On May 9, 2023 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported its financial results for the first quarter of 2023 and reviewed recent pipeline progress (Press release, Caribou Biosciences, MAY 9, 2023, View Source [SID1234631270]).

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"We are driving important progress this year across our pipeline of allogeneic CAR-T cell therapies," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "Notably, we are advancing the ongoing ANTLER trial for our lead program CB-010, the first allogeneic cell therapy to be evaluated clinically in the second-line LBCL setting. Our goal is to provide access to a greater number of patients and potentially improve outcomes earlier in the disease course. Additionally, we are excited that the FDA granted CB-011 Fast Track designation for the treatment of relapsed or refractory multiple myeloma and that we have initiated patient dosing in our CaMMouflage trial. The momentum continues as we prepare CB-012, our third CAR-T cell program, for an IND application submission for relapsed or refractory acute myeloid leukemia in the second half of this year."
Accomplishments and Highlights

Pipeline and Technology
•CB-010: Caribou successfully completed dose escalation and has entered the dose expansion portion of the ongoing ANTLER Phase 1 clinical trial of CB-010 in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL).
◦Caribou currently is enrolling second-line patients with large B cell lymphoma (LBCL) in the dose expansion portion of the ANTLER trial in which two different CB-010 dose levels (80×106 CAR-T cells and 120×106 CAR-T cells) are being evaluated, each as a single-dose regimen, in approximately 30 second-line patients (approximately 15 patients per dose level) to determine the recommended Phase 2 dose (RP2D). Once the RP2D is determined, Caribou may enroll additional patients in the ANTLER trial.
◦The FDA has granted CB-010 Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations.
•CB-011: Caribou has initiated patient dosing at dose level 1 (50×106 CAR-T cells) in the CaMMouflage Phase 1 trial for relapsed or refractory multiple myeloma (r/r MM).
◦The FDA recently granted CB-011 Fast Track designation for r/r MM.
•CB-012: Caribou is advancing IND-enabling activities for CB-012, an allogeneic anti-CLL-1 CAR-T cell therapy, to support a planned IND application submission for relapsed or refractory acute myeloid leukemia (r/r AML).
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◦Data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2023 Annual Meeting (View Source) demonstrated in preclinical AML models that CB-012 significantly reduced tumor burden and increased overall survival compared to controls.

Anticipated 2023 Milestones
•CB-010: Caribou plans to provide a safety and efficacy update in H2 2023 from the ongoing ANTLER Phase 1 clinical trial in r/r B-NHL, including data from at least 15 patients from dose escalation with a minimum of six months follow up.
•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.

First Quarter 2023 Financial Results

Cash, cash equivalents, and marketable securities: Caribou had $291.0 million in cash, cash equivalents, and marketable securities as of March 31, 2023, compared to $317.0 million as of December 31, 2022. Caribou expects its cash, cash equivalents, and marketable securities will be sufficient to fund its current operating plan into 2025.

Licensing and collaboration revenue: Revenue from Caribou’s licensing and collaboration agreements was $3.5 million for the three months ended March 31, 2023, compared to $2.7 million for the same period 2022. The increase was primarily due to revenue recognized under the Collaboration and License Agreement with AbbVie and other license agreements.
R&D expenses: Research and development expenses were $25.7 million for the three months ended March 31, 2023, compared to $13.9 million for the same period in 2022. The increase was primarily due to costs to advance pipeline programs, including the ANTLER and CaMMouflage Phase 1 trials; increased personnel-related expenses, including stock-based compensation; and facilities and other allocated expenses.

G&A expenses: General and administrative expenses were $8.9 million for the three months ended March 31, 2023, compared to $9.6 million for the same period in 2022. The decrease was primarily due to lower director and officer insurance, legal, and patent prosecution and maintenance costs. This decrease was partially offset by increased personnel-related expenses due to increased headcount.
Net loss: Caribou reported a net loss of $28.0 million for the three months ended March 31, 2023, compared to a net loss of $19.1 million for the same period in 2022.

About CB-010
CB-010 is the lead product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprising four different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, and tFL). CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR

hybrid RNA-DNA (chRDNA) technology. CB-010 is the first allogeneic CAR-T cell therapy in the clinic, to Caribou’s knowledge, with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR-T cell exhaustion. CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy, to Caribou’s knowledge, to be evaluated clinically in the second-line setting and has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, and Orphan Drug designations by the FDA. Additional information on the ANTLER trial (NCT04637763) can be found at clinicaltrials.gov.

About CB-011
CB-011 is the second product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA technology. CB-011 is the first allogeneic CAR-T cell therapy in the clinic, to Caribou’s knowledge, that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track designation by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is the third product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in investigational new drug (IND)-enabling studies. CB-012 is the first allogeneic CAR-T cell therapy, to Caribou’s knowledge, with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. CB-012 is engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits.

About Caribou’s Novel Next-Generation CRISPR Platform
CRISPR genome editing uses easily designed, modular biological tools to make DNA changes in living cells. There are two basic components of Class 2 CRISPR systems: the nuclease protein that cuts DNA and the RNA molecule(s) that guide the nuclease to generate a site-specific, double-stranded break, leading to an edit at the targeted genomic site. CRISPR systems have exhibited editing at unintended genomic sites, known as off-target editing, which may lead to harmful effects on cellular function and phenotype. In response to this challenge, Caribou has developed CRISPR hybrid RNA-DNA guides (chRDNAs; pronounced "chardonnays") that direct substantially more precise genome editing compared to all-RNA guides. Caribou is deploying the power of its Cas12a chRDNA technology to carry out high efficiency multiple edits, including multiplex gene insertions, to develop CRISPR-edited therapies.