AI-enabled, metabolically enhanced CAR-T project financing completed

Recently, Shenzhen Laimang Biotechnology Co., Ltd. (hereinafter referred to as "Laimang Bio"), a biotechnology enterprise focusing on research and development, production and commercialization of new tumor immunotherapy innovative drugs, announced the completion of two new financing rounds of Angel+Round and Angel++Round totaling 50 million yuan. The new shareholders of this financing include Fuhui Venture Capital, Yun Fan Science and Technology Investment and private financial investors, while the old shareholders Tiantu Investment and Jingtai Technology continue to be blessed. In addition, the CAR-T project of Leman Bio-and its metabolic enhancement has successively received various kinds of funding of about 20 million yuan. So far, Leman Bio has accumulated about 150 million yuan in angel financing and project funding. This financing will be mainly used for the declaration of metabolic enhanced CAR-T cell therapy drug IND, and accelerate the clinical research of metabolic enhanced cell therapy drugs for solid tumors.

About Leman organisms

Founded in July 2021 by the team of Professor Li Tang from EPFL and Jingtai Technology, it was officially put into operation in February 2022. Meta-10, the core technology of Leman biology, shows great potential for curing solid tumors, and related achievements are published in the top international academic journals Nature Immunology(2021) and Nature Biotechnology(2024). On this basis, Leman Bio has established a technical platform for the discovery, research and development and production of biomacromolecules and new immunotherapy cell drugs with independent intellectual property rights. At the same time, the company uses cutting-edge artificial intelligence (AI) technology to iteratively upgrade existing drugs, forming three core drug research and development pipelines: metabolic reprogramming biomacromolecule drugs, anti-depletion cell therapy drugs and super factor drugs.

The metabolism-enhanced CD19 CAR-T cell drug unique to Lyman is currently undergoing IIT clinical research in the First Affiliated Hospital of China University of Science and Technology (Anhui Provincial Hospital) and the First Affiliated Hospital of Zhejiang University School of Medicine. The project has successfully completed the treatment of more than 20 adult patients with relapsed or refractory leukemia/lymphoma, all of whom achieved complete remission (CR) and were discharged. In addition, the Metabolic Enhanced CD19 CAR-T Clinical Study (IIT) was successfully launched in Children's Hospital affiliated to Zhejiang University School of Medicine at the end of March, 2024, which indicates that the indication of this therapy will be further extended to children with recurrent or refractory CD19 positive B-cell hematological malignancies.

It is worth mentioning that metabolism-enhanced CD19 CAR-T cell drugs in IIT clinical research not only make more than 20 patients with advanced relapsed refractory leukemia/lymphoma all reach CR, but also require a very low dose-as low as 1% of the commercial CAR-T dose. This breakthrough will greatly shorten the drug production cycle and significantly reduce the production cost of CAR-T, which is expected to greatly reduce the original "sky-high" price of cell therapy drugs, and provide the possibility for this product to be included in the national medical insurance catalogue in the future.

On metabolically enhanced CD19 CAR-T

A core factor that prevents CAR-T from playing a role in the treatment of solid tumors is the dysfunction caused by T cell exhaustion. Immunosuppressive tumor microenvironment (TME) characterized by acidity, hypoxia, nutrient depletion and metabolite accumulation caused by high metabolic demand of tumor cells can lead to T cell depletion, which is characterized by the decrease or loss of proliferation ability and effector function, while the expression of multiple immunosuppressive receptors is up-regulated. However, by improving the metabolic capacity of cells, we can reverse the exhaustion of T cells and help them restore their original functions. This is the core idea of metabolic-enhanced CAR-T-adjusting the metabolic pattern of T cells and restoring the vitality of T cells by means of metabolic reprogramming.

The innovation breakthrough of Leman Bio lies in the metabolic reprogramming of T cells by using Meta 10, the company's core AI technology platform. Based on AI Qualcomm screening, the company successfully constructed CAR-T cells secreting IL-10. The modified cells can effectively resist the negative factors leading to T cell depletion in the microenvironment of immunosuppressive tumor (TME), thus significantly improving the proliferation ability and effector function of T cells. Specifically, IL-10 optimizes the mitochondrial adaptability of CAR-T cells and strengthens the oxidative phosphorylation (OXPHOS) process of mitochondria by means of mitochondrial pyruvate carrier (MPC) dependence. These two aspects are precisely the key links of TME's damage to T cell metabolism. Through metabolic reprogramming, T cells can enhance oxidative phosphorylation metabolism, achieve sustained proliferation and maintain better killing activity, and get rid of exhaustion.

AI empowerment r&d platform

Inspired by the structure-based IL-10 sequence optimization article published by Professor Christopher Garcia of Stanford University in Science, Leman Bio started an innovative project of AI-empowering drug research and development. Although Professor Christopher's research successfully transformed IL-10 through traditional wet experiments, its transformation scope was limited to a few sites.

In order to break through this limitation, Lyman Bio and Jingtai Technology joined hands and adopted a brand-new R&D strategy: abandoning the traditional wet experiment method and using high-precision computational chemistry and advanced AI algorithm to systematically transform and optimize IL-10.

After just two rounds of efficient iteration, Lymantria has screened out thousands of mutants with significantly improved affinity. After further in-depth analysis and testing of 20 mutants, Leman Bio found that the affinity of several candidate mutants was hundreds or even thousands of times higher than that of Super 10 reported by Stanford University. It is worth mentioning that the whole iterative process was successfully completed in less than one month.

Future prospects

The clinical research results of Lyman's biology have attracted great attention from colleagues at home and abroad, and successively obtained the oral reports of the latest breakthrough of American Cancer Society (AACR 2024), American Association for Gene and Cell Therapy (ASGCT 2024), European Hematology Association (EHA 2024) and China Society for Cell Biology (CSCB 2024). This new round of financing will further promote the clinical transformation research of metabolic enhanced CAR-T cell therapy in our company.

This financing has obtained additional investment from the original shareholders Jingtai Technology and Tiantu Investment. XtalPi, as a global leading platform-based technology company with AI and robot-driven innovation, has been actively looking for and supporting start-ups with breakthrough innovation and huge market prospects, enabling advanced research results in the biomedical field to accelerate clinical transformation. The additional investment of the original shareholders such as Jingtai Technology and Tiantu Investment shows that investors fully affirm the research progress of Lymantria in the field of immunotherapy and have confidence in the future development of Lymantria.