The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients.

Inclusion Criteria:

Part A (SAD phase) inclusion:

• Healthy adult males aged 18 to 40 years inclusive at Screening.
• Subjects with adequate complete blood counts and liver function tests.
• Willing to provide written informed consent and willing to comply with study requirements.

Part B & C (MAD & MD phase) inclusion:

• Adult male hemophilia patients aged 18 to 65 years inclusive at Screening.
• Patients with adequate complete blood counts and liver function tests.
• Patients with moderate or severe, clinically stable hemophilia A or B (Factor VIII or Factor IX ≤5%).
• Willing to provide written informed consent and willing to comply with study requirements

Part D (MD Phase in patients with inhibitors) Inclusion:

• Same as Parts B/C
• A Bethesda inhibitor assay > 0.6 BU/mL

Exclusion Criteria:

Part A (SAD phase) exclusion:

• Subjects with a personal history and/or family history of venous thromboembolism (VTE)
• Subjects with a known co-existing thrombophilic disorder
• Subjects with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
• Subjects with a history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
• Subjects who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological including osteoarthritis and other inflammatory diseases, dermatological including rash, eczema, dermatitis, or connective tissue diseases or disorders.

Part B & C (MAD & MD phase) exclusion:

• Patients with a current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity.
• Patients who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory or other diseases that in the judgment of the investigator precludes their participation in the study.
• Patients with a known co-existing thrombophilic disorder
• Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
• Patients who are known to be HIV positive and have a CD4 count <400 cells/μL

Part D (MD Phase in patients with inhibitors) exclusion:

• Same as Parts B/C
• Patients who are known to be HIV positive and have a CD4 count <200 cells/μL