On March 9, 2022 Transgene 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 that an abstract reporting preclinical studies of BT-001, a novel oncolytic virus, has been selected for a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, Transgene, MAR 9, 2022, View Source [SID1234609806]). The conference will be held in person in New Orleans, LA, April 8-13, 2022.
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The poster will highlight that BT-001, a 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.
The preclinical data to be presented demonstrate 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 cell (Treg) depletion than currently available immune checkpoint blockade (ICB) therapies.
The studies also provide several key insights into likely mechanisms underlying the efficacy of BT-001. Vectorized anti-CTLA-4:
· triggered both Fcγ-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 details of the poster presentation are as follows:
Abstract Title: Comprehensive preclinical studies of BT-001: an oncolytic vaccinia virus armed with Treg-depleting @CTLA4 and GM-CSF.
Authors: Jean-Baptiste Marchand, Monika Semmrich, Christelle Remy, Matilda Rehn, Laetitia Fend, Petra Holmkvist, Nathalie Silvestre, Carolin Svensson, Patricia Kleinpeter, Jules Deforges, Fred Junghus, Linda Mårtensson, Johann Foloppe, Ingrid Teige, Björn Frendéus, Éric Quéméneur.
Session Category: Immunology
Session Title: Vaccines: Oncolytic and Prophylactic
Session Date and Time: Tuesday Apr 12, 2022, 1:30 PM – 5:00 PM
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 40
Poster Board Number: 17
Abstract Number: 3567
The abstract can be accessed on the AACR (Free AACR Whitepaper) annual meeting website: View Source
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 currently in a Phase I/IIa clinical study (NCT04725331) and recruitment 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.
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.