Slide 1: Enozertinib (ORIC-114) Program Update
Exhibit 99.1 Enozertinib (ORIC-114) Program Update December 6, 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this presentation, including statements regarding ORIC Pharmaceuticals, Inc.’s (“ORIC”, “we”, “us”
Slide 3: Program Update Agenda
Enozertinib Program Update Agenda • Executive Summary • Preclinical Differentiation • ESMO Asia Clinical Highlights – 2L EGFR exon 20 – 1L EGFR exon 20 – Pretreated EGFR PACC • 1L EGFR PACC (Preliminary Data) • Executive Summary and Next Steps ORIC Participants • Jacob Chacko, Chief Executive Office
Slide 4: Executive Summary
Executive Summary
Slide 5: Establishes Potential Best-in-Class Profile in EGFR-Mutated NSCLC
Enozertinib Establishes Potential Best-in-Class Profile in EGFR-Mutated NSCLC Ø Systemic activity in 2L EGFR exon 20 and pretreated EGFR PACC exceeds competitor benchmarks Ø Highly competitive preliminary 1L systemic activity, with 67% ORR in EGFR exon 20 and 80% ORR in EGFR PACC Ø Convincing 1L CNS
Slide 6: Significant Commercial Opportunity Across Patient Populations Lacking an Approved CNS Active Agent
Enozertinib Is Pursuing a Significant Commercial Opportunity Across Patient Populations that Lack an Approved CNS Active Agent Estimated Enozertinib Commercial Opportunity (US Only) 10,000 • ~9,000 patients (~5% of NSCLC) diagnosed annually 8,000 • EGFR exon 20 mutant NSCLC: no approved CNS-active 5
Slide 7: Best-in-Class Profile Yet to Emerge in Treatment Landscape
Best-in-Class Profile Yet to Emerge in Treatment Landscape for NSCLC Patients Harboring EGFR Exon 20 and EGFR PACC Mutations What is a Best-In-Class Target Product Profile for an EGFR Exon 20 and EGFR PACC Inhibitor? q Manageable on-target toxicities (e.g., GI and skin) Safety / q No significant off
Slide 8: High Burden of CNS Disease in NSCLC Patients with EGFR Mutations
High Burden of CNS Disease in NSCLC Patients with EGFR Mutations Leads to Disease Progression and Limited Survival with Current Therapies Initial Diagnosis Disease Progression on Treatment CNS Disease Highly ~50% of patients eventually develop Prevalent in EGFR ~30% of patients have known brain meta
Slide 9: Phase 1b Data Establishes Potential Best-in-Class Profile
Enozertinib Phase 1b Data Establishes Potential Best-in-Class Profile in EGFR Exon 20 and PACC Mutated NSCLC Enozertinib Updated Phase 1b Data Highlights 2L EGFR Exon 20 Median 3L EGFR PACC 45% 36% ORR ORR Enozertinib Enozertinib Previously Treated 22% 40% Benchmark ORR Benchmark ORR 1L EGFR Exon 20
Slide 10: Preclinical Differentiation
Preclinical Differentiation
Slide 11: Enozertinib Target Candidate Profile
Enozertinib Is a Promising Candidate for NSCLC Patients with EGFR Exon 20 and PACC Mutations, Including Those with Brain Metastases Enozertinib Target Candidate Profile Differentiated Profile Validated in Phase 1b in Patients with • Strong potency against EGFR exon 20 and EGFR Exon 20 and PACC Mutat
Slide 12: Best-in-Class Potency Across Breadth of EGFR Mutations
Enozertinib Best-in-Class Potency Across Breadth of EGFR Exon 20 and Atypical Mutations In Vitro Potency Comparison EC50 (nM) >100 Zipalertinib Firmonertinib Silevertinib Enozertinib 100 L858R Classical del19 763_FQEA 769_ASV Exon 20 770_NPG Insertion 770_SVD 80 773_NPH E709A E709K L718Q L718V 60 G7
Slide 13: Designed to Selectively Target EGFR: Kinome Selectivity
Enozertinib Was Designed to Selectively Target EGFR with High Potency Against Exon 20 and Atypical Mutations Kinome Selectivity Comparison Zipalertinib Firmonertinib Silevertinib Enozertinib Off-target Wildtype Kinases Inhibited ≥80% at 1µM Enozertinib Zipalertinib Firmonertinib Silevertinib 0 7 4
Slide 14: Superior Brain Penetration of Enozertinib
Superior Brain Penetration of Enozertinib Differentiates from Comparator Agents Enozertinib Exhibits High Ratio of Free (Unbound) Enozertinib CNS Efficacy vs. Mobocertinib in Intracranial Brain/Plasma Exposure in Mice NSCLC EGFR Mutant In Vivo Model 9 10 10 Vehicle 8 10 1 7 10 0.1 Mobocertinib 6 (30
Slide 15: ESMO Asia Clinical Highlights EGFR Exon 20 Mutant NSCLC
ESMO Asia Clinical Highlights EGFR Exon 20 Mutant NSCLC
Slide 16: Phase 1b Trial Design in EGFR Exon 20 Mutations
Enozertinib Phase 1b Trial Enrolled Patients with Previously Treated and Treatment- Naïve NSCLC with EGFR Exon 20 Mutations Enozertinib Phase 1b Trial Design in EGFR Exon 20 Mutations Key Eligibility Criteria: Enozertinib 2L post-chemotherapy 1:1 Randomization 80 mg QD • Locally advanced or Primary
Slide 17: Phase 1b Patient Demographics and Baseline Characteristics (2L)
Phase 1b Trial Patient Demographics and Baseline Characteristics 2L post-chemotherapy, advanced NSCLC with EGFR exon 20 mutations 80 mg 120 mg (n=24) (n=21) Age, years, median (range) 63 (44-75) 70 (28-86) Female, n (%) 17 (71) 16 (76) Non-smoker, n (%) 22 (92) 21 (100) Race: Asian / White / Other,
Slide 18: Generally Well Tolerated in Heavily-Pretreated Patients (2L)
Enozertinib Has Been Generally Well Tolerated Despite Enrolling Heavily-Pretreated Patients and a Less Stringent Enrollment Criteria for Baseline CNS Disease 2L post-chemotherapy, advanced NSCLC with EGFR exon 20 mutations Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 80 mg 120 mg 80
Slide 19: Robust ctDNA Responses (2L)
Enozertinib Achieved Robust Circulating Tumor DNA (ctDNA) Responses 2L post-chemotherapy, advanced NSCLC with EGFR exon 20 mutations Patients with Available ctDNA (n=25) 40 80 mg 120 mg 20 0 • ctDNA clearance rate of 69% (11/16) at 80 -20 mg and 67% (6/9) at 120 mg -40 -60 -80 -100 Enozertinib achie
Slide 20: Strong Antitumor Activity, Including CNS Disease at Baseline (2L)
Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline 2L post-chemotherapy, advanced NSCLC with EGFR exon 20 mutations 80 mg (1) Evaluable Population 80 mg (n=20) (n=20) 20 † Best ORR, % [95% CI] 45 [23, 69] Confirmed ORR, % [95% CI] 45 [23, 69] * * * * *
Slide 21: Tumor Responses Generally Achieved Early (2L)
£ * £ £ £ £ £ £ £ £ £ * * * * * * * * Tumor Responses on Enozertinib Were Generally Achieved Early, and Most Patients Remain on Treatment 2L post-chemotherapy, advanced NSCLC with EGFR exon 20 mutations CNS Disease at Baseline Confirmed PR Start £ Treatment Ongoing 0 4 8 12 16 20 24 28 32 36 40 44 4
Slide 22: Phase 1b Trial Design in EGFR Exon 20 Mutations (1L)
Enozertinib Phase 1b Trial Enrolled Patients with Previously Treated and Treatment- Naïve NSCLC with EGFR Exon 20 Mutations Enozertinib Phase 1b Trial Design in EGFR exon 20 Mutations Key Eligibility Criteria: Enozertinib 2L post-chemotherapy 1:1 Randomization 80 mg QD • Locally advanced or Primary
Slide 23: Phase 1b Patient Demographics and Baseline Characteristics (1L)
Phase 1b Trial Patient Demographics and Baseline Characteristics 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations 80 mg 120 mg (n=18) (n=15) Age (years), median (range) 72 (43-95) 66 (48-82) Female, n (%) 13 (72) 11 (73) Non-smoker, n (%) 18 (100) 15 (100) Race: Asian / White / Other,
Slide 24: Generally Well Tolerated (1L)
Enozertinib Has Been Generally Well Tolerated Despite Less Stringent Enrollment Criteria for Baseline CNS Disease 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 80 mg 120 mg 80 mg 120 mg Event, n (%) Event, n (%) (n=18) (n=
Slide 25: Robust ctDNA Responses (1L)
Enozertinib Achieved Robust ctDNA Responses 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations Patients with Available ctDNA (n=14) 40 80 mg 120 mg 20 0 • ctDNA clearance rate of 71% (10/14) -20 -40 -60 -80 -100 Enozertinib achieved robust ctDNA responses in 1L NSCLC patients with EGFR e
Slide 26: Strong Antitumor Activity, Including CNS Disease at Baseline (1L)
Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations Best % Change in Lesions Systemic Objective Response Rate in Patients Receiving 120 mg Dose (n=15) 120 mg 20 (1) Evaluable Population (n=1
Slide 27: Tumor Responses Generally Achieved Early (1L)
£ £ £ £ * £ £ £ £ £ £ £ ** **** ** Tumor Responses on Enozertinib Were Generally Achieved Early and the Vast Majority of Patients Remain on Treatment 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations • Initial cohort of efficacy evaluable patients were treated at 120 mg; given 80% dose
Slide 28: Strong CNS Antitumor Activity as Measured by BICR-RANO
Enozertinib Achieved Strong CNS Antitumor Activity as Measured by BICR-RANO 1L treatment-naïve, advanced NSCLC with EGFR exon 20 mutations Best % Change in CNS Lesions 120 mg in Patients Receiving 120 mg Dose (n=7) † CNS Response (1) (n=7) 20 ‡ Best ORR, % [95% CI] 71 [29, 96] Confirmed ORR, % [95%
Slide 29: Complete Intracranial and Partial Systemic Responses in Treatment-Naïve Patient
Complete Intracranial and Partial Systemic Responses in a Treatment-Naïve EGFR Exon 20 Mutant NSCLC Patient With Active CNS Metastases Patient: 60-year-old female Prior Therapy: None CNS Metastases at Baseline: 5 active non-target lesions (no prior radiation or surgery) Enozertinib Dose: 120 mg oral
Slide 30: ESMO Asia Clinical Highlights Previously Treated EGFR PACC NSCLC
ESMO Asia Clinical Highlights Previously Treated EGFR PACC NSCLC
Slide 31: Phase 1b Trial Design and Demographics in EGFR Atypical Mutations
Enozertinib Phase 1b Trial Enrolled Patients with Previously Treated NSCLC with EGFR Atypical Mutations Enozertinib Phase 1b Trial Design and Patient Demographics in EGFR Atypical Mutations 80 mg 120 mg Patient Characteristic (n=25) (n=22) Key Eligibility Criteria: Age (years), median (range) 65 (37
Slide 32: Generally Well Tolerated in More Heavily-Pretreated Patients
Enozertinib Has Been Generally Well Tolerated Despite More Heavily-Pretreated Patients and Less Stringent Enrollment Criteria for Prior Therapy and Baseline CNS Disease Previously treated, advanced NSCLC with EGFR atypical mutations Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 80 mg
Slide 33: Strong Antitumor Activity, Including CNS Disease at Baseline (PACC)
Enozertinib Achieved Strong Antitumor Activity, Including in Patients with CNS Disease at Baseline Previously treated (median 3L), advanced NSCLC with EGFR PACC mutations Best % Change in Lesions Effective Dose 80 mg in Patients Receiving 80 mg Effective Dose (n=22) (1) Efficacy Evaluable Population
Slide 34: Tumor Responses Generally Achieved Early (PACC)
£ £ * £ £ £ £ £ £ £ £ ££ * ** ** *** *** ** Tumor Responses on Enozertinib Were Generally Achieved Early, and Most Patients Remain on Treatment Previously treated (median 3L), advanced NSCLC with EGFR PACC mutations Effective Dose 80 mg (n=22) CNS Disease at Baseline Confirmed PR Start £ Treatment O
Slide 35: 1L EGFR PACC NSCLC Preliminary Data
1L EGFR PACC NSCLC Preliminary Data
Slide 36: Early Data in 1L EGFR PACC Patients Show Antitumor Activity
Early Enozertinib Data in 1L EGFR PACC Patients Demonstrated Impressive Antitumor Activity, Including in Patients with CNS Disease at Baseline 1L treatment-naïve, advanced NSCLC with EGFR PACC mutations Best % Change in Lesions 40 in Patients Receiving 80 mg Dose (n=10) 80 mg Preliminary Response As
Slide 37: Early Data in 1L EGFR PACC Patients Show Strong CNS Activity
Early Enozertinib Data in 1L EGFR PACC Patients Demonstrated Strong CNS Antitumor Activity 1L treatment-naïve, advanced NSCLC with EGFR PACC mutations Best % Change in CNS Lesions 80 mg 40 Preliminary CNS Response (1) in Patients Receiving 80 mg Dose (n=5) (n=5) ‡ 80 Best ORR, % 20 1 (20) Complete r
Slide 38: Partial Intracranial and Systemic Responses in Treatment-Naïve PACC Patient
Partial Intracranial and Systemic Responses in a Treatment-Naïve EGFR PACC Mutant NSCLC Patient with Active CNS Disease Patient: 67-year-old male PACC Mutation: G719A Prior Therapy: None CNS Metastases at Baseline: 1 target lesion Baseline BOR Timepoint (no prior radiation or surgery) Enozertinib Do
Slide 39: Executive Summary and Next Steps
Executive Summary and Next Steps
Slide 40: Phase 1b Data Establishes Potential Best-in-Class Profile
Enozertinib Phase 1b Data Establishes Potential Best-in-Class Profile in EGFR Exon 20 and PACC Mutated NSCLC Enozertinib Updated Phase 1b Data Highlights 2L EGFR Exon 20 Median 3L EGFR PACC 45% 36% ORR ORR Enozertinib Enozertinib Previously Treated 22% 40% Benchmark ORR Benchmark ORR 1L EGFR Exon 20
Slide 41: Establishes Potential Best-in-Class Profile in EGFR-Mutated NSCLC
Enozertinib Establishes Potential Best-in-Class Profile in EGFR-Mutated NSCLC Ø Systemic activity in 2L EGFR exon 20 and pretreated EGFR PACC exceeds competitor benchmarks Ø Highly competitive preliminary 1L systemic activity, with 67% ORR in EGFR exon 20 and 80% ORR in EGFR PACC Ø Convincing 1L CNS
Slide 42: ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer
ORIC Pharmaceuticals: Dedicated to Overcoming Resistance In Cancer • Potential best-in-class PRC2 inhibitor for prostate cancer Validated Targets in High Unmet Need Populations • Potential best-in-class TKI for NSCLC with EGFR exon 20 and EGFR PACC mutations • ORIC-944 and enozertinib are both rapid
Slide 43: Thank You
OrIC @ Thank You