A Phase 1/2a, Single- and Multiple-dose Escalation Study of KRRO-110

Inclusion Criteria:

Part A SAD cohort Inclusion Criteria (Healthy Volunteers)

• Adult male or female participants, 18 to 65 years of age

• Documented PiMM genotype

• Participants who are willing to and able to provide signed written informed consent

PiZZ Genotype (Part A SAD and Part B MAD cohorts) Inclusion Criteria (PiZZ Genotype)

• Adult male or female participants 18 to 70 years of age (inclusive)

• Documented PiZZ genotype

• Baseline blood total AAT level < 11 µM/L

Exclusion Criteria:

Exclusion Criteria (Healthy Volunteers)

• Female participant of childbearing potential or male participant that is unable orunwilling to use an approved, reliable means of contraception

• Body mass index (BMI) > 32 or < 18.5 kg/m2

• History or current clinical evidence of hepatic disease

• Evidence of active infection

• History of medical condition(s), eg, advance cardiac disease, current or recentmalignancy, organ transplantation, or other illness

• Serology result indicative of any exposure (past or active) to hepatitis C,hepatitis B, or human immunodeficiency virus (HIV)

• Respiratory or other acute illness within 8 weeks

• Tobacco use of any kind within 6 months

Exclusion Criteria (PiZZ Genotype)

• Female participant of childbearing potential or male participant that is unable orunwilling to use an approved, reliable means of contraception

• BMI > 32 or < 18.5 kg/m2 or weight > 90 kg

• History of FEV1 < 50%

• History or current clinical evidence of advanced hepatic disease and/or pulmonarydisease

• Use of an experimental therapy except KRRO-110 within 6 months or 5 half-lives forthe experimental therapy, whichever is greater

• Tobacco use of any kind within 6 months

• Use of conventionally dosed AAT augmentation therapy within 5 half-lives

• Serology result consistent with exposure to HIV, or serology consistent with activehepatitis B or hepatitis C infection