TD1414

TD1414 is a small molecule neprilysin (NEP) inhibitor developed by Theravance Biopharma for the treatment of heart failure. Neprilysin is a zinc-dependent metallopeptidase that degrades various endogenous vasoactive peptides, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), as well as bradykinin and adrenomedullin. By inhibiting this enzyme, TD1414 increases the concentration of these peptides, which exert beneficial cardiovascular effects such as vasodilation, natriuresis, and diuresis, while also inhibiting the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system. TD1414 was evaluated in Phase 1 clinical trials; however, it is no longer listed in Theravance's active development pipeline, as the company shifted focus toward lung-selective neprilysin inhibitors like TD-0714 for heart failure with preserved ejection fraction (HFpEF).