This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1 will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing schedule is IV every 3 to 4 weeks.

Inclusion Criteria:

• Documented alpha-1 antitrypsin (AAT) serum concentration <11 μM.
• Diagnosis of alpha-1 antitrypsin deficiency (AATD) with any allelic combination with exception of the null/null genotype.
• For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: post-bronchodilator FEV1 of at least 40% of predicted normal value.
• For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: subjects eligible for bronchoscopy per judgment of investigator.
• Nonsmoker for at least 6 months prior to study and must remain nonsmoking for the entire study duration.
• Adequate hepatic and renal function as defined per protocol.
• Willing to undergo current augmentation therapy washout (if applicable) and refrain from initiating augmentation therapy, other investigational drug trials for AATD, therapy with IV immunoglobulins or monoclonal antibodies during the entire study, including follow-up.

Exclusion Criteria:

• Known or suspected allergy to components of INBRX-101 (AAT or human IgG) or pdAAT.
• Participation in any investigational drug trial within 30 days prior to this trial, or subjects receiving IV immunoglobulins or monoclonal antibodies within 30 days prior to this trial.
• History of and/or on the waiting list for lung or liver transplant, lobectomy, or lung volume reduction surgery.
• Acute respiratory tract infection or COPD exacerbation that required antibiotic treatment and/or increase in systemic steroid dosage within the 4 weeks prior to screening. Subjects are permitted to continue to receive steroids if the investigator judges the subject to have a history of stable dosing.
• Subjects with ongoing or history of unstable cor pulmonale.
• Infection with hepatitis A, B, or C or human immunodeficiency virus (HIV).
• Active autoimmune disease or documented history of autoimmune disease that 1) required systemic steroids or immune-suppressive medications and 2) tested positive for auto-antibodies. Exception: Endocrinopathies managed with hormone replacement therapy (HRT).
• Current substance and/or alcohol abuse with protocol defined exceptions.
• Current narcotics abuse with protocol defined exceptions.