Caribou Biosciences Expands Clinical Development of CB-010

April 04, 2024

BERKELEY, Calif.  (GLOBE NEWSWIRE) -- Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, announced that it received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) for CB-010, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout (KO), for the treatment of lupus nephritis (LN) and extrarenal lupus (ERL). The Phase 1, multicenter, open label GALLOP clinical trial of CB-010 in patients with LN and ERL is expected to initiate by year-end 2024.

“CB-010 has demonstrated encouraging initial safety and efficacy in patients with relapsed or refractory B cell non-Hodgkin lymphoma, and we are excited to expand CB-010’s clinical development to include autoimmune diseases,” said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. “By targeting CD19-positive B cells involved in the production of autoantibodies and the perpetuation of the autoimmune response, our off-the-shelf CAR-T cell therapy CB-010 has the potential to greatly improve the standard of care for patients with lupus, a prevalent and severe autoimmune disease.”

CB-010 is the lead clinical-stage product candidate from Caribou’s allogeneic CAR-T cell therapy platform. As previously reported, CB-010 has demonstrated encouraging initial safety and efficacy from the dose escalation portion of the ongoing ANTLER Phase 1 trial in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL). Caribou continues to enroll patients with large B cell lymphoma (LBCL) in the second-line setting, and initial dose expansion data from ANTLER will be presented at a medical congress in Q2 2024.

“Despite treatment advancements, fatigue, organ damage, and low health-related quality of life often remain life-long characteristics of lupus,” said Richard Lafayette, MD, professor of medicine, Stanford Medicine Health Care. “An allogeneic anti-CD19 CAR-T cell therapy from healthy donor T cells has the potential to revolutionize lupus treatment, offering a readily available treatment for patients who need new therapeutic options.”

Lupus is an autoimmune disease characterized by widespread inflammation that damages tissues and organs throughout the body. B cells, which normally produce antibodies that protect from infection, can play a devastating role in lupus by producing autoantibodies that cause the immune system to attack healthy tissues. CB-010 targets CD19, a protein on the surface of B cells, and has a PD-1 knockout (KO) that reduces CAR-T cell exhaustion. 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 the ongoing ANTLER trial, depletion and recovery of patients’ B cells is on par with the duration of B cell aplasia recently reported by Müller et al.1 Unlike many autologous and allogeneic CAR-T cell therapies, the manufacture of CB-010 does not rely on lentiviral or other retroviral vectors, which the FDA has recently identified may lead to risk of secondary malignancy potentially due to random integration of the chimeric antigen receptor (CAR) construct. Instead, the chRDNA technology allows for precise insertion of the CAR at an intended location within the T cell genome. The GALLOP trial will include partial HLA matching between donor sources and patients, which may lead to improved clinical outcomes based on data from the ongoing ANTLER trial.

“The human leukocyte antigen, or HLA, system acts as our body’s identity card to know one’s ‘self’ from ‘not self.’ In stem cell transplants, it has been shown that a close HLA match between patients and donors significantly reduces the rejection of the therapy. This same logic can be applied to allogeneic CAR-T cells as well, so that the activity of the therapy persists long enough to target and destroy the diseased cells,” said Mehdi Hamadani, MD, professor of medicine, section chief of hematologic malignancies at Medical College of Wisconsin and investigator for the ongoing ANTLER Phase 1 trial. “Intriguing data from the ongoing ANTLER trial support incorporating an HLA matching strategy into Caribou’s CB-010 trials, an innovative clinical approach that can potentially improve outcomes for patients. I am pleased to be part of the ANTLER trial to advance the development of CB-010 as an off-the-shelf CAR-T cell therapy that aims to address the limitations of currently approved treatment options.”

Caribou continues to expect the $372.4 million cash, cash equivalents, and marketable securities, as of December 31, 2023, to fund the current operating plan into Q1 2026.

About the GALLOP trial
The GALLOP Phase 1 trial is an open-label, multicenter clinical trial designed to evaluate a single infusion of CB-010 in adult patients with LN and ERL. The GALLOP trial will evaluate the safety, pharmacokinetic (PK) profile, and initial clinical activity of a single dose level of CB-010 following a lymphodepletion regimen of cyclophosphamide at 20mg/kg/day for 2 days followed by fludarabine at 25mg/m2/day for 3 days. Patients will be screened for donor-specific antibodies and administered CB-010 manufactured from a donor with partial HLA matching. The primary endpoint is safety.  

About CB-010
CB-010 is the lead clinical-stage product candidate from Caribou’s allogeneic CAR-T cell therapy platform, and it is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) and will be evaluated in patients with LN and ERL. In the ongoing ANTLER Phase 1 trial, Caribou is enrolling second-line patients with large B cell lymphoma (LBCL) comprised of different subtypes of aggressive r/r B-NHL (DLBCL NOS, PMBCL, HGBL, tFL, and tMZL). In the GALLOP Phase 1 trial, CB-010 will be evaluated in patients with LN and ERL.

CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to improve activity against diseases by limiting premature CAR-T cell exhaustion. To Caribou’s knowledge, CB-010 is also the first anti-CD19 allogeneic CAR-T cell therapy to be evaluated in the second-line LBCL setting and, for r/r B-NHL, CB-010 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

About lupus nephritis and extrarenal lupus
Lupus nephritis (LN) and extrarenal lupus (ERL) are sub-categories of systemic lupus erythematosus (SLE), the most common form of lupus. Lupus is a chronic autoimmune disease characterized by B cell dysfunction in which the immune system attacks its own tissues, causing widespread inflammation and organ damage.2 There are approximately 320,000 patients with SLE in the US.3 It has been estimated about 50% of patients with SLE will develop lupus nephritis, and of those, roughly 10-30% of patients will progress to end-stage renal disease, which requires dialysis or kidney transplant.4

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 are capable of editing 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 chRDNA technology to carry out high efficiency multiple edits, to develop CRISPR-edited therapies.

About Caribou Biosciences, Inc.
Caribou Biosciences 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 Cas12a chRDNA technology, enables superior precision to develop cell therapies that are armored to potentially improve antitumor activity. Caribou is advancing a pipeline of clinical-stage off-the-shelf cell therapies from its CAR-T platform as readily available treatments for patients with hematologic malignancies and autoimmune disease.