Leman Biotech: Multiple breakthroughs in clinical trial for hematological malignancies

These achievements include:

1. The first group of ten patients enrolled in the IIT clinical trial all met the criteria for complete remission (CR) and were subsequently discharged from the hospital.
2. The treatment dosage was further reduced from an already low dose (5%) to 1% of the conventional CAR-T dosage.
3. Two patients with primary or metastatic CNS (central nervous system) disease received functionally enhanced CD19 CAR-T cell infusion. CD19 CAR-T cells were infused back into these patients, both of whom are in complete remission (CR). The first patient with metastasis CNS has been in CR status for over 6 months.

The first ten patients enrolled in the IIT clinical trial have all successfully achieved complete remission (CR) and have been discharged from the hospital, the treatment process was gentle and under control.
Leman Biotech's IIT clinical trial on relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) and acute B-lymphoblastic leukemia (r/r B-ALL) aims to investigate the safety and efficacy of functionally enhanced CAR-T System (Meta 10). Therefore, CD19, a relatively well-researched target, has been chosen as the first therapeutic CAR-T cell target in the IIT clinical trial to gather relevant clinical data on Meta 10 technology. This information will allow to proceed subsequently with the development of CAR-T cell therapies against solid tumors. Since the enrollment of the first patient in February 2023, Meta10-19 CAR-T cell therapy has consecutively achieved complete remission in ten patients. These discharged patients are being regularly monitored by clinical specialists, and are currently maintaining complete remission (CR) status post treatment. The first patient in this trial has now been cancer-free for 7 months.

Relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) is a common hematological malignancy. At present, there are several CD19 CAR-T products available on the market for the treatment of r/r DLBCL. However, these conventional CD19 CAR-T therapies are used as second-line or third-line treatments and achieve a complete remission (CR) rate of only 40% to 50%. Additionally, adult acute lymphoblastic leukemia (r/r ALL) accounts for about 20 to 30% of adult acute leukemia cases, and the overall complete remission rate after previous treatment is about 40%, with a 3-year survival rate of only 11%. Hematopoietic stem cell transplantation (HSCT) is the main hope for a cure for r/rALL patients, but only about 30% of adult r/r ALL patients receiving first salvage chemotherapy have the opportunity to undergo HSCT. Therefore, there is an urgent clinical need for more effective treatments for relapsed and refractory lymphoma/leukemia, and Meta10-19 infusion holds promises as a new treatment option and hope for patients.

Furthermore, Meta 10-19 infusion has demonstrated an excellent safety profile in this IIT clinical trial. All treated patients had stable vital signs, with no treatment-related side effects, such as cytokine storms or noticeable neurotoxicity. This is in contrast to conventional CAR-T cell therapies that often lead to cytokine storms, causing systemic inflammation and severe damage to organs and tissues, which is one of the reasons limiting their clinical use. Leman Biotech's Meta10-19 infusion offers a potentially safer and more effective treatment option for patients.

CAR-T cell infusion dosage as low as 1% of the conventional dose, which is expected to significantly reduce the production cycle and treatment costs.
Meta 10, the core technology of Leman Biotech, is the first therapeutic intervention reinvigorating terminally exhausted T-cells in the field of cancer immunotherapy. This technology can induce CAR-T cells to acquire a stem cell-like immune memory phenotype, resulting in more durable and effective anti-tumor effect. In this IIT clinical trial, Leman Biotech's R&D team, in collaboration with clinical experts from the Department of Hematology at Anhui Provincial Hospital, initially administered a low infusion dose at 5% of the standard dose used for conventional CD19 CAR-T therapy on the market.

This IIT clinical trial has shown recently that, this 5% dose of Meta10-19 CAR-T cells can be further reduced to only 1% of the conventional CAR-T cell dose. For example, one patient enrolled has primary central nervous system lymphoma (PCNSL), a rare form of diffuse large B-cell lymphoma with the worst prognosis among all non-Hodgkin's lymphomas. Given the uniqueness of central nervous system primary tumors, clinical experts recommended further reducing the Meta10-19 CAR-T cell infusion dosage to 1% of the standard dose for this PCNSL patient. After a 14-days of hospitalization, this lymphoma patient achieved complete clinical remission and was discharged smoothly. The patient had almost no related clinical side effects, and had a shorter hospitalization length compared to previous patients.

One of the major factors limiting the accessibility of clinical CAR-T therapies is the lengthy production cycle and high costs, preventing most patients from benefiting from CAR-T, “the expensive drugs”, in the long term. Extremely low doses (1% to 5%) can significantly reduce the production cycle and cost of CAR-T cell therapies, increasing accessibility. Leman Biotech's Meta10-19 infusion, with its extremely low dosage, has the potential to substantially reduce the production cycle and treatment costs. This development could potentially expand the accessibility of clinical applications, improve patients’ treatment experience and quality of life, and benefit more patients.

The first central nervous system (CNS) relapse patient has maintained complete remission (CR) status for over 6 months.
It has been reported that 30% to 40% of ALL (Acute Lymphoblastic Leukemia) patients have CNS leukemia at the time of relapse, and ALL patients with CNS leukemia have an overall survival (OS) rate of only 6 months, with a 5-year OS rate of 0, indicating that CNS leukemia remains one of the main reasons for treatment failure in ALL. Furthermore, CNS relapse is one of the most destructive complications, with a median survival rate of only a few months.

Leman Biotech's first CNS relapse patient has maintained CR status for more than 6 months. The IIT clinical trial of Meta 10-19 infusion is currently treating ten patients, including two patients with CNS primary/relapse diseases. One of these patients, a 20-year-old young patient diagnosed with acute B-lymphoblastic leukemia a year ago, underwent a bone marrow transplant and was readmitted to hospital in October 2022 due to severe headaches. Examinations showed CNS metastasis. In this case, conventional treatment doesn’t work. Fortunately, this patient enrolled in Leman Biotech’s IIT clinical trial received three weeks of treatment with Meta10-19 CAR-T cell infusion at Anhui Provincial Hospital, and achieved a successful complete remission after the treatment. Being discharged for more than six months, the patient is maintaining CR, in good condition, able to take exercise normally, travel, and enjoys his new life.