Slide 1: FURTHER (FURMO-002): Firmonertinib at Two Dose Levels in TKI-Naïve NSCLC with EGFR PACC Mutations
FURTHER (FURMO-002): A Global, Randomized Study of Firmonertinib at Two Dose Levels in TKI- Naïve, Advanced NSCLC with EGFR PACC Mutations Xiuning Le1, Yan Yu2, Yanqiu Zhao3, David Planchard4, Ying Cheng5, Xingya Li6, Shirish Gadgeel7, Junqiang Zhang8, Alexander Spira9, Hidetoshi Hayashi10, Jonathan
Slide 2: Background: EGFR PACC Mutations
Background: EGFR PACC Mutations PACC (incl. compound) • EGFR P-loop and ⍺C-helix compressing (PACC) 12.5% mutations accounts for ∼12.5% of all EGFR Exon 20 insertions mutations1,2 located primarily in exons 18-20 9.1% Other uncommon • PACC mutations are similar to Exon 20 insertion (incl. L861Q) mut
Slide 3: Background: Firmonertinib
Background: Firmonertinib • Firmonertinib (previously known as furmonertinib) is an oral, highly CNS-penetrant EGFR inhibitor with broad activity and selectivity across EGFR mutations. • Firmonertinib was approved in China for first-line, advanced NSCLC with EGFR Ex19del/L858R in June 2022 and previ
Slide 4: Preclinically Firmonertinib and its Major Metabolite are Active Against EGFR PACC Mutations
Preclinically Firmonertinib and its Major Metabolite (AST5902) are Active Against EGFR PACC Mutations • 2D molecular model of firmonertinib bound to EGFR G719S (PACC) mutant • IC50 analysis performed with engineered Ba/F3 cell lines and A431 (EGFR • Green dotted outline indicates the proximity WT) c
Slide 5: PACC Cohort in FURTHER Trial with Two Dose Levels (NCT05364073)
PACC Cohort in FURTHER Trial with Two Dose Levels (NCT05364073) Stage 2 Cohort 4 Dose Expansion (PACC Cohort) Primary endpoints: Firmonertinib Overall Response Rate Key Eligibility Criteria: 160 mg QD • Locally advanced or metastatic ORR (by BICR) • Tumor assessments every 6 weeks NSCLC with EGFR PA
Slide 6: PACC Cohort - Demographics and Disease Characteristics
PACC Cohort - Demographics and Disease Characteristics All PACC Patients 1L PACC Patients 160 mg QD 240 mg QD 160 mg QD 240 mg QD N=31 N=29 N=25 N=22 Age (years), median (range) 65.0 (48-86) 68.0 (50-83) 67 (48-86) 67.5 (50-83) Male / Female, % 32.3 / 67.7 34.5 / 65.5 40.0 / 60.0 36.4 / 63.6 ECOG 0
Slide 7: Primary Endpoint ORR (BICR) in 1L PACC NSCLC
Primary Endpoint ORR (BICR) in 1L PACC NSCLC BICR1 INV1 160 mg QD 240 mg QD 160 mg QD 240 mg QD N=23 N= 22 N=25 N=22 Best ORR, % (95% CI)2 47.8 (26.8-69.4) 81.8 (59.7-94.8) 52.0 (31.3 - 72.2) 81.8 (59.7 - 94.8) Confirmed ORR, % (95% CI) 34.8 (16.4 - 57.3) 63.6 (40.7 - 82.8) 52.0 (31.3 - 72.2) 68.2 (
Slide 8: Best Tumor Reduction 1L PACC NSCLC (BICR)
Best Tumor Reduction 1L PACC NSCLC (BICR) 160 mg 240 mg • Confirmed PRs observed in a wide range of EGFR PACC Best Percent Change of SLD from Baseline (%) mutations including: o Responses in more frequent EGFR PACC mutations (G719X or S768I) as well as less frequent mutations (E709X and V774M) o Res
Slide 9: Treatment Duration and Time of Responses by BICR in 1L Patients
Treatment Duration and Time of Responses by BICR in 1L Patients • Responses seen at first tumor 160 mg assessment in the majority of patients • Median follow-up for DoR 4.2 months • Median DoR has not been reached • 90.9% (n=20 of 22) of responders are still on 240 mg treatment • PFS and OS data imm
Slide 10: Confirmed CNS ORR in Response Evaluable CNS Population
Confirmed CNS ORR in Response Evaluable CNS Population 1L patient with no prior CNS radiotherapy 160 mg 240 mg 1L Only Treated with firmonertinib 160 mg QD N=9* N=7* (N=13) 55.6 42.9 46.2 Confirmed ORR, % (95% CI) (21.2 - 86.3) (9.9 - 81.6) (19.2 – 74.9) Best Overall Response, n (%) Complete respons
Slide 11: FURTHER: PACC Cohort Safety and Tolerability Profile
FURTHER: PACC Cohort Safety and Tolerability Profile TRAE of Clinical Interest1 PACC Cohort All patients in PACC Cohort - 160 mg PACC Cohort - 240 mg FURTHER (N=31) (N=29) 160 mg 240 mg 160 mg 240 mg Overview of TRAEs (n, %) (N=31) (N=29) (N=42) (N= 116) TRAEs any grade 26 (83.9) 25 (86.2) 34 (81.0)
Slide 12: Conclusions
Conclusions • Firmonertinib showed promising antitumor activity in a broad range of EGFR PACC mutant NSCLC. o Firmonertinib 240 mg QD showed confirmed ORR 63.6%, best ORR 81.8%, and DCR 100% by BICR. o Firmonertinib had encouraging CNS antitumor activity in EGFR PACC mutant NSCLC. • Firmonertinib sh
Slide 13: Acknowledgments
Acknowledgments • We thank the patients and their families for participation in the FURTHER study. • We thank our global site investigators and their teams for Canada UK Netherlands conducting the FURTHER study. France Japan USA China • This study was sponsored by Spain ArriVent BioPharma, Inc., and