Summit updated data from the global HARMONi trial, evaluating AK112 + chemo vs chemo alone in 2L 3rd-gen EGFR-TKI resistant NSCLC. PFS HR in the Western cohort was less favorable compared to Chinese patients, and Western OS HR at extended follow-up similarly trailed the Chinese subgroup. Investors are concerned about the translatability of AK112’s China data to the global market. However, we focus on the OS and believe the discrepancy in OS may be partially attributable to the shorter follow-up among Western patients, particularly those from Europe. Importantly, at a longer follow-up beyond the final OS analysis, a positive OS trend was observed. We also see strong OS results in the North America patient group. The 2L EGFRm setting represents <5% of AK112’s long-term sales potential, and we see the primary value of AK112 in first-line NSCLC. We anticipate the presentation of results from the China HARMONi-6 study at ESMO 2025, along with further OS updates from the China HARMONi-2 study within the next six months per Summit.
　　Chinese patients demonstrated more favorable PFS outcomes. In the
　　primary PFS analysis (n=345, median follow-up (mFU) of 22.3 months), AK112 + chemo achieved a mPFS of 6.8 months vs 4.4 months with chemo (HR=0.52, p<0.001). Given the intensifying competition in the EGFR-TKI resistant landscape-including emerging TROP2 ADCs, HER3 ADCs, etc. -the PFS benefit observed with AK112 may not offer a strong standalone competitive edge. At extended follow-up (mFU 29.7 months), the PFS HR modestly worsened from 0.52 to 0.57, likely due to increased data maturity in the Western subgroup, where the HR was 0.67 for patients from North America and Europe, compared to 0.55 for Chinese patients.
　　OS improved with longer follow-up. In the final OS analysis with mFU of 29.7 months (n=438; NA & EU mFU: 9.2 months, not yet mature), mOS was 16.8 months for the AK112+chemo arm versus 14.0 months for chemo alone, yielding an OS HR of 0.79 (0.62-1.01; p=0.0570). While this narrowly missed the pre-specified significance threshold of p=0.0448 required by the FDA for BLA submission, the OS trend was directionally positive. With an extended, non-pre-specified follow-up of 32.7 months (China cohort was locked and only Western patients continued follow-up to 13.7 months), median OS remained unchanged, while the OS HR improved to 0.78 (0.62- 0.98; nominal p=0.0332). Although the FDA may base its judgment primarily on the pre-specified analysis, we believe the maturing longer-term OS data will be critical to assess the outcomes for Western patients.
　　Strong OS results in the North America patients. During the longer
　　follow-up period, OS HR for Western patients was slightly less favorable than that of Chinese patients (0.84 vs 0.76), likely due to the shorter follow- up duration especially for the Europe patients. Summit also indicated that the patient number and follow-up duration for European participants were limited compared to North America. Notably, North American patients demonstrated encouraging results, with an OS HR of 0.70, despite wide confidence intervals of 0.38-1.30.
　　Maintain BUY. We believe the HARMONi trial demonstrated a favorable OS trend, which strengthens our confidence in the potential of first-line indications. We maintain DCF-based TP unchanged at HK$182.12 (WACC: 8.37%, terminal growth rate: 4.5%).