ORIC® Pharmaceuticals Presents Enozertinib Data in NSCLC Patients with HER2 Exon 20 Mutations at the ESMO Asia Congress 2025
Rhea-AI Summary
ORIC (NASDAQ: ORIC) reported Phase 1b data for oral enozertinib in previously treated NSCLC patients with HER2 exon 20 mutations presented at ESMO Asia Congress 2025. As of Aug 29, 2025, 49 patients were dosed (26 at 80 mg QD; 23 at 120 mg QD), with 47% having baseline brain metastases.
Key results in the 80 mg cohort: 35% ORR (26% confirmed ORR) and 100% disease control rate; manageable safety with mostly Grade 1–2 TRAEs and only 2 discontinuations. Median follow-up was 50 weeks; 32% of patients remained on treatment. Enrollment in HER2 exon 20 completed and no further development planned for that population; 80 mg QD selected for potential Phase 3 based on related cohorts.
Positive
- 35% ORR in 80 mg cohort
- 100% disease control rate in 80 mg cohort
- Only 2 discontinuations due to TRAEs
- 80 mg QD selected for potential Phase 3 development
Negative
- Higher dose reductions in 120 mg cohort
- Enrollment completed; no further development in HER2 exon 20 population
Key Figures
Market Reality Check
Peers on Argus
Key biotech peers like MAZE, RAPP, ATNF, and ELVN showed modest gains (e.g., MAZE +2.3%, RAPP +3.01%), but no names appeared in the momentum scanner and there were no same-day peer headlines, suggesting today’s ORIC move is driven more by company-specific enozertinib data than a coordinated sector rotation.
Historical Context
| Date | Event | Sentiment | Move | Catalyst |
|---|---|---|---|---|
| Dec 01 | Conference preview | Neutral | -6.1% | Announcement of enozertinib HER2 exon 20 NSCLC poster and webcast timing. |
| Nov 24 | Conference participation | Neutral | -1.4% | Participation in Evercore healthcare conference and investor meetings disclosure. |
| Nov 13 | Earnings and updates | Neutral | -2.3% | Q3 2025 financials plus ORIC-944 and enozertinib clinical and corporate updates. |
| Nov 13 | Clinical trial update | Positive | -2.3% | Dose exploration completion and promising Phase 1b ORIC-944 efficacy and safety data. |
| Nov 07 | Equity inducement | Neutral | +0.9% | Disclosure of inducement stock options and RSUs for a new non-executive employee. |
Over the past month, ORIC’s shares often traded lower on news days, including a -6.14% move on the ESMO poster scheduling announcement, despite largely operational or clinical updates rather than clearly negative events.
In the last few months, ORIC highlighted clinical and corporate progress. On Nov 13, 2025, Q3 results showed a net loss and $413.0M in cash, cash equivalents and investments, funding operations into 2H 2028, alongside encouraging ORIC-944 efficacy and safety data. Multiple 8-Ks furnished updated slides and earnings materials. Earlier in November, ORIC reported inducement equity grants. On Dec 1, 2025, it flagged the upcoming ESMO Asia enozertinib poster and related webcast, which preceded today’s detailed Phase 1b readout.
Market Pulse Summary
This announcement details Phase 1b enozertinib data in HER2 exon 20 NSCLC, showing a 35% ORR, 26% confirmed ORR, and 100% DCR in the 80 mg cohort with a manageable safety profile. The company completed enrollment in this population and selected 80 mg QD for potential Phase 3 work in EGFR-mutated NSCLC. Investors may track upcoming 1L EGFR exon 20 and PACC updates expected by mid-2026.
Key Terms
nsclc medical
phase 1b medical
AI-generated analysis. Not financial advice.
Systemic activity of
Manageable safety profile with low discontinuation rate
Enrollment completed; no further development planned in this patient population
Company to host a conference call and webcast on Saturday, December 6, 2025, at 8:00 pm ET
SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Dec. 05, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, announced data from a Phase 1b trial of enozertinib (ORIC-114) at the ESMO Asia Congress 2025. Data in previously treated NSCLC patients with HER2 exon 20 mutations were presented at a poster session, and the poster can be found in the publication section of ORIC’s website here.
Enozertinib Phase 1b Trial Design
Enozertinib is being evaluated in a Phase 1b trial in patients with locally advanced or metastatic NSCLC with HER2 exon 20 mutations. Notably, enrollment allows patients with active untreated brain metastases. Prior therapies include chemotherapy and HER2 targeted therapies. The primary endpoint of the trial is to determine the recommended Phase 2 dose (RP2D), and secondary endpoints include investigator-assessed objective response rate (ORR), disease control rate (DCR), and safety.
Previously Treated NSCLC Patients with HER2 Exon 20 Mutations
As of the August 29, 2025 cutoff date, 49 patients were dosed — 26 patients received 80 mg QD oral enozertinib and 23 patients received 120 mg QD. Patients were treated with up to 4 prior therapies, with
Preliminary Safety Analysis
Enozertinib was well tolerated with mostly Grade 1 or 2 treatment-related adverse events (TRAEs), and no significant off-target toxicities. Most frequent TRAEs included paronychia, diarrhea, and dermatitis acneiform. Only 2 patients discontinued treatment due to TRAEs. Higher rates of dose reductions occurred in the 120 mg cohort compared to the 80 mg cohort.
Preliminary Activity Analysis
Tumor responses were observed in both the 80 mg and 120 mg cohorts, including in patients with baseline brain metastases. Patients in the 80 mg cohort experienced deeper tumor regressions potentially due to the lower rate of dose reductions.
35% ORR (26% confirmed ORR) and100% DCR in the 80 mg cohort- As of the data cutoff (at a median follow-up of 50 weeks),
32% of patients remained on treatment in both the 80 mg and 120 mg cohorts
Next Steps
Based on data generated in patients with EGFR exon 20 and EGFR atypical mutations, 80 mg QD oral enozertinib has been selected as the dose for potential Phase 3 development. Enrollment and follow-up continues in 1L NSCLC patients with EGFR exon 20 and EGFR P-loop and alpha C-helix compressing (PACC) mutations, with the next update expected in mid-2026, ahead of initiation of potential Phase 3 trial(s). Enrollment in HER2 exon 20 has been completed with no further development planned in this patient population.
Conference Call and Webcast Details
In conjunction with the ESMO Asia Congress, ORIC will host a conference call and webcast on Saturday, December 6, 2025, at 8:00 pm ET. To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. A live webcast and audio archive of the conference call will be available through the investor section of ORIC’s website at www.oricpharma.com. The webcast will be available for replay for 90 days following the presentation.
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, EGFR atypical, and HER2 exon 20 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, statements regarding the clinical development of enozertinib; clinical outcomes from studies of enozertinib, which may materially change as patient enrollment continues or more patient data become available; the potential advantages of enozertinib; and plans underlying ORIC’s clinical trials and development. 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 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 November 13, 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 were the enozertinib results for ORIC (ORIC) in HER2 exon 20 NSCLC at ESMO Asia 2025?
How many patients were dosed in ORIC's enozertinib Phase 1b HER2 exon 20 cohort?
Did ORIC report enozertinib activity in patients with brain metastases?
Why did ORIC select 80 mg QD for potential Phase 3 development?
Is ORIC continuing development of enozertinib in HER2 exon 20 NSCLC?
When is ORIC hosting the conference call and webcast for the ESMO Asia data?
