A month ago, a volunteer recruitment announcement unexpectedly propelled an AI-driven pharmaceutical company focused on gut microbiome therapy onto social media trending lists. The company is publicly recruiting volunteers for stool donations, offering 300 RMB per donation with a maximum monthly subsidy of 6,600 RMB, and the processed microbiota samples will be utilized in research on disease treatment.
Many people are surprised that fecal donation can generate income, and are curious about how feces are linked to disease treatment. To address these questions, EqualOcean Health recently conducted an exclusive interview with Tan Yan, Founder and CEO of Xbiome Co. Ltd., to uncover the actual research and work being conducted by the company behind this "unconventional" topic.
In addition to volunteer recruitment, Xbiome conducts comprehensive health monitoring and screening of volunteers. Following the collection of fecal samples from healthy donors (i.e., volunteers willing to donate stool), the gut microbiota are isolated through a series of filtration, centrifugation, and anaerobic processing steps, and subsequently formulated into therapeutic agents. These products hold promise for treating a wide range of gastrointestinal disorders, as well as immune- and nervous system-related diseases.
The rationale behind this is, "Around 2007, scientists worldwide initiated the Human Microbiome Project to investigate the relationship between gut microbiota and health and disease. To date, the medical community has come to refer to the gut microbiome as the "forgotten organ of the human body" and the "second human genome." Research indicates that the gut microbiome may be associated with more than 50 human diseases.”Tan Yan pointed out to EO Healthcare.
Early in his career, Tan Yan conducted doctoral research in bioinformatics and computational biology at the Broad Institute in the United States. Upon returning to China, he initially joined FreeS Fund as an investor. During this professional tenure, he observed that with the continuous advancement of sequencing and multi-omics platforms, the foundation for data-driven biotechnology and pharmaceutical R&D was gradually taking shape. Building on this insight, Tan Yan founded Xbiome in 2017. Anchored in microbiome therapeutics, the company is dedicated to translating scientific research and technological innovations into commercial applications in China.
From an industry-wide perspective, compared to traditional pharmaceuticals, no microbiome drug has yet been formally approved for market launch globally. In China, or even across the entire Asian region, microbiome therapeutics remain in their nascent stage.
Xbiome aims to fill this gap, leveraging artificial intelligence (AI) and biotechnology (BioTech) to drive the research and development of microbiome therapeutics. Four years on, Xbiome is now beginning to achieve preliminary results.Recently, Xbiome announced that its investigational fecal microbiota transplantation (FMT) drug, codenamed "XBI-302", has received Investigational New Drug (IND) approval from the U.S. FDA, officially allowing it to enter the clinical trial phase for the treatment of acute graft-versus-host disease.
Tan Yan stated that, according to official data disclosed by the U.S. FDA, this is the first Investigational New Drug (IND) application approved by the FDA for a Chinese microbiome pharmaceutical company. It signifies that Chinese pharmaceutical enterprises have officially established a complete regulatory pathway for domestic microbiome drugs to be submitted to the U.S. FDA for approval. Meanwhile, Fecal Microbiota Transplantation (FMT) has historically been conducted primarily as a novel medical technology. Xbiome, however, has developed this therapeutic approach as a microbiome-based drug, successfully transforming FMT from a clinical procedure into a standardized pharmaceutical product.
AI + Data-Driven: Achieving a Closed-Loop R&D Pipeline for Microbiome Therapeutics
In Tan Yan's view, data, algorithms, and high-throughput screening will significantly advance research paradigms and enhance the efficiency of life science research—the establishment and development of Xbiome are precisely grounded in this judgment and fundamental premise.
The human gut harbors over 1,000 species of microorganisms, with an even greater number of strains. Identifying strains with genuine therapeutic efficacy against diseases from this vast microbial community is highly time-consuming and labor-intensive. Traditionally, pharmaceutical companies primarily rely on large-scale screening, cultivation, and druggability assessment to identify therapeutic strains. Although some progress has been made, only a limited number of strains have proven viable for drug development.
Furthermore, artificial intelligence and high-throughput screening technologies can address the time and cost constraints associated with traditional microbiome drug development, thereby accelerating the pace of microbiome-based pharmaceutical development.
Tan Yan pointed out that,Xbiome regards the gut microbiome as a systemic entity, employing data modeling and machine learning to identify which bacterial strains have a causal relationship with disease treatment. Once identified, these target strains are specifically isolated and ultimately developed into therapeutic drugs.
“The greatest difference from traditional approaches is that we adopt a more systematic, disease-driven strategy to identify solutions, rather than simply starting with one or two bacterial strains that happen to be available, evaluating their functions, and developing them into drugs. Systematic development inevitably relies on data and artificial intelligence,” Tan Yan specifically noted.
Xbiome's data are primarily derived from public databases and investigator-initiated clinical trials conducted in collaboration with hospitals. Regarding AI, "it is primarily applied in two major directions: first, multi-omics, where we utilize modeling to identify associations across various omics datasets and infer which microorganisms are associated with disease treatment; and second, leveraging genomic analysis of bacterial strains for functional annotation and prediction."
Overall, Xbiome has established an Artificial Intelligence (AI) platform and a Biotechnology (BioTech) platform to address the team's challenges in the in-depth mining and analysis of data collected from clinical or public databases, as well as downstream drug development, thereby enabling a complete closed-loop workflow for the research and development of microbiome therapeutics.
Regarding these two major platforms, Tan Yan also provided a further explanation, “On the AI platform, leveraging data and machine learning modeling, we identify which bacterial strains are associated with diseases and which possess therapeutic potential. Subsequently, on the BT platform, we isolate these strains to validate their functions, conduct animal studies, and advance them to clinical trials.”
FMT Drug Receives FDA Clinical Trial Approval, From Fast-Follow to First-in-Class
Having understood the strategic rationale behind Xbiome’s pharmaceutical pipeline, let us now examine its clinical progress. Last October, Xbiome submitted an Investigational New Drug (IND) application to the U.S. FDA for acute graft-versus-host disease (aGVHD). Recently, Xbiome officially announced that the application has received FDA approval, making this compound the company's fastest-advancing drug candidate to date.
Historically, fecal microbiota transplantation (FMT) was primarily administered as a novel medical technology. Such procedures typically involve complex operational protocols, and the fecal microbiota suspension must be freshly prepared for immediate use, posing significant storage challenges. The recent clinical implementation of FMT therapy in oral capsule form marks a major breakthrough for Xbiome. By leveraging proprietary technology to stabilize viable microbial components within capsules, this innovation overcomes the traditional limitations of transportation and time sensitivity, thereby making FMT therapy significantly more accessible.
The primary indication of this FMT drug is acute graft-versus-host disease (aGvHD), which is a major subtype of graft-versus-host disease (GvHD). This disease is a common complication following allogeneic hematopoietic stem cell transplantation, characterized by donor immune cells attacking the recipient's organs, resulting in a clinicopathological syndrome.
Once a patient develops aGvHD, current treatment options are limited to corticosteroids and immunosuppressants. These agents not only carry inherent adverse effects but also severely impair the establishment of a new immune system. Currently, it remains highly challenging to devise an optimal regimen that prevents and treats graft-versus-host disease while simultaneously promoting immune reconstitution and preserving normal immune function.
The FMT drug recently approved for clinical trials by Xbiome operates by replacing the patient's disrupted gut microbiota with a healthy microbial community. It colonizes alongside transplanted hematopoietic stem cells, helping the host restore its gut microbial ecosystem without compromising the prophylaxis and treatment of graft-versus-host disease (GVHD), thereby reducing antibiotic use during treatment and recovery.
However, Tan Yan pointed out,FMT therapeutics represent a novel drug category. Unlike conventional small-molecule drugs, which emphasize batch-to-batch stability and the purity of specific chemical components, FMT drugs are controlled by two key quality attributes: viable bacterial count and microbial purity.
These two key indicators pertain to multiple aspects, including donor screening and manufacturing processes. Given that FMT therapeutics are essentially derived from the microbiota in healthy human stool, donor quality is therefore of paramount importance.
It is reported that, regarding donor screening, the R&D team has developed a donor management protocol that aligns with and exceeds the consensus standards of the United States and Europe, incorporating clinical insights from renowned experts in China. The protocol includes preliminary questionnaire screening, clinical testing, and re-screening within fixed time windows. Furthermore, to mitigate the risk of SARS-CoV-2 fecal transmission during the pandemic, Xbiome has implemented more stringent health monitoring and an expanded panel of stool tests for its donors.
Regarding the manufacturing process, through multiple optimizations, Xbiome has gradually minimized batch-to-batch variability. Alongside securing FDA approval for its drug, the company also achieved an unexpected “bonus”—the establishment of a microbiome drug manufacturing system fully recognized by the FDA across production processes, manufacturing techniques, and quality standards.
The U.S. FDA's IND clearance for this FMT therapeutic marks Xbiome's official entry into the clinical development stage.In addition to the aforementioned FMT therapeutics that have recently achieved new progress, Xbiome is currently collaborating with several renowned medical institutions in China on clinical research, focusing on three major areas: oncology, the nervous system, and the immune system.
Specifically, this includes conducting the "Correlation Study on the Relationship Between Human Gut Microbiome and the Efficacy of Anti-PD-1/PD-L1 Therapy in Cancer Patients" with Peking University Cancer Hospital; collaborating with Nanfang Hospital, Southern Medical University to conduct the "Clinical Study on the Safety and Efficacy of a Novel Fecal Microbiota Transplantation (FMT) Technology (Gut Microbiota Capsule XBI-302) in the Treatment of Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease (GI-aGvHD)"; and carrying out clinical research collaborations across various indication areas with several other renowned Grade-A tertiary hospitals in China, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, West China Hospital of Sichuan University, The Second Xiangya Hospital of Central South University, Peking University First Hospital, and Beijing Anding Hospital, Capital Medical University.
Regarding the company's overall development pace going forward, Yan Tan stated: “Every drug presents its own challenges. Xbiome focuses more on progressing from fast-follow to first-in-class. In other words, we swiftly follow up on what others are already developing, and ultimately aim to achieve our own first-in-class status in specific disease areas.”