1. Introduction to the Project

1.1 Introduction to technical achievements

The technology of this project mainly utilizes plasmid based STAT3 small interfering RNA (siRNA) loaded with attenuated Salmonella to develop a biologically targeted drug for attenuated Salmonella. It belongs to the innovative category of therapeutic biological products, which can precisely guide and target tumors, and release attack weapons to eliminate tumors. It has efficient anti proliferative and pro apoptotic activities against various types of human tumor cells both in vivo and in vitro, effectively improving the body’s immunity and enhancing the killing activity of immune cells against tumors.

The technical achievements of this project involve 7 patented inventions, 6 have been authorized, and 1 is currently under review.

1.2 Technical analysis and advantages

1.2.1 Core technical analysis

Due to its facultative anaerobic properties, attenuated Salmonella can serve as a tumor targeting carrier targeting the low oxygen characteristics of the tumor area to overcome permeation limitations and maximize diagnostic and therapeutic targeting.

1.2.2 Technological innovation and advantages

At present, conventional cancer treatment can be divided into surgery, chemotherapy, and radiotherapy, but due to the lack of indications in the middle and late stages of surgery, radiotherapy and chemotherapy have significant side effects and limited effectiveness. In emerging treatment methods, molecular targeted drugs have limited targets and are prone to drug resistance; immunotherapy drugs are expensive, with a narrow range of beneficiaries. The quality of immune cell adoption therapy varies greatly, and the effectiveness varies greatly. Although small nucleic acid drugs can silence oncogenes or compensate for tumor suppressor genes, and have good efficacy in treating both the symptoms and the root cause, so far there have been no small nucleic acid drugs targeting cancer on the market, mainly due to technological bottlenecks in the use of delivery systems for small nucleic acid drugs. Therefore, finding a small nucleic acid drug delivery vehicle that targets tumors, efficiently suppresses tumors, and minimizes toxic side effects on normal tissue cells, while maintaining a certain stability and drug concentration within the target site, is a key issue that urgently needs to be addressed in the application of small nucleic acid drugs in tumor gene therapy.

The technical synthesis process of this project is simple and efficient; the reaction process is stable and the conditions are mild. Antiviral Salmonella small nucleic acid targeted drugs can target tumors, achieve specific survival, rapidly accumulate in tumors, and have good safety; at the same time, as a tumor targeting delivery system, the attenuated Salmonella biological targeted drug has super strong carrying ability, precise guidance of targeting tumors, and the release of attack weapons to eliminate tumors. It has efficient anti proliferative and pro apoptotic activities against various types of human tumor cells both in vivo and in vitro, effectively improving the body’s immune system and enhancing the killing activity of immune cells against tumors.

By now, the drugs developed have been tested on animals. The growth inhibition rate of PC-3M transplanted tumor of human prostate cancer, MCF-7 transplanted tumor of human breast cancer, Hep-2 transplanted tumor of human laryngeal cancer and SMMC-7721 transplanted tumor of human liver cancer in vivo ranges from 86.7% to 94.2%. The cure rate of H22 in situ transplantation of mouse liver cancer reaches 70%, with no recurrence within two years, ranking first in preclinical treatment effects of similar drugs at home and abroad, and the acute toxicity of this drug is low. At the same time, the drug also attempts clinical treatment on 23 patients with advanced stage cancer, with a clinical complete response rate of 60.9% and a partial response rate of 91.3%, without any toxic side effects. Among them, patients with poorly differentiated colon adenocarcinoma, undifferentiated small cell lung cancer, and esophageal poorly differentiated squamous cell carcinoma show significant tumor reduction to disappearance after treatment, and there is no recurrence after years of follow-up.

1.3 Main products and applications of technical achievements

The main achievements of the project are targeted drugs for reducing Salmonella, mainly used in medical treatment, drug research, and other fields.

1.4 Stage of technological achievements

It has entered the pilot stage.

1.5 Technical team

The project leader and team members are all members of the Key Laboratory of Pathology and Biology of the School of Basic Medicine of Jilin University and the Key Laboratory of Zootopia of the Ministry of Education. The project leader has been continuously exploring and cultivating in the field of targeted tumor therapy for many years, and has been awarded titles such as Jilin Province Top Innovative Talent, Jilin Province Innovation and Entrepreneurship Talent, and Jilin Province Youth Science and Technology Award, as well as 8 provincial and ministerial level awards. The project team is committed to studying the role of attenuated Salmonella as a carrier in anti-tumor therapy, demonstrating that attenuated Salmonella can be used as a carrier and has good biological targeting properties. They have obtained 10 national invention patents related to attenuated Salmonella and cancer, as well as 1 US invention patent; I have hosted and participated in more than 30 projects, including China-Japan intergovernmental technical cooperation projects, international cooperation projects of the Ministry of Science and Technology of China, National Natural Science Foundation of China, and provincial key research and development projects, and have published over 100 SCI articles.

2. Market Potential Analysis

The overall number of new cancer cases and deaths in China is on the rise, therefore, the market size of anti-tumor drugs in China is huge. The attenuated Salmonella biologically targeted drug developed in this project has not only been used for the treatment of pet dog tumors, but also for the trial treatment of advanced cancer patients, all of which have achieved good results. Compared with the current clinical cancer treatment methods such as radiotherapy, chemotherapy, and targeted therapy, it has the advantage of significantly reducing drug dosage and reducing cancer recurrence rate. Currently, there are no similar products on the international market. At the same time, no similar products that have obtained clinical approval have been retrieved; there are no similar products in China that have entered the clinical stage. The research and development achievements have won multiple awards, including the Ministry of Education Science and Technology Progress Award, Chinese Medical Award, Jilin Province Science and Technology Progress Award, and Jilin Province Natural Science Award.

The global small nucleic acid industry has entered a fast lane of development. Considering that the design and development of small nucleic acid drugs will not be limited by the producibility of proteins and the discovery of targets, with the continuous progress of delivery systems and modification technologies in the future, small nucleic acid drugs are expected to cover a wider range of indications and replace some existing therapies, with a very broad potential market size. According to the data from CIC, it is expected that global sales of small nucleic acid drugs will have exceeded 10 billion US dollars by 2025. Among them, RNAi therapy is expected to achieve rapid growth due to its significant effects, and is expected to have reached 4.5 billion US dollars by 2025, with a compound growth rate of 66%.

The small nucleic acid drug market in China is still in its early stages of development. Compared with the world, the development of small nucleic acid drugs in China started relatively late. The first small nucleic acid drug research and development enterprise was established 10 years later than Ionis, and the clinical approval of the first siRNA drug was 11 years later than the world. Therefore, the domestic small nucleic acid industry is still in its early stages of development, with only one product approved for launch, that is, Ionis Spinraza. However, due to the large number of patients and high demand in China, with the continuous promotion of the development of small nucleic acid drugs and the gradual maturity of domestic enterprise technology, the small nucleic acid drug market in China is expected to experience rapid development in the future.

The attenuated Salmonella small nucleic acid targeted drug developed in this project has a wide range of indications and a large target user group. If approved for clinical treatment, it will effectively reduce the economic burden on cancer patients and the toxic side effects of traditional treatment drugs on the body, benefiting a large number of cancer patients. It has broad industrialization prospects and profound social ecological benefits.

3. Financing Needs and Financing Purposes

The project is planned to raise 50 million yuan, with the funds mainly used for:

In 2024, preclinical pharmacology research will cost 5 million yuan and preclinical pharmacology research will cost 15 million yuan;

In 2025, the pharmacokinetic evaluation will cost 15 million yuan, and the preclinical safety evaluation will cost 15 million yuan.

4. Analysis of Technical Achievements and Benefits

4.1 Economic benefits

After the industrialization of the project, the annual output value of technical achievements is about 100 million yuan.

4.2 Social benefits

The construction of the project conforms to industrial policies, serves people’s lives and health, and helps Changchun City focus on building a billion level industrial cluster of biopharmaceuticals and life and health, making contributions to the local economy and the development of the “big health” industry in Changchun City. After project operation, injecting new impetus into social development can increase the local fiscal revenue and play a positive role in promoting the regional economic growth.

5. Contact Method

Contact person: Xu Wan

Tel: 13756652164