About this program
IPH5401 is a first-in-class therapeutic antibody that specifically binds and blocks C5a receptors (C5aR) expressed on subsets of myeloid-derived suppressor cells (MDSC) and neutrophils. Part of the innate immune system, these types of cells promote tumor growth by secreting inflammatory and angiogenic factors. They potently suppress T and NK cells and hamper the activities of PD-1 checkpoint blockers.
C5a, a factor in the complement cascade, is often overexpressed in tumors, where it attracts and activates MDSC and neutrophils in the tumor microenvironment.
IPH5401 is a fully human antibody that blocks the binding of C5a to C5aR, thereby reducing the accumulation and activation of MDSC and neutrophils in tumors. Treatment with IPH5401 may unleash anti-tumor activities of T cells and NK cells. Preclinical experiments support development of IPH5401 as single agent and in combination with PD-1 checkpoint blockers or other cancer immunotherapies.
In June 2017, Innate Pharma announced that it enters into an agreement with Novo Nordisk A/S granting Innate Pharma full worldwide exclusive rights to develop and commercialize the anti-C5aR antibody (see the press release).
Mechanism of action of IPH5401
Ajona et al, 2017. A Combined PD-1/C5a Blockade Synergistically Protects against Lung Cancer Growth and Metastasis Cancer discovery Wang et al, 2016. Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression Cancer discovery Liang et al, 2016. The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis Cancer Immunol Res. Hwu et al, 2016. Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell-Mediated Antitumor Immunity Cancer discovery Kim et al, 2014. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells PNAS Janelle V et al, 2014. Role of the complement system in NK cell-mediated antitumor T-cell responses Oncoimmunology Corrales et al, 2012. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression J Immunol Markiewski et al, 2008. Modulation of the antitumor immune response by complement Nat Immunol.