Slide 1: Enozertinib (ORIC-114), a Highly Selective, Brain Penetrant EGFR and HER2 Inhibitor in Previously Treated NSCLC
Enozertinib (ORIC-114), a Highly Selective, Brain Penetrant EGFR and HER2 Inhibitor in Previously Treated NSCLC with EGFR Atypical Mutations Min Hee Hong1, Konstantinos Levantakos2, Eun-Kyung Cho3; Yu Jung Kim4, Adnan Khattak5, Omar Saavedra6, Sarah Goldberg7, Nisha Mohindra8, Danny Nguyen9, Julia R
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS Min Hee Hong, MD Honoraria • AstraZeneca, Amgen, Beigene, BMS, Daiichi Sankyo, Janssen, MSD, Ono pharmaceutical, Takeda, Roche, Yuhan Consulting or advisory role • AstraZeneca, BeOne Medicines, BMS, Daiichi Sankyo, Janssen, MSD, Ono pharmaceutical, Takeda, Roche, Yuhan Inves
Slide 3: EGFR Atypical Mutations in Non-Small Cell Lung Cancer (NSCLC)
Epidermal Growth Factor Receptor (EGFR) Atypical Mutations in Non-Small Cell Lung Cancer (NSCLC) • EGFR atypical mutations are a heterogenous group of non-classical C797S 2% mutations that comprise ~30% of all NSCLC EGFR mutations1 Other 9% • P-loop and αC-helix compressing (PACC) mutations comprise
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 in patients with NSCLC and EGFR atypical mutations (NCT05315700) • First-in-human, global study evaluating the safety and preliminary efficacy of enozertinib in patients with advanced NSCLC harboring 80 mg 120 mg Total EGF
Slide 6: Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients
Treatment-Related Adverse Events (TRAEs) in ≥20% of Patients Previously treated advanced NSCLC with EGFR atypical mutations 80 mg 120 mg Total 80 mg 120 mg Event, n (%) Event (n=25) (n=22) (n=47) (n=25) (n=22) TRAEs Grade ≥3 7 (28) 8 (36) 15 (32) Preferred term, n (%) Grade 1-2 Grade 3 Grade 1-2 Gra
Slide 7: Objective Response Rate (ORR) and Best Tumor Reduction
Objective Response Rate (ORR) and Best Tumor Reduction Previously treated advanced NSCLC with EGFR atypical mutations, PACC cohort Efficacy Evaluable Population* Effective Dose 80 mg (n=22)† Best % Change in Lesions in Patients Receiving 80 mg Effective Dose Best ORR,‡ % [95% CI] 36 [17, 59] (n=22)
Slide 8: Treatment Duration and Time of Responses
Treatment Duration and Time of Responses Previously treated advanced NSCLC with EGFR atypical mutations, PACC cohort Effective Dose 80 mg (n=22) £ £ * ** £ £ £ Effective Dose 80 mg QD ££ ** *** *** ** (n=22) ££ £ ££ CNS Disease at Baseline * Confirmed PR Start £ Treatment Ongoing 0 4 8 12 16 20 24 2
Slide 9: Conclusions
Conclusions • Enozertinib is a selective, CNS-penetrant, orally bioavailable EGFR inhibitor with best-in-class potency against EGFR atypical mutations • Enozertinib 80 mg dose was generally well tolerated; given high rate of dose reductions at 120 mg dose, most patients received an effective dose of
Slide 10: Acknowledgments
Acknowledgments • 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