ATOR-1017: Stimulation of both T and NK cells induces potent killing of tumor cells

ATOR-1017 is distinct from other 4-1BB antibodies, partly because of its unique binding profile, but also because its immunostimulating function is dependent on crosslinking to Fc-gamma receptors in immune cells. This localizes the immunostimulation to the tumor region where both 4-1BB and Fc-gamma receptors are expressed at high levels – totally in line with the treatment strategy for Alligator’s drug candidates.
The objective is to achieve an effective tumor-targeting immune response with minimum side effects.

1. ATOR-1017 binds to the target molecule 4-1BB on the surface of T cells.
2. The immune activating function is dependent on binding to Fc-gamma receptor on macrophages.
3. The beneficial T cells are activated to kill tumor cells.

Project

In 2018, new preclinical data for ATOR-1017 was presented at various scientific conferences including the 14th Annual Essential Protein Engineering Summit (PEGS), the 3rd Annual World Preclinical Congress and the 2018 Immuno-Oncology Summit, all held in Boston, US.
These new data show that ATOR-1017 stimulates both NK (Natural Killer) and T cells, both of which contribute to an effective immune-mediated killing of tumor cells. As well as leading to amplification of the tumor-targeted immune response, the 4-1BB stimulation of T cells also develops an immunological memory of the tumor. NK cells are immune cells that specifically target tumor cells trying to evade the immune system’s response. NK cells also strengthen cell-death signaling from the immune system’s tumor-specific T cells. Stimulatory antibodies against 4-1BB therefore strengthen the ability of both NK and T cells to attack tumor cells.
These preclinical data provide additional support for the positioning of ATOR-1017 as a best-in-class 4-1BB antibody with the potential to reduce side effects, but also to generate a potent and long-lasting immune response.
A preclinical data package is currently being compiled with the aim to submit an application for Clinical Trial Authorization (CTA) in mid-2019.