ARIAD Announces Presentation on Its Investigational Lung Cancer Drug Candidate, AP26113, a Dual Inhibitor of ALK and EGFR, at World Conference on Lung Cancer
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jul 5, 2011 - ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the presentation of new preclinical data on AP26113, its investigational dual inhibitor of anaplastic lymphoma kinase (ALK) and epidermal growth factor receptor (EGFR), demonstrating that its novel profile allows targeted inhibition of these two clinically validated oncogenic kinases in non-small cell lung cancer (NSCLC). These data are being presented at the International Association for the Study of Lung Cancer (IASLC) 14th World Conference on Lung Cancer being held in Amsterdam, The Netherlands.
“First-generation inhibitors of EGFR provide clinical benefit for many patients with NSCLC, but unfortunately, mutation-based resistance to the available therapies develops commonly in this patient population,” said Frank G. Haluska, M.D., Ph.D., vice president of clinical research and development and chief medical officer at ARIAD. “The data being presented today show that beyond targeting of ALK, AP26113 has additional potential to treat the most resistant form of EGFR-mutant lung cancer, while maintaining a high degree of selectivity to avoid inhibition of native EGFR, which is likely the cause of the well-known adverse events of EGFR inhibitors."
The new preclinical studies show that AP26113 potently inhibited activated EGFR or its T790M mutant, both in cell culture and in mouse tumor models following once daily oral dosing. Importantly, the effective oral doses in these preclinical models were similar to those previously achieved and shown to be effective in resistant ALK models. The T790M mutation of EGFR accounts for about 50 percent of the resistance seen clinically with currently available EGFR inhibitors. When tested against the native (unactivated) form of EGFR, present in normal, non-cancer cells, AP26113 lacked activity, indicating a favorable selectivity for activated EGFR.
“These new data on the EGFR activity of AP26113 significantly expand the potential target patient population for AP26113,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “We have filed the investigational new drug application for AP26113 and expect to begin a Phase 1/2 clinical trial in the third quarter of this year, exploring this unique dual inhibitor in lung cancer patients with specific molecular profiles.”
ARIAD's internally discovered drug candidate, AP26113, exhibits unique preclinical activity as a potent dual inhibitor of ALK and EGFR. Coupled with desirable pharmacologic properties, these characteristics confer a best-in-class potential in these subsets of non-small cell lung cancer (NSCLC). ARIAD filed an IND for AP26113 in the second quarter of 2011 and expects to begin a Phase 1/2 clinical trial based on patients' molecular diagnoses in the third quarter of 2011.
Aberrant ALK expression is a key feature of certain non-small cell lung cancers, neuroblastomas, sarcomas and lymphomas. As an ALK inhibitor, AP26113 overcomes mutation-based resistance in NSCLC models. Multiple mutations in ALK were identified that conferred resistance to crizotinib, but not AP26113, including the L1196M “gatekeeper” mutation which has now been observed clinically in patients who initially responded to crizotinib and then relapsed.
AP26113 also inhibits activated EGFR in preclinical models, including the T790M “gatekeeper” mutant that confers resistance to current EGFR inhibitors. Constitutive EGFR activity due to activating mutation is a key feature of certain non-small cell lung cancers, and the T790M mutation causes resistance to inhibitor therapy in approximately 50 percent of these cases. In preclinical studies, AP26113 was shown to be specific for mutated EGFR and avoids inhibition of native (endogenous or unmutated) EGFR; such inhibition is thought to be associated with the toxicity of other EGFR inhibitors.
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 http://www.ariad.com.
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.
Posted: July 2011