Dicerna Pharmaceuticals, Inc. presented results from its Phase 1 double-blind, placebo-controlled, randomized trial of belcesiran, an investigational GalXC? RNAi therapeutic in development for the treatment of alpha-1 antitrypsin (AAT) deficiency-associated liver disease (AATLD). These data expand upon interim results announced in July 2021, demonstrating the safety and tolerability of single ascending doses of belcesiran in healthy volunteers (up to and including the final 12 mg/kg dose cohort) and further reaffirming the dosing regimen established for the ESTRELLA Phase 2 study of belcesiran. In addition, the data demonstrated robust, dose-dependent reductions in serum AAT through the 6 mg/kg dose level, with a maximum individual reduction of 91%. The data were presented in a poster at The Liver Meeting? 2021, the annual meeting of the American Association for the Study of Liver Diseases (AASLD). The Phase 1 trial was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single subcutaneous dose of belcesiran 0.1, 1.0, 3.0, 6.0 or 12.0 mg/kg compared to placebo (n=6, 2:1 randomization per cohort) in 30 adult healthy volunteers. A validated, standard-of-care quantitative nephelometry assay was used to measure serum AAT levels. Repeat measurements of spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) were performed to monitor pulmonary function. All participants completed their treatment periods (through Day 57). All participants receiving belcesiran and who met certain criteria entered conditional follow-up post Day 57. Results: Robust, dose-dependent reductions in serum AAT were observed up to 6 mg/kg following a single dose of belcesiran, with the 6 mg/kg and 12 mg/kg cohorts achieving similar AAT reductions. Mean serum AAT reductions from baseline at end of treatment for doses greater than 0.1 mg/kg were 48% (1.0 mg/kg), 67% (3.0 mg/kg), 77% (6.0 mg/kg) and 78% (12.0 mg/kg), with maximum reductions occurring approximately eight weeks post-dose. Two participants achieved a maximum serum AAT reduction of approximately 90%; both participants received belcesiran 6 mg/kg. No severe or serious treatment-emergent adverse events (TEAEs) were reported. Most TEAEs were mild (39) or moderate (3 in two participants; common cold, gastroenteritis and staphylococcal folliculitis) and were determined to be unrelated to belcesiran treatment. No dose-dependent increases in frequency or severity of TEAEs, or abnormalities in safety labs, ECGs, physical exams or vital signs were observed. Normal lung function was maintained. There were no dose-dependent changes in spirometry measurements, and percent predicted DLCO repeat measurements remained within normal limits. No clinically significant changes in laboratory safety tests, including liver function tests, were reported for any belcesiran dose.