ATOR-1015: Tumor-localizing bispecific CTLA-4 antibody with dual immunostimulatory function

ATOR-1015 binds to two different immunomodulatory receptors – the CTLA-4 inhibitory receptor, and an OX40 costimulatory receptor. In preclinical studies, the biospecificity has been shown to cause a significant increase in the immunostimulatory effect and is expected be achieved mainly in environments where both of the target molecules are expressed at high levels, such as in a tumor. This means that ATOR-1015 may have potent immunostimulatory effects in the tumor environment, but not in the rest of the body, with the goal of reducing the side effects while maintaining efficacy.

1. ATOR-1015 binds to CTLA-4 and OX40 on the regulatory T cells, the cells which restrain the immune system.
2. The macrophages are activated to kill Tregs, removing the inhibitory effect of Tregs on the beneficial T cells.
3. The effector T cells (light green) are multiplied in number and are activated to kill the tumor cells.

Project status

Preclinical data presented at various conferences in 2018 show that ATOR-1015 localizes to the tumor, with increased immunostimulation in the tumor compared with normal tissue. The drug candidate ATOR-1015 is primarily designed for combination therapies and the preclinical results presented include data indicating an amplified anti-tumor effect in combination therapy with a PD-1 pathway-blocking antibody.

In December 2018, the Swedish Medical Product Agency (MPA) approved the start of a Clinical Phase I trial, a dose escalation study in patients with metastatic cancer. The trial will be conducted at five different clinics across Sweden and Denmark, and include up to 53 patients. The principal investigator is Dr Jeffrey Yachnin at the Clinical Trials Unit, Department of Oncology at Karolinska University Hospital in Stockholm. The main objective of the trial is to evaluate the safety and tolerability of ATOR-1015, and to determine a recommended Phase II dose. For further information, refer to https://www.clinicaltrials.gov/ct2/show/NCT03782467?term=1015&rank=1.