A Study to Evaluate the Safety and Efficacy of BEAM-302 in Adult Patients With Alpha-1 Antitrypsin Deficiency (AATD)

Part A:

Inclusion Criteria:

• Males or females 18 - 70 years of age inclusive at the time of consent.

• Diagnosis of AATD and homozygous for the PiZZ mutation (confirmed by genetictesting).

• Blood total AAT level <11 μM or equivalent protein in mg/dL.

• Patients receiving augmentation therapy in regions where augmentation is not SoCmust be willing to washout augmentation therapy for at least 6 weeks prior tosigning the ICF and for the length of the study (unless clinically indicated)

• A postbronchodilator FEV1 ≥40% of predicted and an FEV1/FVC <70% at screening. (PFTsobtained within 1 year of signing the ICF may be used for eligibility.)

• Evidence of emphysema on a historic CT scan or a DLCO ≤70% of the predicted value (corrected for hemoglobin) at screening. (PFTs obtained within 1 year of signing theICF may be used for eligibility.)

Exclusion Criteria:

• Body mass index >30

• Lung or liver transplant or on waiting list for lung or liver transplant or statuspost lung volume reduction surgery.

• Clinical evidence of severe bronchiectasis as per the discretion of the investigator (eg, excessive sputum production or recurrent infections requiring antibiotic use [>4x/year]).

• Liver disease with any of the following:

• FibroScan liver stiffness measurement ≥7.5 kilopascals (kPa). (For siteswithout access to FibroScan, APRI >0.5 can be used as a surrogate exclusioncriterion [Yilmaz, 2011].

• Known history of liver cirrhosis or complications of cirrhosis (eg, varices,ascites, hepatic encephalopathy).

• Presence of ≥F2 liver fibrosis if a patient has previously had a liver biopsy.

• Have ALT or AST > upper limit of normal (ULN).

• Total bilirubin levels > ULN; if documented Gilbert's Syndrome, total bilirubin >2 × ULN.

• INR ≥1.2 at screening. If deemed appropriate by the investigator and/orprescribing physician, the patient may stop taking anticoagulants for anappropriate washout period or reversal with vitamin K and if indicated, arepeat INR within <1.2 would be acceptable.

• Seropositive for hepatitis B (positive surface Ag).

• Active hepatitis C by hepatitis C virus (HCV) antibody. If HCV antibodypositive, must be HCV RNA polymerase chain reaction (PCR) negative.

Part B:

Inclusion Criteria:

• Males or females 18 - 70 years of age inclusive at the time of consent.

• Diagnosis of AATD and homozygous for the PiZZ mutation (confirmed by genetictesting).

• Evidence of METAVIR F1, F2, or F3 liver fibrosis based on a central read of abaseline liver biopsy during the screening period or a histological diagnosis madeno more than 6 months before enrollment and stage confirmed by central read.

• A postbronchodilator FEV1 ≥40% of predicted at screening. (PFTs obtained within 1year of signing the ICF may be used for eligibility.)

Exclusion Criteria:

• Lung or liver transplant or on waiting list for lung or liver transplant or statuspost lung volume reduction surgery.

• Clinical evidence of severe bronchiectasis as per the discretion of the investigator (eg, excessive sputum production or recurrent infections requiring antibiotic use [>4x/year])

• Previous diagnosis of liver cirrhosis or complications of cirrhosis (eg, varices,ascites, hepatic encephalopathy).