Plexxikon Inc. has submitted an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for its lead oncology compound, PLX4032.

This targeted anticancer agent selectively inhibits the cancer-causing BRAFV600E gene found in subsets of different cancers, including 70 per cent of malignant melanomas and a significant number of colorectal and thyroid tumours. The company will use a new test to detect the presence of this cancer-causing gene to identify patients most likely to respond to PLX4032, enabling an exquisitely personalized medicine.

"PLX4032 blocks one of the most common genetic mutations known to cause cancer, and has the potential to become a first-in-class oral therapeutic for the treatment of advanced skin cancer," said K Peter Hirth, CEO of Plexxikon Inc. "Initially, we will develop PLX4032 for advanced melanoma, followed by colorectal and potentially other cancers in the future. With this compound entering clinical development, we have a broad portfolio of clinical and preclinical stage assets in metabolic disease, cardiovascular disease, inflammation and oncology--all generated by our robust drug discovery platform."

Preclinical studies in both melanoma and colorectal cancer models demonstrate that PLX4032 reduces tumour size or slows the progression of tumours for extended periods, even after the completion of treatment. Highly selective against B-RafV600E compared to a panel of over 70 other kinases, PLX4032 works specifically on cancer cells, leaving healthy cells untouched.

Thus, PLX4032 has demonstrated a very favourable side effect profile, and should be able to be used safely in combination with other anticancer drugs. Pending activation of the IND by the FDA, Plexxikon intends to initiate phase 1 dose escalation studies in cancer patients by the end of this year.

Plexxikon is collaborating with Roche Molecular Systems, Inc. to develop an in vitro assay to screen for the presence of the BRAFV600E mutation in patients' tumors. Using a diagnostic test to correlate the presence of this genetic mutation with clinical outcome may potentially expedite clinical development of PLX4032.

PLX4032 is a selective inhibitor of the activated BRAFV600E gene found in 70 per cent of malignant melanomas and a significant percentage of other cancers. The Wellcome Trust Sanger Institute estimates that 100,000 cancer patients in the US have tumors bearing the BRAFV600E oncogene. This mutation is often correlated with decreased patient survival. Compounds like PLX4032 that target activated kinases have shown significant efficacy in the treatment of cancers, as in the case of Gleevec (imatinib) in CML patients and Tarceva (erlotinib) in non-small lung cancer patients.