An Extension Study to Learn About the Long-Term Safety of Fazirsiran and if Fazirsiran Can Help People With Alpha-1 Antitrypsin Liver Disease

Inclusion Criteria:

• Participants must meet all of the following criteria to be eligible for inclusion inthe study:

• The participant is willing and able to understand and fully comply with studyprocedures and requirements, in the opinion of the investigator.

• The participant is able to read, understand, and complete the study questionnaireselectronically per investigator's judgment.

• The participant has provided informed consent (ICF) (that is, in writing, documentedvia a signed and dated ICF) and any required privacy authorization before theinitiation of any study procedures.

Note: For participants who comprehend, can provide informed consent, and are unable to sign the ICF, an impartial witness may sign the ICF on behalf of the participant after the participant has orally consented to the participant's participation in the study.

• The participant enrolling in this open-label extension (OLE) study will haveparticipated in a previously qualifying study, and will be considered foreligibility based on the following study-specific criteria:

• AROAAT2001:

• Participants with fibrosis may roll over into this OLE study after they reachtheir next regularly scheduled, Q12W visit.

• Participants with fibrosis who have completed the AROAAT2001 study may beenrolled into the OLE study.

• AROAAT2002:

• Participants in Cohorts 1 and 1b may roll over after completing the 24-weekprimary study period.

• Participants in Cohort 2 may roll over after completing the 48-week primarystudy period.

• Participants who have completed the study may be enrolled into the OLE study.

• The participant is a nonsmoker (defined as: does not smoke cigarettes daily for atleast 24 weeks) with current nonsmoking status confirmed by urine cotinine at Day 1.

• E-cigarettes (vapor) are not permitted.

• The participant may be on nicotine replacement (patch or gum). A positive urinecotinine result due to nicotine replacement is acceptable for enrollment at thediscretion of the investigator.

• The participant must have suitable venous access for blood sampling.

• It must be confirmed that the participant does not have hepatocellular carcinoma (HCC). Participants will be screened for HCC with alpha-fetoprotein (AFP) andabdominal ultrasound. If the participant has any of the following, they will berequired to have contrast-enhanced computed tomography (CT) or magnetic resonanceimaging (MRI) imaging to exclude HCC before enrollment.

• AFP >20 nanogram per milliliter (ng/mL).

• AFP 15 to 19 ng/mL at enrollment if that is >2 times prestudy levels (ifavailable).

• Any liver lesion >10 millimeter (mm) (longest diameter) detected by ultrasound.

• Poor visibility of liver on ultrasound.

• A person of childbearing potential (POCBP) must have a negative urine pregnancy testperformed within 3 days prior to Day 1 dosing in this study (sensitive to 25International Unit [IU] human chorionic gonadotropin [hCG]).

• The participant must use appropriate contraception methods (that is, highlyeffective methods for female and medically appropriate methods for male studyparticipants) for the entire duration of the study. Participants who terminate earlymust use appropriate contraception methods for 6 months after the last dose of studyintervention. Male participants who terminate early must not donate sperm for atleast 6 months after the last dose of study intervention.

• Sexual abstinence, for the purposes of this study, is only considered a highlyeffective method of contraception when considered to align with the preferred andusual lifestyle of the participant. It will be employed for the entire duration ofthe study and the 6 months after last dose of study intervention.

• Periodic abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are notconsidered "true" abstinence and are not acceptable methods of contraception.

Exclusion Criteria:

• The participant will be excluded from the study if any of the following exclusioncriteria are met:

• The participant is likely to require major surgery. Major surgery typically requiresat least 1 night in the hospital. Examples include laparoscopic surgery (exceptcholecystectomy and tubal ligation); Gastrointestinal tract (GI) tract surgeryincluding 1 or more segments of the colon or terminal ileum; open resection oforgans; large joint replacements; mastectomy with reconstruction; and spine,thoracic, vascular, or intracranial surgery.

• The participant has evidence of other forms of chronic liver diseases, includingviral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis,Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history ofbiliary diversion, or autoimmune hepatitis.

• The participant has abnormal finding(s) of clinical relevance during the evaluationbefore the first study dosing that, in the opinion of the investigator, couldadversely impact participant safety during the study or adversely impact studyresults.

• The participant had major protocol deviation(s) in AROAAT2001 or AROAAT2002 thatwould affect the conduct of this study.

• The participant permanently discontinued investigational product because of an AE,adjudicated as related to the study intervention, in AROAAT2001 or AROAAT2002.

• Female participants who became pregnant during Study AROAAT2001 or AROAAT2002,female participants who are lactating or planning to become pregnant during thestudy period; or males or female participants of childbearing potential not agreeingto continue using appropriate contraception methods through the conclusion of studyparticipation.

• The participant has a Child-Turcotte-Pugh (CTP) score >=7 OR (Model for End-StageLiver Disease) MELD score >14.

• The participant meets Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatinine criteria as per the protocol. All laboratory tests used asexclusion criteria may be repeated once and the repeat value may be used for studyeligibility determination.

• Participants who have a newly-diagnosed malignancy or recurrence of malignancy (except for resected cutaneous basal cell carcinoma, squamous cell carcinoma,superficial bladder tumors, or carcinoma in situ of the uterine cervix that has beentreated with no evidence of recurrence).

• The participant is experiencing a pulmonary exacerbation at the time of enrollment (participant enrollment may be temporarily delayed after the clinical resolution ofan exacerbation).

• The participant has unstable, poorly controlled, or severe hypertension.Participants may be reevaluated once their blood pressure is successfullycontrolled.

• The participant has a history of more than moderate alcohol consumption within 12months before the Day 1 visit.

• The participant has a history of hypersensitivity or allergies to fazirsiran or anyassociated excipients.

• The participant has any concomitant medical or psychiatric condition or socialsituation that would make it difficult to comply with protocol requirements or putthe participant at additional safety risk.

• The participant has a history of clinically significant hematologic, renal, hepatic,cardiovascular, infectious, pulmonary, neurologic, psychiatric, GI, systemicinflammatory, metabolic, or endocrine disorder or any other condition that, in theopinion of the investigator, rendered the participant a poor candidate for inclusioninto the study.

• The participant has a history of thromboembolic disease (including deep veinthrombosis or pulmonary embolism), within 24 weeks before enrollment; or is takingchronic anticoagulants. (Note: Participants taking stable doses of chronicanticoagulants may be allowed after consultation with the medical monitor, if theydo not have cirrhosis or a history of liver decompensating events).

• The participant is unable to return for all scheduled study visits.

• The participant has known or suspected coronavirus disease 2019 (COVID-19) that inthe opinion of the sponsor and investigator does not resolve during screening.Positive antibody testing for COVID-19 without other evidence of current or recentactive infection does not exclude participation. Enrollment of participants who failinclusion due to COVID-19 infection may be temporarily delayed at the discretion ofthe sponsor and investigator. If the participant has a positive polymerase chainreaction (PCR) with no other evidence of infection, a retest may be allowed;however, to enroll in the study the participant must have a negative PCR.

• The participant is a study site employee, an immediate family member (for example,spouse, parent, child, sibling), or is in a dependent relationship with a study siteemployee who is involved in conduct of this study, or may consent under duress.

• The participant who, in the opinion of the investigator or the sponsor, will beuncooperative or unable to comply with study procedures.

• The participant who participates in other studies involving an investigationalproduct.