Akeso - Ivonescimab PDUFA preview - limited expectations, with more upside on approval

Ahead of the Nov 14 PDUFA for ivonescimab in 2L EGFRmut NSCLC, J.P. Morgan believes investor expectations are quite limited and sees a roughly 60% chance of FDA approval, supported by the improving OS trend in Western patients in HARMONi, longer follow-up suggesting improved OS benefit, and FDA precedents for approval on significant PFS despite OS not meeting significance (belzutifan in LITESSPARK-005, pembrolizumab in KEYNOTE-177). HARMONi's PFS HR of 0.52 is numerically stronger than the 0.75 and 0.60 seen in those trials. The July HARMONi post-hoc update showed Western population OS now in line with ITT (HR 0.76), addressing concerns that OS benefit was skewed toward Asian patients, though the analysis was outside the original statistical plan and does not change the primary OS result of HR 0.79, p=0.057. Scenario analysis points to 10-15% upside on approval versus 5-10% downside on a CRL. Beyond the PDUFA, the HARMONi-3 squamous-cohort final PFS readout matters more for the longer-