HUTCHMED (China) (HCM) Investor Update summary

Key clinical results and study design

• Savolitinib plus osimertinib significantly improved progression-free survival (PFS) versus chemotherapy in EGFR mutant NSCLC with MET amplification, meeting the primary endpoint.

• Median PFS was 9.8 months (savo + osi) vs 5.4 months (chemo) in first/second-generation EGFR TKI-resistant patients, and 6.9 vs 3.0 months in third-generation TKI-resistant patients, with hazard ratios of 0.34 and 0.32, respectively.

• Objective response rate was 58-60% for the combination versus 34% for chemotherapy; disease control rate was 89% vs 67%.

• Median duration of response was 8.4 months for the combination compared to 3.2 months for chemotherapy.

• PFS benefit was consistent across all predefined subgroups, including those with brain metastases.

Comparative analysis and biomarker testing

• SHI study used FISH for MET amplification detection, identifying a higher proportion of patients (30-35%) compared to ctDNA-based NGS (14%) in MARIPOSA-2.

• FISH remains the most reliable method for MET amplification detection; companion diagnostic kits are mature and widely used in China.

• Clinical benefit for savolitinib plus osimertinib was numerically greater in SHI than in MARIPOSA-2, with consistent chemo comparator PFS across studies.

• Future studies like SAFFRON will use both FISH and IHC for patient selection, expanding the eligible population.

CNS activity and clinical implications

• Savolitinib plus osimertinib demonstrated strong CNS activity, with median PFS of 8.3 months in patients with brain metastases.

• No new CNS lesions were observed in the combination group among patients with PFS events, indicating robust CNS disease control.

• Standard chemotherapy offers limited CNS coverage, highlighting the importance of the combination's CNS efficacy.

• Disease control in CNS patients is a key clinical advantage, as brain metastases are a major cause of mortality.