Recently, Coherent Biopharma disclosed the latest preclinical research progress of CBP-8008, at the 2024 American Association for Cancer Research (AACR) Annual Meeting in San Diego, USA. Developed by CBP’s Bi-XDC technology platform, CBP-8008 represents the first PROTAC conjugate drug equipped with a bi-specific targeting ligand system. This innovation enables efficient and precise delivery of PROTAC to specific cells, enhancing both safety and drug efficacy. The details are as follows:
Poster presentation–
Title: CBP-8008: A first-in-class targeted pan-Bet protein degradation therapy using bi-specific XDC (Bi-XDC) technology for TNBC and mCRPC
Abstract Number: 6042
Presentation Time: April 9, 2024, Tuesday, 1:30 PM to 5:00 PM (Pacific Time)
Background:
PROTACs (Proteolysis Targeting Chimeras) utilize the ubiquitin-proteasome system (UPS) to degrade target proteins, representing a promising drug development technology. Despite recent advancements, challenges such as poor bioavailability and limited cell targeting have hindered PROTACs’ clinical applications, leading to poor efficacy and potential off-target toxicity.
The Bet protein family (BRD2, BRD3, BRD4, and BRDT) regulates numerous genes and metabolic pathways associated with immunity and cancer, including oncogenes (c-Myc) and androgen receptor (AR). Dysregulation of Bet proteins, particularly BRD4, correlates closely with the development and progression of TNBC and mCRPC.
Conclusion:
CBP-8008, developed by CBP’s Bi-XDC technology platform, represents a pioneering PROTAC conjugate drug incorporating FRα/PSMA dual ligands. This design significantly enhances PROTAC’s cell targeting and tumor penetration capabilities, thereby improving its druggability.
Preclinical studies have validated CBP-8008’s mechanism of action, safety, and efficacy. By carrying FRα/PSMA-conjugated PROTACs, CBP-8008 achieves targeted degradation of pan-Bet proteins via UPS and consequent downregulation of c-Myc expression. Notably, CBP-8008 demonstrates potent anti-tumor activity and safety in CDX/PDX models expressing FRα/PSMA receptors, particularly in TNBC and mCRPC models.
This research provides scientific rationale for the clinical development of CBP-8008 in the treatment of TNBC and mCRPC.