1 million IBD patients in China, 30%-50% of whom have no response to existing therapies: JiuZhi Biotech is betting on the untapped local drug delivery gap in the distal colon with "exosome enema"
Inflammatory Bowel Disease (IBD) has evolved from a prevalent disorder in Western countries to a common chronic refractory intestinal disease in China. According to data from the Chinese Society of Gastroenterology of the Chinese Medical Association, the number of IBD patients in China has reached approximately 1 million, and the figure is expected to rise to 1.5 million by 2030, with the disease predominantly affecting young adults aged 15 to 35. This lifelong recurrent disease, known as "green cancer", has long-standing shortcomings in response rate and safety for traditional treatment methods, and there is an urgent clinical need for a new generation of safe, effective, and highly accessible local treatment regimens. Recently, JiuZhi Biotech, headquartered in Tiankai Higher Education Innovation Park in Tianjin, is carrying out research and development on engineered exosome enema preparations, exploring the local delivery of stem cell-derived exosomes to break the deadlock in IBD treatment, and launching the next round of financing to advance early pipeline R&D and process platform construction.
The treatment dilemma of chronic intestinal diseases remains to be solved
IBD mainly includes Ulcerative Colitis (UC) and Crohn's Disease (CD), characterized by chronic, progressive, and lifelong recurrent digestive tract inflammation, with clinical manifestations of repeated abdominal pain, diarrhea, mucopurulent and bloody stools. Severe patients can have 10 to 30 episodes of diarrhea per day, and the risk of colon cancer for patients with a disease course of more than 20 years is 10 to 15 times higher than that of healthy people. Patients not only suffer physical pain, but also are accompanied by psychological burdens such as anxiety and depression, as well as economic pressure caused by long-term medication.
The current mainstream clinical treatment pathway presents obvious "stepwise limitations". Patients with mild to moderate conditions rely on aminosalicylic acid and glucocorticoid enema preparations, which can relieve symptoms in the short term, but carry risks such as hormone dependence and local mucosal atrophy after long-term use; patients with moderate to severe conditions turn to biologics targeting TNF-α, IL-12/23, IL-23 and other targets, as well as JAK small molecule inhibitors. However, 30% to 50% of patients will develop primary non-response or secondary loss of efficacy, and the risk of infection and tumors caused by systemic immunosuppression makes patients have many concerns about long-term medication. Especially for patients with distal ulcerative colitis whose lesions are concentrated in the left colon and rectum — this group accounts for about 40% to 50% of UC patients — the concentration of drugs reaching the lesion after oral or intravenous administration is limited, while the existing enema preparations still only focus on simple anti-inflammation, and cannot solve the fundamental problem from the aspects of immune microenvironment remodeling and mucosal barrier repair.
From the market perspective, the global IBD treatment market has reached a scale of tens of billions of US dollars. According to the forecast of Mordor Intelligence, the global IBD treatment market size will be about 27.4 billion US dollars in 2025, and is expected to reach 37.9 billion US dollars by 2031. The Chinese market is in a period of rapid growth. In 2026, the IBD field will not only witness the patent cliff of multiple biologics and the window of domestic substitution, but also become a strategic track that multinational pharmaceutical companies such as Novartis, Sanofi, and AbbVie are intensively increasing their layout through mergers, acquisitions and cooperation. However, in the direction of dosage form innovation and local precise drug delivery, the existing pipelines are still dominated by systemic administration, and new non-hormonal, non-immunosuppressant enema preparations for distal colon lesions are still a clear supply gap.
Engineered exosomes reshape the local drug delivery pathway
JiuZhi Biotech has focused its R&D direction on engineered exosome enema preparations derived from Mesenchymal Stem Cells (MSCs). Exosomes are endogenous extracellular vesicles with a diameter of 30 to 150 nanometers, carrying active molecules such as proteins, lipids, mRNA and microRNA, and naturally have low immunogenicity, high biocompatibility and cross-barrier delivery capabilities. After the regulatory mechanism of vesicle transport won the Nobel Prize in Physiology or Medicine in 2013, the research transformation in this field has been significantly accelerated. Relying on its engineered modification technology platform, JiuZhi Biotech performs targeted modification and functional enrichment on MSC-derived exosomes to make them carry specific immunomodulatory molecules and tissue repair factors, and directly deliver them to the colitis site through enema administration.
From the perspective of mechanism of action, this technical route has multiple differentiated advantages. First, enema administration allows exosomes to bypass the degradation in the upper part of the digestive tract, directly contact the mucosa of the distal colon lesion, the local concentration is significantly higher than that of systemic administration, and the systemic exposure and off-target risk are reduced at the same time. Second, MSC exosomes are inherently rich in immunomodulatory factors such as TGF-β, IL-10, PGE2, as well as a combination of miRNAs with repair functions, which can synergistically exert anti-inflammatory effects through multiple pathways such as regulating Th17/Treg balance, inhibiting the release of pro-inflammatory factors, and promoting M2 polarization of macrophages, breaking through the limitation of single-target inhibition of traditional drugs. Third, as natural nanovesicles, exosomes can be efficiently taken up by intestinal epithelial cells and infiltrating immune cells through membrane fusion, and their delivery efficiency and retention time are better than synthetic nanocarriers. According to the research results published in recent years in journals such as Signal Transduction and Targeted Therapy, MSC exosomes enhanced by genetic engineering or pre-treatment have shown significant effects of reducing disease activity index, improving colon length, and repairing mucosal barrier in mouse colitis models, and no obvious liver or kidney toxicity has been observed after intravenous injection.
At the engineering level, the team focuses on promoting three core links: large-scale preparation of exosomes, targeted modification and formulation stability. Upstream, by establishing standardized MSC culture and exosome harvesting processes, the common pain points in the current industry such as low yield and large batch-to-batch difference are solved; midstream, genetic engineering methods are used to modify exosome membrane proteins to enhance their homing and adhesion ability to the inflamed intestinal endothelium; downstream, a buffer system and aseptic filling process suitable for enema administration are developed to ensure the activity stability of the product during storage and use. Compared with direct stem cell transplantation, engineered exosome preparations have more advantages in safety — there are no risks such as abnormal cell differentiation and microvascular embolism, and the lyophilized formulation can theoretically greatly reduce transportation and storage costs, creating conditions for out-of-hospital administration and popularization in primary hospitals in the future.
Early-stage projects seek financing acceleration relying on Tiankai Park's ecosystem
Industrial and commercial information shows that JiuZhi Biotech (Tianjin JiuZhi Biotech Co., Ltd.) was established in April 2026, with its registered address at Tianjin Science and Technology Plaza, Keyuan West Road, Nankai District, Tianjin, located in the core area of Tiankai Higher Education Innovation Park. Its legal representative is Xu Qin, and its business scope covers cell technology R&D and application, human stem cell technology R&D and application, medical research and experimental development, sales of Class I and Class II medical devices, etc. As a sci-tech innovation source and achievement transformation highland focused on building by Tianjin, Tiankai Park has registered more than 5,000 sci-tech enterprises in total since its opening three years ago, gathered 48 sci-tech innovation funds with a total scale of over 21.9 billion yuan, and has a special biomedical innovation and entrepreneurship base, which can provide full-cycle services for early biotech enterprises including proof of concept, pilot incubation, inspection and testing, investment and financing docking. This industrial ecosystem provides support for JiuZhi Biotech's early R&D and resource docking.
The current project is still in the early stage of R&D, and the core work includes the construction of engineered exosome strains/cell lines, optimization of preparation process parameters, in vitro functional verification, and in vivo animal model efficacy evaluation. The core members of the team have cross backgrounds in cell biology, exosome engineering modification and gastroenterology, and are actively connecting with the gastroenterology resources of top tertiary hospitals in Tianjin and the Beijing-Tianjin-Hebei region to prepare for subsequent Investigator Initiated Trials (IIT). In terms of business model, the project plans to advance through two paths of innovative medical devices and biological preparations: in the early stage, it can be used as Class II or Class III medical devices for adjuvant treatment of IBD and mucosal repair, and later explore the declaration as therapeutic biological products according to the accumulation of clinical data; at the same time, the patent portfolio formed by the exosome preparation process platform and targeted modification technology can be extended to adjacent indications such as local drug delivery for intestinal tumors, radiation enteritis repair, and perianal lesion treatment in the future.
It is understood that JiuZhi Biotech is advancing the next round of financing, and the raised funds will be mainly used for three aspects: first, complete the preclinical efficacy and safety evaluation of the engineered exosome candidate preparation, and build a small-scale preparation system that meets GMP requirements; second, expand the R&D team, introduce core talents in the directions of exosome quality analysis, formulation development and registration declaration; third, deepen cooperation with clinical institutions to promote the launch of IIT research for the first indication. In the global exosome therapy field, international companies such as Codiak, Evox, and Capricor have products entering Phase II clinical trials, and domestic enterprises such as Enze Kangtai and Aima Biotech are also advancing rapidly in the direction of engineered exosome drug loading, but pipelines focusing on intestinal local administration and entering the IBD track with enema dosage form are still scarce. Whether JiuZhi Biotech can take the lead in completing proof of concept in this niche track with differentiated dosage form design and local immunomodulatory mechanism is worthy of continuous attention.