BMS-962476

BMS-962476 is a novel, engineered protein therapeutic developed as an alternative to monoclonal antibodies for lowering low-density lipoprotein cholesterol (LDL-C). It is an approximately 11-kDa polypeptide derived from the human fibronectin type III domain, classified as an "Adnectin," and conjugated to polyethylene glycol to enhance pharmacokinetics. BMS-962476 binds with high affinity to proprotein convertase subtilisin/kexin type 9 (PCSK9), inhibiting its interaction with the LDL receptor. This inhibition prevents PCSK9-mediated degradation of LDL receptors, thereby increasing receptor recycling and promoting greater clearance of LDL-C from plasma. Preclinical studies demonstrated potent reductions in free PCSK9 and LDL-C levels in animal models, while early-phase clinical trials showed dose-dependent reductions in both free PCSK9 (>90%) and LDL-C (up to 48%). The drug was initially developed by Adnexus Therapeutics and Bristol Myers Squibb for hypercholesterolemia and cardiovascular disease but has not advanced beyond phase I clinical trials[1][2][3][4][5][7].

Other names

PCSK9 AdnectinPCSK-9 AdnectinPCSK 9 Adnectin