Product
APG350 is one of several TRAIL-(TRAIL: Tumour necrosis factor related apoptosis inducing ligand) receptor agonists which have been developed by Apogenix. They are fully human Fc-fusion proteins consisting of two single chain TRAIL-molecules fused covalently to an Fc-part of a human IgG molecule. The proteins can be produced in very good yields using standard laboratory techniques and have a half-life of up to 24 hours. Preliminary toxicological investigations showed an excellent tolerability of these drug candidates. Currently, Apogenix works on the selection of the candidate which will be used for cell line development to be initiated in 2012. This is the first step towards the later GMP production.
Mode of Action
Based on the unique molecular architecture of Apogenix´ TRAIL-receptor agonists, the compounds bind to several TRAIL-receptors without the necessity of additional cross-linking (e.g., by Fcγ-receptors). These agonists activate TRAIL receptors 1 and 2 (a.k.a. death receptors 4 and 5). Cross-linking of other TRAIL-receptor agonists such as agonistic TRAIL-receptor antibodies which specifically bind either to TRAIL-receptor 1 or 2 seems to be a prerequisite for their biological activity, namely to stimulate TRAIL-receptors and thereby induce apoptosis. The novel mode of action of Apogenix´ compounds leads to a very effective apoptosis induction in tumour cells. The dose-dependent activity is significantly higher compared to other compounds in development. Numerous in vitro and in vivo experiments have been performed using established cancer cell lines, cancer stem cells and primary cancer cells. They all show an impressive and highly reproducible biological activity.