BMS-962476 + statin

**BMS-962476 + statin** is a combination therapy studied for lowering LDL cholesterol in patients with hypercholesterolemia. BMS-962476 is a pegylated Adnectin-based protein therapeutic that acts as a high-affinity inhibitor of proprotein convertase subtilisin/kexin type 9 (**PCSK9**)[1][3]. By blocking PCSK9 from binding to the LDL receptor (LDLR), BMS-962476 increases receptor recycling and LDL uptake, resulting in reduced circulating LDL-C. Statins, which are HMG-CoA reductase inhibitors, are well-established medications that lower cholesterol by upregulating LDL receptor expression in the liver, but also increase PCSK9 expression[5]. Combining BMS-962476 with a statin aims to synergistically lower LDL-C: statins upregulate LDL receptors but increase PCSK9, while BMS-962476 inhibits PCSK9, potentially maximizing LDL-C reduction[1][5]. Clinical trial data show that this combination leads to significant, dose-dependent reductions in LDL-C (up to 48%) and PCSK9 (over 90%) in patients on background statin therapy[1].