AZD4063

**AZD4063** is an investigational small molecule drug developed by AstraZeneca for the treatment of phospholamban (PLN) R14del dilated cardiomyopathy, a genetic form of heart failure characterized by a mutation in the PLN gene leading to super-inhibition of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and impaired cardiac contractility. It functions through an RNA interference (RNAi)-based mechanism, specifically designed to knock down PLN mRNA expression, thereby alleviating SERCA2a inhibition, enhancing calcium handling in cardiomyocytes, and potentially improving cardiac function. Currently in Phase 1 clinical development, it is administered as a subcutaneous injection in single ascending dose (SAD) and multiple ascending dose (MAD) regimens to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics (including PLN mRNA knockdown in endomyocardial biopsies), and efficacy endpoints in adults aged 18-80 with confirmed PLN R14del mutation and stable heart failure symptoms.[5][7][9]