Founder of China's First Oncolytic Virus Drug Achieves New Breakthrough with Kangwandar's Innovative Pipeline and Submits IPO Prospectus

Research and development of oncolytic virus drugs have a century-long history, with oncolytic viruses undergoing successive generations of iterative upgrades. However, the industry still lacks an “optimal solution” in terms of efficacy, administration routes, and manufacturing processes.

As more startups enter the field, research and development of next-generation oncolytic viruses are in full swing. Among them,Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. is among the first batch of enterprises in China to conduct R&D on oncolytic virus drugs.The company has assembled a full-process new drug development team with international R&D experience, establishing core technology platforms for the development of various novel oncolytic virus drugs based on clinical needs.They focus on source innovation, not only proposing new theories for oncolytic virus therapy but also innovatively developing multiple distinctive product pipelines and combination therapies.

Since its establishment in 2016, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. has maintained a low-profile development strategy, making few public appearances within the industry, yet it has accumulated substantial R&D capabilities,More strikingly,Dr. Hu Fang, founder of Kangwanda, once led his team to complete the full-process research and development of China’s first oncolytic virus drug, “Ankerui.”

Restarting the Entrepreneurial Journey: How Will Hu Fang Lead Kangwanda to Explore Innovative Pathways for Novel Oncolytic Virus Drugs? Which R&D Technologies and Strategies Will Undergo Iterative Upgrades? VCBeat New Medicine spoke with Dr. Hu Fang about his journey of growing alongside Kangwanda.

To date, Dr. Hu Fang has been researching oncolytic viruses for 25 years. He stated that he is unlikely to leave this field in his lifetime.

In the 1990s, after completing his postdoctoral research at the University of California, San Francisco, Hu Fang returned to China and joined Shanghai Sanyuan Biotechnology as President, where he began developing oncolytic virus drugs.

In 2005, Sunway Biotech obtained the new drug certificate for H-101 in China, branding it as “Ankerui,” thereby becoming China’s first oncolytic virus-based novel drug.At that time, when signs of innovation in China’s biopharmaceutical sector had yet to emerge, Hu Fang propelled domestic biopharmaceutical companies onto the global stage. Shanghai Sunway Biotech made history by acquiring the project patents for Onyx-015 and bringing the drug to market, an achievement that was repeatedly covered by international media outlets such as The New York Times and Bloomberg.

Throughout the development of Oncorine, Hu Fang continuously refreshed his understanding of the oncolytic virus field while accumulating valuable experience and lessons. Shanghai Sunway Biotech assembled a team of outstanding overseas-educated professionals whose perspectives differed from those of domestic pharmaceutical companies that primarily focused on generic drugs at the time; they placed significant emphasis on the processes and outcomes of clinical trials. Through these clinical trials, Hu Fang and his team identified greater potential and promising prospects for oncolytic viruses.

At that time, the United States classified oncolytic virus therapy as a form of gene therapy. Due to a fatal incident in the clinical trial of an investigational gene therapy product, the FDA imposed a moratorium on the development of all gene therapy drugs, citing insufficient safety. In China, thanks to the team’s relentless efforts, Shanghai Sunway Biotech was not significantly affected and further demonstrated the safety of its oncolytic virus drug during the R&D process. Given that oncolytic viruses selectively replicate within tumor cells, their impact on normal cells is minimal, thereby ensuring safety and resulting in fewer side effects.

Hu Fang and his team made a more significant discovery: oncolytic viruses can exert cytotoxic effects on distant metastatic tumors. This finding stemmed from an unexpected observation during a clinical trial. After intratumoral injection of the oncolytic virus, patients typically developed fever and flu-like symptoms. In one incidental case, a patient did not receive antipyretic medication, and at the three-week follow-up, the researchers observed, for the first time, the disappearance of distant metastatic tumors. “This can be regarded as the first time this phenomenon has been observed in humans. In subsequent studies, we found that heat shock proteins likely played a crucial role,” Hu Fang explained. In subsequent animal experiments, Hu Fang and his team inserted genes encoding heat shock proteins into the oncolytic virus, thereby mechanistically validating the ability of oncolytic viruses to eliminate metastatic tumors. They published their findings in an international academic journal.Cancer Research..., once again drawing the attention of the pharmaceutical industry.

Building on this foundation, Hu Fang and his team conducted various trials combining oncolytic viruses with other cancer therapies. By applying local hyperthermia to tumors to upregulate local heat shock proteins, and concurrently administering immunomodulatory agents such as GM-CSF and thymosin, they observed shrinkage and disappearance of distant metastatic tumors in multiple clinical cases, achieving encouraging results. Thus, one breakthrough after another was ultimately distilled into academic papers published in both domestic and international journals, includingCurrent Cancer Drug Target、Gene TherapyPublished in authoritative journals such as Chinese Journal of Cancer, these findings stand as milestones, accompanying Hu Fang’s deepening understanding of oncolytic viruses.

However,Hu Fang’s initial attempts with oncolytic viruses also had limitations; these innovative therapeutic approaches could only eradicate smaller metastatic tumors. How to completely eliminate larger tumors and prevent metastatic recurrence still requires more in-depth exploration.

Therefore, a few years after leaving Shanghai Sanwei, Hu Fang established Kangwanda.To date, the company has welcomed nine PhD holders, all of whom are seasoned industry experts and interdisciplinary talents.Some team members, with a background in computer science and specialized training in genetics during their studies in the United States, leverage their interdisciplinary expertise to deeply integrate artificial intelligence with biomedical R&D. Others have served as senior research scientists at overseas pharmaceutical companies, possessing profound expertise in anti-tumor immune cell therapy. Furthermore, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. has assembled high-caliber talent who have been dedicated to oncolytic virus R&D since the Shanghai Sanwei Biotechnology era, with specific focuses on clinical trial research and intellectual property strategy.

Hu Fang stated, “Talent is the foundation of our continued success.” The talent team at Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. leverages its expertise across various domains, including early-stage drug research and development, process development, and clinical trials, to drive corporate growth. Through the collective efforts of the team,The company has completed the layout of 85 patents and the research, development, and design of multiple product pipelines.

The establishment and development of Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. represent a shift and further deepening of Hu Fang’s research approach, demonstrating not only innovative awareness in R&D but also innovative efforts in industrialization.

Hu Fang has witnessed the biopharmaceutical industry’s transition from industrialization to informatization, and from macroscopic to microscopic perspectives, and holds unique insights into novel oncolytic virus drugs.

“A defining characteristic of the industrial era is that life sciences have been following a path from the macroscopic to the microscopic, known as precision medicine. Currently, precision medicine is a global focus, which is inherently positive; however, precision approaches cannot address systemic issues—they can only resolve problems at specific points.” This also explains why the drug research initially conducted at Shanghai Sanwei Biologics could not fully address metastatic tumors.

At Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd., Hu Fang leads his team to further explore the development of oncolytic virus drugs from a holistic, systems-based perspective, grounded in the theory and practice of precision medicine. This approach goes beyond simple drug combinations; it transcends temporal and spatial constraints to enable iterative advancements in oncolytic virus therapeutics, thereby upgrading combination therapy to synergistic therapy.

“We constructed a triangle with the holographic antigens released after oncolytic viruses destroy tumor cells, antigen-presenting cells, and T cells as its vertices, referring to these vertices as the ‘Three Peaks.’ Meanwhile, we term the corresponding processes of antigen release, antigen presentation, and immune cell-mediated tumor killing as the ‘Three Pathways.’ Only by maximizing the immune effects through optimal antigen release, efficient information transfer by antigen-presenting cells, and full activation of T cells—thereby achieving ‘overlap of the Three Peaks’—and ensuring the unobstructed flow of the ‘Three Pathways,’ can we achieve maximal efficacy in tumor eradication and suppress disease recurrence,” explained Hu Fang.He termed this innovative theory the “Tumor Systemic Immunity” theory.

This theory represents Hu Fang’s summary of years of research and development in oncolytic virus therapeutics, as well as lessons learned from the failures of other clinical trials. In 2015, the U.S. FDA approved Amgen’s oncolytic virus drug T-Vec for market launch. Subsequently, Amgen initiated clinical trials combining T-Vec with the PD-1 inhibitor Keytruda and reported promising early breakthrough efficacy data. However, results from a later expanded-sample study presented at the 2021 ESMO Congress indicated that the Phase III clinical trial failed to meet its primary endpoint. Similarly, in 2019, the South Korean biotech company SillaJen announced the early termination of its Phase III clinical trial of the oncolytic virus drug JX-594 in combination with the small-molecule drug sorafenib for the treatment of hepatocellular carcinoma, after an independent data review committee determined that the trial would not achieve its clinical endpoints.

When analyzing the reasons for failure, Hu Fang noted that while these combination therapies are theoretically very promising, they lack a "systematic" concept. When PD-1 is combined with T-Vec, simultaneous administration may fail to achieve the "triple peak overlap" due to poor coordination among a series of tumor immune mechanisms, including antigen-presenting cells and tumor-killing cells, thereby preventing the manifestation of synergistic efficacy. When sorafenib is combined with oncolytic vaccinia virus therapy, it may, to some extent, disrupt the replication foundation of the oncolytic vaccinia virus within tumor cells, preventing the release of antigens within the tumor and failing to ensure the "unobstructed flow through the three pathways."

Based on the "Tumor Systemic Immunity" Theory,During drug development, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. upgraded its combination therapy approach by precisely controlling the administration sequence and timing of various drugs.Aiming to Address the R&D Challenges of Oncolytic Virus Therapeutics.V01 is one of Kangwanda’s most representative core product pipelines.It is developed based on an oncolytic vaccinia virus, with IL-21 innovatively inserted to activate immune cells, and the virus has been ingeniously engineered to enhance tumor specificity and safety.By the end of 2022, the Investigational New Drug (IND) application submitted for V01 had been accepted by the Center for Drug Evaluation (CDE).Hu Fang revealed that, based on the “tumor systemic immunity” theory and supported by preclinical experimental data, they have identified a more innovative combination therapy.

Meanwhile,Leveraging the oncolytic vaccinia virus platform, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. has pioneered the development of “guided oncolytic viruses” and combined them with corresponding CAR-T cell therapies, designating this initiative as the “TT3” project., with the following advantages:

1) To address the issue of solid tumor heterogeneity, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. utilizes oncolytic viruses to specifically induce high expression of a synthetic marker peptide (TT3) on the surface of tumor cells. CAR-T cells targeting TT3 can effectively eliminate residual tumor cells that have been infected by the oncolytic virus but are not completely lysed and killed by it.

2) In terms of target selection, this project leverages digital technologies and bioinformatics big data to identify TT3, an artificial target that is completely non-homologous to the human genome/proteome, thereby entirely eliminating the risk of off-target effects in cell therapy. This technology can be combined not only with CAR-T cell therapy but also with targeted agents such as bispecific antibodies and antibody-drug conjugates (ADCs), enhancing tumor cytotoxicity through a synergistic “inside-outside” mechanism.

In addition to addressing the bottlenecks in oncolytic virus drug development, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. is also striving to achieve breakthroughs in viral manufacturing processes. The difficulty in mass-producing vaccinia virus is a major challenge facing the industry, andHangzhou Kangwanda Pharmaceutical Technology Co., Ltd. has adopted its independently developed patented processes, achieving advancements in multiple production technical indicators, such as a tenfold increase in unit output and a two-order-of-magnitude reduction in impurity content., which will lay a more solid foundation for the industrialization of oncolytic viruses.

In addition to its two core projects, V01 and TT3, Hangzhou Kangwanda Pharmaceutical Technology Co., Ltd. has been implementing and validating a broader range of innovative concepts, which have garnered significant recognition and acclaim from industry experts. Hu Fang has incorporated the company’s next round of financing into his strategic plan, aiming to accelerate the progress of various projects.

Currently, Hu Fang’s top priority is to obtain clinical trial approval from the Center for Drug Evaluation (CDE) as soon as possible, so that formal clinical trials can be launched. He stated, “The theoretical basis of drug development may be subject to debate, but once clinical data from patients are available, the therapeutic efficacy will speak for itself and become indisputable. Meanwhile, we are actively seeking distinctive partners to further optimize our strategic layout for systemic therapy.”