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ARIAD Presents New Preclinical Data on Ponatinib and AP26113

Both Tyrosine Kinase Inhibitors Overcome Drug Resistance Due to “Gatekeeper” Mutations Of Multiple Oncogenic Targets

CAMBRIDGE, Mass. & CHICAGO--(BUSINESS WIRE)--Apr 2, 2012 - 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.”

A second abstract, “AP26113 is a dual ALK/EGFR inhibitor: Characterization against EGFR T790M in cell and mouse models of NSCLC,” will be presented today and describes the activity of AP26113, a dual inhibitor of EGFR and ALK, to overcome gatekeeper mutations of these targets. This preclinical research further confirms that AP26113 is a potent, reversible inhibitor of the T790M gatekeeper mutation of epidermal growth factor receptor (EGFR). Activated EGFR occurs in approximately 250,000 lung cancer patients worldwide, and the single T790M mutation accounts for over 50 percent of resistance to tyrosine kinase inhibitors in these patients who have limited treatment options available.

This poster also presents, for the first time, preclinical data demonstrating that AP26113 potently inhibits non-small cell lung cancer (NSCLC) cell lines that express an activating translocation of the ROS1 tyrosine kinase. Such ROS1 mutations have recently been identified as a feature of approximately two percent of all NSCLC, representing another area for further investigation of AP26113 in NSCLC patients in need of better therapeutic choices.


ARIAD Pharmaceuticals, Inc. is an emerging global oncology company focused on the discovery, development and commercialization of medicines to transform the lives of cancer patients. ARIAD's approach to structure-based drug design has led to three internally discovered, molecularly targeted product candidates for drug-resistant or difficult-to-treat cancers, including certain forms of chronic myeloid leukemia, soft tissue and bone sarcomas and non-small cell lung cancer. For additional information, visit or follow ARIAD on Twitter.

This press release contains “forward-looking statements” including, but not limited to, updates on clinical, preclinical and regulatory developments for our product candidates. Forward-looking statements are based on management's expectations and are subject to certain factors, risks and uncertainties that may cause actual results, outcome of events, timing and performance to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, preclinical data and early-stage clinical data that may not be replicated in later-stage clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct, timing and results of pre-clinical and clinical studies of our product candidates, the adequacy of our capital resources and the availability of additional funding, and other factors detailed in the Company's public filings with the U.S. Securities and Exchange Commission. The information contained in this press release is believed to be current as of the date of original issue. The Company does not intend to update any of the forward-looking statements after the date of this document to conform these statements to actual results or to changes in the Company's expectations, except as required by law.

Contact: For ARIAD Pharmaceuticals, Inc.
For Investors
Maria E. Cantor, 617-621-2208
For Media
Lynn Granito, 212-253-8881


Posted: April 2012