ES009: A Potential Best-in-Class Antibody Targeting LILRB2
ES009 is a potential best-in-class monoclonal antibody targeting LILRB2 designed to reprogram inhibitory myeloid cells to create an immune favorable TME. LILRB2 is an inhibitory receptor that suppresses myeloid cell activation. Blocking LILRB2 reverses immunosuppression by reprograming tumor-associated macrophages (TAMs) from M2 (pro-tumor) to M1 (anti-tumor) phenotype, leading to immune responses including myeloid cell activation and pro-inflammatory cytokine release.
In preclinical studies, ES009 demonstrated potent ligand blockade and effective reprogramming of TAMs from M2 to M1, leading to pro-inflammatory cytokine release from macrophages as well as T cell proliferation and activation.
Our development plan for ES009 is to file a CTN (Clinical Trial Notification) in Australia in the second half of 2022 and start a Phase 1 study in patients with advanced solid tumors in the first half of 2023.
Mechanism of Action
- LILRB2 is a critical inhibitory receptor expressed on myeloid cells (including monocytes, dendritic cells, macrophages and neutrophils), mediated by functional ligands such as HLA-G which are mainly expressed on tumor cells
- LILRB2 blocking promotes macrophage switch from pro-tumor M2 to anti-tumor M1 phenotype and activates pro-inflammatory response in the TME
- LILRB2-mediated immune suppression is regarded as one mechanism of anti-PD-(L)1 resistance
Key Differentiation
- Distinct epitope with multiple-ligand HLA-G and HLA-A2 blocking
- High binding affinity and specificity against human LILRB2
- Higher pro-inflammatory cytokine release in M2-T co-culture
- Promotes T cell proliferation and activation
Clinical Plan Highlights
- Upcoming clinical milestone expected: Initiate Phase 1 study in Australia 1H 2023
- Plans to explore ES009 clinical activity in combination with other therapeutic agents including PD-(L)1 in solid tumors
