PFerrinX26 Files IPO Prospectus to Scale Precision-Fermented Lactoferrin Production

Lactoferrin, a trace protein naturally present in milk, possesses antibacterial, antiviral, and anti-inflammatory properties, garnering significant attention within the health supplement, pharmaceutical, and food industries. However, despite sustained high market demand, the supply of lactoferrin continues to face severe challenges. This is primarily because the extraction process from milk is extremely cumbersome and resource-intensive. This supply shortage has undoubtedly exacerbated the market scarcity of lactoferrin, thereby driving up its market price.

Recently, Earth First Food Ventures Ltd (EFFV), a venture capital firm focused on food technology innovation, announced the launch of PFerrinX26—the first facility in the United States to produce lactoferrin (LF) using precision fermentation technology, achieving the goal of efficiently producing lactoferrin without relying on dairy cows. It is reported that the initial annual production capacity of the PFerrinX26 facility is set at 50 metric tons, with plans to gradually expand to 200 metric tons in the future.

Traditional lactoferrin production methods are heavily reliant on dairy farming, a model that is not only costly—with production costs ranging from $2,000 to $5,000 per kilogram—but also strained in terms of resource utilization.

In contrast, the PFerrinX26 facility in the U.S. Midwest has adopted a novel precision fermentation technology that uses glucose as the primary feedstock, reducing the production cost of lactoferrin to $300–$800 per kilogram. As a commodity, glucose maintains a stable price range of $0.3–$0.5 per kilogram and offers a reliable supply, unaffected by external factors such as fluctuations in feed prices or climate change, thereby providing strong assurance for the stable production of lactoferrin. According to estimates by Earth First Food Ventures Ltd (EFFV), if global lactoferrin production were to fully transition to precision fermentation technology, it could potentially reduce land and water consumption by 90%.

In terms of technological approach, the PFerrinX26 facility leverages the advantages of modern biotechnology. By employing gene-editing tools such as CRISPR, human or bovine lactoferrin genes are efficiently introduced into microbial hosts like *Pichia pastoris*, with deep optimization of their expression systems. Compared to traditional production strains, the new generation of engineered strains has achieved a significant increase in protein expression efficiency of over 200%, and can precisely replicate the glycosylation structure of natural lactoferrin, thereby ensuring consistency in biological activity. Furthermore, through a cleverly designed secretory expression system, microbes can directly release the protein into the culture medium, eliminating the cumbersome cell lysis step and further reducing the difficulty of downstream purification.

It was revealed that the PFerrinX26 facility plans to initially enter the cosmetics and adult nutrition markets, gradually accumulating experience and building a strong reputation before expanding into the more strictly regulated infant formula market. In terms of sales strategy, PFerrinX26 will adopt a B2B model, establishing close partnerships with industry leaders to jointly promote the transformation and upgrading of the lactoferrin industry.

According to the “2020 White Paper on Import Trends in Maternal and Infant Consumption” released by CBNData, consumption of lactoferrin within the infant nutrition subcategory on Tmall Global has exhibited rapid growth. Data show that over the past two years, the compound annual growth rate (CAGR) for dairy products and infant formula containing lactoferrin exceeded 300%, ten times that of the overall category. Looking ahead, the global market for lactoferrin in infant formula is projected to reach USD 110 million by 2027.

Lactoferrin, with its superior nutritional benefits, has become an indispensable selling point for many infant formula products. In recent years, nearly every brand on the market has launched products containing “lactoferrin.” Statistics show that among the 152 infant formula products registered under the new national standards in 2023, more than 40% included lactoferrin as an ingredient.

However, the applications of lactoferrin extend far beyond infant formula. It is gradually expanding into multiple fields, including adult health foods, dietary supplements, and cosmetics. In clinical practice, the use of lactoferrin has evolved from mere nutritional supplementation to precision medicine, playing a significant role in immunomodulation, antibacterial activity, antitumor effects, anti-inflammation, and antioxidant defense. Particularly in immunomodulation, as a key molecule of innate immunity, lactoferrin plays a central role during inflammatory processes. It enhances cytotoxic immunity and blocks receptors for tumorigenic inflammatory mediators, thus being regarded as a potential candidate adjuvant to standard anticancer therapies.

Among these, HY1002, an oral solution of recombinant human lactoferrin and lysozyme developed by Huiyuan Biopharma using a rice endosperm cell bioreactor expression system, has achieved positive results in the treatment of infectious diarrhea in children caused by rotavirus and is currently in Phase II clinical trials in China.

In the arena of antimicrobial defense, lactoferrin’s iron-chelating capacity enables it to directly participate in the front line of antibacterial and antiviral responses. Lactoferrin can inhibit or even assist in killing a variety of microorganisms, demonstrating significant anti-infective, antioxidant, and anti-inflammatory effects. Studies have found that bovine-derived lactoferrin can regulate the bone resorption process through specific pathways; combined with human clinical trial data, this suggests its potential application value in controlling periodontal tissue inflammation in orthodontic settings.

In the broader cancer market, lactoferrin can significantly enhance NK cell-mediated cytotoxicity against breast and colon cancer cell lines. In 2016, Shankaranarayanan et al. developed a chemotherapeutic agent combining doxorubicin (Dox) with lactoferrin as a carrier. Oral administration of iron-saturated bovine lactoferrin-Dox (BLF-Dox) inhibited tumor growth, prolonged survival in mice, and reduced the systemic, cardiotoxic, and neurotoxic effects of Dox. Furthermore, it upregulated serum levels of anti-cancer molecules, including tumor necrosis factor, interferon, and CC chemokines 4 and 7 (CCL4, CCL17). These findings established the promising application of this novel, safer BLF-Dox conjugate—which combines a traditional cytotoxic drug with lactoferrin—for targeting drug resistance, inhibiting tumor growth, and exhibiting potent anti-cancer activity.

Lactoferrin, also hailed as "liquid gold from milk," is extremely difficult to produce due to its heat-sensitive nature. Once exposed to temperatures exceeding 90°C, lactoferrin becomes completely inactivated; even with direct consumption, improper handling can significantly compromise its bioactivity. Typically, it takes 10 metric tons of raw milk to extract just 1 kilogram of lactoferrin. Its scarcity and high price are self-evident, with international market prices reaching over RMB 20,000 per kilogram at their peak.

For a long time, China’s supply of raw lactoferrin has relied almost entirely on imports, resulting not only in high prices but also frequent shortages. The extraction of lactoferrin has become an industry challenge primarily due to dual constraints in technology and production capacity. Technologically, the production and purification processes for lactoferrin are highly demanding and extremely temperature-sensitive. Advanced cold-spray techniques must be employed to minimize both the temperature and duration of heat exposure, thereby preserving its natural biological activity as much as possible.

In terms of production capacity, lactoferrin extraction technology is equally critical. Although ultrafiltration membrane separation is low-cost and easy to operate, the purity of the extracted lactoferrin is only around 60%, falling far short of the industry requirement of 95% purity. In contrast, while ion-exchange chromatography can achieve a purity of over 90%, it significantly increases costs.

However, as the lactoferrin market continues to expand and demand keeps growing, China’s upstream raw material sector has begun to emerge. In 2018, Dongying Ruida Biology successfully obtained a production license for lactoferrin. By integrating mature technologies such as low-temperature sterilization, molecular adsorption, and membrane separation purification, the company achieved continuous industrial-scale production of lactoferrin, with product purity reaching as high as 97.2% and relatively low costs.

Subsequently, in May 2022, Feihe announced that it had successfully obtained production licensing for lactoferrin, marking the official commissioning of China’s first automated lactoferrin production line in the dairy industry. Meanwhile, Yili pioneered a targeted extraction and protection technology for lactoferrin, significantly increasing the retention rate of lactoferrin in shelf-stable pure milk to over 90%, thereby filling a domestic gap and breaking through foreign technological barriers.

Notably, the emergence of precision fermentation technology has brought about a revolutionary transformation in lactoferrin production. By genetically engineering microorganisms such as yeast, lactoferrin can be produced without relying on livestock. In August 2022, Singaporean biotechnology company TurtleTree announced the successful production of lactoferrin, becoming the first company globally to manufacture sustainable lactoferrin using precision fermentation technology. Subsequently, U.S. biotechnology firm Helaina also announced that its developed lactoferrin is poised to enter large-scale commercial production.

Furthermore, in December 2024, the Australian company All G became the second company globally, after TurtleTree, to obtain “GRAS” certification in the United States for animal-free lactoferrin. All G plans to commercialize its lactoferrin and anticipates that its production costs will be lower than those of dairy-derived lactoferrin.

Meanwhile, in the field of synthetic biology, the innovative enterprise NewPro has improved lactoferrin yield and reduced production costs by employing protein expression systems based on *Pichia pastoris* and various filamentous fungal chassis, combined with its proprietary protein separation and purification processes. Reportedly, the primary challenges in developing product strains during this process are as follows: first, most microbial chassis contain multiple proteases that degrade bovine lactoferrin, ultimately preventing the complete expression of the target protein; furthermore, most functional proteins undergo complex post-translational modifications, such as the glycosylation of bovine lactoferrin. Consequently, it is difficult to replicate glycosylation patterns in microbial chassis that are identical to those of natural sources, thereby affecting product efficacy.

To address this challenge, the NewPro team has also developed a plug-and-play toolkit for “personalized customization of different proteases and glycosidases targeting specific proteins,” leveraging their 15 years of accumulated expertise in genomic editing tools and elements, while synergizing with AI algorithms for the optimization of personalized components and high-throughput screening of target proteins.

Driven by both technological advancements and market forces, the applications of lactoferrin will continue to expand, while production costs will steadily decline. Once dubbed “liquid gold” in milk, this substance is poised to make greater contributions to human health and emerge as a shining star in the healthcare sector.