Apogenix develops protein therapeutics that could transform the treatment of life-threatening diseases by targeting critical pathways involved in the growth, migration, and apoptosis of diseased cells. The company’s lead drug candidate APG101 is currently being evaluated in patients with glioblastoma (GB), the most frequent and aggressive brain tumor with a tremendous need for new and effective therapies. A randomized controlled phase II trial in recurrent GB has shown that APG101 prolongs overall survival and improves quality of life, while exhibiting an excellent safety profile. Apogenix is also developing a companion diagnostic to identify patients who may respond best to treatment with APG101. APG101’s unique mode of action supports its significant potential for the treatment of other malignant diseases, such as myelodysplastic syndromes (MDS) – a stem cell disorder that can lead to severe anemia – as well as solid tumors beyond GB.
The company’s lead drug candidate APG101, a CD95 ligand inhibitor, is currently in clinical development for the treatment of GB and MDS. In a randomized controlled phase II trial with APG101 in patients with recurrent GB that compared the efficacy and safety of a combination therapy of APG101 and radiotherapy versus radiotherapy alone, all endpoints were achieved or exceeded. The study’s primary endpoint – progression-free survival at six months (PFS6) – was met with a statistically significant fivefold improvement in the rate of patients reaching PFS6. The results demonstrate that patients having a newly-identified epigenetic biomarker associated with the CD95 ligand – the target of APG101 – experienced the greatest benefit from treatment with APG101. The trial showed a statistically significant prolongation of overall survival in biomarker-positive patients treated with APG101, with a median overall survival of 16.1 months compared to 6.5 months in patients treated with radiotherapy alone.
In January 2013, Apogenix initiated a phase I trial with APG101 to treat patients with MDS. First results are expected by the end of 2014. APG101 was granted orphan drug status for the treatment of glioma in the EU and for the treatment of GB and MDS in the US.
Apogenix has developed a novel class of hexavalent TRAIL receptor agonists – which include the prototype APG350 – for the treatment of solid tumors. Their unique molecular structure allows for effective induction of apoptosis of tumor cells without the need for cross-linking via Fcγ receptors on the surface of immune cells, thus overcoming the limitations of other TRAIL receptor agonists. Apogenix’ TRAIL receptor agonists have demonstrated potent anti-tumor efficacy in vitro and in vivo and are well tolerated by mice and cynomolgus monkeys, as determined by preliminary toxicological investigations. Since the TRAIL pathway plays an important role in many tumor types, Apogenix’ TRAIL receptor agonists have the potential for wide use in oncology.