Crispr finally gets its CAR into the clinic

Over 18 months after first touting its allogeneic CAR-T approach, Crispr Therapeutics has started a clinical trial of its wholly owned candidate CTX110. The company joins Allogene, Cellectis, Celyad and Poseida in the off-the-shelf CAR-T therapy race, but Crispr believes its project to have an advantage over other assets. Crucially, according to the company, Crispr/Cas9 editing allows insertion of the CAR construct into a precise location. In the same step, this could disrupt endogenous T-cell receptors, preventing graft-versus-host disease, and also hit the cell’s major histocompatibility complex to prevent the CAR-T cells being destroyed by an immune response. CTX110, previously known as CTX101, is not the first Crispr/Cas9 engineered CAR-T contender to enter the clinic – that honour went to Tmunity’s autologous NY-ESO-directed T cells. There are a couple of other clinical-stage Crispr/Cas9-based projects, including Allergan and Editas’s AGN-151587, which began human trials last week in Leber congenital amaurosis 10, an inherited form of blindness. Editas has taken even longer to get its candidate into the clinic; having initially hoped to file an IND by the end of 2017. Editas also has an interest in CAR-T via a 2015 deal with Juno – now Celgene – but things have gone quiet here.

Western trials of Crispr approaches
Project Companies Description Indication(s) Trial details
NY-ESO-1 redirected T cells Tmunity Autologous, ex vivo edited NY-ESO-targeting CAR-T therapy Multiple myeloma, sarcoma, melanoma NCT03399448
CTX001 Crispr Therapeutics/Vertex Autologous, ex vivo edited haematopoietic stem cell therapy Beta thalassaemia, sickle cell disease NCT03655678, NCT03745287
AGN-151587/EDIT-101 Allergan/Editas In vivo Crispr-based therapy Leber congenital amaurosis 10 Brilliance, NCT03872479
CTX110 Crispr Therapeutics Allogeneic, ex vivo edited CD19-targeting CAR-T therapy B-cell malignancies NCT04035434
Source: & company releases.

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