Apeximmune is developing a diverse pipeline of innovative monoclonal and bispecific antibody therapeutics for oncology and autoimmune diseases. The AI-306 program targeting a novel myeloid-expressed immune suppressor is anticipated to be a first-in-class therapeutic with utility across a wide range of oncology indications. Apeximmune's Macrophage Engaging Bispecific Antibody (MEBA) platform combines a potentially class-leading activator of macrophage phagocytosis with tumor associated antigen targets in unique pairings to induce superior tumor-specific tumor cell killing.

PLA2G2D is novel negative immune checkpoint target with highly elevated expression in numerous cancers, especially those enriched with a high T cell signature. Apeximmune is developing AI-306, an antagonist monoclonal antibody against PLA2G2D designed to reverse its immune suppressive functions and thereby reinvigorate anti-tumor T cell immunity.

Primarily expressed by dendritic cells and macrophages, PLA2G2D is a member of the secreted phospholipase A2 family whose enzymatic activity specifically shifts the microenvironmental lipid metabolite balance towards a pro-resolving state by suppressing pro-inflammatory cytokines and dampening DC activation. Pioneering research at Apeximmune has further uncovered novel immune suppressive mechanisms of PLA2G2D that are completely independent of its catalytic activity. These newly discovered enzyme-independent functions include inhibition of T cell proliferation and IL-2 expression through direct T cell binding, suppression of macrophage differentiation and phagocytic activity, and perturbation of DC maturation and activation.

AI-306 is a first-in-class antibody designed to bind PLA2G2D with high affinity and inhibit both its enzyme dependent and independent immune suppressive functions, thus leading to enhanced anti-tumor immunity. AI-306 is expected to be highly complementary to anti-PD-1 therapies, as PLA2G2D expression has been observed to be upregulated in patients following anti-PD-1 treatment, particularly in PD-1 refractory patients.

Apeximmune’s macrophage engaging bispecific antibody (MEBA) platform is designed to augment macrophage phagocytosis of tumor cells by inhibiting AIM-104 to activate macrophage phagocytic activity, while simultaneously binding to a tumor-associated antigen (TAA) to direct tumor-specific killing.

Our bispecific macrophage engager platform leverages Apeximmune’s anti-AIM-104 antibody, which binds to AIM-104 with high affinity, blocks its association with the receptor, and induces superior macrophage phagocytosis compared to other clinical and pre-clinical stage anti-AIM-104 antibodies in development.

Using this platform, AI-328, AI-201, and AI-614 represent unique TAA pairings which provide several advantages:

• Unleashing of a tumor cell-specific “killing” signal to macrophages through both ligand-receptor blockade and myeloid cell Fc receptor engagement.
• Broad indication coverage in both solid and hematologic cancers, especially those with low lymphocyte but abundant myeloid infiltration.
• Improved safety compared to bispecific T cell engagers which are more prone to cytokine release syndrome.

Apeximmune discovers novel immuno-oncology targets and pathways involved in cancer immune tolerance using a bioinformatics approach encompassing thousands of RNA-seq transcriptomes and spanning over 20 different tumor types. Fundamental to our approach is the development of a proprietary T cell gene expression signature that distinguishes between tumors with strong or sparse T cell signatures. Further differential gene expression analysis of these two signature subsets allows for the identification of novel immune attenuating factors that suppress the effector function of tumor infiltrating T cells, or alternatively, genes that inhibit the recruitment of T cells to the tumor microenvironment. Using this approach, Apeximmune currently has more than 30 novel targets of interest from which to choose for future drug development programs. PLA2G2D and AIM-101 were discovered from this platform.