CAMBRIDGE, Mass. & WASHINGTON--(BUSINESS WIRE)--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the presentation of preclinical data on ponatinib (Iclusig™) at the American Association for Cancer Research (AACR) Annual Meeting 2013, in Washington. The study, “Ponatinib, a pan-BCR-ABL inhibitor, potently inhibits key activating and drug-resistant KIT mutants found in GIST,” shows that ponatinib inhibits activated and mutated forms of KIT, a clinically proven oncogenic driver found in approximately 80 percent of patients with gastrointestinal stromal tumors (GIST).
According to the American Cancer Society, approximately 4,000 to 5,000 people develop GIST each year in the United States. Approved agents for the treatment of patients with GIST include imatinib for newly-diagnosed patients, sunitinib for patients in whom imatinib has failed, and regorafenib for patients who have failed imatinib and sunitinib. Patients can develop resistance to any of these therapies by acquiring secondary KIT mutations. ARIAD plans to begin a Phase 2 trial of Iclusig in patients with GIST in the second quarter of 2013.
“ARIAD’s development program for Iclusig focuses on its continued evaluation in patients with CML and exploration of its activity against other clinically validated targets. For the first time we were able to solve the x-ray crystal structure of ponatinib bound to KIT, rationalizing its activity in advance of the Phase 2 trial,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “These data provide important support for the use of Iclusig in patients with GIST who have become resistant to prior tyrosine kinase inhibitor therapy.”
The research conducted by ARIAD scientists used a broad panel of cell lines harboring mutant forms of KIT. Ponatinib showed potent activity against activated forms of KIT and against a range of secondary mutations that confer resistance to imatinib and/or sunitinib. These include mutations at the T670I gatekeeper residue and mutations in the activation loop (A-loop), common mutations found in patients who have failed currently available therapies.
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an integrated global oncology company focused on transforming the lives of cancer patients with breakthrough medicines. ARIAD is working on new medicines to advance the treatment of various forms of chronic and acute leukemia, lung cancer and other difficult-to-treat cancers. ARIAD utilizes computational and structural approaches to design small-molecule drugs that overcome resistance to existing cancer medicines. For additional information, visit http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).
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