Oric Pharmaceuticals, Inc. · NASDAQ:ORIC
Oric Pharmaceuticals — ESMO Asia 2025
19 slides from Oric Pharmaceuticals's conference presentation, Dec 6, 2025
Slide 1: Enozertinib (ORIC-114), a Highly Selective, Brain Penetrant EGFR and HER2 Inhibitor in EGFR Exon 20 Mutant NSCLC
Enozertinib (ORIC-114), a Highly Selective, Brain Penetrant EGFR and HER2 Inhibitor in EGFR Exon 20 Mutant NSCLC Thomas John1, Nisha Mohindra2, Min Hee Hong3, Ki Hyeong Lee4, Natasha Leighl5, Julia Rotow6, Laura Alder7, Rafald Dziadziuszko8, Matthew Krebs9, Joshua Sabari10, Alex Spira11, Chul Kim12,
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Tom John, MBBS, PhD, FRACP Honoraria/Advisory: • BMS, AstraZeneca, Amgen, Arrivent, Roche, Pfizer, Takeda, Boehringer Ingelheim, MSD, Merck, Puma, Specialised Therapeutics, Gilead, Seagen, Johnson and Johnson, Bayer, Beigene Travel/speaker fees • AstraZeneca, Beigene, Dizal
Slide 3: EGFR Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer (NSCLC)
Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations in Non-Small Cell Lung Cancer (NSCLC) • EGFR exon 20 insertion mutations (ex20ins) occur in 2.1% of NSCLC1 and account for 9% of all EGFR mutations2 ~30% of patients with EGFR-mutant NSCLC present with de novo C797S 2% • C797S 2% CN
Slide 4: Enozertinib Was Designed with Best-in-Class Drug Properties Including Brain Penetration
Enozertinib Was Designed with Best-in-Class Drug Properties Including Brain Penetration Enozertinib Demonstrates Superior in vitro Potency Across • Enozertinib is a selective, orally bioavailable, highly CNS- EGFR Mutants Compared with other EGFR Inhibitors1 penetrant, irreversible small molecule in
Slide 5: Enozertinib in Advanced NSCLC with or without CNS Involvement
Enozertinib in Advanced NSCLC with or without CNS Involvement Phase 1/2 Study Design (NCT05315700) • First-in-human, global study evaluating the safety and preliminary efficacy of enozertinib in patients with advanced NSCLC harboring EGFR or HER2 alterations 2L post-chemotherapy Enozertinib 1:1 Rand
Slide 6: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations 80 mg 120 mg Patient Characteristic (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 /
Slide 7: Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients
Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations 80 mg 120 mg 80 mg 120 mg Event, n (%) Event (n=24) (n=21) (n=24) (n=21) TRAEs Grade ≥3 10 (42) 7 (33) Preferred term, n (%) Grade 1-2 Grade 3 Grade 1-2 Grade 3 Dose reductio
Slide 8: Circulating Tumor DNA (ctDNA) Levels
Circulating Tumor DNA (ctDNA) Levels 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations Patients with Available ctDNA (n=25) Change From Baseline to C2D1 in EGFR Ex20ins ctDNA, % • ctDNA clearance rate of 69% (11/16) at 80 mg and 67% (6/9) at 120 mg Enozertinib achieved robust ctDNA re
Slide 9: Objective Response Rate (ORR)
Objective Response Rate (ORR) 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations Evaluable Population* 80 mg (n=20) 120 mg (n=15) Best ORR,† % [95% CI] 45 [23, 69] 20 [4, 48] Confirmed ORR, % [95% CI] 45 [23, 69] 13 [2, 41] Partial response, n (%) 9 (45) 2 (13) Stable disease, n (%) 11
Slide 10: Best Tumor Reduction
Best Tumor Reduction 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations 80 mg (n=20) 120 mg (n=15) Change From Baseline in Target Lesions, % Change From Baseline in Target Lesions, % 20 0 * * * * * -20 -40 -60 -80 -100 *Patients with brain metastases at study entry, including active br
Slide 11: Treatment Duration and Time of Responses
Treatment Duration and Time of Responses 2L post-chemotherapy, advanced NSCLC with EGFR ex20ins mutations 80 mg QD (n=20) 120 mg QD (n=15) • Responses generally occur by 4 weeks, but tumor regression continues over time, with late responses seen after 4+ months on treatment • Median follow-up of 43.
Slide 12: Patient Demographics and Baseline Characteristics
Patient Demographics and Baseline Characteristics 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations 80 mg 120 mg Patient Characteristic (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 /
Slide 13: Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients
Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations 80 mg 120 mg 80 mg 120 mg Event, n (%) Event (n=18) (n=15) (n=18) (n=15) TRAEs Grade ≥3 4 (22) 9 (60) Preferred term, n (%) Grade 1-2 Grade 3 Grade 1-2 Grade 3 Dose reduction d
Slide 14: Circulating Tumor DNA (ctDNA) Levels
Circulating Tumor DNA (ctDNA) Levels 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations Patients with Available ctDNA (n=14) Change From Baseline to C2D1 in EGFR Ex20ins ctDNA, % • ctDNA clearance rate of 71% (10/14) Enozertinib achieved robust ctDNA responses in 1L NSCLC patients with E
Slide 15: Objective Response Rate (ORR) and Best Tumor Reduction
Objective Response Rate (ORR) and Best Tumor Reduction 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations • Initial cohort of efficacy evaluable patients were treated at 120 mg; given 80% dose reduction rate, most patients effectively received 80 mg • Subsequent cohort of patients was tr
Slide 16: Treatment Duration and Time of Responses
Treatment Duration and Time of Responses 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations 120 mg QD (n=15) • Initial cohort of efficacy evaluable patients were treated at 120 mg; given 80% dose reduction rate, most patients effectively received 80 mg • Responses generally occur by 4 we
Slide 17: CNS Objective Response Rate (ORR) by BICR-RANO
CNS Objective Response Rate (ORR) by BICR-RANO 1L treatment-naïve, advanced NSCLC with EGFR ex20ins mutations Complete Intracranial Responses in 1L CNS Response† 120 mg (n=7)* Patient with Active Brain Metastases • 60-year-old female, no prior Best ORR,‡ % [95% CI] 71 [29, 96] therapy Confirmed ORR,
Slide 18: Conclusions
Conclusions • Enozertinib was generally well tolerated with mainly Grade 1 or 2 adverse events and no significant off-target toxicities; 80 mg cohort experienced lower rate of dose reductions compared to 120 mg cohort • Enozertinib demonstrated strong systemic and CNS antitumor activity in 1L and 2L
Slide 19: Acknowledgements
Acknowledgements • We thank the patients, families, caregivers, and investigators who participated in this study • This study was sponsored by ORIC Pharmaceuticals, Inc. • Editorial assistance was provided by ICON plc (Blue Bell, PA), and was funded by ORIC Pharmaceuticals, Inc. European Society for