ARIAD
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the
presentation of new preclinical data on its investigational pan-BCR-ABL
inhibitor, ponatinib,
and its investigational dual EGFR-ALK inhibitor, AP26113, at the
American Association for Cancer Research Annual Meeting in Chicago. Both
drug candidates, discovered using ARIAD's structure-based drug design
platform, are potent inhibitors of multiple "gatekeeper" mutations that
have been shown to confer clinical resistance to other targeted cancer
medicines.
The first study, "Ponatinib, a potent pan-BCR-ABL inhibitor, retains
activity against gatekeeper mutants of FLT3, RET, KIT, PDGFR and FGFR1,"
was presented yesterday and shows that ponatinib overcomes resistant
gatekeeper mutations well beyond BCR-ABL -- the drug's target in chronic
myeloid leukemia (CML) and Philadelphia-positive acute lymphoblastic
leukemia (Ph+ ALL) -- in other clinically relevant tyrosine kinase
targets.
The preclinical research conducted by ARIAD scientists assessed the
activity of ponatinib using cell lines expressing activated forms of
FLT3, RET, KIT, PDGFR and FGFR1, each a kinase target associated with a
specific tumor type. Ponatinib potently inhibited the activity of these
kinases and maintained potent activity against gatekeeper variants that
have been shown to cause resistance to other tyrosine kinase inhibitors
in acute myeloid leukemia, medullary thyroid cancer, gastrointestinal
stromal tumor (GIST) and rare forms of leukemia driven by these tyrosine
kinases.
"Ponatinib was designed to block the abnormal tyrosine kinase, BCR-ABL,
which drives CML and Ph+ALL," said Timothy
P. Clackson, Ph.D., president of research and development and chief
scientific officer of ARIAD. "The structural design feature that allows
ponatinib to evade the BCR-ABL T315I gatekeeper mutation also enables
the molecule to overcome analogous mutations in its other kinase
targets. We are actively working with academic collaborators to set up
clinical trials aimed at determining the potential role of ponatinib in
these additional forms of drug-resistant cancer."