BB-R12

BB-R12 is an investigational, cardiac-targeted gene therapy being developed for chronic heart failure with reduced ejection fraction that uses an adeno-associated virus vector (AAV6) to deliver a tandem human ribonucleotide reductase RRM1-RRM2 (RNR) cassette specifically to cardiomyocytes, leading to sustained overexpression of RNR and elevated intracellular 2-deoxy-ATP (dATP) levels in the heart.[1][11][14] Because dATP is a more efficient substrate for cardiac myosin than ATP, its local production in a subset of transduced myocytes enhances sarcomeric cross-bridge cycling and contractility, and the nucleotide diffuses via gap junctions to neighboring cells, producing a global positive inotropic effect that is independent of calcium handling pathways.[1][11][14] In preclinical rodent and large-animal (swine) models of post-myocardial infarction heart failure, a single intracoronary administration of BB-R12 improved left-ventricular ejection fraction, systolic function, and hemodynamics without evident cardiac or systemic toxicities, supporting further clinical development as a disease-modifying, myocardial myosin–activating therapy.[1][6][11][13][14]