Huiyan Biotech Files IPO Prospectus: Advancing Domestic Substitution in Protein Purification with Customizable Agarose Microspheres

Not everyone has the ability and opportunity to turn their favorite courses into a career they love. However, Yi Guojun, founder of Wuhan Huiyan Biotechnology Co., Ltd. (hereinafter referred to as “Huiyan Biotech”), devoted himself wholeheartedly to the field of protein separation and purification in 2013, gradually achieving higher purity of proteins in test tubes.

Currently, Huiyan Biotech has become one of the national standard reference enterprises for protein purification chromatography media in China. The company has been certified as a High-Tech Enterprise and is listed on the Hubei Regional Equity Market (the “Fourth Board”).

Yi Guojun, Founder of Huiyan Biotech

Reflecting on the original intention behind founding Huiyan Biotech, founder Yi Guojun remarked, “The downstream segment of the industrial chain—specifically chromatography resins for protein purification—remains largely dominated by foreign companies. There is a significant gap between domestic and international technologies. In my view, this presents a substantial opportunity for Huiyan Biotech to make an impact.”

To achieve domestic substitution, the biggest challenge lies in how to make the performance of Chinese-made products surpass that of foreign counterparts and regain public trust in domestic brands. Yi Guojun gained this profound insight while serving as a production manager at a foreign enterprise. He noted that many Chinese manufacturers struggle to promote their products, as both industrial and research clients are often reluctant to try these domestic brands.

It is not enough to simply deliver high-quality products; we must also cultivate customers’ willingness to try domestic brands and maintain their loyalty. This is the enduring goal that Huiyan Biotech strives to achieve. Seven years on, Huiyan Biotech has steadily turned this vision into reality. Its industrial and research clients now span across China, ranging from Tsinghua University to Sinopharm Group. The shared choice of hundreds of research and industrial clients stands as the strongest endorsement of Huiyan Biotech.

The technology that captivated Yi Guojun during his university years is agarose microsphere purification. Agarose is primarily used to purify and extract macromolecular bioactive substances such as viruses, proteins, and enzymes. It finds applications in industries including biopharmaceuticals, blood products, vaccines, cosmetics, and health supplements. Its main users are large-scale biopharmaceutical, blood product, and vaccine manufacturers, while it also boasts a broad user base among small and medium-sized enterprises as well as research institutions and universities.

Huiyan Biotech's agarose microspheres are manufactured from imported agarose powder. Their purification mechanisms primarily include gel filtration via the microsphere matrix and adsorptive filtration within the microspheres.

Gel filtration using microspheres achieves separation by physically differentiating the sizes of target samples and impurity molecules. The interstitial spaces between microspheres allow viruses or large-molecule targets to traverse via a nearly straight path and elute first, whereas proteins or other small-molecule impurities enter the pores within the microspheres, follow a tortuous path, and elute later. This difference in elution time based on the distinct pathways through the interstitial spaces and internal pores accomplishes the separation.

This screening principle is primarily suited for the separation of viruses and proteins. According to information disclosed by Huiyan Bio, purification via microsphere gel filtration currently achieves a purity of over 90% and a recovery rate of more than 95%, making it a mature chromatography resin for whole-virus vaccine purification.

Another principle of agarose microsphere purification is filtration achieved through internal adsorption within the microspheres. This purification method adsorbs the target substance (or impurities) inside the agarose microspheres, allowing impurities (or the target substance) to flow through, and subsequently elutes the target substance (or impurities) retained within the microspheres, thereby achieving separation and purification.

The principles of adsorption-based separation are mainly categorized into three types: ion exchange based on differences in electrical charge, affinity chromatography based on differences in specific structural features, and hydrophobic interaction chromatography based on differences in water solubility. By covalently bonding functional groups carrying positive or negative charges, specific affinity ligands, or hydrophobic functional groups to the interior of agarose microspheres, target molecules (or impurities) can bind to these groups, while impurities (or target molecules) flow through, thereby achieving filtration.

When faced with the demand for biological products with a purity of 99.9999%, Huiyan Bio can perform multiple rounds of filtration using various types of agarose microspheres on target samples. Yi Guojun stated that, generally speaking, filtration through three to five different types of agarose microspheres is sufficient to achieve a high purity level of 99.9999%.

Currently, Huiyan Biotech’s agarose microsphere-based purification technology covers more than 90% of sample types, with over 100 products having undergone purification process development using the company’s agarose microspheres. Successfully developed human biologics include PEG-rhG-CSF, tetanus vaccine, rabies vaccine, heparin sodium, urokinase, iron caseinate, and recombinant human epidermal growth factor (rhEGF). Animal vaccine varieties developed include insect baculovirus-expressed porcine circovirus type 2 (PCV2) vaccine, insect baculovirus-expressed classical swine fever E2 vaccine, foot-and-mouth disease whole-virus vaccine, rabies whole-virus vaccine, porcine reproductive and respiratory syndrome (PRRS) whole-virus vaccine, diarrhea whole-virus vaccine, influenza whole-virus vaccine, baculovirus-expressed goose parvovirus (GPV) vaccine, and baculovirus-expressed infectious bursal disease virus (IBDV) vaccine.

In the purification of animal vaccines, pharmaceutical companies generally have high requirements for recovery rates. Huiyan Biotech customizes agarose microspheres and develops purification process solutions according to customer needs, thereby achieving higher recovery rates.

The domestic market for protein purification technologies is largely dominated by foreign companies. The first major hurdle for Chinese brands seeking to achieve import substitution is the insufficient reserve of relevant technical talent in China. Yi Guojun was even more direct, stating that at the outset of his entrepreneurial venture, he learned that there were fewer than 50 technicians engaged in protein purification-related work in China.

Leveraging his technical expertise accumulated over more than a decade in the industry, Yi Guojun co-founded Huiyan Biology together with several team members who each possess over ten years of experience in product research, development, and manufacturing. Meanwhile, the company’s core technical team has extensive experience in purifying hundreds of types of proteins and holds several related invention patents.

Huiyan Biotechnology is located in the Wuhan Optics Valley Bio-City, known as "China's Optics Valley." In December 2014, the company underwent restructuring and successfully listed on the New Fourth Board, becoming the fourteenth enterprise in the Wuhan Optics Valley Bio-City to be listed on the Wuhan Equity Custody Center.

At its inception, Huiyan Biotechnology entered a market segment almost entirely dominated by foreign enterprises. The first challenge it faced was the absence of national standards for domestically produced protein purification. Consequently, Huiyan Biotechnology consistently adopted international standards as its own purification criteria, laying the foundation for its role in domestic substitution. By ensuring that its purification efficiency matched or exceeded that of imported brands while reducing costs, the company secured its first customer, who chose to partner with Huiyan Biotechnology precisely for these advantages.

“Our first client had previously been using imported purification products. However, as their company mandated a 10% annual reduction in procurement costs, they began seeking domestically produced alternatives. They provided the specifications of the imported purification process to Chinese manufacturers, looking for companies capable of achieving equivalent purification standards,” recalled Yi Guojun. “Many companies were approached for this project, including our own, Huiyan Bio. At the time, parameters such as sample characteristics were still confidential, so we had to proceed through gradual exploration. After nearly a year of effort, the final process outcomes exceeded expectations. On the day of customer acceptance, they immediately initiated procurement from us.”

To further advance domestic substitution, Huiyan Bio has also launched equipment fully compatible with the requirements of foreign protein purification instruments. This allows customers to directly adopt Huiyan Bio’s comprehensive protein purification solutions without replacing their existing infrastructure, thereby reducing protein purification costs and improving purification efficiency.

It is reported that Huiyan Bio currently has a single-batch production capacity of approximately 500 L of agarose microspheres. The company plans to build a new production line in 2020, aiming to become a leading biopharmaceutical enterprise in China’s core industrial chain for technologies related to protein purification chromatography media.

The company will increase its R&D investment and market development in vaccines, blood products, antibody drugs, and other areas. It is reported that Huiyan Biotech has launched its Series A financing round, aiming to raise 15 million yuan, which will be mainly used for building a new agarose microsphere production line, developing novel chromatography resins and new purification processes, and actively expanding its market presence.