Amplia Therapeutics Limited reported new data which demonstrates the potential of its second focal adhesion kinase (FAK) inhibitor AMP886 for the
treatment of acute myeloid leukemia (AML). AML makes up about 1% of all cancer diagnoses and is a heterogeneous cluster of cancers that affect blood and bone marrow, with around 900 new cases diagnosed in Australia each year, about 50 of which are in children. Adults over 60 are the most
commonly affected and have the poorest prognosis. Optimal treatment for AML depends on the disease subtype for each patient as well as their age/fitness but typically requires use of relatively toxic chemotherapies. Poorer response rates in older patients and high rates of relapse after treatment are
also typical of AML. Amplia's drug candidate AMP886 potently inhibits both FAK and Fms-like tyrosine kinase 3 (FLT3). FLT3 is mutated in around a third of AML patients and is a clinically validated target for chemotherapy. There is a poor duration of response to current FLT3 inhibitors which often leads to an aggressive disease relapse and very poor patient outcomes. Emerging research supports combing inhibition of FLT3 and FAK to overcome disease rebound following to FLT3 monotherapy, and that this approach may have a beneficial impact in AML patients. Amplia has now shown that AMP886 inhibits AML in an industry-standard MV4-11 disease model recognised to carry the FLT3 mutation. In a second experiment, the company measured the efficacy of AMP886 combined with venetoclax, a B-cell lymphoma 2 (BCL-2) inhibitor that is approved as part of combination therapy, typically for older patients with AML. Rationale for adding AMP886 to venetoclax was based on recent reports showing that combination of FLT3 inhibitors and venetoclax may have clinical potential in patients with relapsed or refractory AML. The data show that AMP886 is more effective in reducing AML cell growth than venetoclax alone. Inhibition of MV4-11 AML in mice treated with AMP886, venetoclax or combined AMP886 and venetoclax; (B) Kaplan-Meier survival curves of mice bearing MV4-11 AML when treated with AMP886, venetoclax or combined AMP886 and venetoclax.