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.
TB-403 in paediatric brain tumours
- development in collaboration with Oncurious
TB-403 is currently in a Phase I/II study for the treatment of patients with medulloblastoma in cooperation with a US based pediatric oncology network, Beat Childhood Cancer. The study progresses according to plan, and the third dose level is ongoing.
TB-403 has received Orphan Drug Designation for medulloblastoma from the European Medicines Agency (EMA). TB-403 is developed in collaboration with Oncurious, a subsidiary of Oxurion (formerly known as ThromboGenics). BioInvent’s ownership in TB-403 is 50 percent and it contributes with 50 percent of the development costs.
Patents for TB-403 and similar antibodies have been granted in Europe, the US, Japan and several additional countries, and patent applications are pending in further countries. Patents covering use of antibodies against PIGF, for example for the purpose of treating or preventing cancer, have also been granted, including in the US.
THR-317 in diabetic macular edema
- under development by Oxurion
In July 2018 BioInvent’s partner Oxurion reported Day 150 topline data from a phase l/ll study of THR-317 in patients with Diabetic Macular Edema. The study met its primary endpoint of safety for both the 4 mg and 8 mg doses. Whilst the focus of the study was safety, efficacy was also observed. In September 2018 Oxurion enrolled first patient in phase ll study evaluating THR-317 for treatment of idiopathic MacTel 1.
Oxurion carries all costs for the development of THR-317 in non-oncology indications, and BioInvent is entitled to five percent of the project’s economic value.
Patents for the antibody have been granted in Europe, the US, Japan and several additional countries, and patent applications are pending in further countries.
Developing antibodies that act on regulatory T cells (Tregs) via either novel or validated targets
Tregs can substantially inhibit various immune responses, enabling tumour 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.
BioInvent has identified 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. The most advanced candidate is BI-1808 and a first clinical study is scheduled for H1 2020.
Partnership with Transgene – developing next generation oncolytic viruses expressing an anti-CTLA-4 antibody to treat solid tumours
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.
Transgene is contributing both its OV design and 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 oncolytic viral genome, such as an immune modulatory anti-CTLA-4 antibody, to 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.T.TM platforms.
This novel OV product has the potential to be significantly more effective than the combination of single agents. Transgene has generated preclinical proof-of-concept data showing that an oncolytic vaccinia virus encoded with a checkpoint inhibitor resulted in better overall survival than the corresponding combination of separate single agents.
The research and development costs, as well as revenues and royalties from candidates generated from the collaboration, will be shared 50:50
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. To date, pools of antibodies have been generated and are being characterized for functional activity.
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 and 2018. Pfizer also made a $6 million equity investment in new shares of BioInvent when the agreement was signed.
Antibodies are nature’s own defence molecules. They are highly selective and very well-tolerated in their human form.
The antibody-based drug segment is one of the fastest growing segments in the global pharmaceutical market. Three of the world's top-selling antibody-based drugs are Rituxan/Mabthera® (rituximab, Roche), Herceptin® (rastuzumab, Roche) and Avastin® (bevacizumab, Roche). The combined sales of these drugs amounted to around USD 22 billion in 2017. In the next five years the patent protection for several of the best-selling drugs will expire at the same time as new, improved combination therapies are expected to reach the market.