China's First IND-Approved Drug Leveraging Organ-on-a-Chip Data: The Story Behind HRS-1893 and the Rise of Aivita Biotech

Center for Human Organ-on-a-ChipEstablished in 2017, the year the Research Institute was founded, it was one of the institute’s four major research centers and was personally led by Professor Gu Zhongze, the Dean. After years of project R&D and incubation, and with the joint support of the Jiangsu Industrial Technology Research Institute and Suzhou New District, the Human Organ-on-a-Chip project was approved by the relevant departments of Southeast University, completed intellectual property transfer, and established a project company—Jiangsu Aiweide Biotechnology Co., Ltd.(hereinafter referred to as “iVita”). “The transition from project incubation to company establishment represents two distinct stages of project development. Human organ-on-a-chip technology is one of the many typical success stories at our research institute that have evolved from incubated projects into incorporated companies,” commented President Ge Jianjun.

From Building 1, the Incubator of the Jiangsu Medical Device Industrial Park where the research institute is located, to Building 1, the Accelerator of the same park where the company is headquartered, the distance is not significant—just a 14-minute drive. On a deeper level, Aiweide originated from the research institute; its early-stage development and external collaborations were inseparable from the institute’s support and assistance, including its partnership with Hengrui Medicine.

In late May 2023, when the website of the National Medical Products Administration displayed that,When Hengrui Medicine's HRS-1893 Tablets Were Approved for Clinical TrialsColleagues involved in the related projects at the Institute and iWellD closely monitored this development, which has become the most gratifying news for everyone. This is because the in vitro screening work for this study was jointly conducted by Hengrui Medicine, the Southeast University Suzhou Medical Device Research Institute, and iWellD. As the news spread, major media outlets rushed to report on it. Subsequently, project team members, including Dean Gu Zhongze, Dean Ge Jianjun, and Researcher Chen Zaobao, shared the post on their WeChat Moments, commenting: “A milestone! The first in China!”

On the day of the interview, Suzhou was bathed in bright sunshine, mirroring the vibrant and positive spirit exhibited by the team. Subsequently, members of the team led by Dean Gu Zhongze shared with us the story behind this new drug that has received Investigational New Drug (IND) approval.

When asked about the background and catalysts for the collaboration between the research institute and Hengrui Medicine, Ge Jianjun and Chen Zaozao have yet to disclose any details on social media.

Let’s turn the clock back to 2018. To facilitate external collaborations and align products from the organ-on-a-chip project with market needs, Ge Jianjun believed that the institute should establish a marketing department dedicated to client engagement and partnership negotiations. Moreover, Dr. Chen Zaozao, the Project R&D Director, also stated: “R&D cannot be conducted behind closed doors., we still need to promote the technology and clarify its future application scenarios and potential users.” Immediately thereafter, the institute took action by establishing a marketing department.

However, the market rollout did not proceed smoothly; we visited numerous pharmaceutical companies,Yet, it always hits a wall at the outset.. In the interview, Dean Ge recalled, “At that time, we visited numerous hospitals and pharmaceutical companies, many of which directly rejected us. The feedback we received was mostly‘What Are Organ-on-a-Chip Devices?’ or ‘No Demand’.” In retrospect, the team attributed the causes to two factors:

The first point is thatThe concept is still too new.. Although the concept of organ-on-a-chip had been proposed for seven or eight years, it remained a novel technology at the time, adopted only by leading pharmaceutical companies in the United States and Europe, with limited application scope. Many domestic pharmaceutical companies and hospitals in China were unfamiliar with this concept.

The second point lies inAt that time, most domestic enterprises did not yet need it.. Analyzing the types of pharmaceutical companies they had engaged with, Chen Zaozao observed: “In the past, most of the companies we worked with were generic drug manufacturers. For such companies, it was sufficient to conduct testing solely in accordance with FDA and CFDA requirements; any additional testing was considered a waste. Why, then, would these companies adopt organ-on-a-chip technology?”

So the team shifted its strategy: if generic drug manufacturers had no need for organ-on-a-chip technology, they would target companies focused on innovative drug R&D. This change in approach brought a turning point—Manager Wu and other colleagues from the marketing team opened the door to Hengrui Medicine.

Unlike companies previously engaged with,Hengrui Medicine is the Pioneer of Innovative Drugs in China. Two decades ago, while others were still preoccupied with making quick and short-term profits, Sun Piaoyang, Chairman of Hengrui Medicine, presciently steered the company toward a transformation focused on innovative drugs. In 2011 and 2014, Imrecoxib and Apatinib Mesylate were approved for market launch, respectively, making Hengrui Medicine the only domestic pharmaceutical company at that time to have two Class 1.1 innovative drugs in its portfolio.

Since then, Hengrui Medicine has accelerated its transition from generic drugs to innovative therapeutics. From 2018 to 2022, the proportion of revenue derived from innovative drugs increased from 12% to approximately 40%. Meanwhile, a large number of generic drug projects were discontinued. Financial report disclosures indicate that Hengrui Medicine’s current R&D pipeline contains virtually no generic drugs, having been replaced by rapidly advancing innovative therapies. Currently, the company has seven innovative drugs in the registration and marketing approval stage, 13 in Phase III clinical trials, and another 64 in Phase I or II clinical development.

“We cannot say it was an instant match, but ratherThis “first” was achieved only after extensive communication, collaboration, and joint research and development..”The collaboration between VCBeat Research Institute, iWit, and Hengrui is innovative, groundbreaking, highly efficient, and enjoyable.“This is likely the first case in China of a collaboration between an organ-on-a-chip company and a pharmaceutical company to file an Investigational New Drug (IND) application.“Chen Zaozao said.”

For in vitro drug testing, Hengrui has three options: two-dimensional cell assays, mouse models, and human organ-on-a-chip systems.

This test requires real-time and long-term monitoring of the beating heart, a task that two-dimensional cell experiments cannot accomplish for Hengrui’s new drug. Meanwhile, mouse and rat models—the models most familiar to drug researchers—are also not ideal for this test. On one hand, there are significant physiological and pharmacological differences between mice/rats and humans; on the other hand, it is difficult to achieve long-term observation of the drug’s regulatory effects on the heart and conduct high-throughput screening in animal models.

Organ-on-a-chip, this novel technology, has entered the realm of consideration. Novelty always comes with uncertainty.

Therefore, before selecting human organ-on-a-chip technology for in vitro drug testing, Hengrui Medicine’s R&D personnel need toValidation of Model Accuracy and Reliability“At the initial stage of engagement, they would first review our model to understand which parameters it could measure and how it would respond. Only after they were satisfied with its performance would they begin sending us samples for testing,” recalled Dean Ge.

The collaboration between the Institute and Hengrui Medicine alsoNot starting directly with the in vitro testing of HRS-1893 tablets“We collaborated with scientists from Hengrui to test the pharmacodynamic responses of a series of known drugs on heart-on-a-chip models,” recalled Chen Zaozao, reflecting on the collaborative project. Only after passing the validation tests with these known drugs did Hengrui formally select the human heart organ-on-a-chip project and commission the Suzhou Medical Device Research Institute of Southeast University to conduct in vitro screening for HRS-1893 tablets.

“The compounds for screening were delivered batch by batch by our colleagues from Hengrui’s R&D Department. After each batch, the more promising compounds were identified, and the results were sent back to Hengrui, where their R&D team further optimized them before sending the next batch of compounds for screening. ‘The process was truly exciting and inspiring: the EC50 values decreased significantly with each batch,’ recalls Chen Zaozao, reflecting on the screening results from each round.”

Throughout the iterative process, both research teams consistently maintained a results-oriented approach to exploration. After6 RoundsCommunication and Compound Screening: The effective concentration of the compound has been significantly optimized compared to the initial value, and it has passed multi-batch and long-term stability tests. This result signifies the completion of in vitro activity and drug selectivity screening for the compound, identifying a golden candidate molecule for subsequent in vivo efficacy studies. The value of human organ-on-a-chip technology in innovative drug screening has been perfectly demonstrated.

As previously mentioned, organ-on-a-chip technology is relatively new in China, and Aiweide is a startup that has been established for less than two years. For both Aiweide and its organ-on-a-chip project, being the first to venture into this uncharted territory makes this collaboration with Hengrui Medicine profoundly significant.

"First, it set a landmark precedent for the application of domestic organ-on-a-chip technology in drug screening, drawing greater attention from pharmaceutical companies, CROs, and regulatory agencies to this cutting-edge international in vitro model."The collaboration with Hengrui has also attracted more users and potential users.“, which is good for us and the entire organoid and organ-on-a-chip industry,” said Dean Ge.

Next isGathering Feedback and Improving Products: New Technologies Typically Require Continuous Iteration and Product Enhancement. During the collaboration, we can obtain the most authentic feedback and opinions, enabling timely product improvements and optimizations. In particular, leading domestic pharmaceutical companies such as Hengrui Medicine represent the development of China’s pharmaceutical industry. “Their specific requirements for the model can also guide the R&D direction of organ-on-a-chip technology,” said Chen Zaobao.

Finally, Hengrui’s R&D system and processes have become highly standardized, and this collaboration has also advanced the overall development of organ-on-a-chip technology.Establish a Standardized Work System, to better promote human organ-on-a-chip technology.

There may be many angles from which to dissect the factors behind the success of this collaboration: for instance, perseverance, deep-rooted expertise, win-win outcomes, and the luck that is essential to every success. Yet one trait stands out as particularly prominent:Academic and Commercial Interdisciplinary Thinking.We rarely encounter teams that possess both scientific research acumen and business savvy. However, the Suzhou Medical Device Research Institute of Southeast University and Aiweide have excelled in this regard. During our discussions, Orange Bureau witnessed several instances where academic thinking collided with commercial thinking.

While the spotlight today is on the Suzhou Research Institute of Southeast University and Jiangsu Aiweide Biotechnology Co., Ltd., the many biomedical and medical device researchers and industry translation institutions behind them—and represented by them—are also systematically advancing the ideal and cause of translating scientific achievements into practical applications. They are conducting top-tier research for China’s biomedical industry, launching high-tech, high-quality biomedical products akin to “human body chips.”