To evaluate the efficacy and safety of a single dose of NTLA-2001 compared to placebo in participants with ATTR-CM.

This is a multinational, multicenter, double-blind, placebo-controlled study in approximately 1200 participants, who will be randomized to receive a single infusion of either NTLA-2001 or placebo.

Inclusion Criteria:

• Documented diagnosis of ATTR amyloidosis with cardiomyopathy
• Medical history of heart failure (HF)
• Symptoms of HF are optimally managed and clinically stable within 28 days prior to administration of study intervention
• Screening NT-proBNP, a blood marker of HF severity, greater than or equal to 600 pg/mL and less than 10,000 pg/mL

Exclusion Criteria:

• New York Heart Association (NYHA) Class IV HF
• Polyneuropathy Disability score of IV (confined to wheelchair or bed)
• Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
• History of active malignancy within 3 years prior to screening
• RNA silencer therapy (patisiran, inotersen and/or eplontersen) within 12 months prior to dosing. Any prior vutrisiran use is not allowed
• Initiation of tafamidis or acoramidis within 56 days prior to study dosing
• Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
• History of liver disease
• Uncontrolled blood pressure
• Unable or unwilling to take vitamin A supplementation for the duration of the study