Xinrui Regenerative: A Pioneer in Small Molecule-Driven In Situ Regeneration Attracts Sequoia China and Top-Tier Investors

In early spring 2022,Nanjing Xinrui Regenerative Medicine Technology Co., Ltd.(hereinafter referred to as “Xinrui Regeneration”) announced positive news regarding financing, namely the completion of a Pre-A financing round amounting to tens of millions of RMB, which was led bySequoia China Leads the Investment, with co-investment from Dongpingheng Capital and Haisong Medical Fund.

Regarding this investment, Gu Cuiping, Managing Director at Sequoia China, stated: “Sequoia China has always focused on the development of new technologies and early-stage enterprises. Regenerative medicine is a key area of focus with significant growth potential. Xinrui Regeneration already boasts an outstanding team of scientists, possesses advanced technology and drug screening platforms, and has chosen a unique path for innovative development, demonstrating strong commercial sustainability.”

If you, like the founder and chief scientist of Xinrui Regeneration,Dr. Zhao YangAfter in-depth discussions that shed light on the team’s entrepreneurial journey, technological advantages, and business logic, it becomes clear why Gu Cuiping has spoken so highly of Xinrui Regeneration, and why prominent investment firms such as Sequoia China have extended their olive branches.

Forward-looking VCs tend to observe patiently, plan strategically, and wait for the right moment. At that time, Dr. Zhao Yang, who was still focused on basic research in the laboratory, had already beenZhongke StarListed as a subject of concern.

Dr. Zhao Yang is a researcher at the Institute of Molecular Medicine, School of Future Technology, Peking University, and Principal Investigator (PI) of the Laboratory for Cell Reprogramming and Regenerative Medicine. With over 20 years of experience in stem cell and regenerative medicine research and development, he has served as co-corresponding author alongside his mentor, Professor Deng Hongkui.First Report of Fully “Small Molecule”-Induced Cell Fate Reprogramming Technology（Hou et al,Science,2013; Zhao et al,Cell,2015). This study provided the first demonstration that somatic cell reprogramming can be induced by a combination of small-molecule compounds, without reliance on exogenous transgenes, and was therefore recognized by the Ministry of Science and Technology as“Top 10 Scientific Advances in China” and “Top 10 Scientific and Technological Advances in Chinese Universities.”

"Just as floral scents naturally attract butterflies, Zhao Yang’s significant discoveries in the field of regenerative medicine drew the attention of CAS Star. He told Chengguo Bureau, 'Investors from CAS Star had been in contact with me for two years before I founded my company.' During those two years, CAS Star not only closely monitored his research progress but also particularly endorsed his perspective on scientists becoming entrepreneurs."

Not content with merely satisfying his curiosity about the unknown, he aspired to unlock greater social and economic value from his research. This is the purest motivation driving scientists in the commercialization of scientific and technological achievements, and Zhao Yang was no exception. However, holding onto such original intentions and passion alone is far from sufficient. Having long focused on academic frontiers, Zhao Yang was not well-versed in entrepreneurship.

“The investors at CAS Star were waiting for me to start my own business, even encouraging me to do so. Throughout the process, it was also CAS Star that helped me sort out the business logic from 0 to 1.” With the support of CAS Star, Zhao Yang got off to a fairly smooth start.

From an early stage, Zhao Yang began assigning Li Honglei to manage translational projects in the laboratory. After the company was established, Li Honglei, as the legal representative, was responsible for the company’s operations, while Zhao Yang served as the Chief Scientific Officer (CSO).Continue to devote greater efforts to technological exploration and translation.

Meanwhile, benefiting from the university-local government collaborative project for the commercialization of scientific and technological achievements undertaken by the Nanjing Institute of Translational Molecular Medicine, Peking University (hereinafter referred to as the “Nanjing Translational Institute”), the institute’s incubation platform has provided robust support to principal investigators (PIs) like Zhao Yang, enabling them to fully leverage their professional expertise and translate their research outcomes into practical applications.

“The hardware infrastructure of the incubation platform is tailored to our specifications, enabling the team to move in and commence operations immediately.“Zhao Yang said. With one-click convenience and the support of the university, Zhao Yang did not encounter any difficulties in areas such as site selection for household registration, equipment procurement, and office renovation.”

With achievements secured, a team in place, and a location settled, everything was duly arranged. Finally, in March 2019, Zhao Yang founded Xinrui Regenerative Medicine, and CAS Star completed its angel-round investment in the company.

As a technology-driven company, Xinrui Regenerative Medicine has assembled a team of researchers from prestigious universities such as Peking University, Tsinghua University, and Fudan University, who each bring decades of research experience in fields including stem cells and regenerative medicine, medicinal chemistry, and artificial intelligence.

From the initial two or three people to the present dayNearly 40 peopleteam size, this group of people with Zhao Yang at the core has always persisted in doing one thing—rejuvenating cells.

How to Achieve Cellular Renewal?

The answer is throughPartial Reprogramming Technology, which is also the most important research direction of the Xinrui Regeneration team. The team controls the overall epigenetic state of cells by developing small molecules,Driving global state changes in cells to restore vitality to damaged cells without altering cell type。

“In the past, whenever reprogramming was mentioned, it was commonly assumed to involve a change in cell type, which often raised concerns about the safety of in situ reprogramming. Xinrui Regeneration’s primary focus on partial in situ reprogramming is precisely aimed at reversing the diseased state of cells by leveraging reprogramming technologies and principles, without altering their identity. This represents a shortcut for the translational application of reprogramming technology,” explained Zhao Yang. Currently, the “remarkable” potential of partial reprogramming is leading international trends and developments.

In March 2023, OpenAI CEO Sam Altman publicly disclosed a $180 million investment in Retro Biosciences. It is understood that Retro’s research focuses on three areas: cellular reprogramming, plasma-related therapies, and autophagy. Coincidentally, Altos Labs secured $3 billion in funding in 2022, and other biotechnology companies such as New Limit have also recently obtained substantial financing. These companies are all dedicated to applying partial cellular reprogramming technology in the fields of disease treatment and anti-aging.

Keeping pace with, and even leading, the latest trends. Xinrui Regeneration stands out with its unique characteristics, particularly in certain areas of reprogramming, focusing primarily onDevelopment of Small-Molecule Compounds for Inducing Partial Reprogramming. Furthermore, Xinrui Regeneration has developed a unique small-molecule drug discovery platform based on stem cell technology, high-throughput transcriptomics, and artificial intelligence, targeting the highly promising direction of partial reprogramming -CReDIT(Cell Revitalizing Drug Innovation Technology), and leveraging the advantages of small-molecule drugs—such as non-genomic integration, ease of manipulation, lack of immunogenicity, low cost, ease of standardization, and a clear drug registration pathway—to take the lead in strategic deploymentIn Situ Regeneration of Tissues and Organs, Reversal of Fibrosis, Reprogramming of Tumor Cellsand other fields.

In the field of in situ regeneration following acute liver injury, Xinrui Regeneration has identified highly efficient small-molecule drug hits for partial reprogramming of damaged hepatocytes, based on the CReDIT screening platform.In Situ Regeneration in Liver-Injured Animals Achieved with a Single Small Molecule. Currently, the medicinal chemistry optimization and in vitro/in vivo efficacy and safety evaluations of this product have been sufficiently conducted,An IND application is expected to be submitted within the year.

Inspired by the successful treatment of leukemia through induced differentiation of tumor cell fate, Xinrui Regenerative Medicine has also focused its attention onTumor fields such as liver cancer and gastric cancer. Committed to identifying small-molecule drugs capable of reversing the hallmark phenotypes of tumor cells through reprogramming, Xinrui Regeneration has achieved the "maturation" of poorly differentiated tumor phenotypes while simultaneously inducing immune sensitization, thereby developing first-in-class (FIC) oncology therapeutics designed for combination with immunotherapy. CurrentlyMultiple candidate molecules have been identified, and new relevant targets have been discovered., and will evaluate the safety and therapeutic efficacy of these small-molecule compounds in animal models to further optimize their structures, combinations, and administration regimens.

Furthermore, in the field of fibrosis reversal, Xinrui Regeneration has also initiatedSkin Fibrosis (Hypertrophic Scars) and Cardiac Fibrosis (Chronic Heart Failure)exploration in this direction, and several candidate small molecules have been identified that significantly reverse the activated phenotype of fibroblasts and comprehensively reshape the expression patterns of collagen-related factors,Currently in the animal testing phase.。

The traditional new drug development industry is characterized by extremely high barriers in terms of cost and resources. The mantra of “100,000 compounds, $1 billion, and 10 years” highlights challenges that alone could cripple an innovative enterprise.

But new technologies may change this! Xinrui Regenerative Medicine has deployed its proprietary high-throughput targeted transcriptome sequencing technology, based onMachine Learning Techniques for Cellular Imaging, and collaborate with AI experts from Tsinghua University to develop based onAI Models for Cellular Phenotypes, thereby improving the efficiency of drug screening while reducing its costs.

“Leveraging machine learning-based cellular imaging technology, we capture real-time images of cells during the differentiation process. Our team uses these images to enable artificial intelligence to identify which cells have differentiated correctly and which have differentiated incorrectly. Additionally, the system can assess whether the concentration of the induction factors used and the timing of differentiation initiation are appropriate,” explained Zhao Yang, describing a new technology his team is developing. It is understood that the proof-of-concept work for this technologyXiangRelevant academic articles are also forthcoming.

After launching his startup, Zhao Yang gradually began to feel the pressures of a busy schedule. In addition to his daily R&D responsibilities, he also strove to keep pace with the accelerating rhythm of fundraising, ensuring healthy cash flow before the company achieved profitability. After interacting with numerous investors, Zhao YangFitwas placed first.

Perhaps it is through the mutual selection between Xinrui Regeneration and Sequoia China that we can better understand the “fit” described by Zhao Yang.

On the one hand,Alignment with Professional FieldsIn recent years, Sequoia China has invested in a number of representative innovative regenerative medicine companies, including Shize Biotechnology, Nuopu Regeneration, and Xueji Biotechnology. This has enabled the firm to develop a deep understanding of the field, particularly gaining unique insights into translating academic research into industrial applications. Furthermore, Sequoia China’s extensive portfolio of investment cases and its well-established industrial ecosystem in the healthcare sector have facilitated rapid mutual understanding and resonance in industry research during communications between the two parties.

On the other hand, it isSpiritual Resonance。“Give Scientists More Patience” is a point that Zhao Yang values highly. Similarly, this represents the greatest support Sequoia China offers to scientist entrepreneurs. Early-stage betting, end-to-end partnership, and multi-round increased investment have always been the investment style and distinctive characteristics of Sequoia China.

To date, 45 healthcare companies backed by Sequoia China have completed their initial public offerings (IPOs). In most of these cases, Sequoia China began supporting the companies as early as the angel, seed, Series A, or Series B rounds, accompanying them throughout the entire entrepreneurial journey, with some partnerships lasting up to ten years.

The participation of investment firms such as Sequoia China has also propelled Xinrui Regenerative Medicine onto a fast track, transforming it from a research-oriented company into a clinical-stage enterprise.

“Add to R&D, subtract from translation.Zhao Yang stated, “Add” refers to the R&D team maintaining technological leadership in the future, advancing the development of early-stage pipelines, and providing more and better candidate drugs for further clinical translation; while “Subtract” refers to shortening the translation timeline and prioritizing projects that advance into the clinical translation phase.

In 2021, with years of industry experienceDr. Mo MingguangJoined the team to take charge of medicinal chemistry; in 2022, Xinrui Regeneration’s core team was once again infused with fresh talent, bringing on board professionals with 30 years of experience in new drug development.Dr. Lin YijunandDr. Chen LuJoining Xinrui Regenerative, they are respectively responsible for the company’s operational management and external business development and partnerships. To date, Xinrui Regenerative has built a senior executive team with more extensive industry experience.

Finally, to answer the question posed at the beginning: the continuous influx of capital is driven by investors’ recognition of Dr. Zhao Yang, founder of Xinrui Regenerative Medicine’s, profound academic background; their optimism about the technical advantages and market prospects of partial reprogramming technologies; their trust in the company’s overall planning and strategic layout; and also by their resonance with the original aspiration to develop novel therapeutics for cell injury and age-related diseases, thereby reshaping cell fate and reversing disease progression.