Jun 3 2008
ThromboGenics NV and co-development partner BioInvent International AB today reported that the results from the first Phase l study of novel anti-cancer agent TB-403 showed that it is safe and well tolerated, with pharmacokinetic properties enabling it to be developed for the treatment of cancer.
The companies also announced that they have received approval from the regulatory authorities in Denmark to initiate a second repeat-dose Phase I clinical trial of TB-403 in patients with advanced solid tumors.
TB-403 is a monoclonal antibody that targets the angiogenic factor PlGF (placental growth factor). The product has demonstrated inhibition of PlGF-associated angiogenesis and tumour growth in animal models, without affecting healthy tissues. The completed Phase I study was a double-blind, randomised trial testing a single-dose of TB-403 at three escalating levels or placebo in 16 healthy male subjects. The results of the trial have shown that TB-403 met both primary endpoints regarding safety and tolerability, and secondary endpoints examining pharmacokinetics. These results have provided the basis for a safe and efficient introduction of the compound into a subsequent repeat-dose trial in patients for which ThromboGenics and BioInvent have now received approval.
The second Phase I trial will be a study of tolerability, pharmacokinetics and pharmacodynamics in patients with advanced cancer. Up to 30 patients with metastatic or unresectable solid tumours will be enrolled in this open, dose escalation multi-dose study. The study will take place in Denmark and patient recruitment is due to begin shortly.
Professor Desire Collen, CEO and Chairman of ThromboGenics, commenting on today's announcement said: "This is an important milestone for ThromboGenics and our partner BioInvent. This study reinforces our belief that TB-403 has the potential to become a significant treatment for cancer due to TB-403's unique mode of action. TB-403 blocks the formation of new blood vessels in the cancer tumour without affecting healthy tissues. We are delighted that the vision we shared with BioInvent is progressing and with today's news, is becoming more tangible."
Svein Mathisen, CEO of BioInvent, added: "We are pleased at the continued progress seen in our collaboration with ThromboGenics and at the success of this product in Phase I. Based on these data, we look forward to embarking imminently on the planned second Phase I study in patients with advanced cancer, while we continue to prepare for future development and commercialisation."
Angiogenesis inhibitors such as TB-403 are therapeutic agents that work by blocking the development of new blood vessels, thereby depriving growing cancer tumour cells of oxygen and nutrients. This approach in turn is thought to stop the tumour from growing and spreading to other parts of the body. Currently available angiogenesis inhibitors specifically target vascular endothelial growth factor (VEGF), which plays an important role in promoting the formation of blood vessels. PlGF is a homologue of VEGF but, unlike VEGF, it does not affect normal, physiological angiogenesis and is only involved in the angiogenesis in the diseased tissue. Therefore, as an inhibitor of PlGF, TB-403 is likely to inhibit tumour growth without the side effects associated with other anti-angiogenic therapies.
ThromboGenics and BioInvent also intend to develop TB-403 for eye diseases, to block uncontrolled blood vessel growth in conditions such as age-related macular degeneration (AMD) and diabetic retinopathy.
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