OPN-7486 inhibits tumor associated macrophage infiltration by binding CSF1R

The colony stimulating factor 1 (CSF1) and colony stimulating factor 1 receptor (CSF1R) axis regulates the migration, differentiation and survival of macrophages and osteoclasts.

Within the context of the tumor microenvironment, these tumor associated macrophages (“TAMs”) are known to have an anti-inflammatory, immune-regulatory, and therefore tumor-promoting phenotype and are generically classified as M2 activated macrophages.

This phenotype is a consequence of the continuous presence of growth factors such as CSF1. Tumor cells secrete CSF1 that binds to CSF1R on both the tumor cell itself (autocrine loop) and TAMs (paracrine loop).

Therefore, blocking the CSF1/CSF1R interaction with OPN-7486 inhibits recruitment of pro-tumorigenic TAMs, enabling a natural immune response to occur and potentially reducing the mass of the tumor.

OPN-7486 is a dual inhibitor of CSF1R and tropomyosin receptor kinase (TRK) and is currently positioned to enter Phase 2 clinical trials.