A potential breakthrough in cancer treatment

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TB-403 is a humanized monoclonal antibody against PlGF (placental growth factor), a naturally occurring protein that belongs to the family of vascular endothelial growth factors (VEGF), which promote the formation of blood vessels. TB-403 is intended to be used for the treatment of cancer by blocking the growth of both solid tumors and metastases; and eye diseases, where it will be used to block uncontrolled blood vessel growth in age-related macular degeneration (AMD). Toxicology studies with TB-403 were successfully completed and therefore ThromboGenics and BioInvent have advanced TB-403 into clinical Phase I. The most recent published data* show that antibodies against PlGF can inhibit cancer tumor growth and the development of metastases in preclinical models, without affecting healthy tissues. These attractive properties are due to PIGF inhibitors blocking the formation of new blood vessels, yet only in the cancer tissue.This in contrast to currently available products. Therefore, anti-PlGF antibodies such as TB-403 potentially have an improved efficacy/toxicity profile that would be expected to inhibit angiogenesis in diseased conditions, without, importantly, affecting normal blood vessels in healthy tissues.

ThromboGenics, in cooperation with its partner BioInvent, has completed a first phase I study with TB-403. This 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.

Enrolment of a second Phase I trial is currently ongoing and investigates tolerability, pharmacokinetics and pharmacodynamics in patients with advanced cancer. Up to 30 patients with metastatic or unresectable solid tumors will be enrolled in this open, dose-escalating multi-dose study taking place in Denmark.

ThromboGenics and BioInvent have entered into a license agreement with Roche for the TB-403 program. Roche will assume responsibility for all future development costs for this novel cancer therapy. ThromboGenics and BioInvent in conjunction with Roche will form a Joint Steering Committee to oversee research and development activities. In addition, Roche will also provide funding for research on non-cancer indications and supply of material until transfer of manufacturing.