BioInvent International AB and Transgene jointly announced the publication of extensive preclinical proof-of-concept data for BT-001 in the Journal for ImmunoTherapy of Cancer (JITC). This peer-reviewed article demonstrates that their co-developed clinical stage product, based on Transgene's patented oncolytic vector and encoding BioInvent's proprietary anti-CTLA-4 antibody, has the potential to provide greater therapeutic benefit than systemically administered anti-CTLA-4 antibodies. Systemically administered anti-CTLA-4 antibodies, such as the approved ipilimumab, have demonstrated substantial efficacy but also clinically limiting toxicity.

The JITC paper provides in vivo evidence that vectorized anti-CTLA-4 antibodies delivered intratumorally (i.t.) can improve safety by reducing their systemic exposure. Efficacy may also be improved, with evidence from the immunocompetent murine model showing that vectorized anti-CTLA-4 antibodies have anti-tumoral activity even against `cold tumors' that are resistant to systemically-delivered checkpoint inhibitors. Furthermore, the precise targeting of the antibody to a unique functional epitope of CTLA-4 provides a higher level of regulatory T cells (Treg) depletion than ipilimumab.

The safety-relevant data, published in JITC, show that a murine vector version of BT-001 delivered sustained levels of CTLA-4-receptor-saturating antibodies within tumors but low, sub-saturating exposure in blood and non-tumor tissue. These antibody levels were associated with high depletion of Tregs in the tumor but the absence of systemic Treg depletion, notably in the spleen. The study also provides several key insights into likely mechanisms underlying the efficacy of BT-001.

Vectorized anti-CTLA-4: triggered both Fcy-receptor-dependent Treg depletion and antigen cross-presentation, mechanisms known to trigger and promote long-lasting, systemic, CD8+ T cell antitumor immunity. showed broad antitumor activity, including activity against murine `cold tumor' models which are resistant to systemic checkpoint inhibitors. Showed additive or synergistic anti-tumor activity when combined with anti-PD-1. The JITC paper is titled `Vectorized Treg-depleting anti-CTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject "cold" tumors' and can be accessed here.

Recruitment in the ongoing Phase 1/2a clinical study of BT-001 (NCT04725331) in Europe is progressing steadily. The trial assesses BT-001 as a single agent and in combination with the PD-1 checkpoint inhibitor pembrolizumab against solid tumors. Initial Phase I data are expected in the first half of 2022.