Caribou joins Gilead and Astra in CLL-1

While Car-T work continues to be clustered around a few popular targets like CD19 and BCMA, some different mechanisms are emerging, as highlighted by Caribou yesterday. The group said during its fourth-quarter results that it dosed the first patient with its CLL-1-targeting allogeneic Car-T CB-012, in the phase 1 Amplify study in relapsed/refractory acute myeloid leukaemia (AML). Caribou is following in the footsteps of Gilead and Gracell (now part of AstraZeneca), which already have similarly acting, albeit autologous, projects in the clinic. CLL-1 emerged as a potential target in AML as it is highly expressed in leukaemic cells while being absent in normal hematopoietic stem cells. Still, Gilead’s KITE-222, gained via the acquisition of Kite Pharma, has progressed slowly, with no data yet available from a phase 1 trial listed on clinicaltrials.gov in 2021. And the fate of Gracell’s dual CLL-1 x CD38 Car-T project GC509 looks uncertain: the main focus of the Astra takeout was the BCMA x CD19 Car-T GC012F. Meanwhile, Caribou has exited the hot area of ROR1 inhibition, which has recently seen new entrants, stopping development of CB-020, a preclinical-stage anti-ROR1 allogeneic CAR-NK contender, citing "portfolio prioritisation". 

Anti-CLL-1 clinical-stage pipeline

Notes: all being evaluated in r/r AML; *investigator-sponsored trial. Source: OncologyPipeline.