enozertinib (ORIC-114) / ORIC Pharma, Voronoi - LARVOL DELTA

Enozertinib (ORIC-114), a Brain Penetrant, Highly Selective EGFR Inhibitor, in Treatment-Naive Metastatic NSCLC with EGFR Atypical Mutations (ESMO 2026) - No abstract available

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

P-Loop/αC-Helix Compressing Mutations and Exon 20 Insertions in EGFR-Mutant NSCLC: A Rapidly Evolving Therapeutic Landscape. (PubMed, J Clin Oncol) - "EGFR PACC and ex20ins are established subgroups of kinase domain mutations, distinct from classical mutations, due to structure and responsiveness to available TKIs."

Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A global phase 1b study of ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, in patients with advanced solid tumors harboring EGFR Exon 20 or HER2 alterations (ESMO 2023) - P1 | "Conclusions ORIC-114 has demonstrated an acceptable safety profile and preliminary antitumor activity, including in the CNS, at doses predicted to be active. Enrollment is ongoing and updated data will be presented."

Clinical • EGFR exon 20 • Metastases • P1 data • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

Enozertinib (ORIC-114), a highly selective, brain penetrant EGFR and HER2 inhibitor, in previously treated NSCLC with EGFR atypical mutations: Randomized dose optimization and CNS activity (ESMO Asia 2025) - P1/2 | "Enozertinib demonstrated encouraging antitumor and CNS activity with a tolerable safety profile in a median 3L+ NSCLC population harboring EGFR PACC mutations at an effective dose of 80 mg once daily, supporting its selection as the likely RP2D for further development."

Clinical • Late-breaking abstract • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • EGFR • HER-2

Enozertinib in EGFR Exon 20ins mutants: a game changer for CNS metastases, or a temporary conquest? (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Anticipated Program Milestones1 (GlobeNewswire) - "ORIC anticipates the following upcoming milestones: Rinzimetostat in mCRPC: (i) 2H 2026: Program update; Enozertinib in NSCLC: (i) October 2026: 1L EGFR atypical monotherapy data to be presented at ESMO Congress 2026; (ii) 2H 2026: 1L EGFR exon 20 insertion monotherapy data and combination data with SC amivantamab."

Clinical data • EGFR exon 20 • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Announces Three Presentations at the European Society for Medical Oncology (ESMO) Congress 2026 (Yahoo Finance) - "Enozertinib poster presentation to highlight data from an ongoing Phase 1b trial in first-line EGFR atypical NSCLC; Rinzimetostat trial-in-progress poster presentation to highlight the ongoing Himalayas-1 Phase 3 study design in patients with mCRPC previously treated with abiraterone; Rinzimetostat ePoster to highlight data supporting its potential to enhance AR signaling and restrict lineage plasticity in mCRPC."

P1 data • Preclinical • Trial status • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

First Quarter 2026 and Other Recent Highlights:…Enozertinib (GlobeNewswire) - "Completed enrollment in the Phase 1b trial of enozertinib as a single-agent in first-line patients with advanced NSCLC harboring EGFR exon 20 insertion mutations. Continue to enroll Phase 1b trial of enozertinib as a single-agent in first-line patients with advanced NSCLC harboring EGFR atypical mutations. Continue to enroll Phase 1b trial of enozertinib in combination with subcutaneous (SC) amivantamab in first-line patients with advanced NSCLC harboring EGFR exon 20 insertion mutations."

EGFR exon 20 • Enrollment status • Non Small Cell Lung Cancer

ORIC anticipates the following upcoming milestones:…Enozertinib in NSCLC (GlobeNewswire) - "(i) 2H 2026: 1L EGFR atypical monotherapy data; (ii) 2H 2026: 1L EGFR exon 20 insertion monotherapy data and combination data with SC amivantamab."

EGFR exon 20 • P1 data • Non Small Cell Lung Cancer

ORIC-114 in Combination With Subcutaneous Amivantamab in Patients With EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: ORIC Pharmaceuticals | Trial completion date: May 2027 ➔ Dec 2027 | Trial primary completion date: May 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

ORIC anticipates the following upcoming milestones (GlobeNewswire) - "Rinzimetostat in mCRPC: 1Q 2026: Combination dose optimization data with AR inhibitor; 1H 2026: Initiate first global Phase 3 registrational trial in mCRPC...2H 2026: Program update Enozertinib in NSCLC: 2H 2026: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab; 2H 2026: 1L EGFR PACC monotherapy data."

Clinical data • EGFR exon 20 • New P3 trial • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

Enozertinib (ORIC-114), a highly selective, brain penetrant EGFR and HER2 inhibitor, in EGFR Exon 20 mutant NSCLC: Randomized dose optimization and CNS activity (ESMO Asia 2025) - P1/2 | "Enozertinib demonstrated encouraging antitumor and CNS activity with a tolerable safety profile in NSCLC harboring 1L and 2L EGFR exon 20 insertion mutations. Data to date support 80 mg once daily as the likely RP2D for further development."

Clinical • EGFR exon 20 • Late-breaking abstract • CNS Tumor • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • EGFR • HER-2

Enozertinib (ORIC-114), a highly selective, brain penetrant EGFR and HER2 inhibitor, in patients with HER2 Exon 20 mutant NSCLC: Randomized dose optimization (ESMO Asia 2025) - P1/2 | "In a heavily pretreated population, enozertinib showed encouraging antitumor activity including CNS responses in HER2 exon 20 mutant NSCLC. The safety profile supports 80 mg QD as the potential RP2D, with most TRAEs being Grade 1–2 and with a low rate of dose reductions."

Clinical • HER2 exon 20 • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

ORIC Pharmaceuticals…announced data from a Phase 1b trial of enozertinib (ORIC-114) at the ESMO Asia Congress 2025 (GlobeNewswire) - "In the 22 efficacy evaluable patients with PACC mutations, enozertinib demonstrated strong systemic and CNS antitumor activity. 36% confirmed ORR and 91% DCR, with comparable rates in patients with brain metastases at baseline. Responses observed across a wide range of EGFR PACC mutations including in the most prevalent mutations (i.e., G719X, S768I), and in a broad spectrum of PACC complex mutations....80 mg QD oral enozertinib has been selected as the dose for potential Phase 3 development. Enrollment and follow-up continues in 1L EGFR PACC patients with the next update expected in mid-2026, ahead of initiation of a potential Phase 3 trial."

P1 data • Trial status • Non Small Cell Lung Cancer

ORIC Pharmaceuticals…announced two late-breaking oral presentations highlighting data from a Phase 1b trial of enozertinib (ORIC-114) at the ESMO Asia Congress 2025… (GlobeNewswire) - "The mini-oral presentation will focus on data in previously treated patients with EGFR atypical mutant NSCLC, and the proffered paper oral presentation will focus on data in previously treated and treatment-naïve patients with EGFR exon 20 mutant NCSLC."

EGFR exon 20 • Late-breaking abstract • P1 data • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Announces Enozertinib (ORIC-114) Poster Presentation in HER2 exon 20 NSCLC at the ESMO Asia Congress 2025 (GlobeNewswire) - "The poster will focus on data in previously treated patients with HER2 exon 20 mutant NSCLC....Company to host a conference call and webcast on Saturday, December 6, 2025, at 8:00 pm ET."

HER2 exon 20 • P1/2 data • Non Small Cell Lung Cancer

ORIC anticipates the following upcoming data milestones for enozertinib in NSCLC (GlobeNewswire) - "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."

P1 data • P1/2 data • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Announces Publication in Cancer Research on the Discovery and Development of Enozertinib, a Highly Selective, Brain-Penetrant EGFR Inhibitor (GlobeNewswire) - "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."

Preclinical • Non Small Cell Lung Cancer

Enozertinib is a Selective, Brain-penetrant EGFR inhibitor for Treating Non-small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations. (PubMed, Cancer Res) - "Here, we describe the discovery and development of enozertinib (formerly ORIC-114), a highly brain-penetrant, orally bioavailable, irreversible inhibitor that targets EGFR exon 20 mutations with unparalleled kinome selectivity...In a phase I clinical trial of enozertinib in patients with advanced NSCLC bearing atypical mutations in EGFR, a patient with harboring an EGFR exon 20 insertion experienced sustained complete response of all systemic and brain metastases. Together, these findings identify enozertinib as a promising investigational inhibitor to meet the unmet need for brain-penetrant therapies for NSCLC with EGFR exon 20 insertions or other atypical mutations."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

ORIC Pharmaceuticals Expands Leadership Team with the Appointment of Kevin Brodbeck as Chief Technical Officer (GlobeNewswire) - "The creation of the CTO role and Dr. Brodbeck’s appointment reflect the impending advancement of ORIC’s clinical programs into late-stage development with the potential start of Phase 3 trials for ORIC-944 and enozertinib (ORIC-114) in 2026."

New P3 trial • Solid Tumor

ORIC-114-01: Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration (clinicaltrials.gov) - P1/2 | N=350 | Recruiting | Sponsor: ORIC Pharmaceuticals | Trial completion date: Mar 2026 ➔ Sep 2027 | Trial primary completion date: Mar 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • HER-2

ORIC Pharmaceuticals Reports First Quarter 2025 Financial Results and Operational Updates (GlobeNewswire) - "Announced...registrational development plans to focus ORIC-114 in 1L NSCLC and plans to initiate first Phase 3 trial in 2026....ORIC anticipates the following upcoming milestones:...ORIC-114 (NSCLC): (i) 2H 2025: 1L EGFR exon 20, 2L EGFR exon 20, 2L+ HER2 exon 20 and 2L+ EGFR atypical data; (ii) Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical data."

Clinical data • EGFR exon 20 • New P3 trial • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Announces Focused Registrational Clinical Development Plans for Lead Programs, Extended Cash Runway, and Updated Corporate Milestones (GlobeNewswire) - "ORIC-114:...Given favorable enrollment for ORIC-114 in the 1L EGFR exon 20 monotherapy cohort and the 2L+ atypical EGFR cohort, ORIC now expects to provide a comprehensive data update during 2H 2025 that will include these two cohorts along with cohorts for 2L EGFR exon 20 and 2L+ HER2 exon 20. ORIC-114 in combination with subcutaneous (SC) amivantamab in patients with 1L EGFR exon 20 has recently been initiated. Initial data from this trial in addition to ORIC-114 data as a monotherapy in 1L EGFR atypical mutations are expected in mid-2026. ORIC expects to initiate Phase 3 trial(s) for ORIC-114 in 1L NSCLC in 2026, in EGFR exon 20, HER2 exon 20, and/or atypical EGFR mutations. ORIC does not currently plan to pursue registrational trials of ORIC-114 in 2L EGFR and 2L+ HER2 exon 20 NSCLC..."

EGFR exon 20 • HER2 exon 20 • New P3 trial • P1 data • P1/2 data • Non Small Cell Lung Cancer

ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov) - P1 | N=76 | Recruiting | Sponsor: ORIC Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ORIC Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Updates (GlobeNewswire) - "ORIC anticipates the following upcoming data milestones: (1) ORIC-114 (NSCLC): (i) 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20; (ii) 2H 2025: 2L+ EGFR atypical; (iii) 1H 2026: 1L EGFR exon 20; (iv) Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical; (2) ORIC-944 (mCRPC): 4Q 2025 / 1H 2026: Combination with AR inhibitors."

P1 data • P1/2 data • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer