ATOR-1144: Tumor-localizing bispecific CTLA-4 x GITR antibody with the capacity to activate several parts of the immune system

ATOR-1144 is a first-in-class bispecific tumor-localized antibody targeting the checkpoint inhibitor CTLA-4 and the co-stimulatory receptor GITR (Glucocorticoid-Induced TNFR family Related). It works through several pathways, making it suitable for treating both solid tumors and for the treatment of solid tumors as well as hematological cancers.

1. ATOR-1144 binds to CTLA-4 and GITR on the regulatory T cells (Treg). Macrophages or NK cells are activated to kill Tregs, removing the inhibitory effect of Tregs on the beneficial T cells.
2. ATOR-1144 activates effector T cells by binding to CTLA-4 and GITR, which in turn kill tumor cells.
3. ATOR-1144 binds to GITR on NK and tumor cells, which has a tumor-killing effect.

Project status

ATOR-1144 comprises two binding components: a GITR-specific antibody isolated from ALLIGATOR-GOLD and a CTLA-4-specific binding component developed by FIND optimization of CD86, a natural ligand for CTLA-4. ATOR-1144 entered the preclinical development phase shortly before the end of 2018.

In April, 2019, new preclinical data was presented at the Annual Meeting of the American Association for Cancer Research (AACR) demonstrating that ATOR-1144 works through several pathways: activation of effector T cells, depletion of regulatory T cells (Tregs) and tumor cells, and activation of NK (natural killer) cells, with potential for enhanced tumor cell killing. In addition, GITR is shown to be expressed on tumor-infiltrating lymphocytes and neoplastic cells in tumor samples from, for example, head and neck, esophageal, ovarian cancer, melanoma and B and T cell lymphoma, allowing for direct tumor cell killing.