On November 9, 2021 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and BioInvent International AB ("BioInvent") (Nasdaq Stockholm: BINV), a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, reported 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 (Press release, Transgene, NOV 9, 2021, View Source [SID1234594944]).

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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) (Free SITC Whitepaper) (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 (Free SITC Whitepaper) 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.

"These impressive data, demonstrating the multiple mechanisms of action and anti-cancer properties of BT-001, played a key role in our decision to take this unique oncolytic virus into the clinic. We are pleased to be able to share them with our scientific and clinical peers at SITC (Free SITC Whitepaper)" said Martin Welschof, CEO of BioInvent and Hedi Ben Brahim, Chairman and CEO of Transgene.

SITC 2021 will take place on November 10–14, 2021, at the Walter E. Washington Convention Center in Washington, D.C. and virtually. The poster, entitled "Vectorized Treg-depleting aCTLA-4 elicits antigen cross-presentation and CD8+ T cell immunity to reject "cold" tumors", will be presented on the Virtual ePoster Hall and presented in the Poster Hall (Hall E) on Saturday, November 13, 2021.

Authors: Monika Semmrich, Jean-Baptiste Marchand, Matilda Rehn, Laetitia Fend, Christelle Remy, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Eric Quéméneur and Björn Frendéus.

Abstract and poster number: 746

About BT-001
BT-001 is an oncolytic virus generated using Transgene’s Invir.IO platform and its patented large-capacity VVcopTK-RR- oncolytic virus, which has been engineered to encode both a Treg-depleting human recombinant anti-CTLA-4 antibody generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms, and the human GM-CSF cytokine. By selectively targeting the tumor microenvironment, BT-001 is expected to elicit a much stronger and more effective antitumoral response. As a consequence, by reducing systemic exposure, the safety and tolerability profile of the anti-CTLA-4 antibody will be greatly improved.

BT-001 is being co-developed as part of a 50/50 collaboration on oncolytic viruses between Transgene and BioInvent. To know more on BT-001, watch our video here.