ORIC® Pharma Showcases ORIC-114 Data for EGFR Exon 20 Insertions at EORTC-NCI-AACR Symposium

ORIC Pharmaceuticals, Inc., a clinical-stage oncology company, presented promising data on their product ORIC-114 at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. ORIC-114 is an orally bioavailable, irreversible inhibitor targeting EGFR exon 20, HER2 exon 20, and other atypical mutations, designed to treat non-small cell lung cancer (NSCLC) patients.

The company's recent poster presentation highlighted the superior properties of ORIC-114, particularly its effectiveness against EGFR exon 20 insertions and atypical mutations. This compound has demonstrated notable results in preclinical studies, outperforming other EGFR inhibitors in terms of potency and selectivity across different EGFR mutational classes. These findings were emphasized by Lori Friedman, PhD, the chief scientific officer at ORIC Pharmaceuticals. According to Friedman, clinical studies have shown ORIC-114's significant systemic and central nervous system (CNS) responses, even in patients who had undergone extensive previous treatments for NSCLC.

ORIC Pharmaceuticals is actively evaluating ORIC-114 in multiple Phase 1b expansion cohorts focusing on NSCLC patients with specific EGFR and HER2 exon 20 mutations and atypical EGFR mutations. Updated data from these studies are anticipated in the first half of 2025.

Key takeaways from the poster presentation include the following:

1. ORIC-114 has shown regression in all tested EGFR mutant in vivo models, which include cell-derived xenografts, patient-derived xenografts, and intracranial models. One model with complex atypical mutant EGFR displayed 100% tumor regression, with all tumors achieving a complete response.

2. In an expanded preclinical comparative analysis involving exon 20 insertions, atypical PACC, and other mutations, ORIC-114 emerged as the most potent inhibitor across various EGFR mutational classes while maintaining a comparative wild-type selectivity in cell-based assays. This performance was superior to other inhibitors such as firmonertinib, zipalertinib, lazertinib, and BDTX-1535.

3. Head-to-head comparisons revealed that ORIC-114 has superior kinome selectivity with no off-target kinase liabilities. This suggests a robust therapeutic profile with minimal unintended interactions.

4. Molecular responses in circulating tumor DNA (ctDNA) from patients with EGFR exon 20 insertion and PACC mutations were observed during Phase 1 dose escalation studies. The molecular responses across dose escalation cohorts indicate a broad therapeutic window for ORIC-114.

5. ORIC-114 is being evaluated in a global clinical trial, and it shows promise as a best-in-class therapeutic candidate for patients with NSCLC, particularly those with EGFR exon 20 insertions and atypical mutations, including cases with active CNS metastases.

ORIC Pharmaceuticals is a clinical-stage biopharmaceutical company dedicated to overcoming therapeutic resistance in cancer. In addition to ORIC-114, their pipeline includes other product candidates such as ORIC-944, an inhibitor targeting the polycomb repressive complex 2 (PRC2) for prostate cancer, and ORIC-533, an inhibitor of CD73 for multiple myeloma. The company continues to focus on developing precision medicines that target key mechanisms of cancer resistance.

ORIC Pharmaceuticals is based in South San Francisco and San Diego, California. The company remains committed to improving patient lives by addressing the challenges of therapeutic resistance in cancer treatment.