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 entered the preclinical development phase shortly before the end of 2018. In April 2019, preclinical data presented at the AACR Annual Meeting (American Association for Cancer Research) showed that ATOR-1144 has several different methods of attack: activating effector T cells (immunostimulatory), killing regulatory T cells (immunosuppressive) and tumor cells, and activating NK cells, which can kill more tumor cells. Furthermore, GITR is also expressed on other cells involved in direct tumor cell killing. ATOR-1144 consists of two binding components. One component is a GITR-specific antibody isolated from ALLIGATOR-GOLD; the other is a CTLA-4-specific binder developed through FIND-optimization of CD86, a natural ligand for CTLA-4.

Promising preclinical data was presented in October 2019 at the European Antibody Congress in Basel. The results demonstrate a potent anti-tumor effect in disease models of cancer. The results also show that treatment with ATOR-1144 can induce an immunological memory.