Arcus is developing two anti-TIGIT monoclonal antibodies: domvanalimab (Fc-silent) and AB308 (Fc-enabled). Both bind to TIGIT and may enable CD155:CD226 interaction and subsequent immune cell activation.
Domvanalimab, our most advanced anti-TIGIT candidate, is an Fc-silent investigational monoclonal antibody that blocks TIGIT and has demonstrated complete receptor coverage on all TIGIT-expressing peripheral leukocytes. This investigational medicine is designed to treat solid tumors because the silent Fc domain is believed to eliminate the potential for depletion of TIGIT-bearing immune cells, which are critical for anti-tumor immune activity. Domvanalimab is currently being evaluated in an ongoing Phase 3 registrational study in combination with zimberelimab, our anti-PD-1 monoclonal antibody in first-line locally advanced or metastatic, PD-L1>50% non-small cell lung cancer.
AB308 is a second investigational anti-TIGIT monoclonal antibody that is Fc-enabled. We believe an Fc-enabled antibody like AB308 may be applicable to hematologic malignancies (eg, B cell malignancies) where the depletion of TIGIT-expressing cancer cells via antibody directed cytotoxicity may be beneficial. AB308 in combination with zimberelimab is currently being investigated in a Phase 1b study of people with advanced solid and hematologic malignancies.