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ESMO 2023 – Nectin-4 in focus

After Padcev stole the show at ESMO on Sunday the target of that Astellas/Seagen antibody-drug conjugate, Nectin-4, has come into focus. This makes yesterday’s disclosure by Kelun that Merck & Co wouldn't take forward two preclinical ADCs especially relevant, not because of their targets – they're undisclosed – but because Kelun separately revealed that the companies’ deal did include the clinical anti-Nectin-4 ADC currently coded SKB410. The targets of three Merck-partnered Kelun ADCs are now known, therefore: Nectin-4, TROP2 (sacitizumab tirumotecan) and Claudin18.2 (MK-1200). It’s possible that the two assets Merck has decided against clash with those it picked up from Daiichi on Friday. Yesterday also saw first-in-human data at ESMO on a Mabwell anti-Nectin-4 ADC, 9MW2821, which at 1.25mg/kg or more yielded a 33% confirmed ORR in various cancers. Urothelial cancer is of special interest, with 50% ORR at the target dose comparing favourably against the 41% generated by Padcev in the EV-301 trial. The discussant, Dr Ulrik Lassen of Rigshospitalet, Copenhagen, said Nectin-4 was a good target owing to its expression on some cancers and despite it not being an oncogenic driver, and said EV-302 data pointed to an obvious future combo of 9MW2821 with checkpoint blockade.

 

Phase 1 data on 9MW2821