A Phase 1b/2a, Open-label Single Ascending Doses and Multiple Ascending Doses Study in Participants with Pi*ZZ AATD

Inclusion Criteria:

• Healthy as determined by the Investigator, based on a medical evaluation, or hasmild to moderate AATD-induced lung disease (FEV1 ≥50%) and/or stable mildAATD-induced liver disease (≤F2 (≤10 kPa) on FibroScan.

• Genetic testing confirming Pi*ZZ.

• Participant has been a non-smoker for at least 1 year prior to screening.

Exclusion Criteria:

• • Participant has a history of multiple drug allergies or of allergic reaction to anoligonucleotide or to N-acetylgalactosamine (GalNAc).

• Participant has a history of intolerance or any medical condition that mightinterfere with subcutaneous injections.

• Any ongoing or recent infections.

• Any recent or planned vaccinations during the study.

• Participant has a history of regular alcohol consumption exceeding 14 standarddrinks/week.

• Unwilling to abstain from alcohol for 48 hours prior to dosing at each of thedosing visits.

• Any recent or planned major surgery during the study.

• Participant has any medical condition or social circumstance that, in theopinion of the Investigator, would make the participant unsuitable forparticipation in the study or for dosing on Day 1, or could interfere with theassessments of safety, pharmacodynamics, or pharmacokinetics, or completion ofthe study.

• Participant currently on AAT augmentation therapy, planned to be onaugmentation therapy anytime during the study, or has been on augmentationtherapy within 30 days prior to Screening Visit.

• Donation of blood or blood products in excess of 500 mL within 12 weeks priorto Screening Visit and/or unwilling to refrain from blood donation for theduration of the study.

• Participant has received an investigational agent within 3 months of theScreening Visit.