Renal AL Amyloid Involvement and NEOD001

This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm,
parallel-group efficacy and safety study of NEOD001 as a single agent administered
intravenously in adults with AL amyloidosis who have a maintained hematologic response to
their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell
transplant [SCT]) and have persistent renal dysfunction. Subject screening will occur during
the 28 days prior to the first administration of study drug (i.e. month 1 day 1). If
screening assessments are completed and all eligibility requirements are met, the subject
will be enrolled. Study visits will occur every 28 days based on scheduling from month 1 day
1. A ±5-day window is allowed for visits starting after month 1. Subjects may receive up to
12 infusions of study drug. Subjects who discontinue study drug before the initial End of
Study (EOS) visit should have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days
after their final administration of study drug. After completing 12 months of treatment and
the confirmatory EOS visit, a subject may enter an open-label extension (OLE) study, during
which subjects will receive active treatment with NEOD001 for 12 months and may receive
concurrent chemotherapy.

Inclusion Criteria:

1. 18 years of age or older

2. Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy
of a tissue biopsy excluding bone marrow

3. Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant
cause of renal damage

4. Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) >
500mg/day in a 24-hour urine collection

5. CKD 1 to 3 (eGFR > 30)

6. ≥1 prior systemic hematologic therapy for a free light chain (FLC) producing
hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at
least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not
requiring further treatment

7. ECOG Performance Status ≤ 2

8. Clinical laboratory values:

1. Absolute neutrophil count > 1000/μL

2. Platelet count > 75,000/μL

3. Total bilirubin ≤ 1.5X ULN

4. Alkaline phosphatase ≤ 5X ULN

5. NT-proBNP < 1800 pg/mL

9. Voluntary written consent must be given before performance of any study-related
procedure not part of standard medical care with the understanding that consent may be
withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria:

1. Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL
amyloidosis

2. Female patients who are lactating, breastfeeding, or pregnant

3. Patients who have not been treated or who have received chemotherapy within 6 months,
or SCT within 12 months, for the light-chain producing hematologic disease causing AL
amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)

4. Patients who at initial diagnosis or later met the International Myeloma Working Group
(IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)

5. Patients whose screening renal biopsies for RAIN show dominant causes of renal damage
not related to AL amyloidosis

6. Medically documented cardiac syncope, uncompensated congestive heart failure,
myocardial infarction within the previous 6 months, unstable angina pectoris,
clinically significant repetitive atrial or ventricular arrhythmias despite
antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant
uncompensated autonomic insufficiency

7. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

8. Ongoing or active infection, known HIV positive, known to be hepatitis B surface
antigen-positive or has known or suspected active hepatitis C infection.

9. Psychiatric illness/social situations that would limit compliance with study
requirements