On November 6, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the publication of a peer-reviewed research paper in Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper). The scientific paper details the discovery and development of enozertinib (formerly ORIC-114), a highly brain-penetrant, orally bioavailable, irreversible inhibitor that targets EGFR exon 20 mutations with exquisite kinome selectivity.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
EGFR mutations are common oncogenic drivers in non-small cell lung cancer (NSCLC), and approximately 50% of patients may develop brain metastases over the course of their disease. Additionally, patients with non-classical EGFR mutations, such as insertions in exon 20, have a worse prognosis compared to patients with classical EGFR mutations. There remains an unmet need for a highly selective EGFR inhibitor that is also brain-penetrant to effectively treat and control intracranial disease.
The Cancer Research publication details preclinical data demonstrating enozertinib’s exquisite kinome selectivity, strong potency, brain-penetrance, and anti-tumor activity, including in intracranial lung cancer models, across a broad range of atypical EGFR mutant contexts. This publication also highlights a patient vignette in which treatment with enozertinib resulted in a sustained complete response of all systemic and brain metastases in a patient with NSCLC whose tumors harbored an EGFR exon 20 insertion mutation. To ORIC’s knowledge, enozertinib is the only EGFR exon 20 inhibitor to demonstrate a systemic complete response and CNS complete response in a patient with untreated, active brain metastases.
"These studies affirm our belief that enozertinib is uniquely positioned to address the unmet needs in patients with NSCLC driven by EGFR exon 20 and atypical mutations," said Melissa Junttila, PhD., vice president, head of biology at ORIC, and first author of the publication. "We look forward to sharing additional clinical data for enozertinib later this year and in mid-2026 and further elucidating its best-in-class potential."
The full manuscript, titled "Enozertinib is a Selective, Brain-Penetrant EGFR Inhibitor for Treating Non-small Cell Lung Cancer with EGFR Exon 20 and Atypical Mutations," is available online at Cancer Research.
ORIC anticipates the following upcoming data milestones for enozertinib in NSCLC:
December 2025: 1L EGFR exon 20, 2L EGFR exon 20, 2L+ HER2 exon 20 and 2L+ EGFR atypical data to be presented at ESMO (Free ESMO Whitepaper) Asia 2025
Mid-2026: 1L EGFR atypical data and 1L EGFR exon 20 combination with SC amivantamab data
(Press release, ORIC Pharmaceuticals, NOV 6, 2025, View Source [SID1234659583])