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Acute Myelogenous Leukemia

Approximately 18,500 new cases of AML are diagnosed worldwide each year and the trend in overall incidence of AML is expected to grow by 7% by 2015.

In order to address this substantial unmet medical need, COTI has undertaken a drug discovery project targeting multiple important kinases. Kinases are enzymes that are critical elements of cellular signaling pathways. These enzymes play critical roles in cellular metabolism, immunity and proliferation.  Kinases are often mutated or missing in many cancers including leukemia.  In AML, the most potentially virulent and lethal leukemia, approximately 40% of cases will have a mutation in one particular gene, known as FLT3.  An abnormal gene produces an abnormal or absent cellular protein. However, in most cancers including leukemias, multiple genes are usually abnormal resulting in multiple abnormal gene products, usually enzymes. Traditional approaches have sought “clean” drugs that have very good efficacy against one cellular target. COTI believes that this is the wrong approach since most cancers will have multiple abnormal gene products. Unfortunately, the adaptive cellular machinery of cancer cells quickly finds a pathway or pathways around the effects of single kinase inhibitors. As a result, resistance to chemotherapy emerges early and often.

COTI’s AML project is different. We have focused on identifying and optimizing multiple kinase inhibitors for the treatment of AML, although it is likely that CML may also be beneficially impacted.  The central kinase targets of the COTI leukemia project include FLT3, PDGF-R, with variable emphasis on CSF-1R and TIE2. COTI has identified multiple scaffolds and optimized several drug candidates on each scaffold.

Licensing/Co-Development Opportunity
At present six compounds on the first three scaffolds are about to enter synthesis prior to kinase screening, in vitro and animal confirmatory testing.  The AML project is based upon US and European patents received by COTI for three tyrosine kinase inhibitor compounds. COTI’s AML product candidates have undergone proof-of-concept clinical testing and COTI is currently looking for licensing partners for these compounds.

For more information on partnering with COTI on this exciting project please contact Brent Norton or Wayne Danter.

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