HillLife Bio Submits IPO Prospectus Highlighting Its Proprietary Oral Colon-Specific Drug Delivery System for Enhanced Live Biotherapeutic Efficacy

The human microbiome is a prominent emerging field globally and represents a key development direction for the health industry. As early as 2008, the U.S. National Institutes of Health (NIH) launched the Human Microbiome Project (HMP), which became another major life sciences initiative following the Human Genome Project (HGP). The HMP aims to investigate the functional associations between the human microbiota and human health, ultimately benefiting all humanity.

In previous studies, scientists have gradually come to recognize the profound impact of the gut microbiome on human health. Research into these microbial communities has laid the foundation for the development of the microbiome industry, with live biotherapeutic products (LBPs) attracting a wave of entrepreneurs and investors. Billionaires such as Bill Gates, Mark Zuckerberg, Li Ka-shing, Salesforce founder Marc Benioff, and Silicon Valley venture capitalist Vinod Khosla are all investing in microbiome startups.

Currently, applications in the microbiome field are primarily divided into three areas: innovative drugs, innovative medical treatments, and innovative foods.

Currently, research on live biotherapeutic products is largely based on strain selection—identifying microbes from nature with appropriate pharmacological effects to develop live bacterial drugs. The screening of microbes primarily evaluates the combined effects of strain efficacy and in vivo survivability. If the activity of live bacterial drugs cannot be guaranteed within the human internal environment, even highly potent microbes are often discarded due to poor overall performance resulting from inadequate in vivo activity after oral administration.

However, few companies have ventured into ensuring the viability of live biotherapeutic products within the human internal environment. Among the top ten global best-selling drugs, biologics account for more than seven; yet, few of these biologic agents can be administered orally. In clinical practice, most biologics are delivered via physical methods (such as enemas) to the patient’s colon—the native ecological niche for microbes. This approach not only carries high procedural risks and precludes repeated administration, but also results in poor patient compliance. For patients with refractory conditions requiring frequent, repeated interventions (more than three times per year), this limitation prevents the achievement of breakthrough therapeutic efficacy.

For oral administration, the ability of live biotherapeutic products to withstand gastric acid, digestive enzymes, and bile while maintaining viability until reaching the target organ is critical to their efficacy. Through years of independent research and development, Xiershou Biotechnology has addressed this key challenge regarding in vivo viability by developing an Oral Colon-Specific Drug Delivery System (OCDDS).

By utilizing an Oral Colon-Targeted Drug Delivery System (OCDDS), live bacterial therapeutics are loaded into a proprietary colon-targeted release formulation. This approach supports oral administration, preventing the release of live bacteria in the stomach, duodenum, jejunum, and ileum. Instead, it delivers the live bacteria directly to the colon for release, thereby exerting their therapeutic effects or other benefits.

By integrating modern pharmaceutical formulation technologies, oral colon-specific drug delivery systems (OCDDS) are primarily categorized into time-delayed, pH-dependent, enzyme-triggered, pressure-dependent, and prodrug-based release systems. However, current technology can only achieve drug release at most in the cecum or ileocecal region, and is not yet capable of achieving release throughout the entire colon.

Products developed by Xiershou Biotechnology, based on its proprietary internationally innovative technology, can increase the number of live bacteria released in the body by more than 10,000-fold through targeted release in the colon rather than in the stomach and small intestine. This approach fully ensures the in vivo activity of live bacterial therapeutics, enabling highly effective treatment of refractory diseases associated with gut microbiota dysbiosis, and paving a new path for the development of biopharmaceuticals.

The OCDDS system is a major technological achievement resulting from the work of an innovative drug formulation expert team led by Professor Zhang Junshou, former head of the Pharmaceutics Laboratory at China Pharmaceutical University. Professor Zhang is a doctoral supervisor in pharmaceutics at China Pharmaceutical University, a former expert reviewer for new drug applications under the National Natural Science Foundation of China and provincial medical products administrations, and the principal investigator for multiple national key research projects. He led the research project on “Colon-Specific Drug Delivery Systems” and, as the primary contributor, received the Certificate of Scientific and Technological Achievement Completion from the Ministry of Education.

To advance the industrial translation of this technological achievement, Professor Zhang Junshou founded Nanjing Hillso Biotechnology Co., Ltd. (hereinafter referred to as “Hillso Bio”) in 2014. The company’s core R&D team includes Academician Chen Hongyuan of the Chinese Academy of Sciences, Researcher Cui Shumao from the School of Food Science and Technology at Jiangnan University, and Chen Qiang, Dean of the Changzhou High-Tech Research Institute of Nanjing University.

Among them, Academician Chen Hongyuan also serves as a Fellow of the American Chemical Society. He is a Professor and Doctoral Supervisor at the School of Chemistry and Chemical Engineering, Nanjing University. With a long-term commitment to research in life analysis chemistry, he has achieved a series of innovative results in fields such as biomimetic catalysis, chemical biology, nano- and supramolecular electrochemistry, micro-total analysis systems, and the study of trace drug metabolites in vivo. Researcher Cui Shumao has presided over one project funded by the National Natural Science Foundation of China and participated in three national-level projects, including key programs of the same foundation. He has also led more than ten industrialization projects. His primary research focuses on analytical testing for industrial technologies, including high-density cultivation of probiotics, freeze-drying formulations and processes, and microcapsule preparations.

Since its establishment (with its predecessor founded in 2000), Hillshou Biotech has been dedicated to the research and development of international innovative drugs for over two decades. Its significant international innovations have been applied in the fields of innovative healthcare, preventive care through microecology, and microecological health management. The company has obtained and is applying for multiple patents. Leveraging its independently developed OCDDS platform, Hillshou Biotech plans to advance several blockbuster international innovative drug candidates through dual regulatory submissions in China and the United States.

Currently, the global insulin market size has exceeded $35 billion, accounting for half of diabetes treatment. One in every 11 adults worldwide has diabetes, with the number of patients reaching 425 million. In China, the number of patients is 114 million, with an incidence rate of 10.4%.

However, insulin is currently administered primarily via injection. Oral insulin is favored by many patients with diabetes due to its advantages, including ease of administration, fewer side effects, and better medication adherence. Research on oral insulin began as early as 1992; however, owing to technical challenges in development and the complexities of human gastrointestinal digestion and absorption of insulin, no orally available insulin product has reached the market to date.

Hillshou Bio leverages its proprietary OCDDS (Oral Colon-Targeted Drug Delivery System) to protect insulin from degradation by gastric acid and enzymes. Using insulin as the active pharmaceutical ingredient (API), the system encapsulates it in a colon-targeted formulation, ensuring safe passage through the stomach and small intestine after oral administration, with release occurring in the colon to preserve its biological activity. Furthermore, Hillshou Bio employs nanotechnology to formulate insulin into nano-preparations and utilizes an absorption-enhancing technology free of aprotinin, significantly improving the oral bioavailability of insulin.

Glucagon-like peptide-1 (GLP-1) has emerged as a major focus of diabetes research in recent years, offering numerous advantages. Currently, GLP-1 therapies are predominantly available as injectables, with Novo Nordisk’s oral semaglutide being the only oral formulation approved for market launch. Given the need for long-term, frequent administration in diabetes management, oral formulations hold significant advantages over injectable ones.

Zhang Hao, co-founder of Xiershou Bio, stated that semaglutide itself has extremely low oral bioavailability and can only be administered via subcutaneous injection. To enhance oral bioavailability, Novo Nordisk employs an absorption enhancer; however, its oral tablets disintegrate in the stomach, making them susceptible to enzymatic degradation and increasing the incidence of adverse reactions. Since GLP-1 is primarily secreted by L-cells in the colon, colonic release is more suitable.Hillshou Bio applies OCDDS technology to a novel oral GLP-1 analog, promising enhanced efficacy, lower costs, and improved safety.。

The gut microbiota is closely linked to human health. Fecal microbiota transplantation (FMT), an innovative therapy for treating various refractory diseases, has been administered to hundreds of thousands of patients worldwide. “Addressing the pain point of maintaining microbial viability in vivo, current clinical practice primarily relies on invasive procedures such as gastroscopy and colonoscopy. Oral FMT using existing oral delivery technologies is rarely adopted due to its highly variable efficacy,” said Zhang Hao, founder of Shiershou Bio. “Surgical approaches can be performed at most three times per year, thereby precluding long-term, continuous treatment for many refractory conditions and limiting clinical outcomes.”

Based on its self-developed, internationally pioneering technology, Xiershou Biology has successfully conducted internationally pioneering colon-targeted fecal microbiota transplantation at Jiangsu Province Hospital of Integrated Traditional Chinese and Western Medicine and the Second Traditional Chinese Medicine Hospital of Jiangsu Province.Of the six patients treated to date, the efficacy rate has reached 100%.. The Company will further promote its application in the clinical treatment of diseases such as inflammatory bowel disease, constipation and diarrhea, tumor immunotherapy, tumor rehabilitation (treatment of diarrhea caused by radiotherapy and chemotherapy), liver disease, autism, Parkinson's disease, Alzheimer's disease, depression, immune system diseases, allergies, lupus erythematosus, and osteoporosis.

Based on the OCDDS platform, Hillshou Biotechnology has also strategically deployed application businesses across three major sectors. According to Zhang Hao, Chairman of Hillshou Biotechnology, these three segments are:Microbial Drug R&D, Colon-Targeted Fecal Microbiota Transplantation Medical Services, Probiotics, and Short-Chain Fatty AcidsDevelopment of food-grade applicationsAmong these, the indications for microbial drugs are not limited to Crohn’s disease, Alzheimer’s disease, and tumors (adjuvant therapy). Colon-targeted fecal microbiota transplantation has been implemented in clinical practice at public Grade 3A hospitals. Furthermore, companies specializing in food-grade applications have collaborated with Jiangsu Provincial Hospital of Traditional Chinese Medicine on research projects and clinical promotion, aiming to prevent diseases before they occur.

Accordingly, to accelerate the clinical development of its microbial drugs and the commercial application of its gut microbiota transplantation services, Hillshou Bio has launched a new round of financing. Interested investment institutions are welcome to contact us.