推进同类最佳的交叉特异性LILRB1/LILRB2抗体IOMX-0675进入实体瘤临床开发

IOMX-0675 is a fully human, cross-specific immunoglobulin G1 (IgG1) antibody targeting LILRB1 (ILT2) and LILRB2 (ILT4), two key immunosuppressive receptors that drive tumor immune evasion and resistance to T cell checkpoint blockade. LILRB1 and LILRB2 recognize both classical and non-classical MHC-I molecules and are highly expressed on tumor-infiltrating myeloid cells, with LILRB1 also being expressed on lymphoid cells. Molecular profiling revealed concurrent expression of highly homologous immune-activating LILRA1/LILRA3 with inhibitory LILRB1/LILRB2, underscoring the critical need for selective receptor targeting.​ IOMX-0675 exhibits a unique, superior binding profile defining its best-in-class potential: selective, high-affinity binding to inhibitory LILRB1/LILRB2 with minimal affinity to immune-activating LILRA1/LILRA3. This differentiated selectivity maximizes anti-tumor efficacy by preserving immune activation, while blocking immunosuppression. Comparative functional studies demonstrate IOMX-0675's superior potency in tumor cell phagocytosis as well as a repolarization activity of M2-macrophages compared to competitor compounds. Notably, only simultaneous blocking of LILRB1 and LILRB2 with dual-targeting IOMX-0675 leads to significant T cell activation in co-culture assays. In support of a potential clinical patient selection approach, a donor screening was performed in vitro which revealed a distinct IOMX-0675 efficacy profile with clear differences between responsive and non-responsive donors. An integrated multi-omics-based biomarker analysis offers strong potential for a future biomarker-driven patient selection process. Functional assays using stimulated PBMCs demonstrate that IOMX-0675 synergizes with anti-PD-1 treatment, potentiating pro-inflammatory cytokine secretion and driving cytotoxic T cell activation in vitro . Co-culture assays modeling patient-relevant tumor or lymph node microenvironments demonstrate that IOMX-0675 repolarizes immunosuppressive milieus and restores T cell function, in a situation where anti-PD-1 monotherapy is ineffective. In summary, IOMX-0675 represents a best-in-class therapeutic antibody that combines selective LILRB1/LILRB2 antagonism with minimal immune-activating receptor binding and demonstrates superior myeloid reprogramming and T cell restoration both in vitro and in vivo . IOMX-0675 will enter a Phase I/II clinical trial in early 2026 as monotherapy as well as combination therapy with anti-PD1 in patients with previously treated advanced/metastatic solid tumors.