Caribou Biosciences, Inc. (NASDAQ:CRBU) is a clinical-stage CRISPR genome-editing biopharmaceutical company dedicated to developing transformative therapies for patients with devastating diseases. The company's genome-editing platform, including its novel chRDNA (CRISPR hybrid RNA-DNA) technology, enables more precise genome editing to develop cell therapies that are armored to improve activity against diseases.

Business Overview

Caribou Biosciences is advancing a pipeline of allogeneic, or off-the-shelf, cell therapies from its chimeric antigen receptor (CAR) T and CAR-natural killer (CAR-NK) cell platforms as readily available therapeutic treatments for patients. The company's lead product candidate, CB-010, is an allogeneic CAR-T cell therapy that is the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in patients with second-line relapsed or refractory large B cell lymphoma (r/r LBCL). CB-010 is also the first clinical-stage allogeneic anti-CD19 CAR-T cell therapy with programmed cell death protein 1 (PD-1) removed from the CAR-T cell surface by a genome-edited knockout of the PDCD1 gene.

In the dose escalation portion of the ongoing ANTLER phase 1 clinical trial, CB-010 was generally well-tolerated, and the company is now evaluating the product candidate in the dose expansion portion of the trial. Based on the ANTLER data, Caribou Biosciences also plans to investigate partial human leukocyte antigen matching and donor-specific antibody screening for CB-010 and its other CAR-T programs. The company expects to present initial dose expansion data, the recommended phase 2 dose in second-line LBCL patients, and emerging translational data from the ANTLER trial at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Caribou Biosciences' second product candidate, CB-011, is an allogeneic CAR-T cell therapy that is the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach. This strategy includes the removal of the endogenous beta-2 microglobulin (B2M) protein and insertion of a beta-2-microglobulin–human-leukocyte-antigen-E–peptide transgene (B2M–HLA-E), which is designed to reduce CAR-T cell rejection by both patient T cells and natural killer (NK) cells. CB-011 is being evaluated in the CaMMouflage phase 1 clinical trial in adult patients with relapsed or refractory multiple myeloma (r/r MM).

The third product candidate from Caribou Biosciences' CAR-T cell platform is CB-012, an allogeneic CAR-T cell therapy targeting CLL-1 (also known as CD371). CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption and immune cloaking strategies. The company believes that CLL-1 is an attractive target for acute myeloid leukemia (AML) due to its expression on myeloid cancer cells, its enrichment on leukemic stem cells, and its absence on hematopoietic stem cells. CB-012 is being evaluated in the AMpLify phase 1 clinical trial in adult patients with relapsed or refractory AML (r/r AML).

Financials

Caribou Biosciences has not generated any revenue from product sales to date and has incurred operating losses since its inception. The company's net losses for the three months ended March 31, 2024, and 2023 were $41.2 million and $28.0 million, respectively. For the full year 2023, the company reported a net loss of $102.1 million on revenue of $34.5 million, and generated negative operating cash flow of $93.3 million and negative free cash flow of $104.9 million.

As of March 31, 2024, Caribou Biosciences had cash, cash equivalents, and marketable securities of $345.9 million, which the company's management expects will be sufficient to fund its current operating plan for at least the next 12 months. The company has funded its operations primarily through sales of its capital stock, including its initial public offering in 2021, which generated approximately $321.0 million in net proceeds, and a follow-on public offering in 2023, which generated approximately $134.4 million in net proceeds. Caribou Biosciences has also received approximately $96.5 million in net proceeds from licensing agreements, licensing and collaboration agreements, a service agreement, patent assignments, and government grants.

In terms of geographic breakdown, the majority of Caribou Biosciences' revenue during the three months ended March 31, 2024, was derived from the United States, accounting for $2.3 million, or 94.0%, of total revenue. The remaining $0.2 million, or 6.0%, of revenue was generated from the rest of the world.

Regarding revenue breakdowns, during the three months ended March 31, 2024, the company recognized $1.8 million of revenue related to performance obligations satisfied at a point in time and $0.6 million of revenue related to performance obligations satisfied over time. This represents a decrease of $1.1 million, or 31.3%, compared to the three months ended March 31, 2023, when the company recognized $3.5 million in licensing and collaboration revenue. The decrease was primarily due to a $1.6 million reduction in revenue recognized under the now-terminated Collaboration and License Agreement with AbbVie, partially offset by a $0.6 million increase in revenue recognized under the company's Information Rights Agreement with Pfizer.

Caribou Biosciences' research and development expenses increased by $8.1 million, or 31.5%, to $33.8 million for the three months ended March 31, 2024, from $25.7 million for the three months ended March 31, 2023. This increase was primarily related to higher expenses for licenses and milestones, personnel-related expenses, and external contract manufacturing and clinical research organization activities for the company's clinical CAR-T cell therapy product candidates.

General and administrative expenses increased by $5.7 million, or 64.3%, to $14.6 million for the three months ended March 31, 2024, from $8.9 million for the three months ended March 31, 2023. This increase was primarily due to higher legal and other service-related expenses, including $3.9 million of accrued litigation settlement costs, as well as increased personnel-related expenses.

Liquidity

Caribou Biosciences' liquidity position remains strong, with $345.9 million in cash, cash equivalents, and marketable securities as of March 31, 2024. The company's management expects this balance to be sufficient to fund its current operating plan for at least the next 12 months. However, the company will continue to be dependent on equity financing, debt financing, collaboration and licensing arrangements, and/or other forms of capital raises to fund its operations and product candidate development, at least until it is able to generate significant positive cash flows from its operations.

Risks and Challenges

In terms of risks, Caribou Biosciences faces the typical risks associated with the development of human therapeutics, including the uncertainty of achieving profitability, the need for additional capital, the risks inherent in the development of cell therapy products, and the potential for delays or failures in its clinical trials and regulatory approvals. The company also faces risks related to its reliance on third parties for the manufacture and testing of its product candidates, as well as risks related to the development of its competitors and the industry.

Conclusion

Overall, Caribou Biosciences is a promising CRISPR genome-editing biotech with a robust pipeline of allogeneic cell therapy product candidates targeting various hematologic malignancies and autoimmune diseases. The company's strong financial position, coupled with its innovative technology and promising clinical data, position it well to continue advancing its pipeline and potentially delivering transformative therapies to patients in need.