RouYi Bio Secures Pre-A Financing Led by DNE Capital to Advance Recombinant Botulinum Toxin Drug Development

VCBeat has learned that Shanghai Ruoyi Biotechnology Co., Ltd. (“Ruoyi Biotech”), a globally leading next-generation recombinant botulinum toxin pharmaceutical company, has recently completed a Pre-A financing round worth tens of millions of RMB. The round was led by Dongjiu Xinyi Capital, with continued participation from Yuan Sheng Venture Capital, an investor in the angel round. The proceeds will be primarily used to advance the industrialization of its fourth-generation Type A botulinum toxin product and to promote the application of its proprietary zinc finger protein drug delivery technology in recombinant protein therapeutics.

Headquartered in the Zhangjiang High-Tech Park of Pudong New Area, Shanghai, Ruoyi Biotechnology is a startup incubated by ShanghaiTech University, specializing in the research and development of macromolecular drug delivery technologies and their applications in biomedical R&D. The company was founded by Dr. Liu Jia from the Institute of Immunochemistry at ShanghaiTech University, whose primary research focuses on the mechanisms underlying cellular uptake of macromolecules and the development of drug delivery technologies.

Currently, Ruoyi Biotechnology’s core technology platform is zinc finger protein-based drug delivery technology; its key product in development is a recombinant botulinum toxin type A protein therapeutic; and its manufacturing platform is based on the insect cell–baculovirus expression system. This proprietary technology will drive reforms in traditional botulinum toxin manufacturing processes, enabling the launch of products that are safe, long-acting, and cost-effective, with broad market applications in both aesthetic medicine and biopharmaceuticals.

The zinc finger protein special issue of the Methods in Molecular Biology series, edited by Dr. Jia Liu (left), and

C2H2Three-dimensional structure diagram of the type zinc finger protein (right)

Botulinum toxin commands a market worth hundreds of billions in both pharmaceutical therapy and medical aesthetics. As a therapeutic agent, it has gained approval for more than 20 indications globally, with hundreds of potential indications under exploration. It ranks as the leading non-surgical medical aesthetic procedure worldwide and the second largest in China, with a global market size exceeding USD 40 billion and a Chinese market size surpassing RMB 10 billion. Shanghai Ruoyi Biotechnology Co., Ltd.’s proprietary iterative recombinant botulinum toxin products can not only compete for existing market share but also exclusively capture incremental market growth by delivering enhanced clinical benefits through technological upgrades, including faster onset of action, prolonged duration, improved safety, and expanded indications.

Dr. Liu Jia, Founder of Ruoyi BiotechnologyIt stated: “Human history has continually demonstrated that social progress and transformation are often accompanied by the emergence of disruptive new technologies. New technologies not only spawn novel scientific concepts and create new disciplines, but also generate larger markets by better meeting human needs. As Sydney Brenner remarked, ‘Progress in science depends on new techniques, new discoveries and new ideas, probably in that order.’ For the foreseeable future, Ruoyi Biotechnology will position itself as a ‘biotechnology company,’ committed to driving the development of the biopharmaceutical and consumer healthcare industries through innovation in biotechnology.”

Ms. Wang Yingpei, Co-Founder of Dongjiu Xinyi Capitalstated: “Shanghai Ruoyi Biotechnology Co., Ltd. possesses globally leading, proprietary foundational technologies for macromolecular drug delivery. Leveraging their unique scalability, the company has built a robust product pipeline. The core team, led by Dr. Liu Jia, enjoys an international reputation in its specialized field, and the company’s novel recombinant botulinum toxin product features significant technical barriers to entry. We are optimistic about botulinum toxin itself, which has been validated over many years in mature markets. Through improvements in manufacturing processes and technological innovation, it holds broader application prospects in both therapeutic and medical aesthetics sectors, ultimately targeting the consumer market. Dongjiu Xinyi Capital will leverage its infrastructure platform and comprehensive resource integration capabilities to assist the company in accelerating its commercialization process, helping it grow into a world-class, platform-based innovative biopharmaceutical company.”

“Over the past year, Dongjiu Xinyi Capital has invested in and strategically positioned itself with multiple globally leading innovative technology platform companies in the biopharmaceutical and healthcare sectors, continuously identifying and nurturing international leaders in core life science tracks. Investment cases include innovative mRNA vaccines, circular RNA novel therapeutics, and ultra-microsurgical robots,” added Ms. Wang Yingpei.

Mr. Chen Jie, Founding Partner of Yuansheng Venture Capitalstated: “Botulinum toxin is a core product in medical aesthetics, with substantial market demand and a shortage of domestic brands. Yuansheng Venture Capital remains bullish on the immense potential of Shanghai Ruoyi Biotechnology’s novel recombinant botulinum toxin products in the medical aesthetics market. We have consistently monitored the company’s growth and believe that, leveraging its outstanding R&D capabilities and strong execution, the company will achieve further breakthroughs and accomplishments in new drug development by utilizing its leading macromolecular drug delivery technology. We are also pleased to co-invest in Shanghai Ruoyi Biotechnology alongside the new shareholder, Dongjiu Xinyi Capital. Yuansheng Venture Capital will continue to support and empower the enterprise from multiple dimensions, helping Shanghai Ruoyi Biotechnology become a representative leader in next-generation macromolecular drug delivery.”

Zinc finger proteins are a family of proteins present in the cells of all eukaryotes. In humans, there are more than 1,000 different types of zinc finger proteins, constituting the largest class of transcription factors. Naturally occurring zinc finger protein transcription factors can bind to activator or repressor elements to regulate gene expression. Engineered zinc finger proteins have also been utilized in the development of gene-editing tools, such as the first-generation gene-editing technology, zinc finger nucleases (ZFNs). In earlier research, Dr. Liu Jia, founder of Shanghai Ruoyi Biotechnology Co., Ltd., discovered that zinc finger proteins exhibit highly efficient cell membrane penetration and endosomal escape capabilities. He subsequently applied these findings to drug development and established a related portfolio of patents, achieving pioneering leadership in this field.

Botulinum toxin is a toxic protein secreted by Clostridium botulinum, which can be classified into different types, such as A–G, based on its sequence and function. Currently, approved botulinum toxin drugs are primarily Type A, all of which are protein complexes or monomers (first-generation products) prepared using Clostridium botulinum and the Schantz process (or improved processes). With advances in biotechnology, recombinant botulinum toxin protein drugs (second-generation products) have begun to emerge. Building upon second-generation products, Shanghai Ruoyi Biotechnology Co., Ltd. has further optimized production processes and protein sequences to achieve reduced toxicity and an improved therapeutic index (third-generation products), as well as enhanced onset time and duration of action (fourth-generation products). Compared with currently marketed and pipeline products, Shanghai Ruoyi Biotechnology’s botulinum toxin products demonstrate significant technological advancement and anticipated clinical benefits.

 Three-dimensional crystal structure of botulinum toxin type A (left)

Domains and Functions of Botulinum Toxin Type A (Right Panel)

The insect cell isolation and culture system was initially established by the U.S. Department of Agriculture and further optimized by Monsanto, achieving high-level expression of exogenous proteins through baculovirus transfection. Since this system does not require the construction of stable cell lines, it offers considerable flexibility in switching between different protein drug molecules. Meanwhile, owing to the large capacity of the baculovirus plasmid genome (bacmid), it facilitates the expression of complex proteins and protein complexes, holding broad application prospects in the production of macromolecular drugs, vaccines, and gene therapy vectors (such as AAV). However, commercial applications of the insect cell–baculovirus system have been significantly limited due to the presence of endogenous viruses (rhabdoviruses) and the instability of existing expression systems during passaging. Shanghai Ruoyi Biotechnology Co., Ltd. has overcome these technical challenges to establish a proprietary insect cell–baculovirus system, which can be used for the industrial-scale production of botulinum toxin type A and other protein drugs, vaccines, and virus-like particles.

(Figure left) Insect cells (white field)

(Figure right) Occlusion-derived virus (ODV)

Leveraging the infrastructure network of ESR Group, we focus on strategic emerging industries such as biopharmaceuticals and healthcare, next-generation information technology, new energy, artificial intelligence, advanced manufacturing, new materials, and green low-carbon environmental protection, to create a closed-loop ecosystem across the entire industry chain. Adhering to a long-term and proactive philosophy, ESR Capital deeply integrates with the national strategic guidelines for green, low-carbon, and circular development, promoting the sustainable development of industry, humanity, the environment, and technology.

Dongjiu Xinyi is a leading investor, developer, and operator of new economy infrastructure in China, with total assets under management exceeding RMB 100 billion and a total gross floor area of over 12 million square meters. Its portfolio encompasses four core business segments—industrial and biopharmaceutical parks, urban renewal, smart logistics and cold chain, and data technology—as well as the private equity investment platform, Dongjiu Xinyi Capital. Dongjiu Xinyi provides comprehensive, integrated infrastructure operational services and solutions to new economy clients, meeting their diverse needs for R&D, production, warehousing, and corporate headquarters. The management team boasts extensive experience in investment, development, operations, asset management, and fund management, offering diversified investment products to global institutional investors while consistently creating long-term value for investors, employees, and society.

Yuansheng Venture Capital is an investment firm focused on early- and growth-stage healthcare and medical companies, headquartered in Suzhou BioBAY with a global reach. To date, it has invested in more than 170 outstanding enterprises in the life and health sector, spanning four key areas: innovative drug development, medical devices, in vitro diagnostics and precision medicine, and healthcare services. The firm has achieved substantial investment returns, with 18 of its portfolio companies having listed on capital markets such as the Hong Kong Stock Exchange and the STAR Market. Yuansheng Venture Capital has been repeatedly recognized as one of the Top 10 venture capital funds in China’s healthcare sector and as one of the most active healthcare investment institutions in China. By bringing together seasoned professional investors and a world-class team of scientific advisors, Yuansheng Venture Capital boasts extensive experience in entrepreneurship, venture capital, and corporate operations within the biopharmaceutical industry and beyond. Leveraging its professionalism, focus, and rich industry resources, the firm is committed to becoming one of the most successful medical and pharmaceutical venture capital funds in China.