MetWare Bio Launches IPO: Building a Leading Multi-Omics Platform with a 290,000-Metabolite Database and Nearly 50 Mass Spectrometers

“Genomics tells you what might happen, while metabolomics tells you what has already happened.”In 2015, when genomics was experiencing a boom, Tang Tang carved out a unique path by strategically positioning himself in metabolomics with forward-looking insight.

Previously, Tang Tang had been focused on genomics. In 2015, the field of genomics in China was booming, with hundreds of domestic enterprises emerging. By chance, Tang Tang met Professor Luo Jie, an expert in metabolomics. Integrating metabolomics data with other omics analyses yielded unexpectedly favorable results, which convinced Tang Tang thatMetabolomics is a key direction in precision medicine.

Currently, Metware, founded by Tang Tang in August 2015, has become a leading enterprise in the field of metabolomics. It has established metabolomics and proteomics platforms equipped with nearly 50 mass spectrometers, as well as a collaborative genomics platform. The company has assembled a team of over 400 professionals with diverse backgrounds in chemistry, pharmacy, biology, medicine, computer science, and other disciplines across China and the United States, serving more than 2,000 clients.

Genomics explores life activities at the genetic level, but it cannot fully answer all questions regarding human physiological processes. These processes ultimately arise from the combined actions of macromolecular proteins and small-molecule metabolites.

Metabolomics performs qualitative and quantitative analysis of small-molecule metabolites with a relative molecular mass below 1,500 Da in a given organism or cell. As an emerging discipline in the post-genomics era and a key component of systems biology, it plays a pivotal role in translational research related to biomarker discovery, drug target identification, drug response, and disease mechanisms.

Many cellular life activities occur at the metabolite level, with metabolites directly or indirectly involved in processes such as cell signaling, energy transfer, and intercellular communication. The metabolome, composed of biomolecules closest to an organism’s phenotype, is often referred to as the molecular phenotype of biological systems.

Metabolomics involves the comprehensive and quantitative detection of various types of small-molecule compounds in biological samples to elucidate the changes and patterns of endogenous substances within organisms under the influence of intrinsic and extrinsic factors. It is particularly suitable for clinical studies investigating physiological alterations induced by genetic, developmental, physiological, and environmental factors, as well as by stimuli such as xenobiotics and pathogens.

Metabolomics technologies not only enable the characterization of the status and changes in metabolic functions during disease onset, progression, and treatment, thereby providing new avenues and insights for clinical diagnosis, elucidation of pathological mechanisms, and discovery of novel therapeutic targets; they also reveal the impact of external interfering factors on the body, thus supplying foundational data for drug efficacy evaluation and screening of disease etiologies.

In recent years,With improvements in sensitivity and detection throughput, metabolomics research has entered a new phase.Although metabolomics has not yet seen mature applications in the clinical sector, research teams have already identified a small number of valuable metabolic small molecules through metabolomics for use in clinical diagnosis.

For example, ceramides identified through cohort metabolomics studies are already used for cardiovascular disease prognosis assessment at the Mayo Clinic and Quest Diagnostics, while some hospitals in China are conducting related exploratory research tailored to the Chinese population. Overseas, companies have developed corresponding colorectal cancer screening products based on urine biomarkers identified via metabolomics, as well as diabetes screening products based on blood biomarkers.

Overall, metabolomics is advancing rapidly and holds broad prospects. Its potential in scientific research, drug development, and clinical testing has not yet been fully realized, making it an emerging blue ocean in the field of precision medicine following genomics.

Despite its immense potential, it is undeniable that metabolomics remains in its early stages of development, akin to the state of genomics seven or eight years ago.

Tang Tang stated, “Conducting metabolomics requires overcoming obstacles such as the stability and complexity of metabolite detection, as well as database construction.”

First, how to stably obtain omics data.Genes are relatively static, whereas metabolites change rapidly. After sample collection, biochemical reactions occur at room temperature, posing significant challenges to detection stability. To address this issue, Metware has established standard requirements for sample collection and developed a stable and controllable sample pre-processing system.

Next is the complexity of metabolites.Metabolites encompass a vast array of compounds, including amino acids, organic acids, lipids, and vitamins. Different metabolites require distinct sample preparation protocols, and their separation and detection methods also vary. Analyzing them on the same or a limited number of chromatography-mass spectrometry systems can lead to mutual interference, thereby compromising data quality. In such cases, a large-scale mass spectrometry platform is required to meet the diverse analytical demands of metabolomics across different scenarios. Currently,Metware has established a mass spectrometry analysis platform comprising nearly 50 instruments., meeting the testing requirements for different methodologies and sample types while ensuring assay stability.

Next is the construction of a metabolomics database.Once quality control is ensured and a certain scale is achieved, it is necessary to establish a matched database for identification based on chromatography-mass spectrometry conditions. Just as genomics and proteomics rely on reference sequences in GenBank and UniProt to annotate genes and proteins, metabolomics also heavily depends on reference compound data and reference spectral data to annotate metabolites. “However, this process cannot rely on public databases, because information in public libraries comes from different separation conditions and detection platforms, leading to differences in retention times and fragment ions that can affect the accuracy of identification.”The development of a local metabolomics database is key to metabolomics research.

Building a large-scale metabolomics database not only requires substantial financial investment but also involves the analysis of a vast number of samples from different species/subspecies/disease types, as well as various tissues, organs, and cells. Meanwhile, it places high demands on researchers’ capabilities in spectral analysis, instrument operation, algorithm development, and logical thinking. Metware has made long-term investments in this field,Independently developed a database of 290,000 metabolites, which is continuously expanding.Humans and animals have hundreds of thousands of metabolites, while plants have one million, leaving substantial room for expansion.

“Moreover, a comprehensive exploration of the answers to life requires the integration of metabolomics, genomics, and proteomics. Therefore, we have also established a genomics collaboration platform, creating databases for various omics disciplines. This, in turn, involves challenges related to multi-omics data mining,” added Tang Tang.

To date, Metware has established a business portfolio encompassing high-throughput metabolomics and functional metabolomics testing, as well as multi-omics analysis.

In the scientific research market, the company provides innovative metabolomics technology CRO services, with its business covering research institutes, hospitals, and industrial enterprises across 34 provinces, municipalities, and autonomous regions in China.Serving over 2,000 clients.

For clinical applications, Metware focuses on the development of metabolic kits for "liquid biopsy"-based early cancer screening and prognostic kits for chronic metabolic diseases.

Compared with normal cells, tumor cells exhibit significant alterations in their metabolic mechanisms, characterized by rapid growth and the ability to evade immune recognition. In simple terms, tumors display substantial metabolic differences, and these unique metabolic features can be leveraged for early screening and auxiliary diagnosis.

Metware'sFirst-in-Class Product: Blood Metabolomics Test for Colorectal Cancer, the biomarkers for ultra-early diagnosis of colorectal cancer, screened using widely targeted metabolomics technology, have completed two rounds of multicenter experimental validation across China. At a specificity of 0.9, the auxiliary diagnostic sensitivities for advanced adenomas and stage I colorectal cancer exceeded 0.5 and 0.8, respectively.

Over the past two decades, metabolomics research has made significant progress, extensively penetrating fields such as pharmaceuticals, botany, and environmental science to address practical problems.

Tang Tang believes that the future development trends of metabolomics are mainly in three directions,1. Processing of cohort or population samples, typically encountering queue samples at the scale of tens of thousands to hundreds of thousands, it is necessary to develop faster and more stable instruments along with corresponding detection methods;Second, integrated multi-omics analysis research, the advancement of multi-omics research needs to be promoted through the joint progress of different disciplines and technologies;3. Development of Emerging Technologies and Multi-OmicsAs analyses become increasingly complex, there is a growing pursuit of precision, enabling the analysis of smaller cell populations and even single cells. In recent years, the rise of spatial omics has further spurred increasing demand for spatial metabolomics and single-cell metabolomics.

It is certain that the window of opportunity for metabolomics has arrived. Moving forward, Metware will provide hospitals and pharmaceutical companies with more comprehensive metabolomic data generation services. Simultaneously, it will strategically focus on clinical applications by pursuing biomarker discovery for major diseases, including colorectal cancer, gastric cancer, lung cancer, and cardiovascular and cerebrovascular disorders, thereby advancing disease diagnosis and drug development.

Tang Tang stated, “Metware’s focus is not on traditional offerings such as existing newborn screening for inherited metabolic disorders and therapeutic drug monitoring. Over the next five years, the company will rapidly bring a series of innovative projects to market, providing unique solutions for research into disease mechanisms and precision diagnosis and treatment.”