Pusci Biotech: Can PBPK Modeling Combined with Organ-on-a-Chip Carve Out a Viable Commercial Pathway in China?

The pharmaceutical R&D industry has long sought breakthroughs in research and development approaches, giving rise to organ-on-a-chip technology in recent years and fostering the emergence of a nascent industry. Organ-on-a-chip platforms can construct physiological and pathological models for drug screening, efficacy simulation, and personalized precision medicine. As the industry is still maturing and lacks standardization, any company aiming to stand out must possess its own core competitive technologies and barriers to entry.

Wang Wen, Founder and CEO of Pushi Biotech, served at XEMET, a leading European PBPK simulation software company, for ten years, where he was involved in corporate operations and management.In 2019, the core technologies of XEMET were successfully acquired, and Pusheng Biotechnology was established in China and Finland, respectively.

The founding R&D team at Pushi sought to address the issue in the PBPK industry where estimated values for certain unknown parameters deviate from reality. They proposed leveraging organ-on-a-chip technology to simulate and reconstruct the human microenvironment, thereby generating data that more closely approximates real-world conditions.The integrated service combining PBPK modeling with organ-on-a-chip technology enhances competitiveness and facilitates more substantial growth across the entire organ-on-a-chip industry.

In 2019, Wang Wen and the founding team returned to China with their core technologies and expertise, establishing a parallel R&D and commercialization pipeline for locally developed products in China while maintaining their European R&D team.

Wang Wen observed that after 2015, China’s biopharmaceutical market underwent disruptive changes, revitalizing long-dormant vitality. Regulatory agencies’ evaluation of drug efficacy and safety became a critical challenge for innovative pharmaceutical companies. Among these developments, pharmacokinetic modeling emerged as a crucial factor in new drug development, with most Chinese pharmaceutical companies opting to collaborate with U.S. firms in this field.

Pusi Biotechnology focuses on integrating pharmacokinetic software simulation technology with organ-on-a-chip technology to replicate the complex structures and authentic environments of human organs, while partially simulating the physiological functions specific to the source organs or tissues. By constructing human microenvironments, it enables more precise simulation of the ADMET (absorption, distribution, metabolism, excretion, and toxicity) processes of drugs in the body. Leveraging accurate data, Pusi Biotechnology helps pharmaceutical companies reduce R&D costs at the source stage, shorten the time and cost of new drug development, and lower the proportion of sunk costs.

Compared with traditional 2D static cell culture methods, a key advantage of organ-on-a-chip technology is its ability to control cells and specific tissue architectures to simulate chemical gradients and biomechanical forces. This enables precise regulation of the biochemical and cellular microenvironment, mimicking in vivo conditions and responses, and facilitating high-resolution, real-time imaging and in vitro analysis of the biochemical, genetic, and metabolic activities of living human cells within functional human tissue and organ contexts.

PBPK Model: A PBPK model is a pharmacokinetic model based on physiological anatomy. It integrates the body’s physiological and anatomical characteristics with the physicochemical properties of drugs, as well as drug–body interactions, to simulate and predict the kinetic changes in drug concentrations and their metabolites in tissue systems using computational methods.

The integration of PBPK modeling with organ-on-a-chip technology enables more accurate simulation of the microenvironment of human organs and tissues, thereby enhancing the accuracy and efficiency of in silico experiments. Furthermore, organ chips can generate data that are difficult or impossible to obtain through traditional experimental methods, contributing to further improvement in the accuracy of PBPK simulation results.

Currently, Pusheng Biotechnology’s PBPK simulation software has been upgraded to version 4.0. Meanwhile, the tumor-on-a-chip, gut-on-a-chip, and cervical cancer-on-a-chip have completed their first-generation model construction and are currently undergoing clinical testing.

Overall,Few companies globally have established a market presence with both PBPK simulation software and organ-on-a-chip models,The primary reason is the high technical barrier. The core of Pushi Biotech’s PBPK simulation software lies in using mathematical models to construct the processes of drug absorption, distribution, metabolism, and excretion within the human body. The constructed models require repeated validation and calibration through project collaborations with pharmaceutical companies to enhance system accuracy. Therefore, even if the necessary hardware conditions for R&D are met, long-term experience accumulation and calibration remain indispensable.

With the accumulation of underlying technologies, the gradual maturation of algorithms, and the improvement of services, Pusheng Biotechnology has begun to prioritize commercial implementation as the focal point of its future corporate development.

“The entire team spent nearly a decade on R&D. For over five years abroad, we had no customer base; only after our technology stabilized did we embark on commercialization,” Xu Aili, Co-founder and Chief Operating Officer of Pusheng Biotechnology, told VCBeat New Medicine.

Pusi Biotechnology provides pharmaceutical companies and research institutions with services including high-throughput drug screening, drug absorption and metabolism, drug development, human circulatory system studies, and drug toxicology.The core profit model primarily revolves around bundled services that combine software-based data analysis with organ-on-a-chip experimental data.

In 2016,Bayer Pharmaceuticals encountered a bottleneck in studying the long-term controlled-release metabolism of its star contraceptive product, Mirena, within the body and sought assistance from XEMET to develop software for simulating this controlled-release process.This product has been launched in local markets after receiving approval from regulatory authorities in various countries.

Mirena is a hormonal intrauterine device (IUD) that provides long-term contraception. The device is a T-shaped plastic frame inserted into the uterus, where it releases progestin. It prevents pregnancy by thickening cervical mucus, thereby blocking sperm from reaching and fertilizing the egg. Since Mirena can remain in the human body for up to eight years, its metabolic process cannot be determined through conventional experiments; however, this process can be simulated using PBPK software.

“The application value of organ-on-a-chip technology in the field of drug development is widely recognized. Beyond pharmaceutical companies, clinicians in oncology, chronic disease, and infectious disease departments at medical institutions are eager to integrate organ-on-a-chip technology into their practice to better guide personalized clinical medication, such as in the screening of anticancer drugs,” said Xu Aili.

However, Xu Aili also acknowledged that the greatest challenge facing organ-on-a-chip technology is whether regulatory guidelines can be issued smoothly and promptly. Domestic regulators and academic researchers are conducting extensive studies on the application of organ-on-a-chip systems; before they endorse this new technology, compelling data are needed to demonstrate its superiority over traditional testing methods.

“We are confident that domestic regulatory authorities will actively promote the development of this industry.” Xu Aili believes that the organ-on-a-chip industry is currently at a tipping point; once regulatory agencies issue relevant guidelines or standardized documents, organ-on-a-chip technology will inevitably see widespread application.