A Study to Evaluate the Efficacy and Safety of CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis

Key Inclusion Criteria:

• AL amyloidosis stage IIIb based on the European Modification of the 2004 StandardMayo Clinic Staging (NT-proBNP > 8,500 ng/L) at the time of Screening

• Measurable hematologic disease at Screening as defined by at least one of thefollowing:

1. Involved/uninvolved free light chain difference (dFLC) > 4 mg/dL or

2. Involved free light chain (iFLC) > 4 mg/dL with abnormal Kappa/Lambda ratio or

3. Serum protein electrophoresis (SPEP) m-spike > 0.5 g/dL

• Histopathological diagnosis of amyloidosis based on polarizing light microscopy ofgreen bi-refringent material in Congo red stained tissue specimens AND confirmationof AL derived amyloid deposits by at least one of the following:

1. Immunohistochemistry/Immunofluorescence or

2. Mass spectrometry or

3. Characteristic electron microscopy appearance/Immunoelectron microscopy

• Cardiac involvement as defined by:

1. Documented clinical signs and symptoms supportive of a diagnosis of heartfailure in the setting of a confirmed diagnosis of AL amyloidosis in theabsence of an alternative explanation for heart failure AND

2. At least one of the following: i. Endomyocardial biopsy demonstrating AL cardiac amyloidosis or ii. Echocardiogramdemonstrating a mean left ventricular wall thickness (calculated as [IVSd+LPWd]/2)of > 12 mm at diastole in the absence of other causes (e.g., severe hypertension,aortic stenosis), which would adequately explain the degree of wall thickening oriii. Cardiac magnetic resonance imaging (MRI) with gadolinium contrast agentdiagnostic of cardiac amyloidosis

• Planned first-line treatment for plasma cell dyscrasia iscyclophosphamide-bortezomib-dexamethasone (CyBorD)-based regimen administered as SoC

• Women of childbearing potential (WOCBP) must have a negative pregnancy test duringScreening and must agree to use highly effective contraception from Screening to atleast 5 months following the last study drug administration or 12 months followingthe last dose of her PCD therapy, whichever is longer

• Men must be surgically sterile or must agree to use highly effective contraceptionand refrain from donating sperm from Screening to at least 5 months following thelast study drug administration or 12 months following the last dose of their PCDtherapy, whichever is longer

Key Exclusion Criteria:

• Have any other form of amyloidosis other than AL amyloidosis

• Received prior therapy for AL amyloidosis or multiple myeloma. A maximum exposure of 2 weeks of a CyBorD-based PCD treatment after Screening laboratory samples areobtained and prior to randomization is allowed

• Has POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy,monoclonal protein and skin changes) syndrome or multiple myeloma defined as clonalbone marrow plasma cells > 10% from a bone marrow biopsy (performed ≤ 3 months priorto signing the ICF) or biopsy-proven (performed ≤ 3 months prior to signing the ICF)bony or extramedullary plasmacytoma AND one or more of the following CRAB features: a. Evidence of end organ damage that can be attributed to the underlying plasma cellproliferative disorder (e.g., multiple myeloma and POEMS syndrome), specifically: i.Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the ULN or > 2.75mmol/L (> 11 mg/dL) OR ii. Renal insufficiency: creatinine clearance < 40 mL perminute or serum creatinine > 177 mol/L (> 2 mg/dL) OR iii. Anemia: hemoglobin valueof > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L OR iv.Bone lesions: one or more osteolytic lesion on imaging tests (performed ≤ 3 monthsprior to signing the ICF): skeletal radiography, CT, or PET/CT, or MRI. If bonemarrow has < 10% clonal plasma cells, more than one bone lesion is required todistinguish from solitary plasmacytoma with minimal marrow involvement OR b. Any oneof the following biomarkers of malignancy: i. 60% or greater clonal plasma cells onbone marrow examination OR ii. More than one focal lesion on MRI that is at least 5mm or greater in size

• Have supine systolic blood pressure < 90 mmHg or symptomatic orthostatichypotension, defined as a decrease in systolic blood pressure upon standing of > 30mmHg despite medical management (e.g., midodrine, fludrocortisones) in the absenceof volume depletion