Non-Hodgkin lymphoma (NHL) is an umbrella term for a group of cancers that develop in the body’s lymphatic system. Examples of sub-indications are patients with Mantle Cell Lymphoma (MCL), Follicular Lymphoma (FL) and Marginal Zone Lymphoma (MZL). Examples of subindications are patients with Mantle Cell Lymphoma, Follicular Lymphoma, and Marginal Zone Lymphoma. Aggressive lymphomas are usually treated with combinations of various chemotherapeutic agents and monoclonal anti-bodies such as rituximab (Rituxan®, Mabthera®, Roche). Low-grade lymphomas have a better prognosis and treatment is often only initiated once a patient has disease symptoms.
Strategic collaboration with Pfizer - developing antibodies that act on tumour-associated myeloid cells
In partnership with Pfizer Inc. since December 2016, BioInvent works to identify novel oncology targets and therapeutic antibodies that may either reverse the immunosuppressive activity of tumor-associated myeloid cells or reduce the number of tumor-associated myeloid cells in the tumor.
BioInvent announced in July 2019 selection of the first target and in December 2019 the second target discovered by BioInvent’s proprietary F.I.R.S.T™ technology platform under the collaboration with Pfizer Inc. The selection of targets triggered two payments from Pfizer to BioInvent of $0.3 million. Under the terms of the 2016 agreement, potential selection and development of antibodies directed against this target, as well as potential selection of further targets and development of antibodies directed at them, would allow BioInvent to be eligible for further milestone payments.
In December 2019 BioInvent announced that the research term under its collaboration and license agreement with Pfizer had been extended by six months. The purpose of the research extension is to permit the companies to further identify and characterize new targets and antibodies binding to these targets.
BioInvent is eligible for potential future development milestones in excess of $500 million (assuming five antibodies are developed through to commercialization). The Company could also receive up to double digit royalties related to product sales. In exchange, Pfizer will have the right to develop and commercialize any antibodies generated from this agreement.
BioInvent received an upfront payment of $3 million when the agreement was signed in December 2016, and research funding has been received during 2017, 2018 and 2019. Pfizer also made a $6 million equity investment in new shares of BioInvent when the agreement was signed.
Developing antibodies that act on regulatory T cells (Tregs) via novel or validated targets
Tregs can substantially inhibit various immune responses, enabling tumor cells to escape detection. BioInvent is utilizing its F.I.R.S.T™ platform to identify and characterize monoclonal antibodies to cancer-associated Treg targets in a function-first, target-agnostic, manner. The company is also pursuing differentiated antibodies to known targets through novel mechanisms and pathways.
BI-1808 and BI-1910 (anti-TNFR2)
BioInvent has identified TNFR2, a member of the so called TNFR superfamily (TNFRS) as a target within the Treg program. The company has antibody candidates with various mechanisms of action that show promising preclinical data. A clinical trial application is expected to be submitted in H1 2020 for BI-1808.
Exciting translational data will be presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting II, taking place June 22-24. An abstract was published in May 2020.
- Targeting TNFR2 demonstrates compelling therapeutic effects in syngeneic solid cancer models spanning “hot” and “cold” tumors.
- Targeting TNFR2 synergizes with anti-PD-1 to achieve cure.
- Careful mechanistic dissection and matching of the human lead clinical candidates and mouse surrogate antibodies enables thorough understanding of TNFR2-targeting and critical guidance of clinical development.
Two antibody variants with distinct molecular and functional properties have been selected for development for treatment of solid cancer based on careful characterization of their mechanisms of action: BI-1808, a ligand-blocking Treg depleting antibody, and BI-1910, a TNFR2 agonist. The two antibody candidates showed strikingly different FcγR-dependence for optimal antitumor activity and - while evoking different initial immune cell mediated events - both elicited transformation of the tumor immune landscape associated with powerful anti-tumor efficacy
BT-001 - Partnership with Transgene – developing next generation oncolytic viruses expressing an anti-CTLA-4 antibody to treat solid tumors
In December 2019 BioInvent and Transgene announced preclinical data for BT-001 in solid tumors. The therapeutic activity was assessed in several immunocompetent preclinical models, showing outstanding antitumoral activity for BT-001 murine surrogate antibody-encoding viruses conferring cures in a majority of mice transplanted with different solid cancer tumors (> 70 % in all tested models). The new preclinical data also confirmed that the anti-CTLA4 antibody expressed by BT-001 in mouse tumor cells retained biochemical integrity and folding, functionality, and biological activity. In addition, BT-001’s biodistribution profile demonstrated higher concentration and prolonged activity of the anti-CTLA4 antibodies in tumors compared to intravenous anti-CTLA-4 antibody therapy. Preclinical data on BT-001 will be presented at scientific meetings in the coming months.
BioInvent and Transgene announced in March 2020 that the first clinical trial application for BT-001 was submitted and that the first-in-human trial is expected to start before the end of 2020 in Europe and the US.
Promising findings will be presented at the American Association for Cancer Research (AACR) Virtual Annual Meeting II, taking place June 22-24. An abstract was published in May 2020.
- The new data demonstrate a powerful therapeutic effect, indicated by curative potential as a single agent in multiple syngeneic mouse models spanning solid tumor models (CT26, EMT6, C38, and A20).
- An improved therapeutic window relative to systemic anti-CTLA-4 blockade was indicated by higher, receptor-saturating, intratumoral anti-CTLA4 antibody concentrations versus much lower levels in the blood compartments.
BT-001’s activity was further enhanced when combined with anti-PD-1 antibody therapy – opening up the potential for powerful dual checkpoint blockade treatment regimens.
BioInvent and Transgene collaborate to co-develop oncolytic virus (OV) candidates encoding a validated anti-CTLA-4 antibody sequence – potentially with additional transgenes – aimed at treating solid tumors, with the potential to be significantly more effective than the combination of a virus and an antibody as single agents.
Transgene is contributing both engineering expertise, as well as its proprietary Vaccinia viruses, designed to directly and selectively destroy cancer cells by intracellular replication of the virus in the cancer cell (oncolysis). Oncolysis induces an immune response against tumors, while the “weaponized” virus allows the expression of genes carried by the viral genome, here an immune modulatory anti-CTLA-4 antibody, which will further boost immune response against the tumor.
BioInvent is providing its cancer biology and antibody expertise to the collaboration, as well as anti-CTLA-4 antibody sequences generated through its proprietary n-CoDeR®/F.I.R.S.TTM platforms.
In March 2019 BioInvent and Transgene announced an extension of their collaboration to co-develop multifunctional oncolytic viruses encoding antibodies targeting an undisclosed target, which can be used in the treatment of a broad range of solid tumors.
The research and development costs, as well as revenue and royalties from candidates generated from the collaboration, are shared 50:50.