CB-012 / Caribou Biosci - LARVOL DELTA

CLL-1-Targeted Allogeneic CAR-T Cells Exhibit High on-Target Specificity and Potent Cytotoxicity in Preclinical Models of Acute Myeloid Leukemia (ASH 2023) - "CB-012 demonstrated highly specific and potent CLL-1-targeted cytolytic activity in vitro and in vivo. Specificity of the anti-CLL-1 scFv was further demonstrated by screening in an unbiased protein-binding study and no adverse safety signals were observed in murine models. These data support advancing the development of CB-012 into a first-in-human clinical trial for patients with r/r AML."

CAR T-Cell Therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Transplant Rejection • B2M • HLA-E • PD-1 • PD-L1

AMpLify: CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Caribou Biosciences, Inc. | Trial completion date: Apr 2028 ➔ May 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2027 ➔ May 2025; Sponsor Decision - Pipeline Reprioritization

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

AMpLify: CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Caribou Biosciences, Inc. | Recruiting ➔ Active, not recruiting | N=70 ➔ 12

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Pipeline prioritization with workforce and cost reduction initiatives (GlobeNewswire) - "Caribou is also discontinuing the AMpLify Phase 1 clinical trial of CB-012 for relapsed or refractory acute myeloid leukemia (AML) as additional data would be needed to advance this program, taking time and resources that can be dedicated to CB-010 and CB-011. Patients treated in the AMpLify Phase 1 trial will continue to be followed as part of the company’s long-term follow up study."

Trial termination • Acute Myelogenous Leukemia

Caribou Biosciences Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update (GlobeNewswire) - "2025 anticipated milestones: (i) CB-010 ANTLER: Caribou plans to present data from both the additional 2L and prior CD19 relapsed LBCL patient cohorts in H1 2025. Caribou plans to initiate a pivotal Phase 3 clinical trial in H2 2025 should data confirm the initial observation that partial HLA matching drives outcomes that are on par with autologous CAR-T cell therapies. The Phase 3 trial would be initiated after agreement with the FDA on a pivotal trial design; (ii) CB-011 CaMMouflage: Caribou plans to present dose escalation data on a minimum of 15 patients at active dose levels from the ongoing CaMMouflage Phase 1 clinical trial in r/r MM in H1 2025; (iii) CB-012 AMpLify: Caribou plans to provide updates on dose escalation as the AMpLify Phase 1 clinical trial in r/r AML advances."

New P3 trial • P1 data • Acute Myelogenous Leukemia • Large B Cell Lymphoma • Multiple Myeloma

Caribou Biosciences Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "Anticipated milestones: (i) CB-011 CaMMouflage: Caribou plans to present dose escalation data from the ongoing CaMMouflage Phase 1 clinical trial in r/r MM in H1 2025; (i1) CB-012 AMpLify: Caribou plans to provide updates on dose escalation as the AMpLify Phase 1 clinical trial in r/r AML advances."

P1 data • Acute Myelogenous Leukemia • Multiple Myeloma

Caribou Biosciences Announces the FDA has Granted Fast Track Designations… (GlobeNewswire) - "Caribou Biosciences...today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designations to...CB-012 for relapsed or refractory acute myeloid leukemia (r/r AML)....'We are pleased to receive Fast Track designations from the FDA. This is a testament to the significant unmet need and the potential of...CB-012 as readily available, off-the-shelf CAR-T cell therapies,...'"

Fast track • Acute Myelogenous Leukemia

Caribou Biosciences Reports Second Quarter 2024 Financial Results and Provides Business Update (Caribou Bio Press Release) - "Anticipated milestones: CB-012 AMpLify: Caribou plans to provide updates on dose escalation as the AMpLify Phase 1 clinical trial in r/r AML advances."

Trial status • Acute Myelogenous Leukemia

A first-in-human phase 1, multicenter, open-label study of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy for adults with relapsed/refractory acute myeloid leukemia (AMpLify). (ASCO 2024) - P1 | "After receiving lymphodepletion therapy with cyclophosphamide (750 mg/m 2 /d) and fludarabine (30 mg/m 2 /d) administered concurrently for 3 days followed by a 2-day break, patients receive a single-dose infusion of CB-012 and are followed for safety and efficacy. The dose escalation portion of the study is actively enrolling patients. The AMpLify trial is registered at clinicaltrials.gov (NCT06128044)."

CAR T-Cell Therapy • Clinical • IO biomarker • P1 data • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Oncology • B2M • HLA-E • PD-1 • PD-L1

Caribou Biosciences to Present Initial Dose Expansion Data from CB-010 ANTLER Phase 1 Trial in r/r B-NHL at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Caribou Biosciences, Inc...announced two abstracts have been accepted for poster presentations at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, which will be held May 31-June 4, 2024 in Chicago, Illinois. The ANTLER poster will provide initial dose expansion data....The AMpLify poster will provide details on the clinical trial design and objectives."

Clinical protocol • P1 data • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Preclinical evaluation of CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, that exhibits specific and potent cytotoxicity in acute myeloid leukemia (AML) xenograft models (AACR 2024) - P1 | "CB-012, the first allogeneic anti-CLL-1 CAR-T cell therapy using both checkpoint disruption and immune cloaking armoring, demonstrated specific and potent CLL-1-targeted cytolytic activity in vitro and in vivo. Specificity of the anti-CLL-1 scFv was demonstrated in an unbiased protein-binding study and no adverse safety signals were observed from CB-012 in murine toxicology models. These preclinical studies supported the IND clearance of CB-012, which is being evaluated in the AMpLify trial, a Phase 1, first-in-human clinical trial for patients with r/r AML (NCT06128044)."

CAR T-Cell Therapy • Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PD-1

Caribou Biosciences Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Business Update (Caribou Bio Press Release) - "2024 anticipated milestones: (i) CB-010: In Q2 2024, Caribou plans to present initial dose expansion data, the recommended Phase 2 dose (RP2D), and emerging translational data from the ANTLER Phase 1 clinical trial; (ii) CB-011: Caribou plans to present initial dose escalation data from the CaMMouflage Phase 1 clinical trial by year-end 2024; (iii) CB-012: Caribou plans to provide updates on dose escalation as the AMpLify Phase 1 clinical trial in r/r AML advances."

P1 data • Acute Myelogenous Leukemia • Multiple Myeloma • Non-Hodgkin’s Lymphoma

AMpLify: CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=70 | Recruiting | Sponsor: Caribou Biosciences, Inc. | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Caribou Biosciences Appoints Tim Kelly as Chief Technology Officer and Highlights Multiple Clinical Catalysts Expected in 2024 (ET Healthworld) - P1 | N=50 | CaMMouflage (NCT05722418) | Sponsor: Caribou Biosciences, Inc. | "CB-011, an allogeneic anti-BMCA CAR-T cell therapy for multiple myeloma...CaMMouflage trial enrollment has concluded for dose level 1 (50x10⁶ CAR-T cells, N=3) and dose level 2 (150x10⁶ CAR-T cells, N=3) without any dose-limiting toxicities (DLTs), and the trial is enrolling patients at dose level 3 (450x10⁶ CAR-T cells)...The first clinical sites are active for the AMpLify Phase 1 trial for CB-012 in r/r AML with additional site activation underway....CB-011: Caribou plans to report initial dose escalation data by year-end 2024."

Enrollment status • P1 data • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

AMpLify: CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=70 | Not yet recruiting | Sponsor: Caribou Biosciences, Inc.

CAR T-Cell Therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

AMpLify: CRISPR-Edited Allogeneic Anti-CLL-1 CAR-T Cell Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=70 | Not yet recruiting | Sponsor: Caribou Biosciences, Inc.

CAR T-Cell Therapy • New P1 trial • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Caribou Biosciences Reports Third Quarter 2023 Financial Results and Provides Business Update (Caribou Bio Press Release) - "CB-010: Caribou plans to meet with the FDA to discuss a potential pivotal clinical trial in second-line LBCL patients and plans to share FDA feedback by year-end 2023. The Company also plans to report initial dose expansion data in second-line LBCL patients from the ongoing ANTLER trial in H1 2024; CB-011: Caribou plans to provide updates on dose escalation as the CaMMouflage Phase 1 clinical trial in r/r MM advances; CB-012: Caribou plans to initiate patient enrollment in the AMpLify Phase 1 clinical trial in r/r AML by mid-2024."

Enrollment status • FDA event • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Caribou Biosciences Announces FDA Clearance of IND Application for CB-012, an Allogeneic Anti-CLL-1 CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (GlobeNewswire) - "Caribou Biosciences, Inc...announced that it received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for CB-012, an allogeneic anti-C-type lectin-like molecule-1 (anti-CLL-1) CAR-T cell therapy. CB-012 will be evaluated in the multicenter, open-label, AMpLify Phase 1 clinical trial for patients with relapsed or refractory acute myeloid leukemia (r/r AML)....Caribou plans to initiate patient enrollment in the AMpLify trial to treat patients with a single administration of CB-012 at dose level 1 (25x106 CAR-T cells) by mid-2024."

IND • New P1 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Caribou Biosciences Reports Second Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "CB-010: Caribou plans to meet with the FDA to discuss a potential pivotal clinical trial in second-line LBCL patients and plans to share FDA feedback by YE 2023. The Company also plans to report initial dose expansion data in second-line LBCL patients from the ongoing ANTLER trial in H1 2024; CB-011: Caribou plans to provide updates on dose escalation as the CaMMouflage Phase 1 clinical trial in r/r MM advances; CB-012: Caribou plans to submit an IND application for r/r AML in H2 2023."

FDA event • IND • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy engineered with next-generation CRISPR technology to resist both the immunosuppressive tumor microenvironment and immune cell-mediated rejection, for patients with relapsed or refractory acute myeloid leukemia (AACR 2023) - "CLL-1 is a compelling therapeutic target as it is highly expressed on AML tumor cells and leukemic stem cells, but not expressed on hematopoietic stem cells. It has also been established as a target in human proof-of-concept studies. CB-012 demonstrated potent and specific CLL-1-targeted cytolytic activity, and the genome-editing strategy employed to manufacture and armor CB-012 conferred a functional advantage in the context of the potentially immunosuppressive tumor microenvironment associated with r/r AML."

Biomarker • CAR T-Cell Therapy • Clinical • Immune cell • IO biomarker • Tumor microenvironment • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • B2M • HLA-E • PD-1 • PD-L1

Caribou Biosciences Presents New Preclinical Data on CB-012, an Allogeneic Anti-CLL-1 CAR-T Cell Therapy, at the 2023 AACR Annual Meeting (Caribou Bio Press Release) - "Preclinical data presented at the AACR meeting show: CB-012 targets, becomes activated, proliferates, and demonstrates antitumor activity against a broad panel of AML cancer cell lines. Immune cloaking protects CB-012 from NK cell-mediated cytotoxicity. Mice harbouring AML xenograft models treated with CB-012 having a PD-1 KO showed extended survival relative to mice injected with control CAR-T cells that express PD-1 and that only contain 4 out of the 5 edits. CB-012 demonstrated significant antitumor efficacy and prolonged survival in AML xenograft models...'Preclinical studies supporting our planned IND submission for CB-012 in relapsed or refractory AML are advancing and we are on track to submit our IND to the FDA in the second half of this year'."

IND • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology

Caribou Biosciences Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Business Update (GlobeNewswire) - "CB-010: Caribou plans to provide an update from the ongoing ANTLER Phase 1 trial for CB-010 in H2 2023; CB-011: Caribou recently activated clinical sites for the recruitment of patients at dose level 1 and plans to provide an update on the clearance of dose levels as appropriate from the CaMMouflage Phase 1 trial for CB-011; CB-012: Caribou plans to submit an IND application for CB-012 in H2 2023."

IND • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Caribou Biosciences Reports Third Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "CB-020: Caribou expects to announce target selection for CB-020, an iPSC-derived CAR-NK cell therapy for solid tumors, in Q4 2022. Additionally, Caribou expects to disclose armoring strategies under development for its CAR-NK cell platform in Q4 2022; CB-012: Caribou expects to submit an IND application for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy for relapsed or refractory acute myeloid leukemia (r/r AML), in 2023."

Clinical • IND • Acute Myelogenous Leukemia • Hematological Malignancies • Oncology • Solid Tumor

Caribou Biosciences Reports Second Quarter 2022 Financial Results and Provides Business Update (GlobeNewswire) - "Anticipated Milestones for 2022 and Beyond: CB-020: Caribou expects to announce target selection for CB-020, an iPSC-derived CAR-NK cell therapy for solid tumors, in Q4 2022. Additionally, Caribou expects to disclose armoring strategies under development for its CAR-NK cell platform in Q4 2022; CB-012: Caribou expects to submit an IND application for CB-012, an anti-CLL-1 CAR-T cell therapy for r/r acute myeloid leukemia (AML), in 2023."

IND • Pipeline update • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Caribou Biosciences Reports First Quarter 2022 Financial Results and Provides Business Updates (Yahoo Finance) - "CB-010: Caribou is scheduled to share initial data from its ongoing ANTLER Phase 1 trial for CB-010, an anti-CD19 CAR-T cell therapy for r/r B- NHL, at EHA in June 2022; CB-011: Caribou expects to submit an IND application for CB-011, an anti-BCMA CAR-T cell therapy for r/r MM, in H2 2022; CB-020: Caribou expects to announce target selection for CB-020, an iPSC-derived CAR-NK cell therapy for solid tumors, in Q4 2022; CB-012: Caribou expects to submit an IND application for CB-012, an anti-CD371 CAR-T cell therapy for r/r AML, in 2023."

Clinical • IND • P1 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor