Haolv Biotech Files for IPO: Pioneering Domestic Isotope Internal Standards to Empower Clinical Mass Spectrometry Growth

“We conducted a survey and found that leading clinical mass spectrometry companies in China currently source their stable isotopes primarily from overseas suppliers such as CIL (USA), Sigma-Aldrich (Merck, Germany), and TRC (Canada), with domestically produced products accounting for only a minimal share,” Dr. An Rui, Partner at Haolv Biotech, told VCBeat.

Stable isotope standards are the most critical raw materials among mass spectrometry consumables, enabling more accurate mass spectrometric detection and ensuring high sensitivity even when analyzing samples with very low concentrations.As China’s clinical mass spectrometry industry experiences explosive growth, the strategic importance of upstream stable isotope products is becoming increasingly prominent, making it urgent to break the import monopoly on isotopic internal standards for clinical mass spectrometry testing.

Haolv Biotech, established in 2016, is a primary manufacturer of stable isotope-labeled compounds. Its business portfolio includes isotopic internal standards for mass spectrometry, deuterated building blocks for the pharmaceutical industry, deuterated solvents for NMR spectroscopy, and customized deuterated intermediates. Covering the entire deuterium-labeling industry chain, the company produces all deuterated raw materials in-house, ensuring traceability, price stability, and independence from imported raw materials. Its annual revenue has exceeded RMB 100 million.

In the clinical mass spectrometry market, Haolv Technology has independently developed isotope-labeled internal standards for 25-hydroxyvitamin D3-d6 and 25-hydroxyvitamin D2-d3, as well as various isotope-labeled internal standards used in therapeutic drug monitoring assays, with the potential to break the long-standing monopoly of imported products.

To ensure the accuracy, efficiency, and regulatory compliance of clinical mass spectrometry testing, stable isotopes must be used as reference standards. Both deuterium and carbon-13 can serve as standards for clinical mass spectrometry. However, the primary raw material source for carbon-13 is supplied by only one vendor in the United States, and its market price is one to two orders of magnitude higher than that of deuterated compounds. This has hindered the industrial-scale application of carbon-13, making deuterated products the preferred choice as reference standards for clinical mass spectrometry assays. With the increasing volume of clinical testing, the consumption of stable isotope reference standards is growing rapidly.

Haolv Biotech focuses on the R&D capabilities of deuterated compound synthesis. According to Dr. An Rui,Deuterated products currently face two major pain points: one is their limited scope of application, and the other is severe import monopoly, leading to significant price fluctuations.

Previously, deuterium labeling was primarily used for scientific research, resulting in a small market size and few participating companies. After 2016, with the booming clinical mass spectrometry market and the rapid development of niche segments such as deuterated new drugs and NMR solvents, deuterium labeling has found broader applications and attracted rapidly growing attention.

U.S.-based CIL, Germany’s Merck Sigma-Aldrich, and Canada’s TRC collectively hold 70%–85% of China’s deuterated compound market. In particular, since the onset of the COVID-19 pandemic, instability in overseas logistics and supply chain fluctuations have significantly prolonged procurement lead times for imported products. The interval from order placement to product delivery often extends to six months or even longer, thereby hindering the development of downstream applications in clinical mass spectrometry.

Against the backdrop of growing demand in the clinical mass spectrometry industry, policy-driven acceleration of domestic substitution, and China’s heightened emphasis on independent intellectual property rights,Domestication of Stable Isotope Products in Clinical Mass Spectrometry Applications Is Imperative.

However, due to the high barriers to entry in the industry, China has long lacked suppliers of high-quality deuterated compounds. Dr. An Rui stated, “On the one hand, it requires a team with extensive experience,to ensure the stable mass production of deuterated compounds,On the other hand, due to the high cost of deuterated compound raw materials and the substantial trial-and-error expenses incurred by companies, the number of manufacturers globally focusing on this field remains limited.”

Haolv Tech isOne of the Few Domestic Enterprises to Achieve Independent R&D of Deuterated Compounds, the company’s founder exemplifies the “scientist-entrepreneur” model, with deep expertise accumulated in the field of stable isotopes.

In the clinical mass spectrometry stable isotope-labeled internal standard business line, Nanjing Haolv Biotech LLC started with the most mature vitamin D testing projects and has developed 25-OH VD3-d6 and 25-OH VD2-d3 stable isotope-labeled internal standards, which have already achieved mass production. Additionally, for reference standards used in therapeutic drug monitoring, Nanjing Haolv Biotech LLC offers dozens of internal standards from stock, such as commonly used Oseltamivir-D5 and Ganciclovir-D5. In mass spectrometry-based metabolomics research, Melatonin-D4 and Amantadine-D15 are also available from inventory.

It is worth noting that clinical mass spectrometry testing imposes stringent requirements on the purity and deuterium enrichment of stable isotope products. How can high-purity, high-quality deuterated compounds be provided? Dr. An Rui stated, “Consideration must be given to two aspects: what the industry requires and what customers need. The team at Nanjing Haolv Biotech LLC has a deeper understanding of deuterated structures, enabling us to optimize structural design according to specific needs and synthesize products that meet industry standards.”

The quality of deuterated compounds produced by Haolv Biotech is comparable to that of the industry benchmark, CIL (Cambridge Isotope Laboratories) in the United States.For example, Nanjing Haolv Biotech LLC possesses advantages across the entire deuterated compound industry chain, enabling it to develop isotopic internal standards with relatively complex structures for vitamin D testing. These standards achieve both chemical purity and deuterium enrichment levels exceeding 98%, while ensuring batch-to-batch consistency and price stability. This independence from imported raw materials safeguards the supply chain security of downstream users. Regarding specific customer requirements, demands for deuterated compounds vary across different sectors. In pharmaceutical synthesis scenarios, customers may require exceptionally high chemical purity and deuterium enrichment, often exceeding 99.9%. In mass spectrometry applications, in addition to sufficiently high chemical purity and deuterium enrichment, it is essential to ensure that stable isotope products do not cause signal interference with target analytes in test samples, exhibit adequate mass spectrometric response, and allow for effective separation. The team at Nanjing Haolv Biotech LLC actively communicates with clients to flexibly address personalized needs based on specific application scenarios, optimizing synthetic routes according to customer requirements.

In recent years, clinical mass spectrometry has emerged as one of the most dynamic new technologies in the field of in vitro diagnostics, owing to its high specificity, high sensitivity, and capability for multi-analyte detection. According to a report by VCBeat Institute, the overall market size of clinical mass spectrometry in China exceeded RMB 10 billion in 2021 and is projected to grow exponentially in the future.

The development trajectory of clinical mass spectrometry in China closely mirrors that of next-generation sequencing (NGS). The domestic clinical mass spectrometry market is in its early stages, with its scale gradually expanding. It is poised for explosive growth in the future.The growing clinical adoption of mass spectrometry will drive increased attention to stable isotopes in the field of clinical mass spectrometry.

Furthermore, the dosage of stable isotopes is contingent upon the analytes being detected. As vitamins are endogenous substances, they require only small amounts; in contrast, applications such as therapeutic drug monitoring necessitate significantly larger quantities per sample. With the widespread clinical adoption of therapeutic drug monitoring and similar assays, the demand for stable isotopes is poised for explosive growth.

“Clinical mass spectrometry isotope internal standards will be a key business segment for Haolv Biotech in the future. As an upstream provider of stable isotopes, we are committed to extensive collaboration with downstream clinical mass spectrometry application companies to jointly develop more new projects with clinical value, promote the establishment of industry rules and standards for deuterated compounds in clinical mass spectrometry, and advance the development of China’s clinical mass spectrometry industry,” said Dr. An Rui.

In fact, in addition to clinical mass spectrometry isotope internal standards, Haolv Biotech leverages its complete industry chain spanning from source raw materials and small-molecule building blocks to end-application products and testing equipment.It has also laid out businesses related to raw materials for deuterated new drugs and NMR solvents, continuously extending its presence along the deuterium-labeled industry chain.

In the business of raw materials for deuterated new drugs, the company offers a wide range of stable isotope-labeled products, with over 500 categories in regular stock, used for new drug development, pharmaceutical analysis, and molecular diagnostics. In the NMR solvent business, the company has achieved complete self-production of common NMR solvents, providing conventional NMR solvents such as deuterated chloroform, deuterated DMSO, and deuterated methanol, as well as novel NMR solvents like deuterated ionic liquids.

Currently, Haolv Biotech has established a comprehensive platform for R&D, analysis, and packaging, leveraging technological innovation to break the foreign monopoly on isotope products.The company has accumulated expertise in customizing over 1,000 deuterated compounds with diverse structures, and certain products are capable of industrial-scale mass production.Established a production base in Germany, gradually realizing a global business layout, with revenue exceeding 100 million yuan.

In the future, Haolv Biotech will remain committed to independent R&D and manufacturing, overcoming critical bottlenecks in deuterated compounds, continuously strengthening its core pharmaceutical business, and expanding its footprint in clinical mass spectrometry and NMR solvents. “Furthermore, since many everyday products are essentially chemical in nature, we will extend the application of deuterated compounds beyond clinical mass spectrometry, deuterated new drugs, and NMR solvents to broader markets, thereby enhancing the industrial value of deuterated compounds.”