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.
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.
In December 2019, the first patient was successfully dosed in the Phase I study for ATOR-1017. The study will comprise up to 50 patients and is a dose-ranging study in patients with metastatic cancer. The study will be conducted at 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. Patient recruitment in the Phase I study was temporarily paused in March and April 2020 due to the Covid-19 pandemic but has been resumed.
In June 2020, the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. US 10,689,454 which covers compositions of matter directed to ATOR-1017. This is the first granted US patent related to ATOR-1017 and its earliest expiry year is 2037.
In August 2020, data were presented showing an encouraging safety profile of ATOR-1017. Few drug related adverse events were observed and all were mild or moderate (grade 1 or 2). The Data Review Committee that monitors the safety of the patients in the ATOR-1017 Phase I study, cleared the 40 mg dose and approved to start dosing with the higher dose level of 100 mg, corresponding to approximately 1.6 mg/kg.