On March 1, 2021 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, and Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported that the first patient in a Phase I/IIa clinical trial of the novel dual mechanism-of-action oncolytic vaccinia virus BT-001 has been enrolled at Institut Bergonié (Bordeaux, France) (Press release, BioInvent, MAR 1, 2021, View Source,c3297110 [SID1234575803]).

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BT-001 has been 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. In addition, delivering the anti-CTLA-4 antibody directly to the tumor microenvironment aims to induce local Treg depletion and strong therapeutic activity. 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 through a 50/50 collaboration between BioInvent and Transgene.

"The inclusion of the first patient in this Phase I/IIa trial marks a further broadening of our clinical pipeline, which now comprises three candidate products and four clinical studies. BT-001 is a unique oncolytic virus, combining multiple mechanisms-of-action, and has outstanding potential in a wide range of indications thanks to its combination of multiple anti-cancer properties," said Martin Welschof, CEO of BioInvent.

Hedi Ben Brahim, Chairman and CEO of Transgene, said: "We are excited to start this clinical trial with BT-001, which is the result of a very productive collaboration between Transgene and BioInvent. This first Invir.IO based oncolytic virus entering the clinic has been shown to induce long-lasting antitumor immune responses and abscopal effects in several preclinical tumor models; in these experiments, the activity of BT-001 was further enhanced through combination with an anti-PD-1 antibody treatment. It has a unique mode of action and the outstanding results so far indicate it could make a significant difference to cancer patients."

This multicenter, open-label, dose-escalation Phase l/lla trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment) will first be including patients in several countries in Europe. An IND submission will follow in the USA.

The Phase I will be divided into two parts. Part A will enroll up to 36 patients with metastatic/advanced solid tumors. Patients will receive single agent, intra-tumoral administrations of BT-001, in cutaneous or palpable subcutaneous lesions or easily injectable lymph nodes. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab in 12 patients. The Phase lla will evaluate the combination regimen in several patient cohorts with different tumor types. These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment.

The trial (NCT04725331) will first be conducted at the UCL Saint Luc (Brussels, Belgium), the Bergonié Institute (Bordeaux, France), the Gustave Roussy Institute (Paris area, France), the Centre Léon Bérard (Lyon, France) and the Hôpital Saint-Louis (Paris, France).

About BT-001
BT-001 is a best-in-class oncolytic virus developed with Transgene’s Invir.IO platform. Invir.IO’s viruses are based on the patented large capacity Vaccinia virus Copenhagen strain genetically modified with the double deletion TK-RR-. This optimization enhances the safety profile of the virus. From this, BT-001 is engineered to encode both a highly differentiated Treg depleting anti-CTLA-4 antibody and the human GM-CSF cytokine. The recombinant antibody recognizing human CTLA-4 was generated by BioInvent’s proprietary n-CoDeR/F.I.R.S.T platforms. The use of an oncolytic virus to deliver the anti-CTLA-4 locally and selectively in the tumor microenvironment allows high intratumoral concentrations of both transgenes eliciting a stronger and more effective antitumor response. By reducing systemic exposure to a very low level, this local therapeutic activity furthermore allows to increase the safety and tolerability profile of the anti-CTLA-4 antibody. Preclinical data have shown that BT-001 has potential for broad single agent activity, and that selective tumor-localized delivery of anti-CTLA4 may allow for a better tolerated, sustained and more effective combination therapy with antibodies targeting the PD-1/PDL1 axis.

The scientific and clinical development of the oncolytic virus candidate BT-001 is a 50/50 collaboration between BioInvent and Transgene.