A Study of TSRA-196 in Adults With PiZZ Alpha-1 Antitrypsin Deficiency (AATD)

Inclusion Criteria: * Males or females who are 18 to 70 years of age, inclusive, at the time of signing the informed consent * Body mass index of 18 to 37 kg/m2, inclusive * Confirmed diagnosis of AATD and PiZZ genotype * At least one previous measure of blood total AAT level \<11 µmol/L * Nonsmoker for at least 6 months before screening and must remain nonsmoking for the entire study duration * Either AAT treatment-naïve or washed out of all investigational or approved treatments that modify AAT levels for 5 half-lives or at least 4 weeks, whichever is longer, before TSRA-196 administration Parts 1A and 2A (AATD lung disease with no or minimal liver fibrosis) * Clinically significant lung disease, defined as 1) evidence of emphysema or bronchiectasis by computed tomography or 2) DLCO \<70% of the predicted value or 3) ppFEV1 \<80% * ppFEV1 ≥35% * METAVIR fibrosis score F0 or F1 confirmed by liver biopsy at screening, or a liver stiffness measure by FibroScan ≤7 kPa at screening * FIB-4 index score ≤3.25 at screening * ALT and/or AST \<ULN at screening Parts 1B and 2B (AATD liver disease with significant or severe liver fibrosis, with or without AATD lung disease) * METAVIR fibrosis score F2 or F3 confirmed by liver biopsy at screening. A liver biopsy conducted within 12 months before screening is acceptable as a substitute. * Liver stiffness measure by FibroScan \>7 and ≤15 kPa at screening * ALT and/or AST \<2 x ULN at screening Exclusion Criteria: * Presence of gene…