ThromboGenics NV and co-development partner BioInvent International AB announce that their partner Roche has dosed the first patient in a phase I b/II study with the novel antibody anti-cancer agent TB-403 (RG7334). The trial is in patients with glioblastoma multiforme, the most common and aggressive type of primary brain tumour in humans.

The multi-centre, phase I b/II trial will examine the safety and clinical effect of TB-403 in combination with Avastin (bevacizumab) in patients with recurrent glioblastoma. Secondary objectives include safety, tolerability and pharmacokinetics of the combination. The trial will also include an evaluation of candidate biomarkers. The study will recruit approximately 100 patients.

The start of the phase I b/II glioblastoma study has triggered a €4 million milestone payment to ThromboGenics and BioInvent. This is the second clinical milestone that they have received from Roche. The first milestone of €10 million was paid last year when Roche initiated an imaging study in patients with colorectal and ovarian cancer.

In April 2011, Roche initiated a phase I b study of TB-403 in patients with primary liver cancer (hepatocellular carcinoma). This study will determine the safety, tolerability and dosage of TB-403 in combination with Nexavar (sorafenib), as well as pharmacokinetics and pharmacodynamics. The study will recruit 60-70 patients.

Dr Patrik De Haes, CEO of ThromboGenics, commented, “The start of these trials reflects a great interest in evaluating TB-403, in combination with more established oncology drugs, in a range of cancer indications. The glioblastoma study, using TB-403 together with Avastin, is designed to find better treatment options for patients with this very aggressive form of brain cancer. I believe that these studies will confirm that the further development of this novel selective anti-angiogenic antibody is warranted.”

Svein Mathisen, CEO of BioInvent added, “We are very pleased that Roche has decided to take TB-403 to the next stage of its development. We believe that TB-403 could make a major contribution to the armamentarium used to treat cancer. In glioblastoma, the medical need is significant and it is our hope that this unique product candidate could improve the prospects for this patient group whose current treatment options are very limited.”

The novel mechanism of action of TB-403 represents a potentially promising cancer therapy. It is a humanized monoclonal antibody directed towards Placental Growth Factor (PIGF), expected to act by blocking the formation of the new blood vessels that are required for tumour growth. Preclinical exploration of PIGF biology suggests a role in tumour angiogenesis and metastasis and a limited role in the maintenance of normal vasculature. This mode of action could result in therapeutic benefit with an acceptable side effect profile.

Two phase I clinical trials have found that TB-403 was well tolerated with no reported dose limited toxicity.

ThromboGenics is a biopharmaceutical company focused on the discovery and development of innovative medicines for the treatment of eye disease, vascular disease and cancer. The company’s lead product ocriplasmin (microplasmin) has completed two phase III clinical trials for the pharmacological treatment of symptomatic Vitreomacular Adhesion (sVMA).

BioInvent International AB, is a research-based pharmaceutical company that focuses on developing antibody drugs. The company currently has four clinical development projects within the areas of thrombosis, cancer and atherosclerosis.