Ambit Biosciences, a private biopharmaceutical company, and Israel based Teva Pharmaceutical Industries Limited, have received Investigational New Drug application (IND) clearance from the US Food and Drug Administration (FDA) for CEP-32496, a novel BRAF (V600E) kinase inhibitor.

The IND filing was based upon promising therapeutic potential for this agent, as evidenced by data revealed in recent publications in the Journal of Medicinal Chemistry and Molecular Cancer Therapeutics characterizing the preclinical properties of CEP-32496. The two publications feature results that demonstrate CEP-32496 is a selective and potent inhibitor of BRAF (V600E) in cells.

The published preclinical findings also demonstrate that CEP-32496 possesses potent and sustained anti-tumour activity in xenograft models of melanoma and colon carcinoma. CEP-32496 possesses attractive pharmacokinetic properties upon oral administration and benchmarks favourably with respect to other kinase inhibitors that have activity at the BRAF (V600E) mutated kinase.

“The data that we have generated to date in these preclinical studies lead us to believe that we have a promising drug candidate with CEP-32496 and is further validation of our successful drug discovery collaboration with Ambit,” said Bruce Ruggeri, PhD, senior director, Oncology and Inflammation Discovery Research of Teva. “We look forward to exploring the full potential of this drug candidate to improve outcomes in patients with tumors possessing the BRAF(V600E) mutation.”

Michael A Martino, president and chief executive officer, Ambit further added “The filing of this IND represents a significant milestone for the Teva-Ambit collaboration and for the CEP-32496 programme, and we look forward to advancement of the molecule into the clinic. The demonstrated selectivity and anti-tumour activity of this kinase inhibitor give it real promise in tumours that express the mutated BRAF gene and is further validation of Ambit’s distinct competencies in kinase inhibitor drug discovery and optimization.

CEP-32496 is a small molecule kinase inhibitor of V600E mutated BRAF that is being developed as part of a collaborative agreement with Teva, initiated in 2006. This mutation in the BRAF gene has been identified in forms of melanoma, thyroid, colon, ovarian, and lung cancers. In addition to targeting mutations in BRAF, CEP-32496 targets other select kinases of interest in oncology with potentially desirable clinical application. Animal models in multiple cancer types suggest CEP-32496 may possess best-in-class potential. The CEP-32496 programme is testament to the successes that can be achieved when two companies leverage their respective strengths in collaboration.

Mutations in the BRAF gene have been identified in approximately 7 per cent of all cancers, including 60 per cent to 70 per cent of melanoma cases, 4 to 16 per cent of colorectal cancer cases, 29 to 83 per cent of papillary thyroid carcinomas and to a lesser extent in serous ovarian cancer and non-small lung cancer. The BRAF gene is a key component of a pathway involved in normal cell growth and survival. Mutations such as BRAF (V600E) are believed to be drivers of disease and can lead to uncontrolled cell growth and disease progression, and therefore represent a promising target for pharmacological intervention.

Melanoma is the most serious type of skin cancer and is growing at a rate of approximately 5-6 per cent annually. Patients with melanoma have limited treatment alternatives and experience some of the poorest outcomes, with 5-year survival rates of less than 20 per cent for people with advanced (Stage IV) melanoma, according to the American Cancer Society.

Ambit Biosciences is engaged in the development of a robust pipeline of small molecule kinase inhibitors for the treatment of cancer, inflammatory disease and other indications.

Teva Pharmaceutical Industries Ltd. is a leading global pharmaceutical company, committed to increasing access to high-quality healthcare by developing, producing and marketing affordable generic drugs as well as innovative and specialty pharmaceuticals and active pharmaceutical ingredients.