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, making it 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
TB-403 is currently being tested by our partner Roche in
two clinical studies. A phase Ib/II study involving around 110
patients with glioblastoma multiforme was initiated in May this
year. The study is looking at a combination of TB-403 and Avastin
(bevacizumab). In March a phase I study in patients with
hepatocellular carcinoma was initiated involving a combination of
TB-403 and Nexavar (sorafenib).
In a Phase Ib dose escalation trial, reported in November 2009, six of 23 patients with advanced solid tumours were observed 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 had also shown that TB-403 is safe and well tolerated. In May 2010 Roche initiated an imaging trial with TB-403 in patients with colorectal and ovarian cancer. The trial was terminated at an early assessment point in August the same year.
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.