As an emerging branch in biology, immunometabolism was first defined in a 2011 article in Nature Reviews Immunology. This field focuses on exploring the role of intracellular metabolic pathways in immune cells, bridging the gap between immunology and metabolism research.

Over the past decade, extensive research has shown that the metabolic intensity occurring within immune cells is closely related to their proliferation and function. Consequently, therapeutic strategies that modulate immune responses by influencing metabolic strength have become attractive potential treatments across various medical conditions.

Recently, META Pharmaceuticals Inc., a small molecule innovative drug development company based on immunometabolism targets, announced the successful completion of a total of over 100 million yuan in seed and Pre-A round financing. The lead investors include Forcefield Ventures, Crystal Technology, IMO Ventures, and TianTu Capital. Additionally, other investors such as Fangyuan Capital, Dexun Investment, Yayi Capital, New Industry Ventures, and Bopu Capital also participated in the funding.

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Reportedly, this financing will be used to accelerate the advancement of META’s three small molecule targeted innovative drugs under development to the clinical trial stage. Additionally, the company will continue to develop its AI metabolism enzyme target discovery platform infrastructure, aiming to extend advanced target prediction and validation efforts to cover a broader range of indications.

As the first domestic biotechnology company focused on metabolic regulation therapy, META specializes in modulating immune system function by regulating immune cell metabolism. This approach aims to improve and treat a wide range of conditions resulting from immune system and metabolic system dysregulation. These conditions include autoimmune diseases, cancer, metabolic disorders, and age-related chronic illnesses.

Based on cutting-edge achievements in immunometabolism theory, META Pharmaceutials has discovered a series of novel targets for metabolic enzymes. These targets are used to safely and effectively regulate immune system function, potentially bringing more ideal treatment options for patients with autoimmune diseases. Dr. Xu Ke, Co-founder and CEO of META, introduced this innovative approach.

Dr. Xu Ke graduated from McMaster University in Canada and Columbia University in the United States. In 2013, he joined the Immunology and Microbial Pathogenesis (IMP) program at Weill Cornell Medicine in the U.S. Throughout his more than ten years of basic biological research career, he has focused on studying the regulatory relationship between the immune system and metabolism. Using molecular and cellular mechanisms, he has demonstrated the crucial role of metabolic regulation in immune responses.

As of now, MetaBiopharma’s research pipeline includes three first-in-class investigational projects. The flagship pipeline involves small molecule inhibitors based on novel mechanisms and targets. Clinical applications for these innovative therapies are expected to begin in both China and the United States in 2024.

The first pipeline has entered the pre-clinical trial stage.

In simple terms, cell metabolism refers to the series of ordered chemical reactions that occur within a cell to support its basic activities. What makes immune cells unique is that their metabolic activity changes in response to the environment. For example, when pathogens are present in the body, the immune system is activated, leading to significant changes and coordination in the activities of various immune cell subtypes.

On the other hand, the normal functioning of all immune cells relies on specific and effective metabolic pathways. Therefore, researching and regulating the metabolic activity of immune cells will have a crucial impact on immune function.”

Over the past decade, with the gradual rise of research in the field of immunometabolism, scientists have delved deeper into understanding the relationship between cell metabolism and autoimmune and inflammatory diseases.

Taking autoimmune diseases in humans as an example, these conditions are actually caused by excessive immune reactions leading to organ damage. During this process, immune cells absorb significant amounts of nutrients for breakdown, meeting their energy supply demands. In other words, hyperactive and dysregulated immune cell metabolic activity is one of the underlying causes of such diseases,” explained Dr. Xu Ke.

Since 2013, Dr. Xu Ke has been dedicated to research in the field of immunometabolism. After obtaining foundational biological theory results, his research has gradually been validated in animal disease models. Throughout this process, he has witnessed the therapeutic potential of his research findings in the real world. Dr. Xu Ke recognizes that adjusting and influencing immune metabolic pathways to enhance or suppress immune responses will bring attractive emerging therapies to the fields of cancer and autoimmune diseases.

Based on the principles of immunometabolism, META was officially established in August 2021. The founding team includes several researchers from Weill Cornell Medicine and the Memorial Sloan Kettering Cancer Center in New York. Together, they are dedicated to finding novel “cures” for a wide range of diseases by regulating immune cell metabolism.

As of now, the company has developed three investigational pipelines. The flagship pipeline, META-01, targets immune cell metabolic enzymes and aims to cover a broad spectrum of autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis, and inflammatory bowel disease. This pipeline has entered the pre-clinical trial stage and is planned for clinical application in both China and the United States in 2024.

Additionally, META’s subsequent pipelines have entered or are about to enter the early drug discovery phase. The company is committed to building a diverse and differentiated drug pipeline that covers a broader range of metabolic pathways, benefiting various therapeutic areas, including cancer.

By precisely controlling metabolic enzymes, it is possible to effectively suppress energy supply and production in immune cells, without the goal of cell destruction. Therefore, it is safer,” explained Xu Ke. “On the other hand, this common mechanism impacts most autoimmune diseases, making this therapy beneficial for a wide range of conditions.

Metabolic enzymes are responsible for regulating energy production, breakdown, and synthesis processes within cells. They play a crucial role in gene expression, cell cycle regulation, DNA damage repair, cell proliferation, survival, apoptosis, and modulation of the tumor microenvironment.

Current treatments for autoimmune diseases heavily rely on immunosuppressive drugs. However, these medications often come with side effects such as liver toxicity and organ damage, which are difficult to avoid. Additionally, the eligible population for such drugs is limited. In comparison, an alternative approach involves modulating immune responses by influencing the metabolic processes of immune cells. This method is not only highly effective but also gentler. It significantly reduces damage to normal tissue cells, mitigating the high toxicity and organ-related side effects associated with traditional medications. Furthermore, it has the potential to expand its applicability to a broader range of patients.

AI + Immunometabolism: From theoretical preparation to lead compounds, it only takes 8 months.

After more than a decade of research and development, therapeutic strategies that regulate metabolism to enhance or suppress immune responses have garnered significant attention from experts in various disease fields.

Early studies indicated that overactive immune system responses have broad implications. As far back as 1993, Hotamisligil and colleagues discovered that obesity affects the immune system, subsequently promoting inflammatory diseases. Since then, it has been confirmed that immune metabolism impacts conditions such as age-related chronic diseases, autoimmune diseases, inflammatory disorders, and cancer. However, the discovery process for relevant drugs has been notably slow.

In fact, the human body contains nearly 3,000 different metabolic enzymes, forming a complex metabolic network. This network includes various intertwined and interacting signaling pathways like PI3K/AKT and mTOR, collectively responsible for metabolic regulation. Consequently, identifying a disease-specific metabolic pathway and precisely targeting a key metabolic enzyme as a therapeutic focus is an immense and intricate task.

“Finding a target that is truly relevant to a disease, possesses immune specificity, and does not compensate for other metabolic pathways is no easy feat,” explained Xu Ke. “Initially, researchers could only painstakingly unravel the underlying mechanisms by inefficiently knocking out individual metabolic enzymes. Now, with the aid of advanced AI technology platforms and algorithmic tools, target discovery work has made rapid progress.

“META has recently established an AI-powered metabolic pathway drug target discovery platform. Their specialized database aggregates hundreds of publicly available datasets, and they’ve built disease models and intelligent analysis models based on multi-omics analyses to rapidly obtain innovative target data.

In addition, the company has partnered with XtalPi to extend AI technology downstream for target validation and drug development processes. These two platforms mutually validate and provide feedback, linking biological mechanisms with drug development data. This approach breaks free from the limitations of traditional linear pharmaceutical processes, challenges the scarcity of research data, and tackles the development complexities of novel targets. It continues to drive META’s pipeline development.

“Undoubtedly, AI technology has effectively helped us overcome bottlenecks in immunometabolism research. Its impact on proteinase drug target discovery has exceeded expectations,” explained Xu Ke. “From theoretical preparation to achieving the milestone of lead compounds, it took only 8 months.

“If AI technology is the engine of drug development, then emerging biological mechanisms serve as the steering wheel for direction. According to XtalPi, for AI to truly gain widespread application in the pharmaceutical field, it requires the organic integration of intelligent algorithms, automated laboratories, and expert experience—none of these components can be missing. Our goal is to provide suitable tools to experienced experts, maximizing the value of this triad,” commented Dr. Zhang Peiyu, Chief Scientist at XtalPi.

The global industrialization process is still in its early stages, and research and industry need to develop synergistically.

As the second-largest therapeutic field after cancer, the field of autoimmune diseases includes conditions such as multiple sclerosis, systemic lupus erythematosus, allergic asthma, rheumatoid arthritis, and ulcerative colitis. It affects approximately 350-400 million patients worldwide, with significant unmet clinical needs and a gap in innovative drugs.

According to forecast data published by Zhongjin Qixin International Consulting, the global autoimmune disease treatment market is projected to grow from $120.6 billion in 2020 to $175.2 billion in 2030. The domestic market size is also expected to reach $800 million by 2025, with the potential to reach $24.7 billion by 2030.

However, over the past two decades, biological research in this field has stagnated. Patients have long relied on outdated biological theories for drug development, including large-molecule antibody drugs and small-molecule JAK inhibitors. Among these, AbbVie’s immunosuppressant Humira has consistently topped the annual drug sales rankings, generating nearly $20 billion in sales each year. However, both Humira and other antibody drugs suffer from serious side effects and low patient response rates. Therefore, the urgent need to develop efficient and safe biologic drugs for autoimmune diseases remains.

The immense market prospects have attracted some advanced biotechnology companies to venture into the field. Simultaneously, pharmaceutical giants have taken notice, marking the beginning of the development of immunometabolism drugs.

In 2019, Rheos Medicines, a rising star in the immunometabolism field based in Cambridge, Massachusetts, secured a global exclusive collaboration, selection, and licensing agreement worth nearly $800 million from Roche. This agreement aims to discover, develop, and commercialize new therapies in the immunometabolism domain. Rheos’ flagship pipeline candidate, RHX-317, is a novel MALT1 (Mucosa-Associated Lymphoid Tissue Protein 1) inhibitor that has demonstrated efficacy in various disease models, including graft-versus-host disease (GVHD) and lupus nephritis.

In 2020, another biopharmaceutical company, Sitryx, specializing in cell metabolism regulation, signed a research collaboration agreement valued at nearly $900 million with Eli Lilly. This collaboration aims to advance their four novel immunometabolism-targeted therapeutic drug candidates. Clearly, the global competition in immunometabolism therapy involves only a handful of players, and most are still in the early stages.

“The fundamental biology of this field still holds tremendous untapped potential. Immunometabolism research is gaining momentum, and the number of laboratories engaged in related studies has multiplied in recent years. However, clinical research data remains limited,” says Xu Ke. At this stage, substantial investments in research talent and funding are still required for foundational research.

“In response to this challenge, META has prepared in terms of talent acquisition. Additionally, we plan to collaborate extensively with relevant domestic hospitals and laboratories. While developing our drug pipeline, we aim to feed clinical data back into theoretical research, leveraging AI to achieve efficient synergy between research and industry. Our goal is to accelerate progress in the domestic immunobiology field and bring the next generation of immune-related disease drugs to clinical use.””