ARIAD Presents Preclinical Data on Its Investigational ALK Inhibitor, AP26113, Demonstrating That It Can Overcome Mutation-Based Drug Resistance in Cancer Models
WASHINGTON & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr 20, 2010 - ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced results of preclinical studies on its investigational anaplastic lymphoma kinase (ALK) inhibitor – AP26113 – showing potent inhibition of the target protein and of mutant forms that are resistant to the first-generation ALK inhibitor, which currently is in clinical trials in patients with cancer. ARIAD scientists presented these data today at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C.
Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as anaplastic large cell lymphoma. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy.
An in vitro assay was used to identify mutations in ALK that confer resistance to the investigational dual Met/ALK inhibitor developed by Pfizer, Inc., PF-02341066 (PF1066), or to AP26113. This resistance-profiling method has successfully predicted the specific mutations that confer clinical resistance to other tyrosine kinase inhibitors, such as the BCR-ABL inhibitors used in chronic myeloid leukemia (CML). Multiple mutations in ALK were identified that conferred resistance to PF1066, but not to AP26113. Three of these ALK mutants were also tested in mouse tumor models, and in each case, AP26113 potently blocked tumor growth while PF1066 was ineffective.
“Similar to data on our investigational pan-BCR-ABL inhibitor, AP24534, these preclinical results suggest that more potent compounds, such as AP26113, may be able to minimize the development of mutation-based drug resistance,” stated Timothy Clackson, Ph.D., senior vice president and chief scientific officer of ARIAD. “The data clearly support further study to determine if AP26113 can provide a more complete response than PF1066 in cancer patients with abnormal ALK expression.”
In a second study, direct comparative studies were performed on AP26113 and PF1066 in a series of ALK-dependent cell culture and in vivo models. In all models, AP26113 was at least ten-fold more potent than PF1066. In addition, AP26113 exhibited approximately 100-fold selectivity for ALK-positive cell lines compared with an approximate 10-fold selectivity for PF1066, and demonstrated excellent properties, including the potential for once daily oral dosing.
“We specifically designed AP26113 as a highly potent and selective inhibitor of ALK with superior drug-like properties and best-in-class potential,” added Clackson. “This preclinical work supports our ongoing evaluation of AP26113 as a potential treatment for cancers that express ALK. We look forward to moving AP26113 into clinical trials as soon as possible.”
Additional Data and Recognition from AACR
ARIAD scientists also presented at AACR results from preclinical studies of its investigational pan-BCR-ABL inhibitor, AP24534, being studied in a Phase 1 clinical trial of patients with hematological malignancies, notably CML. The AACR program committee each year recognizes meritorious abstracts being presented in poster sessions at the Annual Meeting to help identify the best science in these large sessions. This year, the scientific abstract on AP24534 is recognized by the AACR program committee as a highly rated presentation that scored in the top three percent of all abstracts presented in the meeting's poster sessions.
In addition, Merck scientists presented data on ARIAD's investigational mTOR inhibitor, ridaforolimus, which is being co-developed by Merck & Co. In all, there are seven scientific presentations on ARIAD product candidates at the AACR meeting this year.
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 lead product candidate, ridaforolimus, is an investigational mTOR inhibitor in Phase 3 clinical development in patients with advanced sarcomas and is being developed in collaboration with Merck. ARIAD's second internally discovered product candidate, AP24534, is an investigational pan-BCR-ABL inhibitor completing Phase 1 clinical development in patients with hematological cancers, notably chronic myeloid leukemia. ARIAD has an exclusive license to pioneering technology and patents related to certain NF-ÎºB cell-signaling activity, which may be useful in treating certain diseases. For additional information about the Company, please visit http://www.ariad.com.
This press release contains “forward-looking statements.” 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 that may not be replicated in clinical studies, the costs associated with our research, development, manufacturing and other activities, the conduct and results of pre-clinical and clinical studies of our product candidates, difficulties or delays in obtaining regulatory approvals to market products resulting from our development efforts, our reliance on our strategic partners and licensees and other key parties for the successful development, manufacturing and commercialization of products, the adequacy of our capital resources and the availability of additional funding, patent protection and third-party intellectual property claims relating to our and any partner's product candidates, the timing, scope, cost and outcome of legal and patent office proceedings concerning our NF-ÎºB patent portfolio, future capital needs, risks related to key employees, markets, economic conditions, prices, reimbursement rates and competition, 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: ARIAD Pharmaceuticals, Inc.
Maria E. Cantor, 617-621-2208
Posted: April 2010