After zolbetuximab investors look for a Claudin18.2 encore

The good news is that a drug targeting Claudin18.2, an area numerous companies have piled into in the past few years, is approvable. However, for the world’s first such approval to occur in Japan is somewhat unusual; that’s the fate of Astellas’s zolbetuximab, now branded Vyloy, which today got the nod from Japan’s MHLW as part of a chemo combo for Claudin18.2-positive gastric cancer. This came about because the drug’s US filing was hit by a January FDA complete response letter, which Astellas put down to deficiencies at a third-party manufacturer. The US filing is backed by the same Spotlight and Glow trials that support the Japan green light, so the hope is that once manufacturing problems are resolved US approval will be automatic. A major theme for investors now is how a follow-on Claudin18.2-targeting asset might improve on zolbetuximab, a naked antibody, and much attention has fallen on ADCs. Among these at least one company, Elevation Oncology, has ridden the zolbetuximab wave, seeing its stock climb sevenfold this year despite no specific updates on its project, EO-3021. Even limiting the competition to ADCs shows this to be a very crowded space, however. Clinical-stage Claudin18.2-targeting ADCsProjectCompanyADC payload/linkerStatusIBI343Innovent BiologicsTopo1 inhibitor, cleavable linkerPh3 in Claudin18.2+ve gastric cancerAZD0901/ CMG901AstraZeneca/ KeymedAuristatin, cleavable linkerPh2 in Claudin18.2+ve solid tumoursRC118RemeGenAuristatin, cleavable linkerPh1/2 in solid tumoursSHR-A1904Luzsana (Jiangsu HengRui)Topo1 inhibitor, cleavable linkerPh1/2 in solid tumoursMK-1200Merck & Co/ KelunTopo1 inhibitor, cleavable linkerPh1/2 in solid tumoursXNW27011Evopoint BiosciencesUnknownPh1/2 in solid tumoursSOT102Sotio/ NBE-TherapeuticsTopo2 inhibitor, non-cleavable linkerPh1/2 gastric cancer trial suspendedEO-3021/ SYSA1801Elevation Oncology/ CSPC PharmaceuticalAuristatin, cleavable linkerPh1 in solid tumours “likely to express” Claudin 18.2JS107Junshi BiosciencesAuristatin, cleavable linkerPh1 in solid tumoursTORL-2-307-ADCTorl BiotherapeuticsAuristatin, cleavable linkerPh1 in solid tumoursATG-022Antengene CorporationAuristatin, cleavable linkerPh1 in solid tumoursBA1301Boan BiotechAuristatin, unknown linkerPh1 in solid tumoursTQB2103Chia Tai Tianqing PharmaceuticalTopo1 inhibitor, cleavable linkerPh1 in solid tumoursTPX-4589Bristol Myers Squibb (ex Turning Point/ LaNova)Auristatin, cleavable linkerPh1 in Claudin18.2+ve solid tumours, but no longer in Bristol's pipelineNote: updated to reflect the status of TPX-4589. Source: OncologyPipeline.