PKN605

**PKN605** is a small molecule drug developed by Novartis Pharma AG as a selective inhibitor of histone deacetylase 6 (**HDAC6**), an enzyme involved in epigenetic regulation and implicated in cardiac remodeling processes that contribute to atrial fibrillation (**AF**). By blocking HDAC6, PKN605 aims to reduce atrial fibrillation burden, defined as the proportion of time spent in AF, in patients with paroxysmal or persistent AF who have a history of at least two episodes. It is currently in **Phase 2** clinical development, with an ongoing multinational, randomized, placebo-controlled, participant- and investigator-blinded trial (NCT07217067) evaluating its efficacy, safety, tolerability, and pharmacokinetics over 24 weeks of oral dosing (twice daily tablets at low or high doses). The trial targets adults ≥18 years with documented AF, elevated stroke risk (CHA2DS2-VASc score ≥2 in males or ≥3 in females), stable heart failure (NYHA class I/II), and NT-proBNP ≥300 pg/mL, excluding those with permanent AF, recent ablation, or implanted devices. Early data from healthy volunteers suggest good tolerability, with common mild side effects like headache and gastrointestinal discomfort at higher doses.