Diff Biotech Completes Series A Financing to Advance Intranasal Multivalent COVID-19 and Universal Trivalent Influenza Vaccines into Clinical Trials

VCBeat (WeChat: vcbeat) has learned that Zhejiang Difu Runsi Biotechnology Co., Ltd. (“Difu Runsi”) has recently completed its Series A financing round, with a total amounting to tens of millions of yuan. This round was jointly invested by a fund under the Hefei High-Quality Industry Development Guidance Fund Co., Ltd. in Anhui Province (“Hefei Zhongke Fund”), Hangzhou Fanoksen Enterprise Management Partnership (Limited Partnership) (“Fanoksen”), and the Binjiang District 5050 Talent Fund under Hangzhou Gaoxin Jintou Group (“5050 Fund”).

The proceeds from this financing round will be used to file Investigational New Drug (IND) applications for two proprietary innovative vaccine products: an NDV vector-based multivalent COVID-19 vaccine administered via nasal spray and a trivalent influenza vaccine administered via nasal spray. This aims to expedite the entry of these distinctive nasal mucosal immune vaccines into clinical trials and accelerate the industrialization of mucosal immune vaccines.

Dr. Song Jiasheng, Founder of Difu RunsiIt stated: “Since the outbreak of the COVID-19 pandemic, multiple vaccines have been launched globally. Their primary role is to reduce severe disease and mortality, but they have limited efficacy in preventing infection and blocking transmission. Regarding the functional requirements for COVID-19 vaccines, there is a need to shift from a single metric of ‘preventing symptoms’ to a dual metric of ‘preventing infection + preventing symptoms.’ This transition is an inevitable requirement dictated by the objective scientific laws of viral evolution. If vaccines cannot prevent infection and block transmission, we will fall into an infinite vicious cycle of ‘infection–vaccination–mutation–reinfection.’ Mucosal immune vaccines hold significant potential for preventing infection and blocking transmission, and will become one of the key directions for future respiratory virus vaccine product development. These vaccines can induce specific mucosal immunity in the respiratory tract through nasal administration, establishing an immune barrier in the upper respiratory tract, which is crucial for blocking transmission, while also enhancing systemic cellular and humoral immunity.”

As early as the initial outbreak of the pandemic in 2020, Dr. Song Jiasheng, founder of Zhejiang Difu Runsi Biotechnology Co., Ltd. (hereinafter referred to as "Difu"), designed and planned the development of mucosal immune vaccines. In June 2020, the company officially announced the construction of the world’s first recombinant Newcastle Disease Virus (NDV) vector-based COVID-19 vaccine candidate, more than a month earlier than the formal report by a team of U.S. National Academy members. Currently, the nasal spray COVID-19 vaccine NDV-HXP-S developed by the U.S. academician team has successfully entered Phase II clinical trials.Due to limitations in funding and resources, Difu’s progress in the industrialization of NDV vector-based COVID-19 vaccines lagged behind international counterparts. However, over the past two years, the R&D team has focused on technological innovation and excellence, constructing and testing hundreds of candidate strains, completing three iterations of the NDV vector-based COVID-19 vaccine technology, and establishing independent core intellectual property rights. Research results indicate that the novel third-generation nasal spray NDV mucosal immune COVID-19 vaccine provides 100% protection in humanized hACE2 mouse models, induces high levels of neutralizing antibodies, and completely clears live viruses from the nasal cavity and lungs, demonstrating potential for preventing infection and blocking transmission. During the technological iteration process, the Difu team evaluated similar NDV vector-based COVID-19 vaccine candidates reported globally and found that they failed to match the immunogenic efficacy of Difu’s third-generation vaccine candidate in key indicators such as neutralizing antibody levels, animal protection rates, and viral clearance in vivo. In light of this, Difu’s third-generation NDV vector vaccine technology is poised to become the most advanced technology in this field globally, offering the potential for leapfrog advancement in industrialization. The company is currently making intensive preparations for the Investigational New Drug (IND) application for this novel mucosal immune vaccine.

Another star mucosal immune product of the company is a broad-spectrum nasal spray trivalent influenza vaccine. In 2022, the R&D team discovered for the first time a new attenuation method for restricted replication of type A influenza virus based on M2 gene modification, and developed this vaccine using this patented technology. The significant features of this nasal spray trivalent influenza vaccine are high safety, strong protection, and broad-spectrum efficacy, which is expected to overcome the challenges posed by emerging variant strains to existing vaccines. Challenge studies have shown that using the 2021 epidemic strain as an immunogen can protect against heterologous epidemic strains from 50 years ago or even earlier (such as the H1N1 strain prevalent in 1934 and the H3N2 strain prevalent in 1968). This product benchmarks against MedImmune's marketed vaccine Flumist, aiming to achieve new breakthroughs in broad-spectrum efficacy and safety, making it more suitable for vulnerable populations such as the elderly and children.

Zhejiang Difu Runsi Biotechnology Co., Ltd.Since its establishment in 2017, Zhejiang Difu Runsi Biotechnology Co., Ltd. has been committed to building a world-class recombinant virus technology platform. Guided by the mission of “Making a Difference for the World, Creating Opportunities for Employees,” the company focuses on differentiated innovation in technologies such as gene-engineered vaccines for major infectious diseases, oncolytic viruses, viral vectors, gene therapy, mRNA delivery, in vivo viral tracing, and visualized nucleic acid detection. The company possesses a BSL-2 negative-pressure animal evaluation laboratory, as well as standardized production, quality management, and regulatory submission systems for human biomedical products (including vaccines and oncolytic viruses). To date, the company’s technological achievements have resulted in more than 30 domestic and international invention patents (including over 10 PCT international patents), and it was awarded the Excellence Award at the 23rd China Patent Awards in 2022. The company has been recognized as a National High-Tech Enterprise, a Gazelle Enterprise in Hangzhou High-Tech Zone (Binjiang), and an Enterprise Reserved for Listing.

Hefei Zhongke Fund is a technology innovation and commercialization fund jointly established by Hefei High-Quality Fund of Funds, Huainan High-Tech Investment, Hefei Zhongke Yashang Venture Capital Management Co., Ltd., and other participants. The fund focuses on strategic emerging industries such as integrated circuits, new materials, new energy, intelligent manufacturing, and general health. It plays a significant role in fostering innovation and entrepreneurship, facilitating expansion and upgrading, and strengthening and extending industrial chains for the development of Hefei’s emerging industries. Furthermore, it promotes enterprise establishment and growth through the fund’s “dual recruitment and dual attraction” model.

The 5050 Fund primarily invests in Class A, B, C, and D enterprises under the “5050 Talent Program” in the High-Tech Zone (Binjiang), supporting the High-Tech Zone (Binjiang) in advancing the third round of the “5050 Program.” It effectively serves as a sci-tech financial pillar for “building a first-class talent ecosystem,” guiding more high-caliber, specialized, and scarce talents and high-quality projects to settle in the High-Tech Zone (Binjiang).

Vanxun Capital is a private equity firm rooted in the Yangtze River Delta, specializing in pharmaceuticals and biotechnology, innovative medical devices, digital health, and digital therapeutics. Its investment scope covers companies at all stages of development. The firm established the “Wenyuan Bio” industrial incubation platform in Hangzhou. Guided by the investment philosophy of “investing early and investing in innovation,” this approach stems from the Vanxun founding team’s complete trust in the projects and products of Zhejiang Difu Runsi Biotechnology Co., Ltd., demonstrated through their follow-on investments as existing shareholders.