124I-p5+14 Injection Safety in Subjects With Systemic Amyloidosis

The rationale for this study is the discovery of a synthetic polypeptide, designated p5+14, a
synthetic 45 amino acid peptide that binds many forms of amyloid, including human AL-, ATTR-
and ALect2-associated amyloid, as well as human and murine serum amyloid protein A-associated
(AA) amyloid. In preclinical studies, using SPECT and PET imaging, as well as
microautoradiography, it has been shown that radioiodinated p5+14 binds rapidly and
specifically to all amyloid deposits in abdominothoracic organs and tissues.

This is a single site, exploratory, open-label Phase I PET/CT imaging and dosimetry study.
The investigational drug product (designated 124I-p5+14 Injection) is an amyloid-reactive
synthetic peptide, p5+14 (also known as APi1832), radiolabeled with iodine-124 (I-124 or
124I). All patients enrolled in this exploratory trial will be outpatients with a confirmed
diagnosis of systemic amyloidosis.

The first three patients enrolled in the trial (Part 1) will take part in a dose-escalation
dosimetry study and will receive a single intravenous (IV) dose of 11.1 Megabecquerel (MBq)
(0.3 millicuries (mCi); n = 1), 37 MBq (1 mCi; n = 1) or 74 MBq (2 mCi; n = 1) of 124I-p5+14
Injection for the purpose of determining estimates of organ-associated and whole body
radioactive dosimetry. Thereafter, the trial will be opened to include another 40 patients
who will be administered a single IV bolus injection of 124I-p5+14 Injection at a dose, to be
determined in Part 1 of the study, based on the dosimetry data. Likely, 2 mCi will be used.
Every patient participating will receive < 2 mg of peptide p5+14

Inclusion Criteria:

- 1. Patients must have a confirmed diagnosis of systemic amyloidosis, based on
histologic confirmation that a biopsy contains deposits of apple-green birefringent,
Congophilic material. Additionally, the type of amyloidosis (AL, ATTR, ALect2, or
other) should be characterized.

- 2. Patients enrolled in Part 1 must have widespread AL amyloidosis, defined as biopsy
proven or clinically detectable involvement, of at least two organs (excluding the
peripheral nervous system).

- 3. All patients will be 18 years of age or older, and there are no gender or racial
restrictions.

- 4. Women of child bearing potential (those who have not been surgically sterilized,
are not postmenopausal [typically understood to mean last menstrual period >2 y ago
without pharmaceutical intervention], and women who are fertile) must test negative
for pregnancy in a laboratory test administered by the site physician.

- 5. Patients who have had or are currently receiving therapy or other drug-based
anti-amyloid regimens can be included on study.

- 6. Patients must provide signed, written, informed consent and be willing to comply
with eligibility requirements, scheduled visits, and follow-up studies.

- 7. Due to annual dosimetry limitations, patients who have participated in another
nuclear medicine amyloid imaging clinical trial protocol can be included in this study
no earlier than 12 months after the previous radiotracer injection.

- 8. Inclusion of patients with amyloid subsets: AL, ATTR, and ALect2 will continue
until the trial has achieved recruitment goals for each subset: 20 AL; 10 ATTR; 5
ALect2; and 5 "Other".

Exclusion Criteria:

-1. Individuals with significant cardiac dysfunction (New York Heart Association class IV -
"Unable to carry on any physical activity without shortness of breath or angina.

Shortness of breath at rest. If any physical activity is undertaken, discomfort increases")
or renal insufficiency that requires dialysis.

- 2. Those with significant co-morbidity (e.g., Eastern Cooperative Oncology Group
(ECOG) score of 3 or greater), uncontrolled infection, or other serious illness.

- 3. Patients with an Saturation of Peripheral Oxygen (SpO2) of ≤ 92% as noted in the
medical record.

- 4. Women who are of child bearing potential (those who have not been surgically
sterilized, are not postmenopausal [typically understood to mean last menstrual period
>2 y ago without pharmaceutical intervention], and women who are fertile), are
pregnant, or are nursing. Women who test positive for pregnancy in a laboratory test
administered by the site physician.

- 5. Patients who have received any amyloidophilic radiotracer within the past 12
months.

- 6. Patients with exposure to heparin, or heparin-based medications, within 7 days
prior to the imaging study.

- 7. Patients who have a known allergy to acetaminophen, Benadryl, or iOSAT iodine
treatment.