a inhibitors(complement C5a inhibitors)

Therapeutic Areas

Immune System DiseasesOther Diseases

Active Indication-

Inactive Indication

Autoimmune DiseasesInflammation

Originator Organization

InflaRx NV

Active Organization-

Inactive Organization

InflaRx NV

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

AbstractThe release of inflammatory cytokines, namely tumor necrosis factor‐α (TNF‐α), plays an important role in the pathogenesis of cardiomyopathy. TNF‐α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF‐α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg−1, i.p) twice weekly for 3 weeks (21 mg. kg−1 cumulative dose). DCM rats were treated with RPL (1 mg. kg−1 orally, daily), IFX (5 mg. kg−1; i.p. once) or their combination for 4 weeks starting next day of last DOX dose. Echocardiography was conducted followed by a collection of blood and left ventricle (LV) for biochemical and histological investigations. DCM rats revealed deteriorated cardiac function (increased CK‐MB activity, LVIDs, LVIDd, ESV, and EDV, while decreased EF% and FS%), hypertrophy (increased HW/TL, β‐MHC, and α‐actin), inflammation (increased IL‐1β, IL‐6, and TNF‐α). The activation of Wnt/β‐catenin along with increased gene expression of RAS components (RENIN, ACE, and AT1) were evident. LV architecture also revealed abnormalities and some degree of fibrosis. Treatment with RPL and/or IFX suppressed TNF‐α and consequently improved most of these parameters suppressing Wnt/β‐catenin/RAS axis. Combined RPL and IFX treatment was the best among all treatments. In conclusion, Wnt/β‐catenin/RAS axis is implicated in DOX‐induced cardiomyopathy. The upstream TNF‐α was proved for the first time in‐vivo to stimulate this axis where its inhibition by RPL or IFX prevented DCM. Targeting this axis at two points using RPL and IFX showed better therapeutic efficacy.

100 Deals associated with IFX002

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