Interview with Puheng Technology: China's First Organoid Company Tackling NASH

Over the past decade, the development of organoids has been regarded as one of the most exciting advances in stem cell research. Since the first intestinal organoids were cultured by Hans Clevers’ laboratory in 2009, organoid technology has advanced rapidly, with particularly notable progress in the Netherlands, Germany, and the United States. These European and American countries began their organoid research early and have actively promoted the translation of scientific achievements into industrial applications.

Although China started later in basic organoid research, its accumulated expertise is rapidly growing. By 2020, the number of organoid-related publications from China had risen to second place globally. Meanwhile, China’s 14th Five-Year National Key R&D Program has highlighted the substantial application potential of organoid technology. Although a fully formed domestic organoid industry cluster has yet to emerge, a wave of innovative companies has appeared in the past two years; among them is Puheng Technology, which focuses on in vitro 3D organs and disease model development.

Not long ago, Puheng Technology secured an angel-round investment of nearly RMB 10 million from Guoqian Venture Capital. Puheng Technology’s NAC-Organ technology is a novel in vitro 3D culture platform developed using nucleic acid materials and AI, enabling high-throughput, standardized production of complex disease models.

VCBeat recently conducted exclusive interviews with Dr. Song Guangqi, Founder of Puheng Technology, and Dr. Teng Songsong, Investment Director at Guoqian Venture Capital and Head of Investment at Puheng Technology.

Traditional 2D cell culture techniques require large-scale animal studies for validation, resulting in high development and application costs. In vitro 3D culture technologies provide a variety of preclinical models for drug screening. In a 3D environment, cellular responses to endogenous and exogenous stimuli more closely mimic their in vivo behavior. In recent years, 3D spheroid culture, organoid technology, organ-on-a-chip systems, and 3D bioprinting of organs have all undergone rapid development.

The organoid field has also recently reached a milestone: the FDA has approved the first new drug to enter clinical trials with preclinical data derived from “organ-on-a-chip” studies, marking the first time that “organ-on-a-chip” experiments have replaced traditional animal testing and gained official recognition.

Dr. Song Guangqi, founder of Puheng Technology, stated, “One advantage of in vitro microphysiological systems is the ability to circumvent the influence of species differences., thereby obtaining more precise data on safety and efficacy. If it can replace animal testing on a large scale, drug development efficiency will be significantly improved, enabling high-throughput, real-time screening at a lower cost than animal models.”

Internationally, the shift away from animal-based models is an inevitable trend, with continuous progress being made.

However, Dr. Teng Songsong, Head of Investment at Puheng Technology and Investment Director at Guoqian Venture Capital, candidly stated, “The new drug submitted for IND this time targets a rare disease, making it impossible to establish an animal model. Therefore, data from organ-on-a-chip experiments are suitable for supporting the application.”This is a highly groundbreaking attempt, but for some broader diseases, data from animal experiments may still be needed to support it.”

Although organoid technology is continuously evolving, it still suffers from numerous limitations and challenges. For instance, the self-organization process of stem cells, which underpins organoid development, is difficult to control and proceeds stochastically. This results in a widespread lack of reproducibility among most existing organoid cultures, thereby limiting their utility in elucidating the overall effects involved in normal or disease processes related to cell-type specificity.

This is also the starting point for Puheng Technology’s entrepreneurship.Puheng Technology Seeks More Controllable 3D Cell Culture Methods:Nucleic Acid-Based In Vitro 3D Organ Culture Technology (NAC-Organ). The company has developed Nucleic Acid-Cell Linker (NAC-Linker) based on cell membrane engineering and synthetic biology technologies. This technology enables the integration of various cell types, allows for more precise control over cell quantity and ratios, and regulates spatial cell distribution. It can carry small molecule compounds, peptides, proteins, and other agents to stimulate the formation of physiological and pathological microenvironments within 3D models.

“Puheng Technology’s unique NAC-Organ technology, which simulates in vivo organs while enhancing reproducibility and modeling efficiency, represents a significant methodological innovation in the construction of in vitro 3D models and possesses strong market competitiveness,” commented Teng Songsong.

The development of this technology is based on “DNA origami.” DNA materials exhibit excellent biocompatibility, allow for precise design at the nanoscale, and possess high editability, making them ideal carrier materials. DNA origami enables nucleic acid materials to form stable structural conformations.

The ability to approach the market from this niche perspective is inextricably linked to the team’s multidisciplinary background. Song Guangqi previously worked at Zhongshan Hospital, Fudan University, and has many years of experience in regenerative therapy and 3D culture technology research. Professor Pei Hao, the team’s Chief Scientist, is a senior expert in the field of nucleic acid biomaterials, with his team long dedicated to the design and development of nucleic acid molecular devices. Another co-founder, Researcher Zhu Tong, has been deeply engaged in AI-driven drug screening for many years.

Organoids represent a multidisciplinary field encompassing biomedicine, materials science, tissue engineering, and artificial intelligence (AI). For companies competing in this industry, the interdisciplinary nature of their teams constitutes a significant competitive barrier.

China’s organoid field started late, largely due to relatively weak foundational disciplines; advancing this frontier industry requires coordinated strengthening across all relevant disciplines.The diverse, seasoned, and professional backgrounds of the founding members will help the team go further.

Data shows that the global organoid market size was approximately USD 500 million in 2020, and is projected to grow at a compound annual growth rate (CAGR) of 18.2% from 2021 to 2026.

The exploration of new technologies is always exciting,However, the market’s sustained growth will ultimately depend on the commercialization value of technological implementation.

Organoids already have clear commercialization prospects, with broad potential in new drug discovery, regenerative medicine, and basic research areas such as developmental biology and disease pathology.

However, no company with a highly mature commercialization model has yet emerged on the global stage. Many venture capital firms also remain on the sidelines, adopting a wait-and-see approach toward the long-term development and returns of organoid technology.

Currently, the majority of startups in China are positioned toward disease modeling, research, and drug screening for cancer patients.Puheng Technology is targeting another blue ocean: the research and development of chronic, complex multifactorial diseases, represented by non-alcoholic steatohepatitis (NASH).

There are nearly 400 million NASH patients worldwide. In the United States, it has become the leading cause of liver cancer and is expected to surpass hepatitis B as the primary cause of liver cancer in China in the future.

This disease is part of metabolic syndrome, and its complexity is several orders of magnitude higher than that of viral hepatitis. There are many factors driving the progression of the condition, and its natural history is very slow; therefore, modeling all these factors using animal models presents significant challenges.

There are currently over 700 clinical trials targeting NASH worldwide; however, the Phase III clinical results of the vast majority of therapeutic candidates have been disappointing. A key reason for this is the lack of ideal pathological and predictive models. To date, no pharmacological treatments have been approved for non-alcoholic steatohepatitis (NASH), and lifestyle interventions, such as weight loss and dietary control, remain a cornerstone of management.

The pathogenesis of NASH is explained by the "two-hit" hypothesis, wherein hepatocellular steatosis constitutes the first hit, and subsequent production of pro-inflammatory cytokines by macrophages represents the second hit. In vitro models can facilitate a better understanding of the mechanisms underlying NASH and the therapeutic efficacy of drugs.

Several international companies have established a presence in the field of liver disease. For instance, InSphero, founded in Switzerland in 2009, has developed 3D cell models that simulate the complexity of non-alcoholic steatohepatitis (NASH) and enhance the efficiency of drug discovery and safety testing. In April this year, CN Bio, a company specializing in human organ-on-a-chip development, launched the NASH-in-a-Box (NIAB) kit for constructing preclinical models of non-alcoholic steatohepatitis (NASH).

Puheng Technology is the first of its kind in China.

According to Puheng Technology, NAC-Organ can achieve secondary and tertiary assembly through programmable methods, repeatedly stimulating cells to generate biochemical and physiological responses. By integrating the immune system into organoids, Puheng Technology has developed pathological microenvironment modeling technologies for various chronic diseases, including non-alcoholic steatohepatitis (NASH).

Puheng Technology is also collaborating on chip-system design for microphysiological systems, while jointly developing automated culture and detection equipment as well as AI-based analysis and prediction systems. The AI system serves a dual purpose: enabling high-throughput monitoring and enhancing the accuracy of drug toxicity and efficacy predictions. For organoid companies, automation capabilities will be a key focus for pharmaceutical firms when seeking partnerships.

Furthermore, liver transplantation remains the only definitive treatment for advanced NASH to date. Therefore, organoid technology serves as a promising alternative regenerative approach to address the demand for organ transplants. Puheng Technology is leveraging the advantages of its NAC-Organ technology in structural regulation to attempt to resolve the issue of immune rejection.

Puheng Technology showcases the broader potential of organoids beyond cancer research. Although a truly competitive market for organoids has yet to emerge in China, it is evident that an increasing number of startups are entering the field, driving the commercial implementation of organoid technology.