On September 14, 2024 BioInvent International AB, a biotech company focused on the discovery and development of novel and first-in-class immune-modulatory antibodies for cancer immunotherapy, and Transgene, a biotech company that designs and develops virus-based immunotherapies for the treatment of cancer, reported new initial data from their ongoing Phase 2/2a study on the multifunctional oncolytic virus BT-001, demonstrating antitumor activity in patients with refractory solid tumors (Press release, BioInvent, SEP 14, 2024, https://www.bioinvent.com/en/press/bioinvent-and-transgenes-oncolytic-virus-bt-001-shows-promising-antitumor-activity-ongoing [SID1234646619]). The data presented today at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting, showed that BT-001 induced tumor regression in patients unresponsive to prior anti PD(L)-1 treatment, both as a monotherapy and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab).
Preliminary translational data suggest that BT-001 replicates in the tumor where the payloads are expressed with undetectable systemic exposure. BT-001 alone or in combination with pembrolizumab was well tolerated and showed first signs of efficacy with clinical responses in 2 of 6 refractory patients when given in combination with pembrolizumab. BT-001 treatment turned "cold" tumors to "hot" inducing T cell infiltration, a higher M1/M2 ratio, and a shift to PD(L)-1 positivity in the tumor microenvironment.

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Dr. S. Champiat, Medical Oncologist, Head of the Inpatient Unit, Drug Development Department (DITEP) at Institut Gustave Roussy, commented: "The immunological data generated by BT-001 suggest that, as hoped, BT-001 is replicating in the tumor and its payload of transgenes is expressed, with very limited exposure outside of the tumor thereby limiting systemic toxicity. I look forward to additional results from this ongoing study which will provide further evidence of the safety and clinical activity of BT-001 and its potential role as a new therapy for cancer patients with solid tumors."

Transgene and BioInvent are co-developing BT-001, an oncolytic virus developed using Transgene’s Invir.IO platform armed to express GM-CSF and BioInvent’s full-length anti-CTLA-4 monoclonal antibody, to elicit a strong and effective anti-tumoral response in solid tumors.

Alessandro Riva, Chairman and CEO of Transgene, said: "We are pleased to present the first promising clinical data on BT-001 at ESMO (Free ESMO Whitepaper) 2024 which confirm its mechanism of action as a single agent injected intratumorally and importantly demonstrate first signs of anti-tumor activity. Added to its good safety profile alone and in combination with pembrolizumab, BT-001 has the potential to shrink lesions and induce stable disease in refractory patients who may have few other treatment options. We will further explore the safety and efficacy of BT-001 in this development program with our partner BioInvent and report additional data when it becomes available."

Andres McAllister, MD, PhD, Chief Medical Officer at BioInvent International AB, concluded: "We are encouraged by the early clinical results presented at ESMO (Free ESMO Whitepaper) for BT-001, which encodes a potent Treg-depleting recombinant human anti-CTLA-4 antibody generated by our proprietary n-CoDeR and F.I.R.S.T platforms,. This clinical proof of concept confirms our ability to identify antibodies that bind to a selected target but exhibit a differentiated activity, allowing the development of promising new drug candidates such as BT-001."

The abstract and Poster titled: "Initial clinical results of BT-001, an oncolytic virus expressing an anti-CTLA4 mAb, administered as single agent and in combination with pembrolizumab in patients with advanced solid tumors.".

The poster can be accessed at the company’s website https://www.bioinvent.com/en/our-science/scientific-publications.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the trial
The ongoing Phase 1/2a (NCT: 04725331) study is a multicenter, open label, dose-escalation trial evaluating BT-001 as a single agent and in combination with pembrolizumab (anti-PD-1 treatment). Patient inclusions are ongoing in Europe (France, Belgium) and the trial has been authorized in the US.
Phase 1 is divided into two parts. In part A, patients with metastatic/advanced tumors receive single agent, intra-tumoral administrations of BT-001. Part B explores the combination of intra-tumoral injections of BT-001 with pembrolizumab. In this part, KEYTRUDA (pembrolizumab) is provided to the trial by MSD (Merck & Co).
Phase 2a will evaluate the combination regimen in several patient cohorts with selected 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.

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 may 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.