Caribou Biosciences, a clinical-stage CRISPR genome-editing biopharmaceutical company, has commenced the GALLOP Phase 1 clinical trial, evaluating CB-010 in patients with lupus nephritis (LN) and extrarenal lupus (ERL). This open-label, multicenter trial will assess the safety, pharmacokinetics, and initial clinical activity of a single infusion of CB-010 in adult patients. The trial marks a significant step in expanding the application of Caribou's allogeneic CAR-T cell therapy platform to autoimmune diseases.
CB-010: Targeting CD19 in Lupus
CB-010 is an allogeneic anti-CD19 CAR-T cell therapy engineered using Cas9 CRISPR hybrid RNA-DNA (chRDNA) technology. It is designed to target CD19, a protein found on B cells, which play a crucial role in autoantibody production and the perpetuation of the autoimmune response in lupus. The therapy also features a PD-1 knockout, a genome-editing strategy aimed at improving CAR-T cell activity by limiting premature CAR-T cell exhaustion.
The GALLOP trial incorporates a partial human leukocyte antigen (HLA) matching process between donor sources and patients. This approach is based on data from the ongoing ANTLER trial in relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL), which suggests that partial HLA matching may lead to improved clinical outcomes. Patients will receive a lymphodepletion regimen consisting of cyclophosphamide at 20mg/kg/day for 2 days, followed by fludarabine at 25mg/m2/day for 3 days, prior to CB-010 infusion.
Fast Track Designation and Unmet Need
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to CB-010 for refractory systemic lupus erythematosus (SLE), highlighting its potential as an innovative treatment for this challenging condition. Lupus is a chronic autoimmune disease affecting approximately 320,000 people in the US, characterized by widespread inflammation and organ damage. Current treatments often fail to provide adequate control of the disease, leaving many patients with persistent symptoms and organ damage.
Broader Pipeline and Upcoming Milestones
In addition to the GALLOP trial, Caribou Biosciences is advancing several other clinical-stage programs. The company plans to present data from the ANTLER Phase 1 trial of CB-010 in second-line and CD19 relapsed large B cell lymphoma (LBCL) patients in H1 2025. Furthermore, dose escalation data from the CaMMouflage Phase 1 clinical trial of CB-011 in relapsed or refractory multiple myeloma (r/r MM) is also expected in the first half of 2025.
Rachel Haurwitz, PhD, Caribou’s president and chief executive officer, stated, “We are excited to be on the forefront of a new era for allogeneic CAR-T cell therapies, which offer broad access and rapid availability to patients and healthcare systems.”
Caribou anticipates initiating a pivotal Phase 3 trial for CB-010 in second-line LBCL in the second half of 2025, contingent on confirmation of the HLA matching strategy. The company also continues to advance the AMpLify Phase 1 clinical trial of CB-012 in relapsed or refractory acute myeloid leukemia (r/r AML), with updates on dose escalation expected as the trial progresses.
