( ht; position: relative;> AV-412 sho...)AVEO Presents Preclinical Efficacy Data on AV-412, a Novel Oral,Tyrosine Kinase Inhibitor of EGFR/HER2 for EGFR Mutant and,Drug-Resistant Lung Cancer,Health

"AV-412 showed potent inhibition of the EGFR L858R mutations and, in two well-established animal models, demonstrated dose-dependant tumor regression in both small and large lung tumors and complete regression of lung tumors at a dose where erlotinib is inactive," said Tuan Ha-Ngoc, President and CEO of AVEO Pharmaceuticals. "These data, while early, highlight the promise of AV-412 as an option for lung cancer patients who carry the EGFR L858R mutation, as well as patients who become resistant to first-generation tyrosine kinase inhibitors. We are looking forward to initiating Phase 2 trials as soon as we establish an appropriate dose in the current Phase 1 study, which was initiated last October."

To provide robust models for translational research supporting the development of novel agents for lung cancer, AVEO generated a series of inducible mouse lung cancer models using AVEO's Human Response Prediction(TM) Platform. Using this proprietary platform, AVEO generated several different models covering the most prevalent oncogenic mutations including EGFR(L858R), EGFR(L858R/T790M) and KRAS(G12V). Unlike studies in primary genetically engineered tumor models, this approach enables the quantitative and comparative analysis of different drugs, doses, schedules and combinations to optimize drug selection and clinical trial design in the clinic.

Utilizing these novel models, AVEO evaluated the activity of AV-412 in non-small cell lung cancer tumors. Data presented today at the AACR meeting show that AV-412 is highly active against tumors from the chimeric model carrying the EGFRL858R mutation, exhibiting an ED50 of 0.1 mg/kg as a daily dose. AV-412 is greater than 10 times more potent than erlotinib in this model, one mg/kg PO AV-412 resulted in complete tumor regression, whereas erlotinib is active at 10mg/kg, but inactive at 1mg/kg. More importantly, AV-412 was found to be active against tumors from chimeric lung adenocar
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