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Traditional treatments for lymphoma include chemotherapy, radiation, and stem cell transplantation. However, a groundbreaking approach has emerged in recent years - Chimeric Antigen Receptor T-cell therapy (CAR-T therapy). Allogeneic CAR-T therapy, a promising extension of this innovative treatment, has shown tremendous potential in the fight against lymphoma.
The North American cell and gene therapy market, specifically in the allogeneic segment, is projected to experience remarkable growth. It is expected to achieve a Compound Annual Growth Rate (CAGR) of 25.5% from 2023 to 2027, reaching an impressive value of US$3,262.2 million by 2027, up from US$1,313.7 million in 2023. Over the past five years, this sector has already demonstrated significant expansion, achieving a CAGR of 27.6%, and attaining a value of US$1,038.4 million in 2022.
One of the notable areas within allogeneic cell therapies is Chimeric Antigen Receptor T-cell therapy (CAR-T therapy). While allogeneic CAR-T projects have faced challenges in achieving lasting responses, a crucial milestone is the six-month durability of remission in patients. Recently, Caribou, a leading company specializing in CRISPR-edited allogeneic cell therapies, announced promising results. Their project, CB-010, showcased encouraging outcomes, with approximately half of the lymphoma patients treated demonstrating sustained responses lasting at least six months. This breakthrough could have significant implications for the future of allogeneic CAR-T therapy in the fight against lymphoma.
The 50% remission rate achieved by CB-010 is noteworthy as it aligns with what autologous CAR-T therapies typically achieve in the same setting. The convenience of an off-the-shelf therapy, coupled with comparable effectiveness, offers distinct advantages for patients. Nevertheless, Caribou's data also underscore the need for ongoing vigilance as relapses continue to be a concern.
Caribou has managed to allay initial doubts by presenting data from its Antler study of CB-010, which has now expanded to include 16 patients, up from six in December. This substantial dataset has helped bolster confidence in the therapy, and an upsized $125 million equity offering followed the positive news. Despite the drop in share price, this funding injection indicates investor interest in the company's potential.
Adding to the positive sentiment, Caribou secured a $25 million equity investment from Pfizer, a major pharmaceutical company with previous involvement in allogeneic CAR-T therapy through Cellectis, although it took a step back from the field five years ago.
CB-010, the leading candidate in Caribou's pipeline, represents a CRISPR-edited allogeneic cell therapy designed for the treatment of relapsed/refractory lymphoma. Initial data presented at last year's EHA meeting showed complete responses in the first six patients treated with 40 million cells, but three of them experienced relapses by the six-month mark. In December, the focus remained on the same six patients, with only two still in complete response.
However, the recent update brought promising news. At 18 and 24 months, the two responding patients out of the original six were still in full remission. Additionally, five other responders maintained their responses beyond six months, allowing Caribou to claim a 50% remission rate at the six-month mark, with 44% achieving complete responses.
While these results are encouraging, they also pose some puzzles. Despite increasing the dose of CB-010 to 80 million cells for four of the new responders and 120 million cells for three subjects, some patients continue to relapse. On the safety front, CB-010 has demonstrated a promising profile, with no severe cytokine release, a 13% rate of neurotoxicity, and a 6% rate of infections. These safety findings are consistent with the most recent information provided by Allogene for its related CD19-targeting project ALLO-501/501A at the ASCO meeting in June 2023.
Both Caribou and Allogene have made considerable progress with their respective allogeneic CAR-T therapies, but small patient numbers in their datasets limit the robustness of their results compared to the established efficacy of autologous CAR-T therapy. For instance, the Zuma-1 research found that around 70% of lymphoma patients treated with Gilead's Yescarta had complete remissions at two years.
BioIntel360 suggests that although Caribou and Allogene's datasets hold great promise, they will need to mature considerably before reaching the level of confidence and reliability seen in the established therapies. As research and development continue in the field of allogeneic CAR-T therapy, the quest for more durable responses remains a top priority for improving patient outcomes in the treatment of lymphoma and other malignancies.
