ARIAD Pharmaceuticals, Inc. (ARIA) today announced the results of a series of preclinical studies on its investigational tyrosine kinase inhibitor (TKI), brigatinib (AP26113) at the American Association for Cancer Research (AACR) Annual Meeting 2015. Brigatinib is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC), who are resistant to crizotinib.
These data were included in two presentations: “Discovery of AP26113, a potent, orally active inhibitor of anaplastic lymphoma kinase and clinically relevant mutants” and “The potent ALK inhibitor AP26113 can overcome mechanisms of resistance to first and second-generation ALK TKIs in preclinical models.”
Oral Presentation on Brigatinib Discovery
An oral presentation describes, for the first time, the design and chemical structure of brigatinib, discovered using ARIAD’s structure-based drug design platform. With the goal of designing a selective ALK inhibitor with broad-based activity against crizotinib-resistant mutants, ARIAD scientists advanced a series of novel compounds culminating in the identification of brigatinib. Brigatinib incorporates unique chemical-design features, including the distinctive use of a recognition element that confers favorable pharmacologic properties. Brigatinib has at least 10-fold greater potency than crizotinib against ALK+ NSCLC cell lines and was broadly active against clinically relevant crizotinib-resistant mutants in preclinical models.
New Preclinical Data on Brigatinib in Poster Presentation
A poster presentation shows that brigatinib, at clinically achievable concentrations, has potent anti-tumor activity against a panel of 17 distinct ALK mutants known to confer resistance to other ALK inhibitors. In a separate study designed to model the occurrence of brain metastases in ALK+ lung cancer patients, brigatinib significantly reduced the tumor burden in mice with ALK+ brain tumors compared to the tumors in mice treated with crizotinib. Survival of brigatinib-treated mice was also markedly enhanced compared to the survival duration of crizotinib-treated mice.
“These preclinical data highlight key attributes of brigatinib, including its unique design features and its potential to address two major causes of resistance to other ALK inhibitors: ALK point mutations and the occurrence of brain metastases, ” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “As the Phase 2 ALTA trial of brigatinib continues to enroll patients, we look forward to reporting additional clinical data on this internally discovered TKI.”
About Non-Small Cell Lung Cancer and ALK
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 228,190 new cases of lung cancer diagnosed each year in the United States, according to the American Cancer Society. Anaplastic lymphoma kinase (ALK) was first identified as a chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of NSCLC as well. Since ALK is generally not expressed in normal adult tissues, it represents a promising molecular target for cancer therapy. Approximately three to eight percent of patients with NSCLC have the ALK gene mutation.
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, visithttp://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).
This press release contains forward-looking statements. Any statements contained herein which do not describe historical facts, including, but not limited to, statements regarding: preclinical data for brigatinib and additional clinical data from our Phase 2 ALTA clinical trial of brigatinib, are forward-looking statements which 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 factors, risks and uncertainties include, among others: preclinical data and early-stage clinical data may not be replicated in later-stage clinical studies; the costs associated with our research, development, manufacturing and other activities; the adequacy of our capital resources and the availability of additional funding; our ongoing and additional clinical trials of brigatinib may not be successful or initiated, enrolled or conducted in a timely manner; regulatory developments and safety issues; competitive risks; manufacturing issues and those additional factors detailed in our public filings with the U.S. Securities and Exchange Commission, including our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release and we undertake no obligation to update or revise any of these statements to reflect events or circumstances occurring after this press release. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. All forward‐looking statements in this press release are qualified in their entirety by this cautionary statement.