Apeximmune has a diverse pipeline of immune oncology monoclonal antibody therapeutics under development. The AI-306 program targeting a novel myeloid-expressed immune suppressor is anticipated to be a first-in-class therapeutic and is part of Apeximmune’s own novel proprietary product development focus. The AI-520, also identified from our proprietary platform and AI-1178 programs targeting TIGIT and SIRPα, respectively, are designed to be potentially best-in-class therapeutics for which Apeximmune seeks to form strategic partnerships with other pharmaceutical entities for continued clinical development.

AIM-103 is an undisclosed 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 designed to reverse the immune suppressive functions of AIM-103 to reinvigorate anti-tumor T cell immunity. Primarily expressed by dendritic cells and macrophages, AIM-103 possesses enzymatic activity that shifts the microenvironmental lipid metabolite balance towards an anti-inflammatory state, while in parallel also mediating enzyme-independent suppression directly on T cells. AIM-103 hydrolyzes phospholipids, giving rise to anti-inflammatory lipid mediators that suppress pro-inflammatory cytokines and DC activation. AIM-103 also exerts suppression of T cell proliferation and IL-2 production through a mechanism that does not require catalytic activity but instead appears to involve direct T cell signaling.

AI-306 was designed to bind to AIM-103 with high affinity and inhibit both its enzyme dependent and independent T cell suppressive functions, thus leading to enhanced anti-tumor T cell activity. AI-306 represents a first-in-class antibody that we believe has application as a single agent, but is also highly amenable to combination therapy with other immune oncology agents due to its wholly unique biology, particularly from other existing checkpoint inhibitors.

AIM-103 was identified using Apeximmune’s Target Discovery Platform and falls within our proprietary product development focus.

TIGIT is an immunosuppressive cell surface checkpoint receptor expressed on various immune cells, including CD8+ effector T cells and NK cells. It binds CD155 expressed on tumor cells, thereby preventing CD155 interaction with CD226 and leading to evasion of anti-tumor immunity. TIGIT is also expressed on T regulatory cells, or Tregs, a population of immune cells that inhibit the activation and expansion of effector T cells and NK cells. TIGIT expression is correlated with PD-1 and has been associated with poor prognosis and resistance to checkpoint inhibitor therapies such as anti-PD-1.

AI-520 is an anti-TIGIT monoclonal antibody designed to block the suppressive activity of TIGIT. AI-520 binds to TIGIT with high affinity, blocks TIGIT’s interaction with CD155, and leads to re-invigoration of effector T cell function. AI-520 has also been designed to engage FcγR and elicit strong antibody dependent cellular cytotoxicity (ADCC), and can therefore further deplete Tregs within the tumor microenvironment. Our preclinical studies indicate that AI-520 has superior functional activity compared to several other clinical-stage anti-TIGIT molecules under development.

Like many other immunotherapy targets, the CD47/SIRPα pathway is a natural immune regulatory mechanism designed to prevent autoimmunity that is co-opted by cancer cells to evade immune surveillance. CD47, a transmembrane protein that primarily functions as a “don’t eat me” signal on normal healthy cells, binds to its receptor SIRPα expressed on macrophages, thereby preventing phagocytosis. Cancer cells overexpress CD47 and are thus able to evade macrophage phagocytosis and avoid subsequent mobilization of the adaptive immune system.

AI-1178 is an antagonist anti-SIRPα antibody designed to block its interaction with CD47, thereby enabling macrophages within the tumor microenvironment to switch on their phagocytic activity and kill tumor cells. AI-1178 exhibits functional potency both as a single agent and in combination with other tumor targeted antibody therapeutics. Our preclinical studies show that AI-1178 induces superior macrophage phagocytosis compared to a number of other clinical and pre-clinical stage anti-SIRPα antibodies being developed.

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.