Leman Biotech Co., Ltd. (referred to as "Leman Biotech" or "the company") is pleased to announce the successful treatment of the first patient using its metabolically enhanced CD19 CAR-T therapy (Meta10-19). The patient, enrolled in an investigator-initiated trial (IIT) at the First Affiliated Hospital of the University of Science and Technology of China, has achieved complete remission and was subsequently discharged from the hospital. This clinical trial (NCT05715606) was officially initiated in early 2023 to evaluate the safety and efficacy of Leman Biotech's Metabolically Enhanced CAR-T System. The CD19, a well-studied antigen, was chosen as the therapeutic target to gather preliminary clinical data and accelerate the development of future metabolically enhanced CAR-T cell therapies for solid cancers.
This dose escalation study conducted at the First Affiliated Hospital of the University of Science and Technology of China has yielded promising results for Leman Biotech's Meta 10-19 therapy in the treatment of patients with recurrent or refractory diffuse large B-cell lymphoma. Notably, the first patient in the study received a Meta 10-19 therapy dose equivalent to only 5% of the conventional CD19 CAR-T clinical dosage. Preliminary findings indicate that Meta10-19 CAR-T therapy exhibits remarkable safety, robust cell expansion potential, potent tumor-killing activity, and prolonged existence of CAR-T cells within the patient's body. During the initial follow-up examination, it was confirmed that the patient achieved complete remission, indicating a clinical cure.
Significantly, the entire therapeutic procedure using Meta 10-19 therapy did not lead to any adverse events commonly associated with conventional CAR-T therapies, such as fever, cytokine storms, and neurotoxicity. These encouraging initial results highlight the potential of Meta 10-19 therapy to provide a more targeted and safer treatment option for patients with diffuse large B-cell lymphoma, underscoring its clinical significance.
The principle investigator plans to further reduce the CAR-T cell dosage to 1% or less of the conventional dose, which will greatly reduce the preparation time and cost associated with CAR-T cell therapy. This advancement holds the potential to provide high-quality CAR-T products and a more accessible treatment option for patients with recurrent or refractory diffuse large B-cell lymphoma, emphasizing the platform's potential clinical significance and value.
Meta10-19 CAR-T Cell product developed based on Leman Biotech's Metabolically Armed CAR-T Cell Therapy Platform, which integrates cutting-edge technologies like artificial intelligence, genome editing, immune metabolism, and synthetic biology. This platform enables the development of metabolically armed CAR-T cells that have significant advantages in overcoming T cell exhaustion and inducing the formation of stem immunological memory cells, thereby exhibiting excellent expansion potential and prolonged persistence in patients.
The Meta10-19 cell therapy product is the Leman Biotech's first pipeline to enter the clinical research stage. Based upon the companies advanced immune metabolic reprogramming technology, this therapy harnesses the potential of CAR-T cells by enhancing their anti-exhaustion capabilities through the promotion of oxidative phosphorylation metabolism. Additionally, it induces CAR-T cells to acquire a stem cell-like immunological memory phenotype, resulting in a more durable and effective anti-tumor response.
In preclinical studies using animal solid tumor models, Meta10-19 has demonstrated excellent anti-tumor efficacy, surpassing conventional CD19 CAR-T therapies. In some cases, it achieved a remarkable cure rate of up to 100%, highlighting its advantages in terms of effectiveness and persistence. These findings position Meta10-19 as a novel and highly potent immune metabolic intervention strategy for CAR-T cell therapy in the treatment of tumors.
Non-Hodgkin lymphoma (NHL) represents the most prevalent form of hematological malignancy, with diffuse large B-cell lymphoma (DLBCL) being its primary subtype. Recent retrospective analysis of 636 patients with refractory or recurrent DLBCL in a multicenter international study revealed that despite receiving the standard first-line treatment regimen R-CHOP, approximately 30% to 40% of patients remained refractory or experienced relapse following initial remission. Given the limited treatment options available, DLBCL patients who have failed R-CHOP, are ineligible for autologous stem cell transplantation (ASCT), or have relapsed/refractory high-dose chemotherapy followed by ASCT face an extremely grim prognosis. Response rates to subsequent treatment are as low as 26%, complete response rates are merely 7%, and the median survival time is a mere 6.3 months.
CAR-T cell therapy has emerged as a highly effective approach for treating B-cell malignancies, including relapsed or refractory DLBCL. CD19, widely expressed on B-cell lymphoma cancer cells, stands out as a crucial target for the treatment of relapsed or refractory DLBCL. Currently, several international CD19 CAR-T therapies are available for the management of relapsed or refractory DLBCL. Nevertheless, these conventional CD19 CAR-T therapies, employed as second or third-line treatments, achieve only a 40% to 50% complete response rate, with over half of the patients experiencing relapse within a year following complete response. Consequently, the majority of patients do not obtain long-term benefits from these expensive CAR-T therapies. Therefore, there exists an urgent clinical need to enhance the complete and long-term response rates of CAR-T immunotherapy in relapsed or refractory DLBCL. The Meta10-19 cell therapy holds the potential to address this urgent clinical need and offer a novel strategy for improving the efficacy of CAR-T therapy in the treatment of solid tumors.
