ORIC® Pharmaceuticals Announces Publication in Cancer Research on the Discovery and Development of Enozertinib, a Highly Selective, Brain-Penetrant EGFR Inhibitor

Rhea-AI Summary

ORIC (Nasdaq: ORIC) announced a peer-reviewed publication in Cancer Research describing the discovery and preclinical development of enozertinib, an oral, irreversible EGFR inhibitor designed for EGFR exon 20 and atypical mutations. The paper reports enozertinib’s exquisite kinome selectivity, strong potency, and brain penetration, with anti-tumor activity in intracranial lung cancer models. The publication includes a patient vignette reporting a sustained systemic and CNS complete response in an NSCLC patient with an EGFR exon 20 insertion. ORIC said it will present multiple clinical datasets in December 2025 (ESMO Asia 2025) and additional 1L combination data in mid-2026.

Positive

• Peer-reviewed publication in Cancer Research
• Brain-penetrant activity shown in intracranial lung cancer models
• Demonstrated exquisite kinome selectivity and strong potency
• Reported systemic and CNS complete response in a patient vignette
• Planned clinical data presentations in Dec 2025 and mid-2026

Negative

• Evidence relies on preclinical data plus a single patient vignette
• No regulatory approvals reported; program remains clinical-stage
• Key clinical readouts are pending and subject to timing risk

Insights

Oncology drug development expert

Publication confirms preclinical brain-penetrant EGFR exon 20 inhibitor and sets clear clinical data milestones through mid-2026.

ORIC presents peer-reviewed preclinical evidence that enozertinib is a brain-penetrant, orally bioavailable, highly selective irreversible EGFR inhibitor with activity against exon 20 and atypical mutations; the paper reports strong in vivo potency, intracranial anti-tumor activity, and a single-patient complete systemic and CNS response.

The business mechanism is straightforward: a literature-backed preclinical package plus a notable patient vignette strengthens the scientific rationale for ongoing clinical development and supports upcoming presentations at ESMO Asia December 2025 and additional data in mid-2026. Key dependencies include reproducible clinical responses across cohorts and safety/tolerability in planned cohorts; a single-patient result is hypothesis‑generating but not definitive.

Watch for the specified data readouts: 1L and 2L EGFR exon 20, 2L+ HER2 exon 20, and 2L+ EGFR atypical data at ESMO Asia December 2025, and 1L atypical plus 1L exon 20 combination data with SC amivantamab in mid-2026. These are the concrete milestones that will materially change the clinical evidence base over the next ~6–18 months.

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Nov. 06, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced the publication of a peer-reviewed research paper in Cancer Research, a journal of the American Association for Cancer Research. 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.

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 Asia 2025
• Mid-2026: 1L EGFR atypical data and 1L EGFR exon 20 combination with SC amivantamab data

About ORIC Pharmaceuticals, Inc.
ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (2) enozertinib (ORIC-114), a brain-penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the continued clinical development of enozertinib (formerly ORIC-114); the potential advantages and best-in-class potential of enozertinib; the development plans and timelines for enozertinib; plans underlying ORIC’s clinical trials and development; anticipated program milestones, including timing of data disclosure; and statements by the company’s vice president, head of biology. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC-944, enozertinib or any other product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements or its clinical trial collaboration and supply agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the SEC) on August 12, 2025, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

Contact:
Dominic Piscitelli, Chief Financial Officer
dominic.piscitelli@oricpharma.com
info@oricpharma.com

FAQ

What did ORIC announce about enozertinib on November 6, 2025?

ORIC announced a Cancer Research publication detailing enozertinib’s discovery, selectivity, brain penetration, preclinical activity, and a patient complete response.

How does enozertinib perform against EGFR exon 20 and atypical mutations (ORIC)?

The publication reports enozertinib has strong potency, exquisite kinome selectivity, and activity across atypical EGFR mutant contexts.

Did enozertinib show activity in the brain for NSCLC patients (ORIC)?

Preclinical intracranial models showed brain activity, and the paper includes a patient vignette with a sustained CNS complete response.

When will ORIC present clinical enozertinib data for investors?

ORIC plans presentations in December 2025 at ESMO Asia 2025 and additional 1L combination data in mid-2026.

Is enozertinib approved for NSCLC treatment?

No; ORIC is a clinical-stage company and the announcement describes preclinical data and early clinical reporting, not regulatory approval.

What is the investor impact of the Cancer Research publication for ORIC (ORIC)?

The peer-reviewed publication supports potential differentiation for enozertinib, but material clinical outcomes and regulatory progress remain pending.