AEterna Zentaris advances novel anticancer agent into clinic

AN-152 is a novel cytotoxic conjugate with the potential to target cancer cells that express luteinizing hormone releasing hormones (LHRH) receptors (LHRH receptor positive tumors) and thus may offer a better safety and efficacy profile as compared to the cytotoxic agent alone.

The phase I study, which will be conducted at university clinics in Germany, will evaluate the safety and pharmacokinetics of intravenously-administered AN-152 in patients with LHRH receptor positive ovarian, endometrial or breast cancer. A high percentage of these cancers, in addition to hormone-refractory prostate cancer, are known to be LHRH receptor positive and, therefore, represent logical initial indications for AN-152.

AN-152 is designed to achieve targeting of the cytotoxic agent to cancer versus normal cells. In AN-152, doxorubicin (an FDA-approved cytotoxic agent) is chemically linked to an LHRH agonist, a modified natural hormone with affinity for the LHRH receptor. This design allows for the specific binding and selective uptake of the cytotoxic conjugate by LHRH receptor positive tumors.

Potential benefits of this targeted approach are several-fold, and include a more favorable safety profile with lower incidence and severity of side effects, as normal tissues are spared from toxic effects of doxorubicin. In addition, the targeted approach may enable treatment of LHRH receptor positive cancers that have become refractory to doxorubicin given in its non-targeted form.

In preclinical studies conducted to date in several animal models of LHRH receptor positive human cancer, AN-152’s anti-tumor activity and tolerability were shown to be superior to that of doxorubicin.

AEterna Zentaris has in-licensed worldwide rights to AN-152 from Tulane University. AN-152 is the lead compound in a series of cytotoxic conjugates that are designed to target certain tumor cells expressing receptors for peptide hormones such as LHRH, bombesin and somatostatin.