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 pipelineProjectCompanyDescriptionTrial detailsKITE-222GileadAutologous CLL-1 Car-TPh1 completes Oct 2024GC509AstraZeneca (via Gracell)Autologous CLL-1/CD38 Car-TEarly ph1* completes Aug 2026CB-012CaribouAllogeneic CLL-1 Car-T1st pt dosed in ph1 AmplifyCLL1 CAR-NK cellQihan BiotechnologyAllogeneic CLL-1 Car iPSC NK cellsChina ph1* completes Aug 2026CD33/CLL1 CAR-NK cellQihan BiotechnologyAllogeneic CLL-1/CD33 Car iPSC NK cellsChina ph1* not yet recruitingBG-1805Guangzhou Bio-gene TechnologyCLL-1 Car-TChina ph1 not yet recruitingLB-LCAR-AMDRLegend BiotechAllogeneic CLL-1/CD33 Car-TPh1* terminated, no longer in pipelineCLL1/CD33 CARTGuangzhou Bio-gene TechnologyCLL-1/CD33 Car-TChina trial withdrawn owing to “change in strategy”Notes: all being evaluated in r/r AML; *investigator-sponsored trial. Source: OncologyPipeline.