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.

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

Data from the ongoing Phase I study have shown that ATOR-1015 is associated with infusion-related reactions considered related to the development of anti-drug antibodies. This leads
to a need for thorough evaluation of the clinical data. The dose escalation in the Phase I study is expected to be completed during the fourth quarter 2020.
A re-design of the planned efficacy study in malignant melanoma will be required. Preclinical assessments, a new study protocol and associated regulatory interactions will be needed
before further clinical activities can be initiated. In parallel Alligator will seek a clinical partner for further development.

For further information about the study, refer to https://www.clinicaltrials.gov/ct2/show/NCT03782467?term=1015&rank=1.