ARIAD Presents New Preclinical Data on Ponatinib in Solid Tumors, Demonstrating Inhibition of All FGF Receptor Kinases
ORLANDO, Fla. & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr 5, 2011 - ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of preclinical studies on ponatinib, its investigational pan-BCR-ABL inhibitor, showing potent inhibition of all four members of the fibroblast growth factor receptor (FGFR) family of tyrosine kinases that are abnormally expressed in multiple cancers. ARIAD scientists are presenting the data this morning at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida.
Recent research has established that FGF receptors 1 to 4 are activated through multiple mechanisms in certain solid tumors and represent promising targets for antitumor therapy. The new data on ponatinib demonstrate potent activity against a broad range of tumor cells activated by all four FGFRs, in vitro and in vivo. In a panel of 14 cell lines representing multiple different tumor types including endometrial, bladder, gastric, breast, lung and colon cancer, ponatinib potently and selectively inhibited FGFR-mediated signaling and cell growth. Four other tyrosine kinase inhibitors with FGFR inhibitory activity that are in clinical development were substantially less active, and none potently blocked all four FGF receptors.
In mouse models of FGFR-driven tumors, daily oral dosing of ponatinib reduced tumor growth and inhibited signaling in all 3 FGFR-driven models examined. Ponatinib reduced tumor growth by 80 percent in mouse models of bladder and endometrial cancers and induced tumor regression in a model of gastric cancer. Potency was similar to that previously observed in BCR-ABL-driven models of chronic myeloid leukemia (CML). Importantly, the Phase 1 trial of ponatinib in CML shows that plasma concentrations of ponatinib required for inhibition of all four FGFRs can be sustained at well-tolerated doses in patients.
“These data demonstrate, for the first time, that in addition to its profile as a pan-inhibitor of BCR-ABL, ponatinib is also an investigational pan-FGFR inhibitor,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “The data also show that ponatinib potently inhibits the activity of all four FGFRs at clinically achievable drug levels and provide strong rationale for ponatinib's evaluation in patients with FGFR-driven cancers.”
ARIAD's vision is to transform the lives of cancer patients with breakthrough medicines. The Company's mission is to discover, develop and commercialize small-molecule drugs to treat cancer in patients with the greatest and most urgent unmet medical need - aggressive cancers where current therapies are inadequate. ARIAD's product candidate, ridaforolimus, is an investigational mTOR inhibitor being developed by Merck that has successfully completed a Phase 3 clinical trial in patients with soft-tissue and bone sarcomas and is being studied in multiple cancer indications. ARIAD's second internally discovered product candidate, ponatinib, is an investigational pan-BCR-ABL inhibitor in a pivotal Phase 2 clinical trial in patients with chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. For additional information, please visit www.ariad.com.
This press release may contain “forward-looking statements” concerning the preclinical activity of ponatinib. 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. 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: ARIAD Pharmaceuticals, Inc.
Maria E. Cantor, 617-621-2208
Posted: April 2011