Ivonescimab (AK112) has demonstrated an OS benefit trend over pembrolizumab in monotherapy. In the head-to-head Ph3 HARMONi-2 study comparing Ivonescimab to pembrolizumab (Keytruda), Ivonescimab showed a notable efficacy advantage and was recently approved in China for first-line treatment of PD-L1 positive (TPS ≥1%) NSCLC. In the interim OS analysis conducted at 39% maturity, Ivonescimab achieved a hazard ratio (HR) of 0.777 versus pembrolizumab, reducing the risk of death by 22.3%. Although the interim analysis may not have reached statistical significance partly due to the very small alpha spending (0.0001), it suggests a favorable OS trend. Notably, the final OS analysis reserves a larger alpha (approximately 0.0207) with an HR threshold of 0.774, indicating a reasonable likelihood of achieving statistical significance in the final OS analysis.
Remain optimistic about Ivonescimab’s global commercialization potential. We believe Ivonescimab possesses strong potential for success in global markets. Summit is conducting the Ph3 HARMONi-7 study overseas, comparing Ivonescimab monotherapy with pembrolizumab in first-line NSCLC patients with PD-L1 TPS ≥50%. With a larger sample size (780 patients vs 398 in HARMONi-2), we believe HARMONi-7 has an even higher probability of demonstrating a statistically significant OS benefit. Domestically, Akeso’s Ph3 HARMONi-6 trial evaluating Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in first-line sq- NSCLC has shown strongly positive PFS results at the interim analysis, achieving statistical significance. Summit is also conducting the Ph3 HARMONi-3 trial overseas, evaluating Ivonescimab plus chemotherapy against pembrolizumab plus chemotherapy in a large patient population (1,080 patients) across both non-squamous and squamous NSCLC settings. Given the robust design and scale, we are optimistic about the trial’s primary OS endpoint. Furthermore, Summit’s Ph3 HARMONi trial targeting EGFR-TKI resistant NSCLC is expected to complete the interim data readout by mid-2025, which may provide data support for the drug’s first global BLA.
Maintain BUY. We are increasingly positive about the potential of Ivonescimab as a next-generation IO therapy. Following the inclusion of Ivonescimab and Cadonilimab in the NRDL earlier this year, we anticipate Akeso’s product sales to grow by 60% YoY to RMB3.3bn in FY25. Additionally, we expect Akeso to pursue NDRL inclusion for AK101, AK102, and new indications of AK104 (1L GC), and AK112 (1L PD-L1+ NSCLC) late this year. We raise our target price from HK$102.61 to HK$108.03 given Ivonescimab’s potential as the next-generation IO therapy (WACC: 9.17%, terminal growth rate: 3.0%).