Shanghai JeYou Pharmaceutical Technology Co., Ltd. announced that the company's preclinical CDK4 inhibitor (JYC010145) and CDK2-PROTAC (JMKX009137) candidate drug molecules have initiated a new drug clinical trial application, intended to treat HR+/HER2-breast cancer and CCNE1-amplified cancer.

Addressing the safety and drug resistance of anchored breast cancer therapies

Breast cancer is the malignant tumor with the highest incidence in women in the world. Among all breast cancer patients, HR+/HER2-(hormone receptor positive/human epidermal growth factor receptor 2 negative) is the most common subtype, accounting for approximately all cases. 60% ~ 70%. A generation of CDK4/6 inhibitors have become the first-line standard treatment, but their non-selective inhibition of CDK6 leads to severe grade 3/4 neutropenia, forcing patients to frequently discontinue or reduce doses. There is an urgent need to develop highly selective CDK4 inhibitors to reduce the corresponding hematological toxicity, achieve better safety and sustained suppression at maximum doses.

At the same time, clinical studies have confirmed that after a generation of patients are resistant to CDK4/6 inhibitors, the most important molecular mechanism is the compensatory high expression of CDK2/Cyclin E pathway. The combination of highly selective CDK4 inhibitors (responsible for blocking the proliferation of cancer cells)+ CDK2 degraders (responsible for blocking compensatory pathways) can delay or even avoid the development of drug resistance in breast cancer. In addition, for other tumors amplified by CCNE1 gene, such as esophageal cancer, gastric cancer and endometrial cancer, there are currently no targeted drugs for CCNE1 amplification on the market. Therefore, there is a huge unmet clinical need to develop drug molecules against CDK2.

JYC010145 is the best in class (BIC) CDK4 inhibitor

The nominated molecule JYC010145 is the drug molecule with the highest selectivity for CDK4 currently reported, with a selectivity of more than 200 times for CDK6, which is significantly higher than other clinical competitor drug molecules (~30 times). In vitro cytotoxicity studies of CD34 + HSPC and CFU, JYC010145 can significantly reduce hematologic toxicity than first-generation CDK4/6 inhibitors and second-generation CDK4 inhibitors; in vivo neutrophil hematologic toxicity studies, JYC010145 has a higher safety window. JYC010145 has the attributes of best in class (BIC) and is expected to provide patients with safer and more effective solutions.

JMKX009137 is a highly efficient and selective CDK2 degradant

The molecule of JMKX009137 using PROTAC technology achieves an activity below nM for the degradation of CDK2 protein. Compared with inhibitors, they can continuously inhibit downstream signals p-Rb2 and avoid drug resistance mechanisms such as Rb rebound; at the same time, they are much more selective for other members of the same family such as CDK1 and CDK6 than inhibitors, significantly broadening the treatment window. In gastric cancer, tumor regression was achieved in the CCNE1 amplified CDX model. In breast cancer, the combination of JYC010145 and JMKX009137 can exert synergistic anti-tumor activity in vivo and in vitro, making CDK4/6 inhibitor response models more sensitive and restoring sensitivity to drug-resistant models. This highly efficient and low-toxicity synergistic combination therapy has the potential of BIC in the treatment of HR+/HER2-breast cancer.

JeYou Pharmaceutical will vigorously promote the subsequent development of these two products to bring new treatment options with clear clinical benefits to the majority of cancer patients.

Statement:

1. This information is intended to share research and development progress. It is for medical and health professionals only and is not for advertising purposes. For clinical use, please follow the opinions or guidance of your doctor or other medical and health professionals and follow the drug instructions.

2. JeYou Pharmaceuticals does not recommend any drug or the*utic use.

About JeYou Medicine

Shanghai JeYou Pharmaceutical Technology Co., Ltd. focuses on the "3+1" core treatment areas of cancer, kidney disease, pain, and autoimmunity, focusing on the research and development, manufacturing and commercial transformation of innovative drugs. The company has built a differentiated product matrix with international competitiveness, covering multiple drug types such as mono/dual antibodies, TCE, ADC, small molecule drugs and PROTAC. Currently, there are 40+ internally-developed products/in-house products in a portfolio, and more than 10 have entered the clinical stage. In February 2026, the company's independently developed Class 1 innovative anti-tumor drug Jilemax ® (Socimerose Sulfate Tablets) was approved for marketing by the State Food and Drug Administration.