Amplia Therapeutics Ltd (ASX:ATX) has released new data demonstrating the potential of its second focal adhesion kinase (FAK) inhibitor AMP886 to treat acute myeloid leukemia (AML).
AML 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. The disease makes up about 1% of all cancer diagnoses.
Adults over 60 are the most commonly affected and have the poorest prognosis, poorer response rates and high rates of relapse after treatment.
The treatment for AML currently requires the use of relatively toxic chemotherapies.
Potent inhibitor
Amplia is confident that its drug candidate AMP886 can potently inhibit 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 currently available FLT3 inhibitors, which often leads to an aggressive disease relapse and very poor patient outcomes.
The emerging research supports combining inhibition of FLT3 and FAK to overcome disease rebound following FLT3 monotherapy.
Beneficial impact
This approach may have a beneficial impact in AML patients. Amplia is confident it has now shown that AMP886 inhibits AML in an industry-standard MV4-11 disease model recognised to carry the FLT3 mutation.
The work Amplia has done shows that 21 days after inoculation with MV4-11 cells, oral doses of AMP886 significantly reduced the tumour burden in mice.
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.
The 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.
Reducing AML cell growth
The results show that AMP886 is more effective in reducing AML cell growth than venetoclax alone.
While both AMP886 and venetoclax improve survival in the MV4-11 model of AML, Amplia’s work demonstrates that the combination of the two drugs tends to further enhance survival.
Amplia CEO Dr John Lambert said: “The impressive results we are reporting tell us that there may be a clinical rationale to include AMP886 as part of new treatment regimens for unmet needs in AML.
“With an eye to expanding Amplia’s clinical development pipeline, further experiments are already underway with AMP886 to build on this data and establish a scientifically solid foundation for initiation of formal development of AMP886.”