AQu Biotech Files IPO Prospectus: The 'SF Express' of Metabolomics Detection Sets Sights on Capital Markets

Metabolomics, like genomics, proteomics, and transcriptomics, is an emerging research field with the suffix “-omics,” and it contributes to the understanding and application of biological processes in organisms and their interactions with the environment.

Metabolomics is a research approach that involves the quantitative analysis of all metabolites within an organism and investigates the correlations between metabolites and physiological or pathological changes, serving as an integral component of systems biology. The primary subjects of study are small-molecule substances with relative molecular masses below 1,500.

Due to the high technical barriers, metabolomics testing is a path few entrepreneurs choose to take. Deng Junliang, founder of BIOTREE, which specializes in mass spectrometry-based metabolomics testing, told VCBeat (WeChat ID: vcbeat) that when BIOTREE decided to focus on metabolomics testing in 2012, China’s metabolomics testing industry was still a blank slate.

He stated, “In 2012, it had been less than 13 years since the concept of metabolomics was proposed. Different academic schools of thought still existed internationally, indicating that metabolomics was still in a very early stage. Many researchers in China were unfamiliar with this technology, and many even questioned its reliability.”

At that time, metabolomics testing was still a largely undeveloped field, while the genetic testing industry was booming. After careful consideration, Deng Junliang chose to start a business in the field of metabolomics testing. Upon truly entering the metabolomics testing sector, Deng Junliang frankly stated, “It is really, really difficult.”

Fortunately, since its establishment nearly eight years ago, BIOTREE has established and refined testing and research platforms encompassing untargeted metabolomics, high-throughput targeted metabolomics, routine targeted metabolomics, and functional metabolomics. In October 2018, BIOTREE partnered with Nanjing Yangzi Sci-Tech Innovation to build a world-leading mass spectrometry testing center. Leveraging the technical capabilities of BIOTREE’s Shanghai R&D Center, this facility is now capable of processing up to 100,000 samples. Furthermore, BIOTREE has constructed a GMP-compliant R&D and production base for mass spectrometry-based in vitro diagnostic kits, positioning the company to enter the field of clinical mass spectrometry testing.

Genomics and proteomics explore life activities at the genetic and protein levels, respectively, while many intracellular life activities occur at the metabolic level. Processes such as cellular signal release, energy transfer, and intercellular communication are all regulated by metabolites. As some have stated, “Genomics and proteomics tell you what might happen, whereas metabolomics tells you what has already happened.”

Within the gene–protein–metabolite–phenotype framework, metabolomics represents the most downstream stage of the entire biological dynamic system.

Metabolomics is also referred to by some as the most challenging “-omics” discipline, because while genomic and transcriptomic analysis systems have become highly standardized and proteomics has established universal methodologies, metabolomics presents higher technical barriers in terms of analytical platforms, data processing, and data mining.

Deng Junliang stated, “The application of metabolomics in medicine primarily focuses on the discovery of diagnostic biomarkers and the study of disease mechanisms. In the biopharmaceutical field, it is mainly used for new drug discovery and the identification of drug targets. For instance, in clinical testing applications, newborn screening for metabolic disorders primarily involves the detection of amino acids and acylcarnitines.”

However, at present, the application of metabolomics testing in clinical diagnostics remains limited, as it is still primarily used for scientific research.

“In the research services market, most PhD students, researchers, and professors have a deep understanding of scientific research but lack access to robust platforms and tools that can provide them with data. Our service serves as such a tool, helping clients obtain high-quality data efficiently and conveniently.”

Currently, BIOTREE’s clients are primarily drawn from universities, hospitals, research institutes, and corporations. Among these, universities account for approximately 40%, while the company serves around 300 hospital clients, most of which are Grade A tertiary hospitals.

As an early entrant into this market, BIOTREE has faced relatively few competitors. However, this also means that there are no established development pathways or industry standards to reference; the company must navigate uncharted territory through trial and error.

BIOTREE first encountered a shortage of talent during its development.

“Three cobblers combined might equal one Zhuge Liang at best, but you’d still need the Five Tiger Generals to get things done,” Deng Junliang said with a smile.

Fortunately, BIOTREE has engaged Dr. Zhu Zhengjiang, a researcher at the CAS Center for Excellence in Molecular Cell Science, as its technical expert advisor.

In 2013, Dr. Zhu Zhengjiang returned to China from the research group of Professor Gary Siuzdak at the Scripps Research Institute in California, USA, and joined the Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences, as a principal investigator. Professor Gary Siuzdak’s research group is regarded as a world-leading authority in the field of metabolomics; the Metlin database and XCMS software developed by his team are widely used by scientists worldwide.

Subsequently, BIOTREE specially appointed Dr. Zhu Zhengjiang as its Chief Technical Expert Advisor. Dr. Zhu not only helped BIOTREE establish its technical system but also cultivated a team of core technical personnel for the company.

While introducing professional talent, BIOTREE is also actively cultivating and building its talent reserve. Since 2014, BIOTREE has continuously organized training courses on metabolomics, with thousands of students having graduated to date.

After resolving its talent challenges, BIOTREE began to establish its core competitive advantages within the industry.

In metabolomics analysis, the primary technical bottleneck remains metabolite identification. The specific metabolites detected and their quantities can only be determined by referencing a standard spectral library.

Under the influence of Dr. Zhu Zhengjiang, BIOTREE has established its own metabolite database. The database now contains over 20,000 compounds with MS/MS spectra, making it compatible with data from high-resolution LC-MS platforms, such as QTOF and Orbitrap instruments, across major manufacturers.

For a single sample, the current international state-of-the-art using both positive and negative ionization modes can identify over 1,000 compounds. In contrast, by leveraging BIOTREE’s database in combination with innovative algorithms developed by Dr. Zhu Zhengjiang, more than 2,000 compounds can be identified.

Eliminate dependence on instrument processing software and develop a more stable end-to-end analysis system

Metabolomics presents high technical barriers; the diverse parameter selection, massive data volumes, and varied statistical methods involved in metabolite qualitative and quantitative analysis and data processing have deterred many researchers.

In metabolomics testing, high-throughput data collection has become achievable with the advancement of multi-omics research, including metabolomics. However, data analysis in metabolomics remains a challenge. The understanding of data and scenario-based analytical judgment have become the main bottlenecks in metabolomics research.

Deng Junliang candidly stated that in the early stages, BIOTREE also adopted a “borrowing” approach to metabolomics testing.

“When we first launched our metabolomics testing and analysis services, we relied on imported instruments, utilizing the software and databases provided by the instrument manufacturers, along with methods documented in the literature. Gradually, we realized that we had full control over pre-analytical sample processing and post-analytical statistical and bioinformatics analyses, as we thoroughly understood both the procedures and their underlying principles. However, one ‘black box’ remained before us: raw spectrum interpretation. We were merely using it without truly understanding how it worked.”

Due to the monopoly of imported manufacturers on mass spectrometry instruments, metabolomics analysis service providers generally learn how to use the instrument’s software to set parameters for signal extraction, deconvolution, integration, and data table generation based on training provided by the instrument vendors. However, they do not understand the specific algorithms and principles underlying the software.

Deng Junliang stated, “It was only when we found that the test results were sometimes unsatisfactory that we realized the algorithms in the instrument’s built-in software were not perfect. Later, when we came across open-source software such as XCMS, we felt a sense of enlightenment.”

With optimization support from the algorithm team, BIOTREE has developed the MAPS Metabolomics End-to-End Analysis System. This system can be deployed on private or public cloud servers, breaking through the performance limitations of traditional desktop software and enabling the one-time processing of raw data from thousands of samples. Furthermore, the system incorporates the aforementioned metabolomics database, facilitating the seamless execution of the entire complex metabolomics data analysis workflow.

Metabolomics testing is currently primarily applied in the scientific research services market. Deng Junliang estimates that the total size of China’s metabolomics research services market is approximately RMB 500 million. However, demand in this market remains unmet, indicating substantial room for future growth.

“Compared to the approximately RMB 3.5 billion market size for genetic testing research services, the metabolomics testing market still has substantial room for growth. We anticipate that metabolomics will become the central focus among various omics disciplines over the next 5–10 years; in other words, current research users of genetic testing will become our customers. Therefore, we expect a period of rapid growth in the next 5–10 years,” analyzed Deng Junliang.

With the development of metabolomics, the number of market players has gradually increased. Leveraging years of experience deeply rooted in metabolomics testing, BIOTREE has established its own significant competitive advantages.

First and foremost, BIOTREE is deeply committed to delivering high-quality services. Deng Junliang believes that BIOTREE’s market positioning is akin to that of SF Express in the courier industry.

BIOTREE has also established a comprehensive suite of platforms to provide customers with one-stop services. Its capabilities span from GC-Q-MS to GC-TOF-MS, as well as from LC-QQQ-MS to LC-QTOF-MS and LC-Orbitrap-MS. Recently, BIOTREE has also planned to extend its services into mass spectrometry imaging, nucleic acid mass spectrometry, ion chromatography, and CE-MS.

Leveraging the large-scale platform and big data analytics algorithms established by BIOTREE, the company is capable of handling testing and analysis for up to 100,000 samples. In this regard, there are very few comparable platforms in China that can competently manage such high-volume sample testing and analysis.

In the future, BIOTREE will continue to deepen its presence in the metabolomics research services market. Additionally, this May, BIOTREE completed a Pre-A financing round of tens of millions of RMB, invested by Guozhong Venture Capital.

Driven by capital investment, BIOTREE has also initiated the research and development of clinical mass spectrometry testing products, aiming to launch offerings that align with market demand within the next two to three years.