TB-403

Product description
TB-403 is a humanised monoclonal antibody that blocks the activity of Placenta Growth Factor (PlGF), a protein involved in the development of new blood vessels (angiogenesis). The product is being developed to treat solid tumours that are dependent on the growth of new blood vessels for their survival.

Product rationale
PlGF is often over-expressed in cancer and chronic inflammatory conditions, and so is a good target for treating these diseases. Like Vascular Endothelial Growth Factor (VEGF), PlGF supports the growth of blood vessels, but unlike VEGF it does not affect normal physiological angiogenesis. This means that TB-403 is expected to have a good side effect profile.

Treatment with some anti-angiogenic drugs can increase the expression of PIGF. This suggests that PIGF is involved in an adaptive response which leads to drug resistance. BioInvent therefore expects that TB-403 could enhance the efficacy of these angiogenesis inhibitors, as well as being an effective supplement to chemotherapy. The antibody could also be used to treat patients who become resistant to VEGF-inhibitors.

Clinical status
Roche initiated a multi-centre study in patients with patients with colorectal and ovarian cancer in May 2010. In a Phase Ib dose escalation trial, reported in November 2009, six of 23 patients with advanced solid tumours were oberved with stable disease after treatment with TB-403. The antibody drug was well tolerated with no dose limiting toxicity. An initial Phase I clinical trial also showed that TB-403 is safe and well tolerated.

Preclinical studies in animal models proved that the antibody can inhibit PlGF-associated blood vessel development and tumour growth, without affecting healthy tissue.

Development and commercialisation strategy
The development of TB-403 was initially carried out as part of BioInvent's strategic alliance with ThromboGenics Ltd. In June 2008 the two companies entered a strategic alliance with Roche for the product. Roche has a worldwide exclusive license to develop and commercialise TB-403. BioInvent and ThromboGenics retain co-promotion rights for the product in the Nordic, Baltic and Benelux regions. Roche is now funding the development of TB-403. BioInvent and ThromboGenics could receive up to EUR 500 million in upfront and milestone payments, of which EUR 65 million have been received so far, as well as royalties on product sales.