1. Introduction to the Project

1.1 Introduction to technical achievements

The product developed in this project can be used alone to treat castration resistant prostate cancer, or can be combined with the existing first-line and second-line drugs such as enzalutamide and abiraterone to delay the development of drug resistance, solve the problem of drug unavailability in advanced prostate cancer patients, improve the patient’s survival rate, and prolong the survival time.

1.2 Technical analysis and advantages

1.2.1 Core technical analysis

The mechanism of prostate cancer progression to castration resistant prostate cancer is complex, but overexpression of aldehyde ketone reductase (AKR1C3) leads to tumor cells having the ability to synthesize androgens themselves, causing the tumor to accelerate growth without relying on androgens produced by organs such as the testes and adrenal glands. In addition, abnormal generation of androgen receptor variant AR-V7 induces prostate cancer metastasis and drug resistance, both of which are independent and mutually reinforcing, becoming the two driving forces for castration resistant prostate cancer. Therefore, this project designed a dual target gene nanomedicine that simultaneously blocks AKR1C3 and AR-V7 for targeted treatment of prostate cancer.

In this project, the dual target gene drug OnCastra uses the small RNA interference technology to specifically silence two genes at the same time, and uses the “nucleic acid antibody” - the nucleotide aptamer A10-3.2 of the prostate cancer cell surface facial mask antigen to navigate. PEG modified PAMAM acts as a carrier to escort the small interfering nucleic acids of AKR1C3 and AR-V7 so as to achieve targeted delivery of gene therapy drugs to tumor sites via blood vessels. Meanwhile, OnCastra successfully reduces the expression of AKR1C3 and AR-V7 in mouse prostate tumors, achieving a tumor inhibition rate of 55% in the enzalutamide resistant group.

1.2.2 Technological innovation and advantages

Currently, AKR1C3 and AR-V7 each have one separate chemical inhibitor in clinical trials. The drugs that simultaneously block both AKR1C3 and AR-V7 targets are in a blank state both domestically and internationally. OnCastra’s dual silencing of AKR1C3 and AR-V7 has the characteristics of high specificity, tumor targeting, and stable formulation. There are 2 domestic invention patents related to this project, 1 of which has been authorized and 1 is in the substantive examination stage.

1.3 Main products and applications of technical achievements

The product formed by this project is the dual-target gene drug OnCastra, which is suitable for metastatic prostate cancer, metastatic castration resistant prostate cancer, and castration resistant prostate cancer resistant patients (including endocrine therapy and paclitaxel chemotherapy).

1.4 Stage of technological achievements

The technical achievements of the project are in the small trial stage.

1.5 Technical team

The technical team members of this project have been engaged in research in pharmacology, molecular biology, nanocarrier synthesis, and other fields for a long time. The project leader is the director of the Pharmacology Teaching and Research Office of the School of Basic Medicine, the main technical director of Jilin Province Nanoengineering Laboratory, Jilin Province New Drug Pharmacology Evaluation Technology Innovation Center, and Jilin Province Key Laboratory of New Drug Research and Development. He has accumulated a lot of experience in the research direction of integrated nano diagnosis and treatment of tumor gene therapy, published more than 60 SCI papers, and completed more than 30 new drug technology service and development projects. The project team has won one first prize, two second prizes, and one first prize for scientific and technological progress in Jilin Province, and has been granted more than 10 national invention patents.

2. Market potential analysis

Prostate cancer is one of the most common malignant tumors in the world, ranking second in the incidence rate and fifth in the mortality rate of male malignant tumors worldwide. The incidence rate of prostate cancer in China shows a significant upward trend, and most of them are in the middle and late stages at the time of initial diagnosis. Prostate cancer ranks sixth in the number of male malignant tumors in China, and is the male tumor with the fastest growth in incidence rate and mortality in China. At present, the screening rate of prostate cancer specific antigen (PSA) in China is not high, resulting in a low penetration rate of early diagnosis and screening. According to data, the compound annual growth rate from 2015 to 2019 was 5.3%, and the number of mCRPC cases of prostate cancer reached 141700 in 2022. Prostate cancer is a male androgen dependent tumor, and patients with metastatic prostate cancer commonly undergo drug castration therapy (ADT), with an initial response rate of 80-90%. However, almost all patients eventually develop metastatic castration resistant prostate cancer (mCRPC) after castration treatment, with a 5-year survival rate of only 30%.

From Nature’s prediction of the prostate cancer drug market, the overall prostate cancer drug market size is expected to increase by nearly 2 times, reaching $30 billion by 2029. The use of traditional castration therapy ADT will decrease, and androgen receptor (AR) antagonists, mainly the heavyweight bomb drugs Zytiga (abiraterone acetate) and Xtandi (enzalutamide), will disrupt the treatment pattern of metastatic prostate cancer, and the market share will continue to increase. The opportunity for PARP inhibitors and PSMA radioligand therapy to compete for a place, including kinase inhibitors such as Akt inhibitors, will also have an impact on segmented populations.

In recent years, the number of new cases of prostate cancer in China has maintained a stable upward trend, and it is expected to have reached 144000 people by 2024. The number of mCRPC cases of prostate cancer in China is expected to have reached 160000 by 2024. From the perspective of market space, the market size of prostate treatment drugs in China reached approximately 19.372 billion yuan in 2022, and it is expected to reach 23.3 billion US dollars in 2024.

3. Financing Needs and Purposes

The project is planned to raise 50 million yuan in financing, mainly used for technology research and development, achievement commercialization, and promotion.

4. Analysis of Technical Achievements and Benefits

4.1 Economic benefits

After the commercialization of the technical achievements of the project, it can generate a market value of approximately 150 million yuan.

4.2 Social benefits

After the commercialization of the technological achievements in this project, it is of great significance to improve the survival rate and quality of life of patients, enhance the accessibility and affordability of high-quality innovative drugs, meet the most urgent clinical needs of China’s prostate cancer patients, and help achieve the grand goal of “Healthy China 2030”.

5. Contact Method

Contact person: Xu Wan

Tel: 13756652164