Simcere's breast cancer innovative drug SIM0270 (SCR-6852) clinical trial application accepted

On October 21, 2021, the clinical trial application for the innovative breast cancer drug SIM0270 (SCR-6852) independently developed by Simcere was accepted by the Center for Drug Evaluation (CDE) of the State Drug Administration.

SIM0270 is a new generation of oral selective estrogen receptor degrading agent (SERD), which is planned to treat ER+/HER2-type locally advanced or metastatic breast cancer. Pre-clinical research data show that SIM0270 (SCR-6852) has high activity, high blood-brain barrier permeability and good safety. It is better than the first-generation SERD drugs and is expected to be used for the treatment of breast cancer brain metastases. Estrogen receptor positive (ER+) is the most common subtype of breast cancer (approximately 80%), and these patients are sensitive to endocrine therapy targeting estrogen. However, about 30% of patients have drug resistance during treatment, leading to recurrence or metastasis of the disease, affecting the quality of life and survival of patients, and this is a major challenge for breast cancer treatment. In metastatic breast cancer, about 15% of ER+ advanced breast cancer patients have brain metastases, and the incidence is rising, and the median overall survival time of patients is only 10 to 14 months. However, the existing endocrine therapy drugs basically cannot penetrate the blood-brain barrier and are powerless to treat brain metastases. Therefore, drug treatment options for breast cancer patients with brain metastases are more limited, and more effective new therapies are urgently needed. Selective Estrogen Receptor Degrader (SERD) is a small molecule that can bind to the estrogen receptor (ER) on the surface of cancer cells. It can block the ER signaling pathway, reduce the stability of the receptor, and can also induce the receptor. Degraded by cells, it is an important therapy for the treatment of endocrine-resistant breast cancer. At present, only the only SERD drug in the world, Fulvestrant (Faslodex), has been approved, but it requires high-dose intramuscular injection, which has obvious adverse reactions, which limits its clinical use to a certain extent. Therefore, the development of a new generation of more convenient and efficient oral SERD has become a current trend. It is expected that the global SERD drug market will continue to expand in the future, reaching US$1.8 billion in 2024 and US$6.6 billion in 20305. SIM0270 is a new generation of oral SERD independently developed by Simcere. It has shown good in vivo and in vitro activities and cross-species pharmacokinetic properties in preclinical studies, and has good safety. It is worth mentioning that the research and development of SIM0270 started from the unmet need for the treatment of brain metastases. While maintaining the characteristics and curative effects of the existing oral SERD, the molecular structure has been differentiated and innovative, making it more clinically advanced. The SERD compounds under investigation have more efficient blood-brain barrier permeability. In animal experiments, the cerebral blood ratio (the ratio of the drug concentration in the brain to the drug concentration in the blood) of SIM0270 is 4-10 times higher than that of similar compounds under investigation, indicating that it can efficiently penetrate the blood-brain barrier and reach the brain Effective drug concentration. In the ER+ breast cancer brain orthotopic model, the brain tumors of mice in the SIM0270 group were significantly reduced and the survival time was prolonged, further verifying that SIM0270 has the potential to be applied to patients with breast cancer brain metastases. The relevant data will be published in the American Association for Cancer Research in 2021. Will (AACR). At present, the second-generation SERD drug clinical trials that have been carried out around the world have not included patients with known symptomatic brain metastases. SIM0270 is currently the only SERD molecule with brain-penetrating properties and will also explore its efficacy in breast cancer patients with brain metastases in the next clinical trials.