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

Preclinical data presented for the drug candidate ATOR-1017 shows that ATOR-1017 triggers potent anti-tumor effects in an experimental model of colorectal cancer (MC38). It has also been shown that ATOR-1017 has a dose-dependent inhibitory effect on tumor growth and improves survival. Large volumes of preclinical data have been presented showing that ATOR-1017 stimulates both natural killer (NK) and T cells, both of which contribute to an effective immune-mediated killing of tumor cells. 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 further support positioning of the 4-1BB antibody ATOR-1017 as best-in-class with the potential to minimize side effects while also triggering powerful immune responses.

Clinical Trial Authorization (CTA) is granted for a Phase I clinical study with ATOR-1017, and dosing preparations for the first patient are ongoing. The study will comprise up to 50 patients and is a dose-ranging study in patients with metastatic cancer. The study will be conducted in three different clinics in Sweden. The primary endpoint of the study is to investigate the safety and tolerability of ATOR-1017, and to determine the recommended dose for subsequent Phase II studies. The Phase I study is estimated to start during the fourth quarter 2019.