CDK4/6

BPI-1178 is a high effective and selective self-developed cyclin-dependent kinase (CDKs)4/6 inhibitor , which is intended to treat hormone receptor positive (HR)/ human epidermal growth factor receptor 2 negative (HER2) breast cancer and other solid tumors. CDK4/6 is activated after binding to cyclin D, which can promote the phosphorylation of retinoblastoma protein (Rb) and play a key role in the signal pathway of cell cycle progression and cell proliferation. However, CDK4/6 inhibitors can inhibit Rb phosphorylation, prevent the progression of G1 to S phase of cell cycle, and thus inhibit the proliferation of tumor cells. Based on its mechanism of action, CDK4/6 inhibitors have become one of the important targets of anti-tumor therapy.

BPI-1178 is an oral CDK4/6 inhibitor, which has a very similar molecular structure with the similar drugs Palbociclib, Ribociclib and Abemaciclib. BPI-1178 is an innovative targeted inhibitor based on the same core structure, developed after optimized design and screening. The results of non-clinical studies, such as molecular level and cell level trials, a number of pharmacodynamics, toxicological evaluation and pharmacokinetic trials of xenograft nude mouse models, show that BPI-1178 is a safe and effective CDK4/6 inhibitor with remarkable anti-tumor effect. BPI-1178 has very favorable DMPK properties, and it can penetrate the blood-brain barrier. It showed BPI-1178  monotherapy or combination therapy inhibited xenograft tumor growth of human breast cancer, lung cancer and glioblastoma. IND Approval is received from NMPA in 2019 November.

Mode of Action

Inhibition of CDK4/6 blocks phosphorylation of the human retinoblastoma protein (Rb), resulting in G1 cell cycle arrest and a shutdown of cell proliferation. Pre-clinical studies showed outstanding anti-cancer activities against breast cancer, lung cancer, and glioblastoma. Animal studies showed BPI-1178 could effectively penetrate through the blood-brain barrier.

Status

• Pre-clinical completed in 2019.
• IND filing was approved by NMPA in November 2019.
• Phase I clinical trial started in Q1 2020.
• Phase IIa clinical trial is expected in Q3 2021.