Esperance Pharmaceuticals has reported positive results from the company’s preclinical program that support the initiation of clinical trials in cancer. EP-100 is the first candidate from the company’s Cationic Lytic Peptide platform technology.
EP-100 consists of a luteinizing hormone-releasing hormone (LHRH) receptor-targeting ligand conjugated to a novel membrane-disrupting peptide called CLIP 71. The drug candidate was tested in vitro and in-vivo for activity in LHRH receptor over-expressing and multi-drug resistant ovarian cancer cells (OVCAR-3). As a negative control, the study utilized LHRH receptor negative SKOV-3 ovarian cancer cells.
In in-vitro studies designed to test the cytotoxicity of EP-100 in ovarian cancer cell lines, cells were cultured in the presence of various concentrations of EP-100 or unconjugated CLIP 71 for one to 24 hours.
Results demonstrated that EP-100 was fast-acting, destroying LHRH receptor over-expressing OVCAR-3 cells within an hour compared to the unconjugated CLIP 71 which was less cytotoxic and was slow-acting (p<0.005). LHRH receptor negative SKOV-3 cells were significantly less sensitive to EP-100 than OVCAR-3 cells and the effects of EP-100 and unconjugated CLIP 71 were similar in this cell line demonstrating that EP-100 is specific for cells that over-express LHRH receptors, the company said.
In in-vivo studies, the efficacy of EP-100 in comparison to saline or unconjugated CLIP 71 or cisplatinum in an ovarian cancer xenograft model (OVCAR-3) was studied. EP-100 regressed established OVCAR-3 xenografts in weekly injections at doses as low as 0.2mg/kg bodyweight (p<0.03 versus baseline).
In comparison, tumor growth was observed across the saline control, unconjugated CLIP 71 and cisplatinum arms. In addition, in the EP-100 arm tumor volumes, weights and CA125 were reduced. LHRH receptor levels were also reduced and positron emission tomography imaging revealed that EP-100 treated tumors became necrotic, lacking viable tumor cells after treatment. EP-100 was well tolerated in all treated groups, according to the company.
Hector Alila, president of Esperance, said: Based on the results observed in these studies, Esperance is actively planning the initiation of a Phase I clinical trial of EP-100 in patients with solid cancerous tumors later in 2009. We believe EP-100 and future candidates arising from our platform technology hold significant potential to more effectively treat multiple indications across oncology, including aggressive cancers known to be resistant to the current standards of care.