Armoring: checkpoint disruption
Target: CD19
Editing: PD-1 KO
Indication: r/r B-NHL
FDA Designations: Regenerative Medicine Advanced Therapy (RMAT)
Fast Track
Orphan Drug

Vispacabtagene regedleucel , vispa-cel (formerly CB-010), is our lead clinical-stage program and is an allogeneic anti-CD19 CAR-T cell therapy for the treatment of patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). Vispa-cel is the first allogeneic CAR-T cell therapy, to our knowledge, in a clinical trial with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. We use Cas9 chRDNA guides to make three edits to manufacture vispa-cel: 1) we knock out the TRAC gene to remove the T cell receptor, 2) we site-specifically insert an anti-CD19 CAR into the TRAC gene, and 3) we knock out PD-1.

Armoring: immune cloaking
Target: BCMA
Editing: B2M KO, B2M–HLA-E insertion
Indication: r/r MM
FDA DESIGNATIONS:
Regenerative Medicine
Advanced Therapy (RMAT)
Fast Track
Orphan Drug

CB-011 is our second clinical-stage program and is an allogeneic anti-BCMA CAR-T cell therapy for the treatment of patients with relapsed or refractory multiple myeloma (r/r MM). We use the Cas12a chRDNA genome-editing technology to make four edits in the manufacture of CB-011: 1) we knock out the TRAC gene to remove the T cell receptor; 2) we site-specifically insert a humanized anti-BCMA CAR into the TRAC gene; and 3) we site-specifically insert a gene encoding a B2M–HLA-E-peptide fusion into the B2M gene, 4) which knocks out the endogenous B2M gene. This method simultaneously eliminates endogenous HLA class I presentation on the surface of the CAR-T cells and expresses HLA-E, a minor HLA class I antigen, to blunt both T and NK cell-mediated rejection of the CAR-T cell therapy by the patient’s immune system.