Caribou Biosciences, Inc. (Caribou or Caribou Biosciences) operates as a clinical-stage Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome-editing biopharmaceutical company. The company is dedicated to developing transformative therapies for patients with devastating diseases.
The company’s genome-editing platform, including its novel chRDNA (CRISPR hybrid RNA-DNA, or chRDNA, pronounced chardonnay) technology, enables more precise genome editing of allogeneic cell therapi...
Caribou Biosciences, Inc. (Caribou or Caribou Biosciences) operates as a clinical-stage Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) genome-editing biopharmaceutical company. The company is dedicated to developing transformative therapies for patients with devastating diseases.
The company’s genome-editing platform, including its novel chRDNA (CRISPR hybrid RNA-DNA, or chRDNA, pronounced chardonnay) technology, enables more precise genome editing of allogeneic cell therapies.
The company’s allogeneic chimeric antigen receptor (CAR) -T (CAR-T) cell therapy product candidates are manufactured in advance with cells from healthy donors, with the goal of enabling broad patient access, rapid patient treatment, and increased manufacturing scale. The company’s allogeneic CAR-T cell therapy product candidates in clinical development are directed at established cell surface targets against which autologous CAR-T cell therapeutics have already demonstrated clinical proof of concept, including CD19 and B cell maturation antigen (BCMA), as well as targets, such as C-type lectin-like molecule-1 (CLL-1). The company uses its chRDNA technologies to armor its cell therapies through multiple genome-editing strategies, such as checkpoint disruption, immune cloaking, or a combination of these two strategies, to enhance activity against devastating diseases.
The company is advancing its pipeline of allogeneic CAR-T cell therapies with the following four clinical development programs targeting the treatment of hematologic malignancies and autoimmune diseases:
CB-010: An allogeneic anti-CD19 CAR-T cell therapy, being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in its ANTLER phase 1 clinical trial
CB-010: Also being evaluated in patients with lupus nephritis (LN) and in patients with extrarenal lupus (ERL) in the company’s GALLOP phase 1 clinical trial
CB-011: An allogeneic anti-BCMA CAR-T cell therapy, being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in its CaMMouflage phase 1 clinical trial
CB-012: An allogeneic anti-CLL-1 CAR-T cell therapy, being evaluated in patients with relapsed or refractory acute myeloid leukemia (r/r AML) in its AMpLify phase 1 clinical trial
CB-010 has received regenerative medicine advanced therapy (RMAT) designation for relapsed or refractory large B cell lymphoma (r/r LBCL) as well as fast track designations for r/r B-NHL and refractory systemic lupus erythematosus (SLE) from the U.S. Food and Drug Administration (FDA); CB-011 has received fast track designation for r/r MM from the FDA; and CB-012 has received fast track designation for r/r AML from the FDA.
CRISPR chRDNA Genome-Editing Technologies
Genome-editing technologies used to date have limited efficiency, specificity, and versatility for performing the multiple, precise genomic edits necessary for allogeneic CAR-T cell therapy manufacturing. The company's CRISPR chRDNA genome-editing technologies are designed to address these limitations and enable it to apply armoring strategies to enhance allogeneic CAR-T cell therapy activity against diseases.
Using its chRDNA genome-editing technologies, the company has successfully demonstrated multiplex genome editing while maintaining genomic integrity. The company's allogeneic CAR-T cell therapy product candidates incorporate increasing numbers of genome edits.
Enhancing the activity of allogeneic cell therapies for potentially durable activity: The company's chRDNA technologies enable it to apply tailored armoring strategies to its allogeneic CAR-T cells, including checkpoint disruption, through the knockout of programmed cell death protein 1 (PD-1) to sustain the activity of CAR-T cells by disrupting a pathway that leads to CAR-T cell exhaustion; immune cloaking of CAR-T cells to reduce rejection by the patient’s immune system; and a combination of these two strategies.
Improving the genomic integrity of its products: The company has observed that its cell therapy product candidates have significantly lower levels of off-target edits compared to those made using first-generation CRISPR-Cas9 genome editing, and it believes it can make multiple edits while maintaining genomic integrity.
Pipeline
The company focuses on the development of its pipeline of allogeneic CAR-T cell therapies. It is advancing four clinical-stage programs from its allogeneic CAR-T cell therapy platform targeting the treatment of hematologic malignancies and autoimmune diseases.
Programs
CB-010 is an anti-CD19 allogeneic CAR-T cell therapy product candidate that is being evaluated in patients with r/r B-NHL in the company’s ANTLER phase 1 clinical trial and in patients with LN and ERL in the company’s GALLOP phase 1 clinical trial. To its knowledge, CB-010 is the first clinical-stage allogeneic anti-CD19 CAR-T cell therapy with a genome-edited knockout of the PDCD1 gene to prevent PD-1 expression on the CAR-T cell surface.
In the dose escalation portion of its ANTLER Phase 1 clinical trial, the company enrolled 16 patients with multiple subtypes of aggressive r/r B-NHL and evaluated three dose levels of CB-010: dose level 1 (40 x 10^6 viable CAR-T cells), dose level 2 (80 x 10^6 viable CAR-T cells), and dose level 3 (120 x 10^6 viable CAR-T cells). Patients received a lymphodepletion regimen that included two chemotherapy agents, cyclophosphamide and fludarabine, which are generally used for lymphodepletion prior to autologous CAR-T cell therapy. To ensure optimal engraftment of the allogeneic CB-010 cells, the company used a deeper regimen of these chemotherapeutic agents, specifically, cyclophosphamide at 60 mg/kg/day for two days, followed by fludarabine at 25 mg/m²/day for five days, than is used with the commercially available autologous CAR-T cell therapies.
The company has expanded its clinical development of CB-010 to include autoimmune diseases. CB-010 holds the potential for deep depletion of disease-causing B cells, which could reset the immune system, leading to sustained drug-free remission. In its ANTLER Phase 1 clinical trial, following a single dose of CB-010, the depletion and recovery of patients’ B cells is on par with the duration of B cell aplasia reported in a recent case series in the literature. The company has initiated its multicenter, open-label GALLOP Phase 1 clinical trial to evaluate a single infusion of CB-010 at the RP2D for oncology (80 x 10^6 viable CAR-T cells), but with a different lymphodepletion regimen, also incorporating partial HLA matching, in adult patients with LN and ERL.
CB-011 is an anti-BCMA allogeneic CAR-T cell therapy product candidate that is being evaluated in patients with r/r MM in the company's CaMMouflage Phase 1 clinical trial. To its knowledge, CB-011 is the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach that includes both the removal of the endogenous beta-2 microglobulin (B2M) protein and the insertion of a beta-2-microglobulin–human-leukocyte-antigen-E–peptide transgene (B2M–HLA-E). This immune cloaking armoring strategy results in no endogenous class I HLA alleles expressed on the CAR-T cell surface. This reduces the number of potential mismatched HLA alleles from 12 to six, resulting in a reduced risk of rapid immunologic clearing of the CAR-T cells by the patient.
In the dose escalation portion of its CaMMouflage Phase 1 clinical trial, dose level 1 (50 x 10^6 viable CAR-T cells), dose level 2 (150 x 10^6 viable CAR-T cells), dose level 3 (450 x 10^6 viable CAR-T cells), and dose level 4 (800 x 10^6 viable CAR-T cells) of CB-011 have cleared without any observed dose-limiting toxicities (DLTs). The company has implemented a deeper lymphodepletion regimen that includes an increased dose of cyclophosphamide (up from the original 300 mg/m²/day to 500 mg/m²/day, together with the same fludarabine dose of 30 mg/m²/day for three days). Dose level 3 (450 x 10^6 viable CAR-T cells) and dose level 4 (800 x 10^6 viable CAR-T cells) with the deeper lymphodepletion have cleared with no DLTs observed. The company is enrolling additional patients at multiple dose levels with the deeper lymphodepletion regimen in order to further define safety and efficacy and to determine a RP2D.
CB-012 is an allogeneic anti-CLL-1 CAR-T cell therapy product candidate that is being evaluated in patients with r/r AML in the company's AMpLify Phase 1 clinical trial. To its knowledge, CB-012 is the first allogeneic CAR-T cell therapy armored with both checkpoint disruption and immune cloaking strategies. Patients in the AMpLify Phase 1 clinical trial receive a lymphodepletion regimen prior to CAR-T cell infusion. The lymphodepletion regimen includes two chemotherapy agents, cyclophosphamide (750 mg/m²/day) and fludarabine (30 mg/m²/day) for three days. Patients then have two days of rest, followed by a single CB-012 dose on day zero. In the dose escalation portion of the AMpLify Phase 1 clinical trial, dose level 1 (25 x 10^6 viable CAR-T cells), dose level 2 (75 x 10^6 viable CAR-T cells), and dose level 3 (150 x 10^6 viable CAR-T cells) of CB-012 have cleared without any observed DLTs, and the company is enrolling patients at dose level 4 (300 x 10^6 viable CAR-T cells).
In July 2024, the company announced that it had discontinued preclinical research activities associated with its allogeneic CAR-natural killer (NK) cell therapy platform to focus resources on its allogeneic CAR-T cell therapy platform and to advance its four clinical programs for oncology and autoimmune diseases.
In addition to its CAR-T cell therapy programs, the company is developing in vivo genome-editing capabilities. Cas12a chRDNA guides may offer improved specificity compared to all-RNA guides for in vivo genome-editing applications. The company is using Cas12a chRDNA guides to optimize the Cas12a mRNA sequence and refine its lipid nanoparticle formulations, with the goal of demonstrating functional gene disruptions in animal models. Its initial research is in non-humanized mouse models to demonstrate genome-editing and gene correction capabilities. In the future, the company aims to take a human sequence target and perform disease-specific edits, demonstrating highly efficient editing across multiple clinically relevant targets to highlight the broad therapeutic potential of this platform.
Strategy
Key components of the company’s strategy include applying its chRDNA genome-editing technology to engineer allogeneic cell therapies from its CAR-T cell platform that have the potential for durable activity against multiple diseases’; developing allogeneic CAR-T cell therapies against clinically validated targets to derisk its clinical programs; developing allogeneic CAR-T cell therapies against additional targets for diseases with limited treatment options; and pursuing select applications of its technology and indications on the company’s own and through strategic collaborations.
CRISPR chRDNA Technologies
The company deploys a new, next-generation CRISPR genome-editing platform, its novel chRDNA technologies, which use hybrid guides containing both RNA and DNA for editing genomic DNA to engineer its allogeneic CAR-T cell therapies. The presence of DNA in a chRDNA guide significantly improves editing specificity relative to an all-RNA guide. The addition of DNA into the guide increases fidelity by reducing the binding of the guide to the target sequence, thereby resulting in even less binding of the chRDNA guide to non-target sequences that may be similar to, but different from, the intended target sequence. The company's chRDNA technologies utilize the canonical Streptococcus pyogenes Cas9 protein or the Acidaminococcus sp. Cas12a protein, along with a guide composed of a mixture of RNA and DNA nucleotides in both the region that interacts with the chromosomal target DNA and in the region that does not interact with the target DNA. Like Cas9, Cas12a is a Cas protein used to edit genomic DNA site-specifically.
Genome-Editing Strategies for Allogeneic CAR-T Cell Therapies
CAR-T cells will generally proliferate in response to antigen engagement via the specificity of their respective CAR. However, allogeneic CAR-T cells are rapidly rejected by a patient’s immune system due to their divergent donor-derived genetic profile and cell surface HLA presentation.
Clinical Programs
The company is advancing four clinical programs from its pipeline of allogeneic CAR-T cell therapies focused on the treatment of hematologic malignancies and autoimmune diseases.
CB-010
CB-010 is an allogeneic CAR-T cell therapy targeting CD19-positive hematologic malignancies and autoimmune diseases. CB-010 is being evaluated in the company’s ongoing first-in-human, open-label, multicenter ANTLER phase 1 clinical trial (NCT04637763) in the United States, Australia, and Israel in adults with r/r B-NHL as well as in its open-label, multicenter GALLOP phase 1 clinical trial (NCT06752876) in the United States in adults with LN and ERL.
To its knowledge, the company's CB-010 product candidate is the first allogeneic CAR-T cell therapy in a clinical trial with a PD-1 knockout, and it believes the PD-1 knockout enhances the potential for durable activity of an allogeneic CAR-T cell therapy. Other CAR-T cell therapies that express endogenous PD-1 could become rapidly exhausted and lose activity due to the interaction between PD-1 and its ligand PD-L1. PD-1/PD-L1 engagement leads to rapid exhaustion in T cells, which occurs when a T cell expressing PD-1 interacts with another cell expressing PD-L1. B cell tumors and the patient’s own cells express PD-L1, leading to interaction with PD-1 and subsequent exhaustion of the CAR-T cells. The company prevents PD-1 expression on the CB-010 CAR-T cells, thereby disrupting PD-1/PD-L1-mediated exhaustion. More than half of B-NHL tumors express PD-L1, correlating with poorer outcomes.
Target Indications
The company is developing CB-010 for the treatment of r/r B-NHL, with a focus on 2L LBCL, as well as for the treatment of LN and ERL.
Overall, for aggressive r/r B-NHL, newer immunologically-mediated therapies under investigation include checkpoint inhibitors, bispecific antibodies, and CAR-T cells. Commercially available autologous anti-CD19 CAR-T cell therapies have shown encouraging complete response (CR) rates, PFS, and overall survival; however, there are many barriers, including limited patient access, length of time to treatment, and manufacturing capacity and scale limitations. Thus, there remains a significant unmet medical need for patients with r/r B-NHL.
ANTLER Phase 1 Clinical Trial for CB-010 in r/r B-NHL
The company is evaluating CB-010 in its ANTLER phase 1 clinical trial for the treatment of adult patients with aggressive forms of r/r B-NHL. In dose escalation, CB-010 was evaluated in patients with several aggressive subtypes of r/r B-NHL, the majority of which were third-line or later treatments. In the ongoing dose expansion portion of ANTLER, CB-010 is being evaluated in 2L LBCL patients.
Patients in the company's ANTLER Phase 1 clinical trial receive a lymphodepletion regimen prior to CAR-T cell infusion. The lymphodepletion regimen includes two chemotherapy agents, cyclophosphamide and fludarabine, which are generally used for lymphodepletion prior to autologous CAR-T cell therapy. To ensure optimal engraftment of the allogeneic CB-010 cells, the company uses a deeper regimen of these chemotherapeutic agents, specifically, cyclophosphamide at 60 mg/kg/day for two days, followed by fludarabine at 25 mg/m²/day for five days, compared to what is used with commercially available autologous CAR-T cell therapies. Lymphodepletion reduces the number of the patient’s immune cells and creates an inflammatory state that is required for the infused CAR-T cells to effectively expand and persist for disease activity. The objective of the ongoing ANTLER Phase 1 clinical trial is to further assess the safety and overall objective response rate (ORR) of CB-010 in r/r B-NHL patients at the RP2D and in patients who are receiving a partially HLA matched dose of CB-010.
The company's ANTLER Phase 1 clinical trial consists of two parts: Part A was the dose escalation portion that followed a standard 3 + 3 design, with sequential, increasing single doses of CB-010, and was completed with 16 patients dosed at dose level 1 (40 x 10^6 viable CAR-T cells), dose level 2 (80 x 10^6 viable CAR-T cells), or dose level 3 (120 x 10^6 viable CAR-T cells). Part B was the dose expansion portion where CB-010 was evaluated in larger numbers of patients to determine the RP2D in 2L LBCL patients. Dose level 2 (80 x 10^6 viable CAR-T cells) was selected as the RP2D. In these portions of the ANTLER trial, patients who had received prior CD19-targeted therapy were excluded.
ANTLER Phase 1 Trial Clinical Data for CB-010 in r/r B-NHL
At a poster presentation during the ASCO annual meeting in June 2024, the company presented safety, efficacy, and translational data for the first 46 patients evaluated in its ANTLER Phase 1 clinical trial, demonstrating safety and efficacy after a single dose of CB-010 with partial HLA matching.
GALLOP Phase 1 Clinical Trial for CB-010 in LN and ERL
The company is evaluating CB-010 in its GALLOP Phase 1 trial for the treatment of adult patients with LN or ERL. The objective of the company’s GALLOP phase 1 clinical trial is to evaluate the safety, PK profile, and initial clinical activity of a single dose of CB-010 (80x106 viable CAR-T cells) following a lymphodepletion regimen of cyclophosphamide at 20mg/kg/day for two days and fludarabine at 25mg/m2/day for three days. Patients are screened for donor-specific anti-HLA antibodies and administered CB-010 manufactured from a donor with partial HLA matching. The primary endpoint is safety.
CB-011
CB-011 is an allogeneic CAR-T cell therapy targeting BCMA-positive malignancies that is being evaluated in the company’s ongoing open-label, multicenter CaMMouflage phase 1 clinical trial (NCT05722418) in the United States in adults with r/r MM. The company acquired a novel humanized single-chain variable fragment (scFv) directed to BCMA that the company uses for the generation of the BCMA-specific CAR in CB-011.
To its knowledge, the company's CB-011 is the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach that includes both the removal of the endogenous B2M protein and the insertion of a B2M–HLA-E peptide transgene. This immune cloaking armoring strategy results in no endogenous class I HLA alleles expressed on the CAR-T cell surface. This reduces the number of potential mismatched HLA alleles from 12 to six, resulting in a reduced risk of rapid immunologic clearing of the CAR-T cells by the patient. CB-011 has received fast track and orphan drug designations for r/r MM from the FDA.
Target Indication
The company is developing CB-011 for the treatment of r/r MM. In 2024, 1.8% of all cancers were MM in the United States, according to the National Cancer Institute SEER database. The median age of diagnosis is 69 years, and there were an estimated 35,780 new cases in 2024 in the United States, with an estimated 12,540 deaths in 2024. The five-year survival rate in these patients is approximately 61%.
Additionally, many treatments for r/r MM are multidrug regimens comprising varying routes of administration and/or complicated dosing schedules; these regimens can be complex and burdensome for both patients and physicians. Due to limited patient access and treatment burden, there is a need for an off-the-shelf, readily available, single dose treatment for patients with r/r MM.
CaMMouflage Phase 1 Clinical Trial for CB-011 in r/r MM
The company is evaluating CB-011 in its CaMMouflage Phase 1 clinical trial in adult patients with r/r MM. These patients have a documented diagnosis of active MM according to International Myeloma Working Group diagnostic criteria. The patient population includes individuals for whom three or more lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody, have failed. Patients who have received a BCMA-targeted therapy within the last three months are excluded from the trial.
Patients in the company's CaMMouflage Phase 1 clinical trial receive a lymphodepletion regimen prior to CAR-T cell infusion. The lymphodepletion regimen includes two chemotherapy agents, cyclophosphamide and fludarabine, which are generally used for lymphodepletion prior to autologous CAR-T cell therapy. The company began clinical trial utilizing 300 mg/m²/day of cyclophosphamide and 30 mg/m²/day of fludarabine, each for a total of three days. The company has recently implemented a lymphodepletion regimen that includes a deeper dose of cyclophosphamide, increased from 300 to 500 mg/m²/day, together with the same fludarabine dose. The objective of the ongoing CaMMouflage Phase 1 clinical trial is to assess safety, including the incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) after CB-011 infusion, identify a maximum tolerated dose (MTD), if appropriate, assess the overall response rate (ORR) at active dose levels, and identify the recommended Phase 2 dose (RP2D).
The company’s CaMMouflage phase 1 clinical trial is being conducted in two parts: Part A is dose escalation following a standard 3 + 3 design, with sequential, increasing single doses of CB-011 with the ability to add additional patients at safe dose levels to further evaluate activity and safety. Part B is the expansion portion where patients receive CB-011 at the dose level(s) determined in Part A to determine the RP2D.
CB-012
CB-012 is an allogeneic CAR-T cell therapy targeting CLL-1 that is being evaluated in the ongoing first-in-human, open-label, multicenter AMpLify phase 1 clinical trial (NCT06128044) in the United States in adults with r/r AML. The company has exclusively licensed, in the field of allogeneic cell therapy, the fully human scFv targeting CLL-1 used in CB-012 from Memorial Sloan Kettering Cancer Center (MSKCC).
The absence of expression on HSCs indicates that these bone marrow cells will not be targeted by the CLL-1-directed CB-012 CAR-T cells, thereby preventing a patient from loss of a critical compartment of their immune system vital to generating immune cells required for fighting infections and cancer. To the company’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion. CB-012 has received fast track and orphan drug designations for r/r AML from the FDA.
Target Indication
AML is a cancer of the bone marrow treated with chemotherapy, radiation, targeted therapies, and/or HSC transplant. There were an estimated 20,800 new cases of AML in the United States in 2024 according to the National Cancer Institute SEER database. Five-year survival in these patients is 32%. Intensive induction chemotherapy, known as 7 + 3, consisting of cytarabine and an anthracycline, is the most effective therapy for adults newly diagnosed with AML, although the treatment has significant associated toxicities. There remains significant unmet need in the treatment of patients with AML.
AMpLify Phase 1 Clinical Trial for CB-012 in r/r AML
The company is evaluating CB-012 in its AMpLify phase 1 clinical trial in adult patients with r/r AML. The company’s AMpLify clinical trial includes patients who have not responded to or relapsed after standard treatment and excludes patients who have been treated with more than three prior lines of therapy and patients with proliferative disease. Patients who received prior allogeneic stem cell transplant are allowed to participate in its AMpLify clinical trial.
Patients in the company’s AMpLify phase 1 clinical trial receive a lymphodepletion regimen prior to CAR-T cell infusion. The lymphodepletion regimen includes two chemotherapy agents, cyclophosphamide (750 mg/m2/day) and fludarabine (30 mg/m2/day) for three days. Patients then have two days of rest, followed by a single CB-012 dose on day zero. The objective of its ongoing AMpLify trial is to assess safety, including the incidence of AEs defined as DLTs after CB-012 infusion, identify an MTD, if appropriate, assess the overall ORR at active dose levels, and identify the RP2D.
The company’s AMpLify phase 1 clinical trial is an open-label study being conducted in two parts: Part A is the dose escalation portion following a standard 3 + 3 design, with sequential, increasing single doses of CB-012. Part B is the expansion portion where patients will receive CB-012 at the dose level(s) determined in Part A to determine the RP2D.
CB-012 Preclinical Data
The company evaluated CB-012 in preclinical mouse models, which demonstrated that CB-012 significantly reduced tumor burden and increased overall survival. As shown in the left graph below, in a CLL-1+ AML xenograft model, a single dose of CB-012 significantly reduced an orthotopically established tumor burden over a long duration compared to vehicle, or negative control, treatment.
In a second model, the company evaluated CLL-1-specific CB-012 CAR-T cells compared to equivalent CAR-T cells that lacked the PD-1 knockout in a xenograft model of CLL-1+ PD-L1+ tumor cells to evaluate the impact of the PD-1 knockout in CB-012. The CLL-1-specific CB-012 CAR-T cells statistically significantly increased overall survival in the tumor-bearing mice compared to mice that received either control CAR-T cells expressing PD-1 (cells engineered with the same edits of CB-012 except the PDCD1 KO) or the vehicle control.
Strategic Agreements
As part of its strategy to maximize the value and benefit of its technologies, the company is exploring mutually beneficial strategic collaborations with other biotechnology or pharmaceutical companies. Additionally, the company has in-licensed or taken assignment of key technologies important for the development of its product candidates.
Pfizer Investment
On June 29, 2023, the company entered into a Securities Purchase Agreement (Securities Purchase Agreement) with Pfizer Inc. (Pfizer).
Memorial Sloan Kettering Cancer Center
On November 13, 2020, the company entered into an Exclusive License Agreement with MSKCC ('MSKCC Agreement'), under which the company exclusively licensed from MSKCC know-how, biological materials, and related patent families to fully human scFvs targeting CLL-1 (also known as CD371) for use in T cells, NK cells, and genome-edited iPSCs for allogeneic CLL-1-targeted cell therapy. The company uses one of the licensed scFvs in its CB-012 product candidate.
Pioneer Hi-Bred International, Inc. (Pioneer, now Corteva Agriscience)
On July 13, 2015, the company entered into an Amended and Restated Collaboration and License Agreement (as amended, 'Pioneer Agreement') with Pioneer (then a DuPont company) that superseded and replaced a prior Collaboration and License Agreement entered into on September 10, 2014. Under the terms of the Pioneer Agreement, the company and Pioneer cross-licensed background CRISPR intellectual property portfolios. Pioneer granted the company an exclusive worldwide license, with the right to sublicense, to its background CRISPR intellectual property in the field of research tools, and a non-exclusive license, with the right to sublicense, for CRISPR in therapeutics and all fields outside of the Pioneer field, including in the field of human and animal therapeutics. The company granted Pioneer an exclusive license, with the right to sublicense, to the company's background CRISPR intellectual property, including the CVC IP discussed below, in certain agricultural crops, specified microorganisms, a defined industrial bio field, and certain nutrition and health applications ('Pioneer Exclusive Field'), and a non-exclusive license, with the right to sublicense, to Pioneer for CRISPR in certain defined fields outside of research reagents.
Intellia Therapeutics, Inc. ('Intellia')
On July 16, 2014, the company entered into a License Agreement (as amended, 'Intellia Agreement') with Intellia, LLC (now Intellia Therapeutics, Inc.), under which the company granted Intellia an exclusive worldwide license, with the right to sublicense, to certain CRISPR-Cas9 technology for a defined field of human therapeutics in exchange for Intellia stock. The Intellia Agreement included a license to certain of the company's future CRISPR-Cas9 intellectual property until such time as the company's direct or indirect ownership percentage in Intellia dropped below 10%, called the IP cut-off date, which occurred on January 30, 2018. Intellia granted the company an exclusive worldwide license, with the right to sublicense, to its CRISPR-Cas9 technology for all fields outside of the defined field of human therapeutics, including a license to certain of Intellia's future CRISPR-Cas9 intellectual property until the IP cut-off date. Each party had the right to opt in to any licenses in its field of use entered into by the other party prior to the IP cut-off date, subject to the terms and conditions of such license, and Intellia opted into the company's Pioneer Agreement and thus has a license to the Pioneer background CRISPR-Cas9 intellectual property.
The Regents of the University of California ('UC') and the University of Vienna ('Vienna')
On April 16, 2013, the company entered into an Exclusive License for Methods and Compositions for RNA-Directed Target DNA Modification and for RNA-Directed Modulation of Transcription with UC and Vienna (as amended, 'UC/Vienna Agreement'), under which the company received an exclusive worldwide license, with the right to sublicense, in all fields to the foundational CRISPR-Cas9 patent family co-owned by UC, Vienna, and Dr. Emmanuelle Charpentier ('CVC IP').
On December 15, 2016, the company entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement (IMA) with UC, Vienna, Dr. Emmanuelle Charpentier, Intellia Therapeutics, CRISPR Therapeutics AG, ERS Genomics Ltd., and TRACR Hematology Ltd. relating to the CVC IP. Under the IMA, each of the owners of the CVC IP (i.e., UC, Vienna, and Dr. Charpentier) retroactively consented to all licenses and sublicenses granted by the other owners and their licensees and also gave prospective consent to any licenses and sublicenses that may be granted in the future.
Intellectual Property
As of March 1, 2025, the company owned 63 granted U.S. patents, 324 granted foreign patents, and 148 pending patent applications throughout the world. The patent portfolio owned by the company includes U.S. and foreign patents and patent applications covering methods and compositions relating generally to its Cas9 chRDNA and Cas12a chRDNA technologies (which, for granted U.S. patents, without PTA or PTE, will expire in 2036). Additionally, the portfolio includes U.S. and foreign patents and patent applications covering methods and compositions relating to the anti-BCMA binding domain of its CB-011 product candidate (which, for granted U.S. patents, without PTA or PTE, will expire in 2040). In general, the company files its patent applications in the United States and Europe, as well as in numerous other foreign patent jurisdictions. The company has exclusively in-licensed intellectual property covering the anti-CLL-1 scFv of its CB-012 product candidate from MSKCC (which, upon grant, without PTA or PTE or other extensions, will expire in 2040).
Additionally, the company has substantial patent protection on CRISPR Type I systems, CRISPR-Cas9 methods and compositions, and other genome-editing technologies. The patent term in the United States and other countries is 20 years from the date of filing of the first non-provisional application to which priority is claimed. In the United States, the patent term may be lengthened by a patent term adjustment (PTA), which compensates a patentee for administrative delays by the USPTO in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent. Additionally, under the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments), the term of a patent that covers an FDA-approved biologic may also be eligible for a patent term extension (PTE) of up to five years, which is designed to compensate for the patent term lost during clinical trials and the FDA regulatory review process. A PTE cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, and only one patent claiming the drug product, methods of use, or methods of manufacturing may be restored. Moreover, a patent can only be restored once, and if a single patent is applicable to multiple products, it can only be extended based on one product. Similar provisions to extend the term of a patent that covers an approved product are available in Europe and certain other foreign jurisdictions. Without any PTE, the earliest expiration date of the company's granted U.S. patents is in 2032, and the latest expiration date of its granted U.S. patents is in 2043.
As of March 1, 2025, the company owned 25 trademark registrations worldwide, including 7 U.S. trademark registrations, and 2 pending trademark applications worldwide. The company has registered CARIBOU, CARIBOU BIOSCIENCES, SITE-SEQ, and the Caribou logo as trademarks in relevant classes and jurisdictions in the United States, European Union, and certain other jurisdictions.
Government Regulation
In the United States, the company’s product candidates are regulated as biological products, or biologics, under the Public Health Service Act (PHSA), and the Federal Food, Drug, and Cosmetic Act (FDCA), and their implementing regulations promulgated by the FDA.
The company's clinical trials involve the administration of the company's product candidate to patients with the disease to be treated and are conducted under the supervision of a qualified principal investigator in accordance with cGCP requirements.
Manufacturers of the company's products are required to register their establishments with the FDA and certain state agencies and are subject to periodic announced or ad hoc inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP regulations, which impose certain procedural and documentation requirements upon these manufacturers.
In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the U.S. Occupational Safety and Health Act, the U.S. Resource Conservancy and Recovery Act, and the U.S. Toxic Substances Control Act, all affect the company's business. These and other state and local laws govern the company's use, handling, and disposal of various biological, chemical, and radioactive substances used in, and wastes generated by, the company's operations.
Research and Development
The company's research and development expenses $130.2 million for the year ended December 31, 2024.
History
Caribou Biosciences, Inc. was founded in 2011. The company was incorporated in 2011.
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