On October 23, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported 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 (Free EORTC-NCI-AACR Whitepaper) Symposium on Molecular Targets and Cancer Therapeutics (Press release, ORIC Pharmaceuticals, OCT 23, 2024, View Source [SID1234647344]).

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"Preclinical data presented today underscore ORIC-114’s superior potency and selectively across EGFR mutational classes compared to other EGFR inhibitors," said Lori Friedman, PhD, chief scientific officer. "These results build on clinical findings that highlight ORIC-114’s potential best-in-class profile, showing notable systemic and CNS responses, along with a favorable safety profile, even in heavily pre-treated NSCLC patients. We are continuing to evaluate ORIC-114 in multiple Phase 1b expansion cohorts for NSCLC patients with EGFR exon 20, HER2 exon 20, and atypical EGFR mutations, with updated data expected in the first half of 2025."

Poster presentation details:

ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, demonstrates best-in-class properties against exon 20 insertions and other atypical EGFR mutations

ORIC-114 previously demonstrated systemic and intracranial clinical responses in heavily pre-treated patients with EGFR and HER2 exon 20 insertion mutations. 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. Evidence of molecular responses observed across dose escalation cohorts supports broad therapeutic window for ORIC-114.

ORIC-114 is a promising therapeutic candidate with best-in-class potential for patients with non-small cell lung cancer harboring exon 20 insertions and atypical mutations in EGFR, including those presenting with active CNS metastases, and is being evaluated in a global clinical trial (NCT05315700).

About ORIC-114
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.