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Jun 1, 2009 (Vol. 29, No. 11)

Ambit Has High Hopes for Kinase Screening Tool

Firm’s KINOMEscan Measures the Active Site of the Enzyme rather than the Activity

  • Click Image To Enlarge +
    Small molecule-kinase interaction maps for three approved kinase inhibitors across a panel of 317 human kinases.
    (Adapted and reproduced with permission from Science and Cell Signaling Technology)

    For some companies, the third incarnation holds the key to success. Ambit Biosciences, founded in 2000 as Aventa, set out to build a comprehensive database of proteins and small molecule interactions. The founders believed that drug researchers would pay to search the database and select small molecules to inhibit biological targets. “At the time, the biotechnology bubble was inflating and lots of money was pouring into genomic and proteomic technologies that promised to accelerate drug discovery,” says Scott Salka, CEO.

    The biotechnology bubble burst, however, and the company was forced to shift  gears. After operating briefly without a name, the company evolved into Ambit Biosciences in 2003 to focus on kinases as drug targets. It leveraged some of its initial technology to create a high-throughput screening (HTS) platform to select small molecule kinase inhibitors.

    Kinases are a rich area for therapeutic drug development, with more than 500 kinases identified and more than 50 kinase inhibitors in clinical trials or approved by the FDA. Ambit’s expertise not only fuels its own pipeline, but also assists a growing list of customers to identify potential drugs, Salka says.

    Ambit’s lead compound, AC220, is a second-generation class III receptor tyrosine kinase inhibitor that acts on FLT3-dependent tumors. Up to 40% of patients with acute myeloid leukemia (AML) have mutations in the receptor tyrosine kinase FLT3.

    Based on the results of its Phase I trial, Ambit met with the FDA to discuss the possibility of conducting a registration trial of AC220 as a monotherapy for elderly AML patients. “If the outcome is good, we could get approval to sell the drug for elderly AML patients after only two clinical trials,” comments Salka.

    In general, no good treatments exist for patients with AML older than 60 years. Elderly AML patients do not tolerate standard chemotherapy, and their life expectancy is less than six months after being diagnosed. “The clinical data we generated to date for AC220 opens the way for a potential major advance in the treatment of AML,” adds Salka.



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