A Study of KB408 for the Treatment of Alpha-1 Antitrypsin Deficiency

Inclusion Criteria:

1. The subject or legally authorized representative must have read, understood, andsigned an Institutional Review Board (IRB) approved Informed Consent Form and mustbe willing and able to comply with study procedures and instructions.

2. Subject is aged ≥18 to ≤70 years, at the time of informed consent.

3. Subject has a genetically confirmed diagnosis of AATD with a PIZZ or PIZNullgenotype.

4. Cohort 2b and Cohort 3: Subjects receiving AAT augmentation therapy must be willingto washout for at least 10 days prior to Screening and be willing to remain offaugmentation therapy for the duration of the study.

5. Cohort 2b and Cohort 3: Serum AAT level <11 μM at Screening.

6. Willing to remain on a stable regimen of treatment during the study.

7. Resting oxygen saturation ≥92% on room air at Screening.

8. Clinically stable and in good general health, except for AATD, as determined by theInvestigator.

Exclusion Criteria:

1. Pulmonary function test with percent predicted forced expired volume in 1 second (ppFEV1) after inhalation of a bronchodilator is <40% at Screening.

2. Diffusing capacity of the lungs for carbon monoxide (DLCO) <30 percent predicted (historical DLCO within 2 years prior to Screening without any intervening change inclinical status since the measurement was taken, or as measured at Screening).

3. Known ongoing or history of clinically significant pulmonary impairment other thanAATD.

4. A pulmonary exacerbation within six weeks (42 days) of first dose.

5. Initiation of any new chronic therapy or any change in ongoing therapy routinewithin 28 days of first dose.

6. Participation in another interventional clinical study or treatment with aninvestigational agent within 30 days or 5 half-lives, whichever is longer, of firstdose. Previous treatment with a genetic therapy for AATD, where the investigationalproduct was demonstrated to be non-efficacious, is not exclusionary.

7. History of or listed for solid organ transplantation or has undergone major lungsurgery (e.g., lobectomy) within 6 months of first dose.

8. Any clinical condition or illness (including a history or current evidence ofsubstance abuse or dependence) that, in the opinion of the Investigator, wouldimpact a subject's ability to complete all study-related procedures and/or poses anadditional risk to the assessment of safety of KB408.

9. An active oral herpes infection 30 days prior to the first dose.

10. Clinically significant hepatic dysfunction defined as any one of the following:

11. AST and ALT ≥3× upper limit of normal (ULN) at Screening

12. Total bilirubin ≥2× ULN at Screening (unless associated with Gilbert'ssyndrome)

13. Evidence of liver cirrhosis with clinical manifestations of portal hypertension (e.g., ascites, encephalopathy, variceal hemorrhage)

14. History of cigarette smoking or any other tobacco use, or use of e-cigarettes orother recreational inhalant, within 6 months of Screening.

15. Unwilling to refrain from smoking, e-cigarette use, or vaping throughout theduration of the study.

16. A positive urine cotinine result that is consistent with active smoking atScreening. (A positive cotinine test due to nicotine replacement therapy for thepurpose of smoking cessation, as attested by the Investigator, is allowed.)

17. Abnormal hematology or chemistry testing at Screening as defined below, or any otherclinically significant abnormalities that the Investigator believes may interferewith the assessment of safety of the study treatment.

• Platelet count <100×10^9/L

• Hemoglobin <9 g/dL

• White blood cell count <3 or >15×10^9/L

• Sodium <130 or >150 mmol/L

• Potassium <3 or >5.5 mmol/L

• Carbon dioxide <16 mmol/L

• Creatinine >2 mg/dL

15. Subject is known to be noncompliant or is unlikely to comply with the requirementsof the study protocol, in the opinion of the Investigator.

16. Females who are pregnant or nursing.

17. Subject who is unwilling to comply with contraception requirements per protocol