First Presentation of Preclinical Data Supports Upcoming Clinical Testing in Non-Small Cell Lung Cancer Patients with EGFR and HER2 Exon 20 Mutations
CAMBRIDGE, MA & NEW ORLEANS, LA, USA I April 19, 2016 I ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the results of comprehensive preclinical studies on its investigational tyrosine kinase inhibitor (TKI), AP32788, at the American Association for Cancer Research (AACR) Annual Meeting 2016. AP32788 is a TKI designed to target specific mutations in EGFR or HER2 present in a subset of patients with non-small cell lung cancer (NSCLC), for whom there are currently no targeted therapies available. The Phase 1/2 clinical trial of AP32788 is expected to begin patient enrollment in the second quarter of 2016.
The data presented were included in an oral presentation entitled, “AP32788, a potent, selective inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions, in preclinical models.” The research conducted by ARIAD scientists showed that in a matched set of engineered cell lines, AP32788 inhibited all tested EGFR and HER2 mutants, including exon 20 insertion mutants, with selectivity over wild-type (WT) EGFR. Inhibition of WT EGFR in non-tumor cells has been associated with dose-limiting toxicities of EGFR inhibitors in patients. Enzymatic analysis confirmed that AP32788 irreversibly inactivated EGFR exon 20 with 20-fold selectivity over WT EGFR, in contrast to other tested EGFR TKIs. AP32788 also induced tumor regressions in a mouse EGFR exon 20 model at doses that were well tolerated.
“These preclinical data on AP32788 demonstrate its potential to potently inhibit exon 20 mutant forms of EGFR and HER2, that are not addressed by currently available TKI treatments,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “The selectivity data suggest that efficacious levels of exposure to AP32788 may be achievable in patients with these challenging mutations —a hypothesis we will be testing in the Phase 1/2 trial. We believe AP32788 is the first TKI that has been designed and optimized to inhibit the underlying mutation present in these orphan oncology disease subsets.”
About Non-Small Cell Lung Cancer, EGFR and HER2
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 221,200 new cases of lung cancer diagnosed in 2015 in the United States, according to the American Cancer Society. EGFR mutations represent the largest known, targetable subset of NSCLC. While the most common types of EGFR mutation are addressed by approved TKI therapies, there are no targeted treatment options available for the approximately 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations1. In addition, patients with HER2 mutations, mostly exon 20 insertion mutations, comprise approximately 2 percent of NSCLC patients2 and also have no current treatment options. ARIAD estimates that there are approximately 6,000 patients in the United States living with EGFR exon 20 or HER2 point mutations, based on available data from 2014 on the number of Stage IIIB or IV NSCLC and the estimated percentage of patients with these mutations.
About AP32788
AP32788 is an investigational oral tyrosine kinase inhibitor (TKI) of activating mutations in EGFR and HER2. The molecule was designed to address the unmet need in patients with non-small cell lung cancer (NSCLC) driven by exon 20 insertion mutations in EGFR and HER2, and is ARIAD’s fourth internally discovered oncology IND to be cleared for clinical development.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an orphan 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 orphan 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).
SOURCE: ARIAD Pharmaceuticals
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First Presentation of Preclinical Data Supports Upcoming Clinical Testing in Non-Small Cell Lung Cancer Patients with EGFR and HER2 Exon 20 Mutations
CAMBRIDGE, MA & NEW ORLEANS, LA, USA I April 19, 2016 I ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the results of comprehensive preclinical studies on its investigational tyrosine kinase inhibitor (TKI), AP32788, at the American Association for Cancer Research (AACR) Annual Meeting 2016. AP32788 is a TKI designed to target specific mutations in EGFR or HER2 present in a subset of patients with non-small cell lung cancer (NSCLC), for whom there are currently no targeted therapies available. The Phase 1/2 clinical trial of AP32788 is expected to begin patient enrollment in the second quarter of 2016.
The data presented were included in an oral presentation entitled, “AP32788, a potent, selective inhibitor of EGFR and HER2 oncogenic mutants, including exon 20 insertions, in preclinical models.” The research conducted by ARIAD scientists showed that in a matched set of engineered cell lines, AP32788 inhibited all tested EGFR and HER2 mutants, including exon 20 insertion mutants, with selectivity over wild-type (WT) EGFR. Inhibition of WT EGFR in non-tumor cells has been associated with dose-limiting toxicities of EGFR inhibitors in patients. Enzymatic analysis confirmed that AP32788 irreversibly inactivated EGFR exon 20 with 20-fold selectivity over WT EGFR, in contrast to other tested EGFR TKIs. AP32788 also induced tumor regressions in a mouse EGFR exon 20 model at doses that were well tolerated.
“These preclinical data on AP32788 demonstrate its potential to potently inhibit exon 20 mutant forms of EGFR and HER2, that are not addressed by currently available TKI treatments,” said Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “The selectivity data suggest that efficacious levels of exposure to AP32788 may be achievable in patients with these challenging mutations —a hypothesis we will be testing in the Phase 1/2 trial. We believe AP32788 is the first TKI that has been designed and optimized to inhibit the underlying mutation present in these orphan oncology disease subsets.”
About Non-Small Cell Lung Cancer, EGFR and HER2
Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 221,200 new cases of lung cancer diagnosed in 2015 in the United States, according to the American Cancer Society. EGFR mutations represent the largest known, targetable subset of NSCLC. While the most common types of EGFR mutation are addressed by approved TKI therapies, there are no targeted treatment options available for the approximately 4 to 9 percent of EGFR-mutated lung tumors with exon 20 insertion mutations1. In addition, patients with HER2 mutations, mostly exon 20 insertion mutations, comprise approximately 2 percent of NSCLC patients2 and also have no current treatment options. ARIAD estimates that there are approximately 6,000 patients in the United States living with EGFR exon 20 or HER2 point mutations, based on available data from 2014 on the number of Stage IIIB or IV NSCLC and the estimated percentage of patients with these mutations.
About AP32788
AP32788 is an investigational oral tyrosine kinase inhibitor (TKI) of activating mutations in EGFR and HER2. The molecule was designed to address the unmet need in patients with non-small cell lung cancer (NSCLC) driven by exon 20 insertion mutations in EGFR and HER2, and is ARIAD’s fourth internally discovered oncology IND to be cleared for clinical development.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and Lausanne, Switzerland, is an orphan 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 orphan 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).
SOURCE: ARIAD Pharmaceuticals
Post Views: 91
