BioWorld International Correspondent

Apoxis SA raised €15 million (US$19.5 million) in a second round of funding to move its first projects into clinical development and perhaps to license in development candidates in the area of oncology.

The Lausanne, Switzerland-based company aims to move its lead drug candidate, MegaFasL, a chimeric protein that acts as an agonist of Fas ligand, a member of the tumor necrosis factor (TNF) family, into a Phase I trial during the first half of 2006, CEO Jean-Pierre Rosat told BioWorld International.

"For the time being we are focused on blood-borne tumors like multiple myeloma or lymphoma," he said. But the molecule has potential application to a much broader range of oncology indications, he said, including ovarian cancer and pleural mesothelioma, the cancer triggered by asbestos exposure. It has, he said, dramatically synergistic activity when combined with standard chemotherapeutic agents. In studies involving several tens of tumor cell lines, only one was resistant either to MegaFasL alone or in combination.

MegaFasL is the most advanced drug candidate based on Apoxis' MegaLigand technology, which was developed by scientific founder Jürg Tschopp, of the University of Lausanne. Although TNF ligands are centrally involved in apoptosis, capturing the activity of many of them in drug form is difficult, as they are active only when expressed on the surface of effector cells, such as activated T cells and natural killer cells.

The MegaLigand platform enables Apoxis to engineer multimeric TNF agonists comprising the extracellular domain of the TNF ligand of interest tethered to a protein stalk derived from adiponectin, a protein secreted by adipocytes that is involved in glucose regulation. Those constructs form hexameric complexes that are both soluble and biologically active, unlike many TNF ligands, which are inactive in their soluble form.

The company also has developed a complementary platform, Mega-Inhibitor, for creating soluble antagonists or inhibitors of TNF receptors that can competitively bind their corresponding ligands and prevent inappropriate apoptosis.

Apoxis has several earlier-stage projects in oncology and inflammation. It plans to move a second project into the clinic by late 2006 or early 2007, Rosat said. But also it is looking to accelerate its progress to maturity by licensing in a suitable drug candidate.

"We are doing due diligence on a couple of molecules. We started the process 18 months ago," he said. So far, the company has looked at around a half-dozen candidates, he said.

Apoxis has raised €23 million in total, with its first round in 2003. The company was established in 1999, by Tschopp and Lars French, of the University of Geneva, but it operated in virtual mode until 2002. It out-licensed two preclinical drug candidates to Biogen Inc., now Biogen Idec Inc., of Cambridge, Mass., during the first phase of its existence.

Novo Nordisk A/S, of Bagsvaerd, Denmark, led the current investment. Existing investors Banexi Venture Partners, of Paris, and HealthCap, of Stockholm, Sweden, also participated.