Ruiyi Biosciences Secures Nearly RMB 100 Million in Series A+ Financing Led by Luxin Venture Capital to Build an Integrated Prevention-Screening-Diagnosis-Treatment Platform

On April 17, 2019, VCBeat learned that Shanghai Realbio Technology Co., Ltd. had successfully completed its Series A+ financing round, raising nearly RMB 100 million. The round was led by Luxin Venture Capital, with participation from Wuxi Financial Investment Group and previous investor Yuanyi Capital. According to Dr. Qin Nan, the company’s founder, the funds will be used for the research and development and clinical trials of new products in the field of gut health, expansion into domestic and international markets, and the establishment of several regional centers.

According to the latest national cancer statistics released by the National Cancer Center, the incidence and mortality rates of colorectal cancer in China are 28.20 per 100,000 and 13.61 per 100,000, respectively, ranking third in incidence and fifth in mortality among all malignant tumors. On average, one person dies from colorectal cancer every three minutes. This type of cancer has been included in the precision medicine and health poverty alleviation policies outlined in the proposals of the “Two Sessions.”

The high incidence and mortality rates of colorectal cancer are directly attributable to its insidious early symptoms and prolonged disease course, with most patients presenting at moderate to advanced stages. Early diagnosis would enable timely resection and favorable prognostic outcomes. Through early screening measures, it is entirely feasible to achieve a significant reduction in colorectal cancer-related mortality in China, underscoring its profound clinical and public health significance. However, traditional fecal occult blood testing suffers from substantial limitations in sensitivity and specificity, resulting in low participation rates and poor detection rates for colorectal cancer under current screening protocols, thereby precluding precise, population-wide coverage.

Using stool samples to detect early-stage colorectal cancer is an industry-recognized effective method, as stool contains shed intestinal epithelial cells that serve as the most direct carriers reflecting early lesions. By detecting and analyzing abnormal methylation of human-derived DNA within these samples, the risk of colorectal cancer in subjects can be assessed. Due to its advantages—such as being painless, non-invasive, requiring no bowel preparation, and allowing for at-home sampling—it has become a popular area of research. However, because the content of human-derived DNA in stool is extremely low and the presence of substantial impurities interferes with DNA extraction and purification, very few companies have successfully overcome these technical barriers to develop mature diagnostic products.

Leveraging its long-accumulated technological advantages, Shanghai Realbio Technology Co., Ltd. pioneered the development of the Changyishu® kit for combined detection of dual-gene methylation of human SFRP2 and SDC2 in fecal samples. The company revealed that current validation data demonstrate the product’s sensitivity and specificity have reached an internationally leading level. During the research and development process, the team had to overcome numerous technical challenges, including extraction and purification, target identification, and data analysis.

1) Extraction and Purification Stage

Over 99.99% of fecal DNA originates from gut microbiota and food residues, while tumor-derived DNA accounts for less than one-fifth of the remaining 0.01% of human-derived DNA. Extracting this extremely trace amount of target human DNA represents a significant technical challenge.

Realbio’s independently developed high-performance nucleic acid extraction kit enables selective lysis of human cells in fecal samples and effective removal of PCR inhibitors. Through specific magnetic bead adsorption, it yields high-quality human DNA with high yield, high purity, and excellent integrity.

2) Target Identification Phase

During the early stages of R&D, Realbio did not blindly replicate the targets used in established foreign products. Instead, the company collected a large number of fecal samples from both cancer patients and healthy individuals, performed high-throughput sequencing on the CpG islands of dozens of colorectal cancer-associated genes—including SDC2, SFRP2, NDRG4, BMP3, TFPI2, and Septin9—and identified the optimal combination of biomarkers for the Chinese population through iterative combinatorial analysis, comparison, and evaluation.

3) Data Analysis Phase

Following target identification, the construction of an accurate diagnostic model is a critical step. The Realbio team collected over one thousand fecal samples to train the data model, fully optimizing the product’s sensitivity and specificity. Concurrently, they developed corresponding diagnostic software that directly outputs diagnostic results based on input values related to target gene detection. This approach eliminates biases associated with manual interpretation, thereby facilitating and ensuring reliable practical application after the product’s market launch.

According to previous multicenter studies conducted in collaboration with multiple Grade A tertiary hospitals, the combined detection of SFRP2 and SDC2 gene methylation in feces achieved both sensitivity and specificity exceeding 90% for colorectal cancer, with diagnostic accuracy significantly higher than that of single-gene testing and fecal occult blood testing. As a pre-colonoscopy early screening methodology for high-risk populations, high sensitivity implies a low miss rate, providing clinicians with confidence in population-based screening. Leveraging its high precision and non-invasive, pain-free characteristics, the fecal human SFRP2 and SDC2 dual-gene methylation combined detection kit developed by Shanghai Realbio Technology Co., Ltd. is poised to become a new avenue for non-invasive colorectal cancer screening.

At the recently held Xijiao Conference, Shanghai Realbio Technology Co., Ltd. officially joined the “National Alliance for Early Diagnosis and Prevention of Digestive Tract Cancers,” becoming a council member unit for general screening. Alliance members will jointly carry out projects for the early diagnosis and treatment of colorectal cancer, with plans to establish more than 200 digestive tract tumor screening centers across China within one to two years, screen over one million individuals at risk for colorectal cancer, and detect 1,000 cases of early-stage colorectal cancer.

In recent years, Shanghai Realbio Technology Co., Ltd. has successfully completed three rounds of financing. It has established a complete industrial chain for gut health management and microbiome research, and is committed to creating a closed-loop system for gut health management by building an integrated platform for “prevention, screening, diagnosis, and treatment.” With the maturation of its early colorectal cancer screening products and the successive establishment of testing centers in Jinan, Qingdao, and Guiyang, the platform has taken initial shape.

As a national high-tech enterprise, the company boasts robust R&D capabilities. Its core technical team comprises alumni from prestigious domestic and international institutions, including Shanghai Jiao Tong University, Zhejiang University, and the University of California. Team members have published numerous articles in leading international journals such as Nature, Science, Nature Genetics, Genome Biology, and PNAS, with their cumulative impact factor ranking among the top in China’s microbiome technology service sector. Meanwhile, the company has secured over 40 software copyrights and multiple patents.

Since 2017, the microbiome has been an absolute star on the covers of major journals, with a surge in related publications. Driven by robust scientific research, the market size of the microbiome industry has continued to expand. In September 2018, uBiome, a U.S.-based company specializing in consumer- and clinical-grade personal microbiome testing, announced that it had raised $83 million in its Series C financing round. Meanwhile, Joseph Jimenez, former CEO of Novartis, joined the company’s board of directors, accelerating its industrial layout and development. In January 2018, Enterome, a European microbial therapeutics and biopharmaceutical company, completed a €32 million Series D financing round, bringing its total funding to €65 million. Statistics show that the total global financing for microbiome companies exceeded $1 billion in 2018. These funds will be used for the development of microbiome-related diagnostic products and drugs, as well as for clinical trials.

As a company founded on scientific research services, Realbio has established in-depth collaborations with over 200 major hospitals and research institutes since its inception. Through its technology service projects, it has built one of the largest microbiome databases in China. Meanwhile, Realbio initiated and championed the Gut Metagenomics Project, collaborating closely with leading physicians and principal investigators (PIs) in the field of microbiomics. The company has established a professional platform encompassing microbiome sequencing, bioinformatics analysis, functional validation in animal models, and the identification of disease biomarkers, laying a solid foundation for the industrial translation of scientific achievements. The company revealed that, leveraging source innovation in basic research and its strong, sustained R&D capabilities, it will build upon its earlier scientific outcomes to strategically expand into the field of early cancer screening and diagnosis. It aims to develop companion diagnostic reagents for tumor immunotherapy and novel live biotherapeutic products for cancer treatment, thereby constructing an integrated platform for “prevention, screening, diagnosis, and treatment.”

“Luxin Venture Capital has been actively promoting the development of outstanding domestic technological innovation enterprises. We are optimistic about the great health industry in the microbiome field, especially the early screening of colorectal cancer, which has broad market prospects,” said Chen Lei, Deputy General Manager of Luxin Venture Capital. “Shanghai Realbio Technology Co., Ltd. has been deeply engaged in the field of intestinal health for many years, possessing abundant international resources and strong R&D capabilities, and is also a pioneer in the blue ocean of early colorectal cancer screening. Shanghai Realbio will be an important part of Luxin Venture Capital's systematic layout in the field of precision medicine, and we believe that Shanghai Realbio will lead the direction of development in China's intestinal health industry.”

“Realbio is a pioneer in the microbiome industry, leveraging its research projects to build a strong technical foundation and robust continuous R&D capabilities,” said Yang Ruirong, Partner at Yuan Yi Capital. “We look forward to Dr. Qin Nan and his team fully capitalizing on their scientific research strengths to develop more products for the diagnosis and treatment of gut health, thereby providing patients with novel precision therapy solutions.”

“The microbiome has frequently featured in headlines in recent years due to a surge of high-profile research findings. The Realbio team boasts profound technical expertise in the field of microbiomics. Driven by insights into gut microbiota and aiming to meet the substantial demand for early screening and diagnosis of colorectal cancer, Realbio has rapidly established leading product development capabilities within the industry. Furthermore, it has solidified its industry-leading position through scientific and clinical collaborations with numerous top-tier experts in China,” stated Li Yishi, Executive Director at Joy Capital, the exclusive financial advisor. “In addition to its colorectal cancer early-screening product, which demonstrates performance metrics far superior to those of domestic and international competitors, Realbio has achieved landmark results in expanding other clinical applications of microbiomics. This successful financing round indicates that mainstream large-scale institutional investors have begun to make in-depth investments in the microbiome sector, marking the field’s gradual transition from research to product commercialization.”

Luxin Venture Capital Group Co., Ltd. (abbreviated as Luxin VC, SH.600783), controlled by Shandong Luxin Investment Holding Group Co., Ltd., is the largest professional venture capital firm in Shandong Province and one with significant influence nationwide. The company’s investment scope covers advantageous industries in Shandong Province, such as advanced manufacturing and the marine economy, as well as national strategic emerging industries, including energy conservation and environmental protection, new energy, new materials, biotechnology, and high-end equipment manufacturing. Healthcare and pharmaceuticals are currently key sectors for Luxin VC’s strategic layout and investments, with projects spanning China, the United States, the European Union, Israel, and other countries and regions. Notable healthcare companies already invested in include 3D Medicines, RemeGen, Abclonal, Silicon-Based Bionics, Boying Medical, Shiling Technology, Cubio, Intarcia, and TCR2 Therapeutics. The company has established standardized and rigorous investment management and risk control systems, adopted scientific and efficient investment philosophies and operational models, built an experienced and high-caliber investment team, and nurtured a portfolio of startups with strong growth potential, high technological content, and industry-leading positions.

Wuxi Financial Investment Co., Ltd. (hereinafter referred to as “Jintou Company”) is a municipal-level comprehensive financial investment platform established in November 2013 in response to the Wuxi Municipal Party Committee and Municipal Government’s policy of “Strengthening Wuxi through Finance.” Adhering to a market-oriented and specialized development path, Wuxi Jintou, as a municipal state-owned financial asset platform, has basically formed three major business segments: fund-of-funds management, equity investment, and operational subsidiaries. It is committed to building a comprehensive, market-oriented, and international financial holding group based in Wuxi with a radiating influence across the Yangtze River Delta region.

Yuanyi Capital, established in 2016, is an early-stage venture capital fund focused on the healthcare technology sector, with offices in Beijing, Shanghai, Suzhou, and Hong Kong. Currently, Yuanyi manages both RMB and USD-denominated funds.

Yuanyi Capital focuses on early-stage investment opportunities in the healthcare technology sector. To date, Yuanyi’s inaugural RMB and USD funds have invested in 38 companies. Among these, more than 12 portfolio companies have either listed on major stock exchanges domestically or internationally, or achieved exit through mergers and acquisitions.

Shanghai Realbio Technology Co., Ltd, established in October 2014, is a national high-tech enterprise specializing in genetic technology and health services. Leveraging its high-throughput sequencing technology platform, Realbio focuses on the translational application of cutting-edge technologies and research findings in human microbiome science to clinical medicine, particularly in the fields of precision medicine such as early screening for colorectal cancer, tumor immunotherapy, and health management. In 2018, the company was honored with the title of “Top Ten Emerging Sci-Tech Entrepreneurial Enterprises in Minhang District.” It has currently established regional centers in Hangzhou, Qingdao, Jinan, Guiyang, and other cities. Notably, the Jinan Laboratory was designated as a “National Demonstration Center for Genetic Testing Technology Application” in 2016, and the Qingdao Laboratory, serving as the North China Medical Inspection Service Headquarters Base, was completed in 2019.