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 Hwu et al, 2016. Complementing T-cell Function: An Inhibitory Role of the Complement System in T-cell-Mediated Antitumor Immunity 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. Janelle V et al, 2014. Role of the complement system in NK cell-mediated antitumor T-cell responses Oncoimmunology Kim et al, 2014. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells PNAS 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.