OSE-172 (Effi-DEM), a new generation immune checkpoint inhibitor (ICI), in preclinical development for immuno-oncology

OSE-172 (Effi-DEM) is a monoclonal antibody: a new generation checkpoint inhibitor which blocks the generation of pro-tumor suppressor cells and restores their effector function.

OSE-172 blocks SIRP-alpha (Signal Regulatory Protein Alpha), on strategic SIRP-alpha/CD47 pathway, a receptor strongly expressed by myeloid and macrophage suppressor cells. It restores effector functions of these suppressor cells, an activity which promotes the immunosurveillance (Hanna R.N. et al ; Science 2015). OSE-172 may also be combined with other immunotherapies, in particular with checkpoint inhibitors acting on T lymphocytes, e.g. checkpoint inhibitors targeting the PD-1/PD-L1 axis or products triggering a stimulation of the immune system.

This innovative product helps modifying Tumor Associated Macrophages (TAM) and Myeloid Derived Suppressor Cells (MDSC) associated with a poor prognosis, by blocking and transforming them into cells with a good prognosis (in blue in the above diagram).

Proof of concept obtained in in vivo models

Proof of concept has been obtained in models of aggressive cancers such as primary liver cancer, melanoma and breast cancer. These studies have confirmed a therapeutic effect of OSE-172 (Effi-DEM) as well as a potential long-lasting effect, in both monotherapy or combined with another checkpoint inhibitor, or with an immune system stimulator.

The therapeutic effect can be considered as long-lasting as reinsertion of a new tumor in animals treated by OSE-172 shown to be impossible : animals had developed an anti-tumor immunization. A treatment with OSE-172 as a monotherapy and combined with other immunotherapies induces a strong and long-lasting anti-tumor effect.

OSE-172 could be developed in all cancers involving TAM and MDSC cells, key cells in the progression of inflammatory cancers. Cytokines secreted by suppressor cells foster this mechanism (IL-10, IL-1β, TGFβ). This therapeutic strategy could be applied to cancers linked to a chronic inflammation such as primary liver cancer or colon cancer (Zamarron B.F. et 2011) (Mallmann MR et al. 2012).