CANbridge Life Sciences, a Beijing-based biotech company, in-licensed China rights to Apogenix’s lead candidate, APG101. The drug is a fusion protein that consists of the extracellular domain of CD95 and the Fc domain of IgG1 and blocks the interaction between CD95 and its ligand. Apogenix has completed a Phase II trial in patients with recurrent glioblastoma.
What interests me is the exact function of CD95 in cancer. CD95 (also known as Fas receptor) is a death receptor on the surface of cells that mediates apoptosis. Cancer cells often downregulate CD95 to evade apoptosis. Thus CD95 agonists were considered to kill cancer cells. However, severe liver toxicity was observed in mice due to CD95-mediated apoptosis of hepatocytes.
In 2010, scientists from the University of Chicago speculated that CD95 could actually promote the growth of tumors. The discovery seems unbelievable because CD95 had previously been defined as a tumor suppressor.
APG101 indeed showed a clinical benefit in patients with relapsed glioblastoma in the Phase II trial. PFS rates at 6 months were 20.7% for reirradiation + APG101 and 3.8% for reirradiation alone (p=0.048). Median PFS was 4.5 months vs. 2.5 months (p=0.0162). Median OS for both two arms were 11.5 months.
In the Phase II trial, there was no difference in median OS. Many scientists still believe CD95 is a tumor suppressor[4,5]. Apogenix announced Phase II results in March 2012, but Phase III study hasn’t been initiated until now. The median OS of 11.5 months in second-line setting is not that attractive.
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