DIFF Biotech Files for IPO: Dual-Engine Strategy Drives Innovation in Mucosal Vaccines and CRO Services Based on Recombinant Viral Vector Platform

Dr. Song Jiasheng is the founder of Zhejiang Difu Runsi Biotechnology Co., Ltd. With decades of experience in the development of genetic engineering vaccines and molecular virology research, he has studied and conducted advanced training at academician research groups in both China and the United States, serving as a key figure in major scientific and technological breakthroughs.He also served as a core executor for the Bill & Melinda Gates Foundation’s Global Health Program and several national 973 Programs, and as the principal investigator for major emergency response projects in Zhejiang Province.

During the period when the U.S. team was overcoming technical challenges in the project, Song Jiasheng drew on the advantages of foreign scientists in technology transfer, while also paying attention to the development trend of encouraging innovation in China.In 2017, Song Jiasheng chose to return to China.Founded and established Difu Runsi, the companyCommitted to building a globally leading recombinant viral vector technology platform and applying it to vaccine development, gene therapy, oncology therapy, and specialtyCRO and other sectors.

Upon returning to China, Song Jiasheng has consistently adhered to technological innovation, leading his entrepreneurial team to achieve numerous scientific and technological breakthroughs and accomplishments: In 2017, he established the world’s first technical platform for Differentiating Infected from Vaccinated Animals (DIVA) inactivated avian influenza vaccines, which won the Excellence Award at the 23rd China Patent Awards; in 2020, he constructed the world’s first recombinantNDV（Newcastle Disease Virus) viral vector-based COVID-19 vaccine candidate strains; in 2021, mastered the technology for human live-attenuated influenza vaccines, developing for the first time a method of attenuation based on restricted replication of the influenza virus; in 2022, achieved major breakthroughs in the mucosal immune vaccine platform based on viral vectors; in 2023, established a non-virus-dependent high-throughput antiviral drug screening platform, which is unique worldwide.

“Domestic technological development presents a great opportunity for innovators in science and technology.”Previously, a major reason we were held back by technological bottlenecks was that those with genuine technical expertise did not personally engage in the commercialization process.“Encouraged by the favorable macro environment, a company founded by scientists and partnered with a professional operations team can achieve technological innovation while keeping risks under control,” remarked Song Jiasheng.

To date, the R&D team at Difu Runsi has expanded to include specialists in virology, cell biology, molecular biology, and other related technical fields. The company has established multiple technology platforms, including viral vector engineering, reverse genetics manipulation of viruses, generation of replication-deficient viruses, pseudovirus construction, high-throughput screening of antiviral drugs and vaccines, in vivo viral tracking, and mucosal immune vaccine development.

Based on core technologies such as recombinant viral vectors,Difu Runsi has strategically focused on areas including influenza, COVID-19, and respiratory syncytial virus,Avian Influenza, IBV (Infectious Bronchitis Virus), PEDV (Porcine Epidemic Diarrhea Virus), FCV (Feline Calicivirus), FHV (Feline Herpesvirus)a pipeline of multiple human and veterinary mucosal immune vaccines, among others.Among these, the company’s key pipeline candidates—the intranasal live-attenuated influenza vaccine (DIFF-Flu) and the intranasal NDV-vectored COVID-19 vaccine—are both in the IND application stage.

Mucosal immune vaccines can induce the production of mucosal antibodies, blocking viral invasion and transmission at the epithelial layer through the body’s first line of defense—the mucosal system—thereby achieving genuine prevention of respiratory and gastrointestinal infectious diseases. Meanwhile, they also induce multi-layered protection, including humoral and cellular immunity, significantly enhancing the ability to respond to mutant strains and achieving broad-spectrum preventive effects against respiratory infectious diseases. Furthermore, their more convenient administration methods (such as nasal sprays and nasal drops; or even spraying and drinking water for large-scale veterinary vaccination) expand their application scenarios and strengthen their competitive advantages, earning them the designation as the next-generation technological route for infectious disease vaccines.

However, enhancing antibody levels for mucosal immune vaccines remains a major technical challenge in the industry.

Leveraging its core foundational technologies—including viral vector engineering, reverse genetics, replication-deficient virus design, and pseudovirus construction—Zhejiang Difu Runsi Biotechnology Co., Ltd. has identified optimal vectors, attenuated viruses, and gene insertion/replacement sites through extensive experimentation. By applying recombinant protein technology and undergoing rigorous construction, screening, and iterative optimization of numerous vaccine candidates, the company has achieved a substantial increase in mucosal immune antibody levels, thereby developing a truly effective, safe, broad-spectrum, and convenient preventive vaccine.

Its live-attenuated influenza vaccine can protect against strains that emerged fifty years ago, the neutralizing antibody titers for its COVID-19 vaccine approach 1:(800–3200), and the neutralizing antibody titers for its PEDV vaccine can reach as high as 1:150, significantly outperforming other vaccines using the same technological platform as publicly reported. Consequently, it has attracted the attention of numerous leading domestic and international enterprises.

Leveraging its robust technological innovation capabilities and differentiated competitive advantages, Difu Runsi has secured tens of millions of yuan in financing since its establishment, with investors including the Binjiang District Government Fund, Shulan Capital, and the Chinese Academy of Sciences Fund. Nevertheless, the founding team has consistently maintained the sense of crisis characteristic of the early startup phase, even as R&D investment continues to increase.The company has decided to leverage its existing technological platforms and hardware facilities, such as its BSL-2 animal facility, to provide CRO services to other innovative pharmaceutical companies., thereby reducing capital risks arising from long-term R&D investment and fluctuations in the external financing environment.

Unlike traditional CROs, Zhejiang Difu Runsi Biotechnology Co., Ltd. does not merely provide standardized R&D and regulatory submission services for innovative pharmaceutical companies; instead, it empowers clients with technology centered around its core platforms. Song Jiasheng told VCBeat, “We do more than just offer operational support; our primary focus is on empowering clients at the technological source and tackling key R&D challenges.”

Song Jiasheng cited an example: if a client requires viral vectors with enhanced safety features, Zhejiang Difu Runsi Biotechnology Co., Ltd. can improve vector safety through genetic modification and regulation, rather than merely standardizing operations to prepare for regulatory filings by pharmaceutical companies. “Difu Runsi focuses more on leveraging technology to address clients’ weaknesses, ensuring their product pipelines are competitive from the outset.”

Currently, Difu Runsi can provide partners with high-throughput screening of antiviral drugs, vaccine/drug/vector design services, drug evaluation services, and customized technical services based on BSL-2 animal facilities.

Taking high-throughput screening services for antiviral drugs as an example, Zhejiang Difu Runsi Biotechnology Co., Ltd. has established three major systems: a reporter virus system, a pseudovirus system, and a non-viral system (protease inhibitors). By integrating these with advanced technologies such as high-throughput screening platforms, live-cell imaging, in vivo tracing, fluorescence detection, and flow cytometry, the company can perform high-throughput directional sorting of viral evolution. This enables the rapid and efficient acquisition of antiviral drug candidates with desired target characteristics, thereby addressing the technical challenge of compound screening and discovery in innovative drug development.

General Process of Drug Discovery, Image Source: Difu Runsi

The platform’s unique advantage lies in its pseudovirus construction technology, which lowers biosafety level requirements. This enables high-containment viral assays to be conducted in BSL-2 or even BSL-1 laboratories, addressing the R&D bottleneck caused by the scarcity of BSL-3 and BSL-4 facilities. Furthermore, it supports high-throughput screening at both cellular and in vivo levels, incorporating positive selection methods to ensure high accuracy.

Meanwhile, live-cell imaging and in vivo tracking enable longitudinal recording of the same experimental subjects at different time points, thereby eliminating inter-individual variability. This approach yields more authentic and reliable data while reducing the number of animals required and lowering costs. Furthermore, high-throughput screening ensures efficient R&D productivity, addressing critical technical challenges that companies face in accelerating product development cycles.

Currently, Difu Runsi enables high-throughput screening for the vast majority of infectious disease viruses, including HIV, HPV, influenza virus, herpesvirus, hepatitis virus, coronavirus, rabies virus, feline infectious peritonitis virus, porcine epidemic diarrhea virus, porcine reproductive and respiratory syndrome (PRRS) virus, and African swine fever virus.

Nowadays,Difu Runsi has established a subsidiary in Singapore., is currently building an overseas business development (BD) team. In the future, Difu Runsi will leverage its Singapore entity as a foundation to expand into the global market, seeking more international business collaborations and technology transfers.

Looking to the future, Song Jiasheng stated, “The competitive trend in the healthcare sector will increasingly center on ‘0’ to ‘1’ innovation, rather than ‘1’ to ‘2’ incremental improvements. Once a foothold is established in the ‘0’ to ‘1’ phase, scaling from ‘1’ to ‘N’ will become easier.”

In terms of its patent moat, Difu Runsi has filed over 40 core patents domestically and internationally to date, and has been awarded the Excellence Award at the 23rd China Patent Awards.

Next, Difu Runsi will rapidly advance its mucosal vaccine pipeline, including the intranasal live-attenuated influenza vaccine (DIFF-Flu) and the intranasal NDV-vector COVID-19 vaccine, into clinical trials, while continuously building a specialized CRO service technology platform.To address the company's rapid future growth, Difu RunsiA new round of financing is expected to be launched by the end of the year,Increase investment in the development of internal systems and core pipelines. We look forward to Difu Runsi becoming a world-class recombinant viral vector technology platform as soon as possible, bringing more high-value innovative products to clinical practice.