BenevolentAI Biologics Announces $Tens of Millions B+ Financing to Advance Clinical Trials of Microbiome Therapeutics

VCBeat has learned that Shenzhen Xbiome Co., Ltd. (hereinafter referred to as “Xbiome”), a leading domestic microecological pharmaceutical company, recently completed a Series B+ financing round worth tens of millions of US dollars. The round was led by Primavera Capital and Gaorong Capital, with participation from Wuyuan Capital (formerly Morningside Venture Capital), Legend Capital, Yimei Capital, and Yayi Capital. The funds will be primarily used to support Xbiome’s clinical trials in 2021, the research and development of new drug pipelines, and the continued R&D and expansion of its six existing platforms. China Renaissance served as the exclusive financial advisor for this financing round.

Established in 2017, Xbiome leverages an innovative drug development model and its proprietary platform to integrate artificial intelligence with gut microbiome technology. This integration enables high-quality data analysis, accumulation, and output, streamlining the translation pathway from “data” to “drugs” and creating a complete closed loop for microbiome-based drug R&D, thereby significantly enhancing the efficiency and success rate of drug development. By tailoring gut microbiome therapeutics to the specific microbial profiles of patients with different indications, Xbiome develops targeted treatments for multiple conditions, effectively advancing microbiome pharmaceuticals from laboratory-stage scientific exploration to industrialized application.

It is reported that Xbiome submitted an Investigational New Drug (IND) application to the U.S. FDA for aGvHD (acute graft-versus-host disease) in October 2020. Upon approval, Xbiome will possess the first FMT drug in Asia and the first microbial drug in China to receive U.S. clinical trial authorization. Furthermore, Xbiome plans to add 3–5 new drug pipelines in 2021.

Dr. Tan Yan, Founder of Xbiome, stated, “With the smooth progress of clinical trials at several U.S. microbiome pharmaceutical companies, the field of microbiome-based therapeutics is gaining increasing international attention and earning recognition and support from various stakeholders, including traditional pharmaceutical manufacturers, regulatory agencies, and the capital market. We appreciate investors’ continued confidence in and support for the microbiome therapeutics industry and Xbiome. As the industry gradually moves toward a more mature stage, we hope that Xbiome can represent China and join the ranks of world-class leaders in this field.”

Zou Ling, Executive Director at Primavera Capital, stated: “The global field of microbiome-based pharmaceuticals is still in its early stages of development, with immense potential for growth and broad applications across various disease areas. Under the leadership of Dr. Tan Yan and his team, Xbiome has not only distinguished itself within China but also demonstrated strong competitiveness on a global scale. Primavera Capital holds a highly optimistic view of Xbiome’s future development. We believe that Xbiome will represent China in achieving leapfrog progress in the microbiome pharmaceutical sector, continue to enhance the application efficiency of AI algorithms in this field, and rise to become a world-class microbiome pharmaceutical company.”

Le Beilin, Project Leader at Gaorong Capital, stated, “Humans have coexisted with thousands of gut microbiota species in a ‘symbiotic’ relationship for millions of years. With the advancement of various omics technologies over the past decade, our understanding of microbial dynamics has evolved from focusing on single fluctuations to examining global perturbations. Coupled with progress in translational medicine, the association between the microbiota and diseases now encompasses not only pathogenic mechanisms but also therapeutic potential. As more proof-of-concept (POC) and mechanism-of-action (MOA) studies across various indications advance and their data are disclosed, we believe the entire industry is poised to enter a golden period of rapid development. As a pioneer in the field of gut microbiota drug development in China, Xbiome has independently developed Strainfinder, an integrated AI algorithm that further facilitates the early pipeline reserve of next-generation (2.0) gut microbiota therapeutics, leading the industry from mixed fecal microbiota transplantation (FMT) toward an era of more precisely formulated bacterial consortia. As the lead investor in Xbiome’s first financing round and having continued to increase its investment in two subsequent rounds, Gaorong Capital recognizes the immense potential of gut microbiota-based pharmaceuticals and highly values the Xbiome team’s dedication and exploratory spirit in this field. We look forward to the company further expanding the boundaries of gut microecological therapy and continuing its journey toward becoming a world-class innovative pharmaceutical enterprise.”

Jing Xutian, Executive Director at 5Y Capital, stated: “Three years ago, 5Y Capital chose to bet on the potential of developing new drugs through gut microbiome modulation. This decision was primarily based on logical deductions drawn from published literature, combined with our understanding of advancements in machine learning and bioinformatics. Three years later, we are pleased to see that North American companies with years of experience in this field have achieved relatively clear technical validation, significantly increasing the certainty of success for the industry. Although Chinese companies entered this field later, China possesses abundant data and clinical resources, which can greatly enhance R&D efficiency. Furthermore, the team at Xbiome boasts world-leading technical capabilities. Over the past three years, Xbiome has established a comprehensive microbiome pharmaceutical platform and an extensive industry resource network. Its drug candidates are currently in the stage of filing for Investigational New Drug (IND) approval with the U.S. Food and Drug Administration (FDA). We believe that in this novel therapeutic category, China’s new generation of biopharmaceutical companies can achieve world-leading progress in drug development across many disease areas.”

Zhao Mingwei, Executive Director at Legend Capital, stated, “As the lead investor in the company’s previous funding round, Legend Capital has continued to increase its investment in this round. Xbiome has achieved numerous breakthroughs by integrating AI with microbiome-based drug R&D, continuously attracting top industry talent and expanding its business scope. Legend Capital is optimistic that Xbiome will leverage its AI capabilities and data accumulation to become a platform-driven innovative pharmaceutical company in this field. Legend Capital will also continue to focus on investment opportunities in AI across various vertical industries, including healthcare.”

Ding Dali, Partner at Yimei Investment, stated, “Yimei Investment has long focused on innovative opportunities within the broader healthcare sector and is optimistic about the application prospects of the microbiome in diagnostics, therapeutics, and health management. With industry pioneers such as Seres Therapeutics achieving highly positive Phase III clinical data this year, we believe the blue-ocean market of microbiome-based pharmaceuticals is on the verge of an explosion. As one of the first innovative companies to enter this field in China, Xbiome boasts a top-tier multidisciplinary team and an internationally competitive, efficient AI and biotechnology R&D platform. Its R&D pipeline design and progress are highly competitive on a global scale. We have high expectations for this leading enterprise in China’s microbiome pharmaceutical industry.”

Liu Chong, Partner at Yayi Capital, stated, “With the explosive growth in microbiome-based drug R&D globally, Xbiome’s AI technology platform, pipeline portfolio, and talent team have advanced in tandem, establishing the company’s unique competitive moat and demonstrating exceptional competitiveness. In China, Xbiome has already secured a leading position in the gut microbiome sector. With its Investigational New Drug (IND) application in the United States this year, along with the filing and advancement of larger-scale clinical trials in the future, its international influence is set to grow rapidly. Yayi Capital is committed to supporting the integrated development of emerging technologies such as artificial intelligence and the biopharmaceutical industry both domestically and internationally, and will continue to focus on investment opportunities in these related fields.”

With the advancement of the Human Microbiome Project, understanding of the relationship between gut microbiota and human health and disease has deepened significantly. Progress by companies such as Seres and Finch Therapeutics indicates that the microbiome-based pharmaceutical industry has entered a mature stage of translational development.

Currently, microbiome-based therapeutics primarily encompass four major modalities: fecal microbiota transplantation (FMT), defined microbial consortia, microbial metabolites, and engineered microbes. Overall, the microbiome pharmaceutical industry is becoming increasingly systematic. The mainstream development strategy involves identifying microbes or microbial products with drug potential based on clinical or human data, followed by in vitro strain isolation and subsequent in vitro and animal studies.

Dr. Tan Yan pointed out that the rapid development of biotechnologies such as culturomics, particularly high-throughput automated culturomics, high-throughput multidimensional in vitro screening assays, and gnotobiotic animals (especially gnotobiotic disease models), along with the widespread application of cutting-edge technologies including multi-omics analysis, ecology and artificial intelligence modeling, and strain analysis algorithms, has accelerated global R&D of microbiome-based therapeutics.

Among these, the clinical development of FMT therapies is advancing rapidly, with one drug having successfully completed Phase III clinical trials. The first FMT drug is expected to receive approval from the U.S. FDA by the end of this year or next year. Meanwhile, defined microbial consortium drugs are gradually entering Phase II clinical trials internationally, while drugs based on bacterial metabolites are progressively entering Phase I clinical trials.

In the microbiome pharmaceutical industry, Xbiome possesses internationally leading data mining and analytical capabilities, significantly reducing data noise and enhancing data interpretability. It provides in-depth analysis of key pathways and major contributing bacterial strains involved in disease onset and improvement, thereby constructing a complete information chain for microbiome-based drugs: “bacteria → genes → pathways → metabolites → functions.” The data-driven mining and analysis efforts are integrated with downstream experimental strain development, achieving a closed-loop system for microbiome drug research and development.

Xbiome's AI Drug Discovery Platform

In terms of data volume, Xbiome possesses the world’s largest library of gut microbiota samples and sequencing datasets from patients before and after PD-1 therapy. Meanwhile, Xbiome has integrated public datasets with its proprietary extensive microbiota data from healthy individuals and patients across various indications, both pre- and post-treatment, to build and continuously enrich its proprietary knowledge base, which is currently the most comprehensive gut microbiota knowledge base globally. All data within this knowledge base, along with their corresponding samples, have undergone standardized reprocessing and effective integration. The team now holds data from over 5,000 individuals spanning healthy and disease populations, more than 8,000 data points on host gene–gut microbiota associations, and over 340,000 data points on microbiota–disease associations. Leveraging this continuously enriched database, Xbiome has developed prediction models using gut microbiota as biomarkers, achieving internationally advanced levels of accuracy in predicting responses to PD-1 therapy in cancer patients.

In the realm of data governance, Xbiome’s independently developed “Xstrain” is the first tool capable of directly resolving strain composition and corresponding genes from metagenomic samples. This innovation not only enhances the sensitivity of strain detection but also enables functional-level analysis and screening of strains, thereby reducing reliance on strain isolation and sequencing while accelerating the strain screening process. Another data tool, MSEA, predicts host functional changes from differential microbes through text mining. Pioneeringly, it directly predicts host gene-level regulation based on changes in microbiota composition, contributing to a deeper understanding of microbe-host interactions and the interpretation of microbial physiological roles.

In terms of knowledge extraction, Xbiome adopts a "data-driven + hypothesis-driven" approach. By integrating microbial correlations extracted from multi-omics data with prior knowledge consolidated in its knowledge base, and leveraging machine learning and deep learning tools, the company identifies key bacterial strains associated with specific indications and their mechanisms of action, thereby guiding downstream strain development efforts.

In terms of medical translation, Xbiome possesses an innovative R&D platform capable of sustainably generating breakthrough microbiome therapeutics, targeted intestinal release technologies for microbiota protection and microencapsulation, full-spectrum gut microbiota drugs with high purity and high activity, a strictly standardized donor screening process, and has developed a high-end animal model validation platform, while employing FDA-approved processes in multiple production stages.

Dr. Tan Yan told VCBeat that Xbiome has collaborated with multiple renowned medical institutions in China on clinical research into gut microbiota, with several microbiome-based drugs demonstrating significant therapeutic efficacy in clinical trials. For instance, the collaborative study between Xbiome and Peking University Cancer Hospital, titled “Clinical Study on Gut Microbiota Transplantation Capsules Enhancing the Efficacy of PD-1/PD-L1 Therapy in Cancer Patients,” represents the world’s first and currently largest combined study exploring the co-administration of microbiome drugs and cancer immunotherapy in the field of gastrointestinal tumors. Meanwhile, Xbiome is collaborating with Nanfang Hospital of Southern Medical University on a project using gut microbiota capsules to treat acute graft-versus-host disease (aGvHD), and submitted an Investigational New Drug (IND) application for aGvHD to the U.S. FDA in October 2020.

“Xbiome’s primary drug pipeline consists entirely of internally developed candidates,” stated Dr. Tan Yan. “Currently, our proprietary pipeline covers multiple therapeutic areas, including combination therapies for anti-PD-1 tumor immunotherapy, autism spectrum disorder, and acute graft-versus-host disease (aGvHD).” In 2021, Xbiome will formally enter a pipeline-driven development phase. While actively advancing clinical trials, the company will continue to strengthen its technological platforms, build a broader and more valuable drug pipeline, and provide patients with an expanded range of high-quality microbiome-based therapeutics.

Xbiome's Pipeline in Development

Dr. Tan Yan plans to continue opening up Xbiome’s various technology platforms, strengthening clinical research and new technology collaborations with more medical institutions on one hand, and enhancing R&D partnerships in the microbiome field with major pharmaceutical and probiotic companies on the other. Leveraging its proprietary germ-free animal platform, AI platform, and culturomics platform, Xbiome aims to empower the entire microbiome-based pharmaceutical industry. “In the future, building on its extensive expertise in microbiome therapeutics, Xbiome will expand its reach to a broader healthy population, providing prevention and healthcare services for microbiome-related diseases, and becoming a pioneer in human health based on the microbiome.”

VCBeat has learned that Xbiome was recently named to the 2020 MIT Technology Review “50 Smart Companies” list, thanks to its precision prediction model for cancer patients receiving PD-1 therapy, which uses gut microbiota as biomarkers. This recognition underscores the growing acknowledgment of Xbiome’s continuous innovation and exploration in the field of microbiome-based pharmaceuticals.

Primavera Capital Group is a China-based premier research, advisory, and global alternative investment firm that manages large-scale onshore and offshore funds in both RMB and USD. Primavera is dedicated to providing professional asset management services for leading large institutions, corporations, and high-net-worth individuals in China and around the world, aiming to deliver superior absolute investment returns. The firm emphasizes rigorous fundamental research, leveraging its deep understanding and unique insights into macroeconomics, industries, and capital markets to generate investment ideas, define investment themes, and capture optimal investment opportunities.

Founded in January 2014 by founding partners Zhang Zhen, Gao Xiang, and Yue Bin, Gaorong Capital focuses on early-stage and growth-stage investments, with an emphasis on innovative ventures in new consumption and new technology sectors. Over six years, the total assets under management of its USD and RMB funds amounted to approximately RMB 20 billion. To date, 14 companies invested in or held equity stakes by Gaorong Capital have successfully completed initial public offerings (IPOs), with many emerging as leaders in their respective industries. These include Pinduoduo (NASDAQ: PDD), Huya Live (NYSE: HUYA), GSX Techedu (NYSE: GSX), Yixian E-Commerce (NYSE: YSG), Yitu Technology, and Nuro.

Yuan Capital (formerly Morningside Venture Capital) is one of China’s earliest firms engaged in early-stage venture capital. It currently manages dual-currency funds in both US dollars and Chinese renminbi, with assets under management totaling several billion US dollars. Yuan Capital seeks out, supports, and empowers solitary entrepreneurs, providing them with comprehensive assistance ranging from moral support to operational guidance. Its portfolio companies include Xiaomi Corporation, Kingsoft Office, XPeng Motors, Agora, Kuaishou, WeDoctor Group, SenseTime, and Pony.ai.

Legend Capital was established in April 2001, with its core business focused on venture capital for start-ups and growth investment for expanding companies. The total assets under management of its USD and RMB funds exceed RMB 50 billion, with a strategic emphasis on innovation and growth opportunities in China. As of 2020, Legend Capital had invested in more than 500 portfolio companies, among which nearly 80 have successfully listed or been quoted on domestic or overseas exchanges, and over 60 have exited through mergers and acquisitions.

Yimei Capital is the earliest multi-currency fund-of-funds management platform established in China and stands as one of the most professional and experienced fund-of-funds management teams in the country. With over 30 years of global investment experience and 20 years of domestic expertise, Yimei Capital has navigated multiple economic cycles and the full life cycles of numerous funds, managing a global asset base exceeding USD 10 billion. Its business footprint spans emerging markets worldwide, where it has built one of the most successful USD-denominated investment portfolios, achieving a 10-year overseas internal rate of return (IRR) of up to 46%.

Yayi Capital is a private equity fund engaged in primary market investments, focusing on early-stage opportunities in the biotechnology sector. Yayi Capital aims to improve the current state of healthcare and pharmaceuticals by identifying and supporting startups with core technologies that address the opportunities and challenges facing the pharmaceutical industry, while introducing world-class biotechnology companies to the Chinese market.