Next-generation allogeneic therapeutic product candidates


Redefining CAR-T cell therapies with enhanced persistence

CB-010

     

Cell Type: T cell
Target: CD19
Editing: CAR into TRAC
armoring: PD-1 KO
Indications: relapsed/refractory B cell non-Hodgkin lymphoma

Our most developed product candidate is CB-010, an allogeneic anti-CD19 CAR-T cell therapy. We use Cas9 chRDNA guides to make three edits to manufacture CB-010: 1) we site-specifically insert the CD19-specific CAR into the T cell genome, 2) we knock out the TRAC gene to remove the T cell receptor, and 3) we knock out the gene encoding PD-1. The goal of the PD-1 knockout is to boost the persistence of CAR-T cell antitumor activity, which we believe has the potential to reduce CB-010 exhaustion and potentially confer a better therapeutic index compared to other allogeneic CAR-T cells. CB-010 is the first allogeneic CAR-T cell therapy with a PD-1 knockout in clinical studies, and it is being evaluated in the ongoing, open-label, multicenter Phase 1 ANTLER clinical trial in the United States in adults with relapsed or refractory B cell non-Hodgkin lymphoma. 

CB-011

     

Cell Type: T cell
Target: BCMA
Editing: CAR into TRAC
armoring: B2M KO, B2M-HLA-E insertion
Indications: R/R MM

CB-011 is an allogeneic anti-BCMA CAR-T cell therapy for the treatment of relapsed or refractory multiple myeloma (MM). It is the first allogeneic CAR-T cell therapy immune-cloaked to prevent both T- and NK-mediated immune rejection. Our immune cloaking strategy is expected to drive CAR-T cell persistence, enabling more durable antitumor activity. We use Cas12a chRDNA guides to make four edits in the manufacture of CB-011: 1) we site-specifically insert a proprietary new humanized anti-BCMA CAR into the T cell genome, 2) we knock out the TRAC gene to remove the T cell receptor, 3) we site-specifically insert a gene encoding a B2M—HLA-E—peptide fusion into the T cell genome, and 4) we knock 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-mediated rejection of the CAR-T cell therapy by the patient’s immune system.

CB-012

     

Cell Type: T cell
Target: CD371
Editing: armoring
Indications: R/R AML

CB-012 is an allogeneic anti-CD371 CAR-T cell therapy for the treatment of relapsed or refractory acute myeloid leukemia (AML). CD371 is expressed on the surface of AML tumor cells and leukemic stem cells, but it is not expressed on normal hematopoietic stem cells, which makes it a compelling target for the treatment of AML. We are applying our genome editing expertise to armor the CB-012 CAR-T product in order to drive persistence and seek maximum patient benefit.

* Phase 3 may not be required if phase 2 is registrational.

Sophisticated, iPSC-derived CAR-NK cell therapies for solid tumors

CB-020

     

Cell Type: iNK cell
Target: undisclosed
Editing: armoring
Indications:solid tumors

We believe that edited iNKs, including CAR-iNKs, hold significant potential for treating a variety of solid tumors. We have successfully demonstrated the ability to edit the genome of induced pluripotent stem cells (iPSCs) at multiple loci and we have developed a robust differentiation protocol to derive iNKs from iPSCs, providing an optimal system for generating multiplex-edited iNKs that have the potential to address the fundamental challenges facing immune cell therapies in the immunosuppressive tumor microenvironment.

* Phase 3 may not be required if phase 2 is registrational.

pipeline lab image


Clinical Trials

We have an ongoing, open-label, multicenter Phase 1 clinical trial (ANTLER) in the United States to evaluate CB-010 in adults with relapsed or refractory B cell non-Hodgkin lymphoma.