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

• WVE-006 (Drug): RNA editing oligonucleotide

Primary outcomes

• The proportion of participants with adverse events [Up to 36 Weeks]

Secondary outcomes

• Single Ascending Dose - Change from baseline in levels of serum M-AAT protein. [Up to 12 Weeks]
• Multiple Ascending Dose - Change from baseline in levels of serum M-AAT protein [Up to 24 Weeks]
• Single Ascending Dose - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) [Up to 12 Weeks]
• Single Ascending Dose - Maximum concentration of WVE-006 in plasma [Up to 12 Weeks]
• Multiple Ascending Doses - Area under the plasma concentration time curve for WVE-006 from time of dosing to the last measurable concentration (AUClast) [Up to 24 Weeks]
• Multiple Ascending Doses - Maximum concentration of WVE-006 in plasma (Cmax) [Up to 24 Weeks]

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* Healthy as determined by the Investigator, based on a medical evaluation, or has mild to moderate AATD-induced lung disease (FEV1 ≥50%) and/or stable mild AATD-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 an oligonucleotide or to N-acetylgalactosamine (GalNAc).

  * Participant has a history of intolerance or any medical condition that might interfere 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 standard drinks/week.
  * Unwilling to abstain from alcohol for 48 hours prior to dosing at each of the dosing visits.
  * Any recent or planned major surgery during the study.
  * Participant has any medical condition or social circumstance that, in the opinion of the Investigator, would make the participant unsuitable for participation in the study or for dosing on Day 1, or could interfere with the assessments of safety, pharmacodynamics, or pharmacokinetics, or completion of the study.
  * Participant currently on AAT augmentation therapy, planned to be on augmentation therapy anytime during the study, or has been on augmentation therapy within 30 days prior to Screening Visit.
  * Donation of blood or blood products in excess of 500 mL within 12 weeks prior to Screening Visit and/or unwilling to refrain from blood donation for the duration of the study.
  * Participant has received an investigational agent within 3 months of the Screening Visit.

• Medical Director, MD, Study director, Wave Life Sciences