ORIC Pharmaceuticals (ORIC) announced the company presented a poster highlighting certain best-in-class properties of ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, to treat EGFR exon 20 insertions and other atypical mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. Key findings of this poster presentation: Demonstrates regressions in all EGFR mutant in vivo models tested, including cell-derived xenografts, patient-derived xenografts and intracranial models that encompass exon 20 insertion and atypical mutant models. An in vivo model with complex atypical mutant EGFR dosed with ORIC-114 notably shows 100% tumor regressions and all tumors experienced a complete response. In an expanded preclinical comparative analysis of exon 20 insertion, atypical PACC and other mutations, overall ORIC-114 is the most potent across EGFR mutational classes whilst displaying comparative wild-type selectivity in cell-based assays, relative to firmonertinib, zipalertinib, lazertinib and BDTX-1535. In head-to-head comparisons with firmonertinib, zipalertinib, lazertinib and BDTX-1535, ORIC-114 has superior kinome selectivity with no off-target kinase liabilities identified. Shows complete molecular responses in ctDNA from patients with EGFR exon 20 insertion and PACC mutations from Phase 1 dose escalation study.
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