San Diego-based Ambit Biosciences is staking its success on the kinome, a set of protein kinases in the genome and an important source for targeted therapies in oncology. Using these targeted therapies has advantages over traditional chemotherapy, which can cause the patient troublesome side effects because it kills healthy cells, in addition to cancerous cells. By focusing on targeted therapies and using diagnostic tests to identify patient subsets who might respond to the therapy, the company believes it can obtain improved patient outcomes, streamline clinical trials, and stratify patient populations.
The company’s lead drug candidate, quizartinib, inhibits FMS-like tyrosine kinase 3 (FLT3), an established target in treating acute myeloid leukemia (AML). The agent is currently in phase II clinical trial development in patients with relapsed/refractory AML who express the FLT3 internal tandem duplication (FLT3-ITD) mutation. The FLT3- ITD mutation affects the growth and spread of leukemic cells, and estimates suggest that more than 35% of patients with AML who are aged 55 years and older have this mutation.
To help identify FLT3-ITD-positive patients, a companion diagnostic test is being developed. The company believes that this test is necessary for quizartinib to gain approval by the FDA.
Ambit is confident that quizartinib can be used in other AML treatment settings, as well. Research suggests that it may be useful as a first-line therapy in combination with chemotherapy, or as frontline treatment followed by continuous single-agent maintenance therapy. The company is also exploring the agent’s use as maintenance therapy following a hematopoietic stem cell transplant or bone marrow transplant.
The second oncology candidate in Ambit’s pipeline, AC708, is a potent and selective small molecule compound that inhibits the colony-stimulating factor-1 receptor (CSF1R), a receptor tyrosine kinase. This compound is in preclinical studies and could be used in oncology and inflammatory diseases.
The third oncology product in the pipeline is CEP-32496, an investigational smallmolecule drug that inhibits the BRAF kinase. The agent was discovered by Ambit and is now being developed by Teva Pharmaceutical Industries Ltd.
The small molecule exhibits sustained antitumor activity in mouse xenograft models of melanoma and colon carcinoma.
CEP-32496 has exhibited positive pharmacokinetic properties with a favorable side-effect profile as compared with other BRAF-kinase inhibitors. Teva submitted an investigational New Drug Application for CEP-32496 in the second quarter of 2012. It is currently undergoing clinical trials.
Ambit Biosciences Pipeline
AML indicates acute myeloid leukemia; HSCT, hematopoietic stem cell transplantation.