Clinical Update: Phase 3 in Sight for Caribou's Lymphoma Candidate, and Positive Clinical Data From Editas Medicine

Caribou Biosciences is heading for Phase 3 trial with large B cell lymphoma candidate

Caribou Biosciences announced yesterday that it has received positive feedback from the FDA on a Phase 3 randomised controlled clinical trial for CB-010 for relapsed or refractory large B-cell lymphoma. According to a press release published by Caribou, the FDA stated that the proposed comparator arm of platinum-based immunochemotherapy followed by high dose chemotherapy and autologous stem cell transplantation is acceptable.

CB-010 is designed to be an 'off the shelf' therapy, which is derived from healthy donor T cells that are edited using Caribou's proprietary Cas9 chRDNA technology. To generate CB-010, a CD19-specific CAR is inserted into the TRAC gene (which encodes the T cell receptor alpha constant) of healthy donor T cells. The PD-1 gene is also deleted in these cells. This gene encodes the PD-1 protein that functions as a safety switch on T cells that cancer cells turn on to protect themselves from T cell-mediated immune responses.

CB-010 is being evaluated in the ANTLER Phase 1 trial, which is currently enroling second-line large B-cell lymphoma patients in the dose expansion portion, based on encouraging data from the dose escalation portion of the trial.

In Q2 2024, Caribou expects to report initial dose expansion data from the ANTLER trial and share the recommended Phase 2 dose for CB-010. The company plans to initiate the Phase 3 pivotal trial with this dose by the end of 2024.

In 2020, CB-010 became the first allogeneic CAR-T cell therapy with a CRISPR-mediated PD-1 deletion to receive FDA clearance for clinical trial initiation. The candidate has been granted Regenerative Medicine Advanced Therapy, Fast Track, and Orphan Drug designations by the FDA.

You can read more about Caribou's Cas9 chRDNA technology in our interview with the company's CSO Steve Kanner Ph.D. here.

Editas Medicine announces new EDIT-301 safety and efficacy data in 17 patients with sickle cell disease or beta thalassemia

Editas Medicine is developing EDIT-301 (now known as renizgamglogene autogedtemcel (reni-cel)) as a one-time treatment for sickle cell disease (SCD) and beta thalassemia (BT).

Reni-cel is an autologous (i.e. patient-derived) CRISPR-edited cell therapy candidate that works by reactivating foetal haemoglobin production, thereby compensating for the lack of functional adult haemoglobin in individuals with SCD and BT. The candidate is developed using a CRISPR-Cas12a ribonucleoprotein to enhance the HBG1/2 promoter region in the beta-globin locus of patient-derived haematopoietic stem cells . Naturally-occurring HbF-inducing mutations in this genomic region support the clinical relevance of enhancing the HBG1/2 promoter, and this strategy has been shown to increase the red blood cell levels of foetal haemoglobin.

Reni-cel is being evaluated in the ongoing Phase 2 RUBY trial for SCD and in the Phase 2 EdiTHAL trial for transfusion-dependent BT. In July 2023, Editas announced positive initial safety and efficacy data in five patients treated with reni-cel, which included four SCD patients and the first BT patient treated in the aforementioned trials.

This week, Editas shared new safety and efficacy data in 17 patients treated with reni-cel. This includes 11 patients enroled in the RUBY trial and six patients enroled in the EdiTHAL trial. This dataset includes the five patients mentioned above and 12 additional patients. The data was presented in a company-sponsored webinar and in a poster presentation at this year's American Society of Hematology (ASH) Annual Meeting, which was held in San Diego.

In both the RUBY and EdiTHAL trials to date, reni-cel has been well-tolerated and continues to demonstrate a safety profile consistent with myeloablative conditioning with busulfan and autologous haematopoietic stem cell transplant by all patients in the two trials. Since treatment with reni-cel, all 11 RUBY patients are free of vaso-occlusive events (VOEs), and all RUBY patients with at least five months of follow-up have maintained a normal haemoglobin level and a foetal haemoglobin level of >40%. All six EdiTHAL patients showed early and robust increases in total haemoglobin, which were above the transfusion independence threshold of 9 g/dl.

In August 2020, Editas announced that it had obtained a Rare Pediatric Disease Designation for EDIT-301 as a potentially best-in-class treatment for SCD in children from birth to 18 years.

You can find all our previous news articles about IND approvals and clinical trials here. For a complete overview of CRISPR IND approvals and ongoing gene-editing trials, check out CRISPR Medicine News' Clinical Trials Database.