HuaGene Biopharma's Huang Wei Presents: Next-Generation Broad-Spectrum Oncolytic Bacteria – Foundations and Clinical Development of SalMet-Vec®

Currently, targeted therapy and immunotherapy have brought significant breakthroughs to the treatment of oncological diseases, yet they still fail to adequately address the issues of tumor recurrence and metastasis. New paradigms are emerging in the field of cancer immunotherapy, such as CAR-T cell therapy, oncolytic virus therapy, and the more cutting-edge oncolytic bacterial therapy.

The concept of oncolytic bacterial therapy was truly proposed around 2016. Its fundamental principle involves leveraging bacteria to “consume” tumor cells while simultaneously activating the human immune system, thereby reducing the risk of post-treatment recurrence and metastasis. This represents a more innovative approach to cancer therapy.

In China, Huajin Pharmaceutical is a representative enterprise in the research and development of oncolytic bacterial therapy.Huajin Pharmaceutical, established in 2016, is dedicated to the development and manufacturing of innovative biologic anti-tumor drugs to meet the global market demand for malignant tumor treatments. Under the leadership of Dr. Zhao Zijian, Chairman of the Board, and three other specially appointed experts, and through the concerted efforts of dozens of researchers, Huajin Pharmaceutical has gradually established the world’s first rapid broad-spectrum oncolytic bacterial technology platform and completed the development of its core product, the oncolytic bacterium Samweike.^®preclinical studies, CMC process development, and the construction of GMP-compliant large-scale production facilities.

Currently,Sanmewick^®IND approvals have been obtained from the U.S. FDA, Taiwan’s TFDA, and China’s NMPA, and international multicenter Phase I/IIa clinical trials involving both intravenous and intratumoral administration for various malignant solid tumors are being conducted simultaneously in the United States, Taiwan, and mainland China.

At the recently held 4th Oncolytic Virus Drug Development Conference in 2023, Mr. Huang Wei, Vice President of Huajin Pharmaceutical, delivered a presentation titled “Basic and Clinical Development of Oncolytic Bacteria: A New Generation of Rapid-Acting, Broad-Spectrum Antitumor Agents.” He reviewed the development history of oncolytic bacterial therapy and provided a detailed introduction to Huajin Pharmaceutical’s progress and the research and development of its core product, Sanmeiweike.

The following are the key points summarized from Mr. Huang Wei’s speech:

Although oncolytic bacterial therapy remains an innovative concept for many, it actually boasts a development history spanning over a century. In recent decades, with advancements in synthetic biology, including genetic engineering technologies, teams both in China and abroad have leveraged bacteria as vectors to advance the research and development of innovative drugs. Among them, Guangzhou Huajin Pharmaceutical Technology Co., Ltd. holds a leading position in the development of in vivo gene therapy products using bacterial vectors.

Huajin Pharmaceutical conducts R&D on oncolytic bacterial products, primarily based on two mechanisms and backgrounds:

# Bacterial Anti-Tumor TherapyIn the late 19th century, William Coley, known as the “father of tumor immunotherapy,” put into practice the concept of using bacteria to treat cancer. He developed the earliest cancer vaccine bacterial preparation, “Coley’s toxins,” and observed favorable therapeutic effects in certain tumors. However, due to unresolved issues regarding the high toxicity of the bacteria, oncolytic bacterial technology remained dormant for many years thereafter.

However, many bacteria exhibit natural tropism toward tumors, resulting in significant concentration differences compared to other organs; bacterial concentrations at tumor sites can be hundreds to tens of thousands of times higher. This constitutes one of the key reasons underlying the therapeutic potential of oncolytic bacterial therapy.

Next are the essential nutrients for tumors.Tumor growth is dependent on amino acids. Although there are variations among different tumor types, virtually all tumors rely on methionine. Extensive basic scientific research has validated this across multiple cancer types, including breast cancer, lung cancer, osteosarcoma, and glioma. The results confirm that once the supply of methionine is cut off, tumor cells rapidly diminish or cease proliferation.

When these two mechanisms are combined, oncolytic bacterial therapy produces a more potent tumor-killing effect.

Based on these two mechanisms of action, Huajin Pharmaceutical has developed its first-in-class core product, the oncolytic bacterium Sanmeiweike.^®Injection.Sanmeweike^®Relevant research literature has been published in top-tier journals such as Cell Reports Medicine.

Sanmewick^®By using attenuated Salmonella as a vector to deliver the expression of specific methionine aminopeptidase, this approach deprives tumors of essential amino acids required for their growth, thereby killing tumor cells and preventing tumor metastasis.

First, Guangzhou Huajin Pharmaceutical Technology Co., Ltd. genetically engineered Salmonella by knocking out two gene segments to ensure the safety of bacterial delivery within the human body; second, Sanmeiweike^®Its development integrates principles of metabolomics. From the perspective of methionine metabolic regulation, depriving its supply can affect multiple downstream mechanisms, including inhibiting methyltransferases and the expression of downstream proteins, transcriptionally activating tumor suppressor genes to inhibit tumor growth and metastasis, and inducing ferroptosis.

Therefore, Sanwei^®Integrating multiple mechanisms, it possesses broad-spectrum anticancer activity and tumor-targeting capability, thereby delivering superior therapeutic outcomes. Furthermore, the development of this drug provides additional options for extending survival in patients with advanced-stage cancer, addressing critical unmet needs in current clinical oncology practice.

Currently, Sanmivik^®Monotherapy for malignant tumors, including liver cancer, lung cancer, sarcoma, melanoma, nasopharyngeal carcinoma, and cervical cancer, has demonstrated favorable safety profiles and significant clinical efficacy; adverse reactions were predominantly Grade 1, with only a few cases of Grade 2.

This helped Sanmeiwei Ke^®

Currently, only a small number of companies are focused on oncolytic bacterial therapy; therefore, industrialization is a key priority for Huajin Pharmaceutical. In compliance with regulatory requirements, Huajin Pharmaceutical has established a pilot-scale production facility in Guangzhou, which has received preliminary recognition from regulatory authorities such as the FDA and the Center for Drug Evaluation (CDE). Multiple batches of clinical trial products have been manufactured at this facility and meet the corresponding quality standards.

In terms of patents, Huajin Pharmaceutical has established a global patent protection system, having obtained multiple invention patent grants in China, the United States, Japan, Australia, and other countries. The company is continuously expanding the scope of its patent protection and accelerating the filing of new patent applications.