R&D Pipeline
KGX101
KGX101 is an engineered interleukin 12 (IL12) masked with protein domains to prevent cognate receptor binding until cleaved and activated specifically in the tumor micro-environment (TME). The IL12 is a proinflammatory cytokine with promising immune-stimulating activity for cancer treatment, but its prior clinical validation has been limited by its significant toxicities. With the mask, KGX101 is protected from binding to immune cell receptors in circulation and therefore avoids overactivation of the immune system until the mask is cleaved by the TME-specific proteases. The Fc fusion domain is designed to overcome the short circulating half-life of the native cytokine and to enhance manufacturing efficiency. Our KGX101 is created to have extended serum half-life, increased tumor specificity and anti-tumor efficacy, and reduced systematic toxicities. In preclinical studies, our KGX101 molecule demonstrated overall better anti-tumor activity and lower systematic toxicity in vivo than original recombinant IL12.
KGX103
KGX103 is a procytokine that exerts its antitumor function in TME for solid tumors and advanced tumors. KGX103 is a powerful agonist that can rescue exhausted CD8+ T cells and NK cells in TME, promoting their proliferation, activation and long-lasting survival. Furthermore, KGX103 has the potential to switch cold tumors into hot tumors that will be responsive to checkpoint inhibitors such as anti-PD-L1. KGX103 is currently in the preclinical stage of drug development.
KGX105/106
T-cell engagers are bispecific antibodies that trigger T cell cytotoxicity toward tumor cells by targeting the CD3 receptor on T cells and an antigen expressed on tumor cells. However, CD3-BsAbs can generate on-target off-tumor toxicities by 1). Binding to the same antigen on healthy cells, thereby redirecting CD3+ T cells toward normal tissues, resulting in permanent tissue destruction; 2). Binding and activating CD3+ T cells in blood circulation, causing cytokine storm. We designed a tumor-specific protease-sensitive CD3-bispecific antibody (BsAb), KGX105/106, that triggers the cytotoxicity of T cells toward tumor cells to improve the safety and specificity of T-cell engager therapy.
