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

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

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

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

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

New P1 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ORIC Pharmaceuticals Provides…Anticipated Upcoming Milestones (GlobeNewswire) - "These accomplishments position us well for 2025 and beyond, with seven anticipated data readouts over the next 18 months as we advance toward potentially initiating registrational studies for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026."

New trial • Oncology

ORIC Pharmaceuticals Provides...Anticipated Upcoming Milestones (GlobeNewswire) - "ORIC anticipates the following upcoming data milestones: ORIC-114 (NSCLC): 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20; 2H 2025: 2L+ EGFR atypical; 1H 2026: 1L EGFR exon 20; Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical."

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

ORIC Pharmaceuticals Announces Clinical Supply Agreement to Evaluate ORIC-114 in Combination with Amivantamab for the First-Line Treatment of NSCLC with EGFR Exon 20 Insertion Mutations (GlobeNewswire) - "Phase 1b combination trial of ORIC-114 and subcutaneous amivantamab in patients with 1L NSCLC with EGFR exon 20 insertion mutations expected to initiate in Q1 2025, with initial data in mid-2026...ORIC Pharmaceuticals...announced that the company has entered into a supply agreement with Janssen Research & Development, LLC...to evaluate ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, in combination with subcutaneous (SC) amivantamab, Johnson & Johnson’s fully-human EGFR-MET bispecific antibody, for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations....Under the terms of the agreement, ORIC will conduct and sponsor the trial and Johnson & Johnson will provide SC amivantamab. ORIC maintains development and commercial rights to ORIC-114 and is free to expand the program in combination with other agents."

Commercial • EGFR exon 20 • New P1 trial • P1 data • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Reports Third Quarter 2024 Financial Results and Operational Updates (GlobeNewswire) - "Third Quarter 2024 and Other Recent Highlights: (i) ORIC-114:...Expect to report updated Phase 1b data in the first half of 2025."

P1 data • Solid Tumor

Voronoi, stock price soars on expectations for new lung cancer drug… Market cap exceeds 2 trillion [Google translation] (Money Today) - "The market cap of Voronoi has already exceeded 2 trillion won...Clinical data for lung cancer new drugs VRN07 and VRN11 are expected to be confirmed in the first half of next year...The recent rise in Voronoi's stock price cannot be left out by expectations for non-small cell lung cancer treatment VRN07 (ORIC-114) and VRN11...Oric is known to be concentrating its research capabilities on VRN07 as its core pipeline. It is expected to confirm the results of phase 1b clinical trials as early as next year and enter phase 2b. The goal is to then apply for accelerated approval in 2026....VRN11, which Voronoi is conducting its own clinical trials, is expected to confirm interim data in the first half of next year."

Clinical data • Filing • Stock price • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, demonstrates best-in-class properties against Exon 20 insertions and other atypical EGFR mutations (EORTC-NCI-AACR 2024) - P1/2 | " ORIC-114 is exquisitely selective in kinome analysis, demonstrating superiority to all current clinical small molecule inhibitors tested, including firmonertinib, zipalertinib and BDTX-1535. ORIC-114 demonstrated best-in-class properties, including brain penetrance, superior selectivity across the kinome, potent activity across atypical mutations in EGFR, including PACC mutations and Exon 20 insertion mutations, and evidence of molecular response in patients. ORIC-114 is a promising therapy for NSCLC patients with atypical mutations in EGFR, including those with active CNS metastases, and is currently being evaluated in a global clinical trial (NCT05315700)."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HER-2

ORIC Pharmaceuticals Presents Data Further Supporting Potential Best-In-Class Profile of ORIC-114 to Treat EGFR Exon 20 Insertions and Other Atypical Mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "ORIC Pharmaceuticals, Inc...announced the company presented a poster highlighting certain best-in-class properties of ORIC-114, a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor, to treat EGFR exon 20 insertions and other atypical mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics....Demonstrates regressions in all EGFR mutant in vivo models tested, including cell-derived xenografts, patient-derived xenografts and intracranial models that encompass exon 20 insertion and atypical mutant models. An in vivo model with complex atypical mutant EGFR dosed with ORIC-114 notably shows 100% tumor regressions and all tumors experienced a complete response....In head-to-head comparisons with firmonertinib, zipalertinib, lazertinib and BDTX-1535, ORIC-114 has superior kinome selectivity with no off-target kinase liabilities identified."

Preclinical • Oncology • Solid Tumor

ORIC Pharmaceuticals Announces Presentation at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "In an expanded preclinical comparative analysis, ORIC-114 demonstrated best-in-class properties including brain penetrance, superior kinome selectivity, potent activity across EGFR PACC mutations and exon 20 insertion mutations, relative to firmonertinib, zipalertinib, and BDTX-1535. Additionally, evidence of molecular response in ctDNA from patients whose tumors harbored PACC mutations and exon 20 insertion mutations was observed with ORIC-114 treatment."

Preclinical • Oncology • Solid Tumor

ORIC Pharmaceuticals Reports Second Quarter 2024 Financial Results and Operational Updates (GlobeNewswire) - "ORIC-114: Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses....Expect to report updated Phase 1b data in the first half of 2025."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor