Study of ALXN2220 Versus Placebo in Adults With ATTR-CM

Inclusion Criteria:

• Diagnosis of ATTR-CM with either wild-type or variant TTR genotype

• End-diastolic interventricular septal wall thickness ≥ 12 mm on echocardiographymeasured at Screening

• NT-proBNP > 2000 pg/mL at Screening

• Treatment with a loop diuretic for at least 30 days prior to Screening

• History of heart failure NYHA Class II-IV at Screening

• Life expectancy of ≥ 6 months as per the Investigator's judgment

• Males and females of childbearing ability must use contraception

Exclusion Criteria:

• Known leptomeningeal amyloidosis

• Known light chain (AL) or secondary amyloidosis (AA), or any other form of systemicamyloidosis

• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack,coronary revascularization, cardiac device implantation, cardiac valve repair, ormajor surgery within 3 months of Screening

• Uncontrolled clinically significant cardiac arrhythmia, per Investigator'sassessment

• LVEF < 30% on echocardiography

• Renal failure requiring dialysis or an eGFR < 20 mL/min/1.73 m2 at Screening

• Polyneuropathy with PND score IV