ATN-249

ATN-249 is a novel, orally available small molecule inhibitor of plasma kallikrein, developed by Attune Pharmaceuticals for the prophylactic treatment of hereditary angioedema (HAE). It is designed to be highly potent and selective, with preclinical studies demonstrating over 2000-fold selectivity for plasma kallikrein compared to other serine proteases. In both biochemical and contact activation assays, ATN-249 showed approximately tenfold greater inhibition of plasma kallikrein than C1 esterase inhibitor (C1-INH), the current standard of care. Pharmacokinetic studies indicate that once-daily oral dosing achieves sustained exposure above pharmacologically relevant thresholds. Phase I clinical trials in healthy volunteers demonstrated dose-dependent inhibition of plasma kallikrein activity with a favorable safety profile and good tolerability at all studied doses (50 mg to 800 mg), with only mild adverse events reported[1][5][6][7][8][10]. As of March 2024, no further development beyond phase I has been reported[1].