Celladon is developing “first-in-class” CDN small molecules which activate SERCA2a, as intravenous or oral drugs for the treatment of acute and chronic heart failure. These allosteric modulators of SERCA2a (e.g., CDN1054) bind to the enzyme and increase the V_{1/2 max} and/or V_max, increase contractility of cardiomyocytes from normal and heart failure animals,  decrease relaxation time of cardiomyocytes, increase Ca²⁺ uptake into the sarcoplasmic reticulum, and increase contractility including ejection fraction in vivo in normal and heart failure animals (but not heart rate or arrhythmias). In addition, these compounds display favorable hERG selectivity in in vitro cell-based assays, have a very clean profile in screens against >150 targets, and have completed pilot toxicology studies (7-Day, dogs) demonstrating an excellent safety profile. All current inotropic drugs have a negative impact on long-term outcomes, and by targeting SERCA2a, CDN compounds have the potential to increase cardiac contractility while improving long-term survival.