Ultra-Low-Dose CAR-T Therapy Could Drive Down Costs: Leman Bio Secures RMB 50 Million in Additional Angel Funding
Leman Biotech
Developer of Novel Tumor Immunotherapy Drugs
Text｜Hu Xiangyun
Editor｜Hai Ruo Jing
36Kr learned that Leman Biotech Co., Ltd. has recently completed a total of 50 million yuan in Angel+ and Angel++ rounds of financing. The new investors in this round include Fuhui Venture Capital, Yunfan Technology Investment, and private financial investors, while existing shareholders TianTu Investment and XtalPi continued to increase their investment; the company also received approximately 20 million yuan in various grants. Since its establishment in 2021, Leman Biotech Co., Ltd. has cumulatively received about 150 million yuan in angel financing and grants.
The proceeds of this fundraising will be used for the company’s IND application for its "ultra-low dose" metabolism-enhanced CD19 CAR-T cell therapy drug, as well as to accelerate the clinical development of metabolism-enhanced cell therapy drugs targeting solid tumors.
Source: Leman Bio
In recent years, although immunotherapy has brought revolutionary breakthroughs to the field of cancer treatment, the low response rate has also become a significant issue limiting its further development. According to research data from Southwest Securities, even for the "miracle cancer drug" PD-1 products, the response rate in most solid tumors is within 30%, and the overall effectiveness of CAR-T therapy in solid tumors is less than 10%. The reason can be attributed to the common bottleneck problem of T-cell exhaustion.
"Including PD-1/PD-L1, current cancer immunotherapies primarily focus on activating precursor exhausted T cells within tumors. However, this is only a subset of exhausted T cells and does not directly address anti-tumor activity. Our target, the terminally exhausted T cells, are characterized by their direct tumor-killing function and sustained therapeutic effects, with generally high response rates in combination therapies. Due to research limitations, it was previously believed in academia that terminally exhausted T cells could not be directly modulated. We have discovered that IL-10, an immunosuppressive factor, can directly act on terminally exhausted T cells, promoting their proliferation and cytotoxic activity, effectively breaking through a major bottleneck in cancer immunotherapy," explained Dr. Yugang Guo, co-founder of Leman Bio.
Specifically, the main causes of T cell exhaustion include persistent antigen stimulation and the tumor immunosuppressive microenvironment. The Leman team found in their research that IL-10 can alleviate T cell exhaustion by enhancing oxidative phosphorylation metabolism in terminally exhausted T cells, thereby achieving metabolic reprogramming of exhausted T cells. Meanwhile, when an IL-10-Fc fusion protein with an extended half-life is used in conjunction with CAR-T therapy, it may also prevent and reverse T cell exhaustion, ultimately improving the response rate and efficacy of cancer immunotherapy.
Based on existing research, Leman Biotech has established the Meta 10 Immunometabolism Reprogramming Technology Platform and developed three categories of pipeline products: macromolecules, cell therapy, and AI super factors. Among these, cell therapy is the company's current key focus. "In the field of cell therapy, we primarily follow a three-step approach: First, we select mature targets such as CD19 and BCMA along with corresponding hematological tumor indications to validate the efficacy and safety of the platform; then, we pursue differentiated innovation by targeting indications where current treatments show limited efficacy, such as adult chronic B-cell lymphocytic leukemia and pediatric malignant hematological tumors. After verifying the product’s effectiveness in these indications, we will further explore more challenging hematological malignancies, such as acute myeloid leukemia. Additionally, the development of this pipeline for solid tumors and autoimmune disease indications will proceed concurrently."
At the American Association for Cancer Research (AACR 2024) in April and the American Society of Gene and Cell Therapy (ASGCT 2024) annual meeting in May, research findings on metabolism-enhanced CD19 CAR-T were selected for the "Late-Breaking" oral presentation. Existing data shows that in IIT trials for relapsed/refractory leukemia or diffuse large B-cell lymphoma, this product enrolled over 20 patients, achieving a 100% complete response (CR) rate, with dosages as low as 1% of conventional CD19 CAR-T therapy. Notably, no severe cytokine release syndrome (CRS) or other common side effects associated with CAR-T treatment were observed in patients, demonstrating the superior efficacy and safety potential of metabolism-enhanced CD19 CAR-T.
In terms of progress, the metabolic-enhanced CD19 CAR-T is expected to enter the pivotal clinical study phase in the first quarter of 2026.
In addition, this study was also selected for oral presentations at the annual meetings of the European Hematology Association (EHA 2024), the European Society for Blood and Marrow Transplantation (EBMT 2024), and the Chinese Society for Cell Biology (CSCB 2024).
Beyond safety and efficacy, the characteristics of the metabolism-enhanced CD19 CAR-T product in terms of dosage are also highly noteworthy. "An extremely low dose also implies that costs can be reduced to a certain extent, thereby leading to a reduction in the price of the end product," explained Dr. Guo Yugang: "In addition to improving the turnover efficiency of manufacturing facilities, an extremely low dose can also save on the costs of consumables and reagents required in the preparation process. Unlike the much-discussed factors behind the price reduction of CAR-T in India, which relies on locally produced substitutes for labor and reagents in India, resulting in more unstable efficacy compared to the original product; our approach of significantly reducing the dosage (as low as 1%) achieves cost reduction while ensuring efficacy."
In the progress of the other two types of pipelines, the large molecule pipeline with relatively rapid advancement is the IL-10-Fc fusion protein, which focuses on combination therapies with CAR-T, TCR-T, and immune checkpoint antibodies to enhance their efficacy in solid tumor treatments. Data from a report published by Leman’s R&D team in Nature Immunology showed that this pipeline achieved a 90% cure rate in both rectal cancer and melanoma models. The AI super-factor, as a reserve technology of the company, will assist in further optimizing the existing technology platform as well as the large molecule and cell therapy pipelines, and has already made positive progress.
In terms of international expansion, Dr. Guo Yugang revealed that Leman Bio is actively promoting overseas BD-related matters. "Despite the current international situation and market environment having some impact, overseas MNCs still maintain strong enthusiasm for the CGT field. During our exchanges, we can feel that they are indeed very cautious and professional, but they show great interest in every meeting, hoping that we can provide more details and data."
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