Transgene and BioInvent International AB announced preclinical data supporting the mode of action of BT-001, their novel dual mechanism-of-action oncolytic Vaccinia virus. The data demonstrate high intratumoral expression of an immune checkpoint-inhibiting antibody and robust anti-tumoral activity in several tumor models. BT-001, developed by BioInvent and Transgene, is a clinical phase oncolytic virus engineered to deliver an anti-CTLA-4 antibody and human GM-CSF in a tumor-specific vehicle (the VVcopTK-RR- virus backbone) for the treatment of solid tumors.

The companies' poster at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC 2021) shows that BT-001 selectively replicates in tumor cells. The murine surrogate of BT-001 delivered sustained and high intratumoral levels of antibody accompanied by low systemic exposure. These differential expression levels were associated with high depletion of intratumoral regulatory T cells (Treg) but the absence of systemic Treg depletion.

Similar effects in humans would allow BT-001 to deliver powerful antitumor immunity. Patient inclusion into the ongoing Phase I/IIa clinical study of BT-001 (NCT04725331) is progressing well. The multicenter trial, authorized in Europe and in the U.S., is assessing BT-001 as single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab for the treatment of solid tumors.

Initial Phase I data are expected in the first half of 2022. Other data highlighted in the SITC poster show improved survival in several syngeneic tumor models following treatment with a murine version of BT-001. There is also evidence of a positive synergistic effect between the murine ‘BT-001' oncolytic virus expressing the CTLA-4 antibody and a systemic PD-1 checkpoint inhibitor.