Aduro’s STING Pathway Activator platform is based on the activation of the cytoplasmic STING (Stimulator of Interferon Genes) receptor to lead to a tumor-specific immune response.
STING is known to be a central mediator of innate immunity. When stimulated, STING induces the expression of type I interferon, cytokines and T cell recruitment factors that result in the activation of macrophages and dendritic cells, innate effector cells such as natural killer (NK) cells, and priming of tumor-specific T cells.
Natural STING Pathway Activators are small molecules expressed by bacteria and immune cells. Aduro has established pioneering expertise in STING Pathway Activator technology and, working in collaboration with academic leaders in the field, has developed synthetic STING Pathway Activators with significantly higher activity than the natural STING ligands produced by bacteria and mammalian cells. These synthetic STING Pathway Activators are being developed for direct injection into tumors to stimulate an immune response against antigens present in the tumor. The process is expected to use the tumor itself as a “vaccine,” enabling the induction of a tumor-specific immune response that is unique to the treated individual; an off-the-shelf small molecule approach to personalized immunotherapy.
STING Pathway Activators are also intended to be combined with other cancer therapies – such as chemotherapy, radiation and monoclonal antibodies (e.g. checkpoint inhibitors and immune agonists) – as part of a more comprehensive approach to fighting certain cancers.
Aduro’s lead molecule, ADU-S100/MIW815, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial in cutaneously accessible tumors, including breast, head-and-neck, and renal cell cancers as well as melanoma and lymphoma. The trial is evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills non-injected distant metastases. In addition, the companies are evaluating the combination of ADU-S100 with an anti-PD-1 checkpoint inhibitor for the treatment of advanced/metastatic solid tumors or lymphomas in a global Phase 1b study.