Summit Therapeutics (SMMT) - 2025 Q3 - Earnings Call Presentation

HARMONi-6 Trial Results (Ivonescimab + Chemotherapy vs Tislelizumab + Chemotherapy in Advanced Squamous NSCLC) - Ivonescimab plus chemotherapy demonstrated a statistically significant improvement in Progression-Free Survival (PFS) compared to tislelizumab plus chemotherapy, with a Hazard Ratio (HR) of 0.60, representing a 4.2-month improvement in median PFS (mPFS)[19, 21] - The median PFS (mPFS) was 11.14 months in the ivonescimab plus chemotherapy arm compared to 6.90 months in the tislelizumab plus chemotherapy arm[21] - Subgroup analysis of PFS by IRRC showed that the PFS benefit favored ivonescimab plus chemotherapy across all key subgroups, including PD-L1 TPS <1% (HR=0.55) and PD-L1 TPS ≥1% (HR=0.66)[29, 31] - The Overall Response Rate (ORR) was higher in the ivonescimab plus chemotherapy arm (75.9%) compared to the tislelizumab plus chemotherapy arm (66.5%), with a p-value of 0.008[37, 38] - The median Duration of Response (mDoR) was 11.20 months in the ivonescimab plus chemotherapy arm compared to 8.38 months in the tislelizumab plus chemotherapy arm, with a p-value of 0.0219[41] - The safety profile of ivonescimab plus chemotherapy was manageable in squamous NSCLC, with Grade ≥ 3 Treatment-Related Adverse Events (TRAEs) occurring in 63.9% of patients in the ivonescimab arm and 54.3% in the tislelizumab arm[46, 47] AK112-206 Trial Results (Ivonescimab + Chemotherapy in Colorectal Cancer) - In the AK112-206 study, the investigator-assessed ORR for ivonescimab + FOLFOXIRI was 81.8% (95% CI: 59.7-94.8) and for ivonescimab + ligufalimab + FOLFOXIRI was 88.2% (63.6-98.5)[97] - The investigator-assessed Disease Control Rate (DCR) was 100% for both ivonescimab + FOLFOXIRI (95% CI: 84.6-100) and ivonescimab + ligufalimab + FOLFOXIRI (95% CI: 80.5-100)[97] - Treatment-emergent adverse events (TEAEs) with Grade ≥3 occurred in 68.2% of patients in the ivonescimab + FOLFOXIRI arm and 66.7% in the ivonescimab + ligufalimab + FOLFOXIRI arm[102] Ongoing and Planned Trials - HARMONi-3, a Phase 3 study of Ivonescimab + Chemo vs Pembrolizumab + Chemo in 1L Metastatic Non-Small Cell Lung Cancer (NSCLC), is ongoing globally with expected enrollment of 600 squamous and 1,000 non-squamous patients[59, 74, 77] - A Phase 3 study of Ivonescimab + Chemo vs Bevacizumab + Chemo in 1L Unresectable Metastatic Colorectal Cancer (CRC) is planned with an enrollment of 600 patients[81, 83]