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.

AIM-103 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 AIM-103 designed to reverse its immune suppressive functions and thereby reinvigorate anti-tumor T cell immunity.

Primarily expressed by dendritic cells and macrophages, AIM-103 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 AIM-103 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 AIM-103 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 AIM-103 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. AIM-103 and AIM-101 were discovered from this platform.