Armoring: checkpoint disruption
Target: CD19
Editing: PD-1 KO
Indications: r/r B-NHL
FDA Designations: Regenerative Medicine Advanced Therapy (RMAT) Fast Track
Orphan Drug
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). CB-010 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 CB-010: 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. CB-010 is being evaluated in the ongoing, open-label, multicenter Phase 1 ANTLER clinical trial in adults with r/r B-NHL.
Armoring: immune cloaking
Target: BCMA
Editing: B2M KO, B2M–HLA-E insertion
Indications: r/r MM
FDA DESIGNATIONS:
Fast Track
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. CB-011 is being evaluated in the open-label, multicenter CaMMouflage Phase 1 clinical trial in adults with r/r MM.
Armoring: checkpoint disruption and immune cloaking
Target: CLL-1
Editing: PD-1 KO, B2M KO, B2M–HLA-E insertion
Indications: r/rAML
CB-012 is our third program and is an allogeneic anti-CLL-1 CAR-T cell therapy for the treatment of relapsed or refractory acute myeloid leukemia (r/r AML). CLL-1 (also known as 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 use the Cas12a chRDNA genome-editing technology to make five edits in the manufacture of CB-012: 1) we knock out the TRAC gene to remove the T cell receptor; 2) we site-specifically insert a human anti-CLL-1 CAR into the TRAC gene; 3) we knock out PD-1; and 4) we site-specifically insert a gene encoding a B2M–HLA-E-peptide fusion into the B2M gene, 5) which knocks out the endogenous B2M gene. Caribou plans to submit an Investigational New Drug (IND) application for CB-012 for r/r AML and is conducting IND-enabling studies.
* Phase 3 may not be required if Phase 2 is pivotal
Cell Type: iNK cell
Target: ROR1
Editing: armoring
Indications:solid tumors
CB-020 is the lead program from our CAR-NK platform and is in preclinical development for targeting ROR1+ solid tumors. ROR1 is a receptor tyrosine-kinase-like antigen expressed on a wide range of tumors including ovarian, lung, pancreatic, and triple negative breast cancer, and it drives tumor cell growth, survival, and metastasis. 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 pivotal
We have two ongoing, open-label, multicenter Phase 1 clinical trials in the United States.
Phase 1 ANTLER clinical trial for CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma
ANTLER clinical trial
Phase 1 CaMMouflage clinical trial for CB-011 in patients with relapsed or refractory multiple myeloma
CaMMouflage clinical trial
At Caribou, we are committed to developing transformative genome-edited allogeneic, or off-the-shelf, cell therapies, including chimeric antigen receptor T (CAR-T) cell therapies for hematologic malignancies and CAR-NK cell therapies for solid tumors. These investigational therapies have not yet been approved by regulatory authorities, such as the U.S. Food and Drug Administration (FDA). We are focused on conducting the clinical trials necessary to apply for regulatory approvals to make our allogeneic cell therapies broadly available to patients.
“Expanded access” refers to the use of an investigational therapy outside of a clinical trial for the potential treatment of a serious or immediately life-threatening condition. At this time, Caribou does not have active expanded access protocols nor does it currently provide access to its investigational therapies on an expanded access basis.
We believe the best way to develop therapies that may provide benefits for the largest number of patients is to conduct rigorous clinical development programs. Participation in one of our clinical trials is the best and preferred route to access these investigational products. Patients and physicians interested in Caribou’s investigational therapies are encouraged to learn more about the company’s ongoing clinical trials by visiting the clinical trials section of the Caribou website or clinicaltrials.gov and searching for Caribou Biosciences.
Physicians with questions about participating in one of Caribou’s clinical trials can submit a request to clinicaltrials@cariboubio.com.
Caribou will acknowledge receipt of requests and respond to inquiries within approximately 5 business days.
Caribou Biosciences periodically reviews its policies to ensure conformity with applicable laws and regulations and reserves the right to revise this position at any time.
