Non-Hodgkin lymphoma (NHL) is an umbrella term for a group of cancers affecting the body’s lymphocytes, including B-cell cancer. Chronic cell lymphoma (CLL) is an incurable cancer that affects B-cells. Both NHL and CLL patients are normally treated with combinations of cytotoxic drugs, targeted therapies, such as Bruton’s tyrosine kinase inhibitors (e.g. Ibrutinib (Imbruvika®, Janssen; Imbruvica, AbbVie), and monoclonal antibodies targeting CD20 (e.g. rituximab (Rituxan®), Mabthera®, Roche). Over 600,000 patients globally are affected annually by NHL and CLL. Sales of rituximab are in excess of $7 billion per annum.
TB-403 in paediatric brain tumours
- development in collaboration with Oncurious, subsidiary of ThromboGenics
TB-403 is a humanised antibody directed against the PlGF protein, which is believed to inhibit its signaling via the Nrp-1 receptor. PlGF is expressed in certain paediatric cancers including medulloblastoma, Ewing’s sarcoma, neuroblastoma and alveolar rhabdomyosarcoma.
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 and the second dose level is ongoing.
TB-403 has received Orphan Drug Designation for medulloblastoma from the European Medicines Agency.
TB-403 is being developed in collaboration with Oncurious, a subsidiary of ThromboGenics. In July 2017, BioInvent’s ownership in TB-403 increased from 40 to 50 percent following renegotiation of the longstanding collaboration agreement signed in 2004. BioInvent continues to contribute 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 ThromboGenics
THR-317 is being evaluated in a Phase II trial in patients with diabetic macular edema (DME). In July 2017 the cooperation agreement from 2004 was renegotiated. Under the amended arrangement, ThromboGenics gains full and exclusive ownership of THR-317 for development and commercialization in all non-oncology indications. ThromboGenics will continue to carry 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 antobodies that act on regulatory T cells (Tregs) via either novel or validated targets
T-regs can substantially inhibit various immune responses enabling tumour cells to escape detection. BioInvent is currently developing antibodies to modulate specific currently undetermined T-reg targets and functions as well as for known targets such as OX-40 and 4-1BB.
BioInvent is currently working to expand the pool of antibodies and targets that have been shown to be associated with T-reg specificity and T-reg depleting activity.
BioInvent is working in cooperation with Cancer Research Technology and the University of Southampton in the UK to develop new immunotherapeutic cancer drugs based on antibodies that target OX-40 and 4-1BB, two known co-receptors that help activate T cells, to produce long-lasting anti-tumour immune responses.
Strategic collaboration with Pfizer - developing antibodies that act on tumour-associated myeloid cells
In December 2016, BioInvent announced that it has entered into a cancer immunotherapy research collaboration and license agreement with Pfizer Inc. to develop antibodies targeting tumour-associated myeloid cells. BioInvent will leverage its expertise to identify novel oncology targets and therapeutic antibodies that inhibit cancer growth either by reversing the immunosuppressive activity of tumour-associated myeloid cells or by reducing the number of tumour-associated myeloid cells in the tumour.
Under the terms of the agreement BioInvent could be eligible for potential future development milestones in excess of $0.5 billion (assuming five antibodies are developed through to commercialisation). The Company could also receive up to double digit royalties related to product sales. In return Pfizer will have the right to develop and commercialise any antibodies generated from this agreement.
Pfizer has paid BioInvent an upfront payment of $3 million when the agreement was signed and is committed to paying $1 million in research funding during 2017. Pfizer has 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® (trastuzumab, Roche) and Avastin® (bevacizumab, Roche). The combined sales of these drugs amounted to around USD 21 billion in 2016. In the next five years the patent protection for Rituxan/Mabthera® and Herceptin® will expire at the same time as new, improved combination therapies are expected to reach the market.