A Study of PRX004 in Subjects With Amyloid Transthyretin (ATTR) Amyloidosis

This Phase 1, open-label consists of 3 phases. The Dose Escalation Phase is a 3+3 dose
escalation component to determine the safety, tolerability, PK, PD, and MTD of IV PRX004 when
given as a single agent in up to 36 evaluable subjects with hATTR amyloidosis. The Expansion
Phase is an expansion component in anticipated PRX004 RP2D cohorts selected from the Dose
Escalation Phase (this may occur in addition to cohorts in which additional subjects were
added due to the observation of a dose-limiting [DLT] in the Escalation Phase). The Long-term
Extension (LTE) Phase is an extended dosing component for eligible subjects from the Dose
Escalation or Expansion phases.

The Dose Escalation Phase will follow a standard 3+3 design, in which cohorts of 3 to 6
subjects with hATTR amyloidosis will be enrolled at each dose level to receive IV PRX004 once
every 28 days, based on scheduling from Month 1-Day 1 for up to 3 doses. Each subject will
participate in only 1 dose escalation cohort. The starting dose of PRX004 will be 0.1 mg/kg.

Dose escalation will occur after the third evaluable subject in a cohort has completed the
first 28 days following the first administration of PRX004. Up to 6 dose levels of PRX004 may
be investigated (0.1, 0.3, 1, 3, 10, and 30 mg/kg) if tolerable. In the event the starting
dose of 0.1 mg/kg is not tolerated, the dose escalationwill be halted and the study stopped.

Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.

Each subject will receive a maximum of 3 infusions of PRX004 in the Dose Escalation Phase.
Subjects who complete the Month 3-Day 22 Visit in the Dose Escalation or Expansion phases may
be eligible to receive up to 15 additional PRX004 infusions in the LTE Phase.

Subjects who completed the EOS Visit in the Dose Escalation Phase prior to implementation of
Protocol Amendment 2 may re-enter the study in the LTE Phase if they meet specific
inclusion/exclusion criteria.

Inclusion Criteria:

1. Age ≥18 years

2. Confirmed diagnosis of ATTR amyloidosis

3. Known TTR mutation

4. Subjects receiving concomitant tafamidis or diflunisal may enroll in the study
(providing the dose has been stable for the last 6 months)

5. Karnofsky Performance Status (KPS) score ≥60

6. If currently receiving a diuretic, must have been on a stable dose for at least 4
weeks prior to the first dose of study drug

7. Subjects with cardiomyopathy must have an NT-proBNP ≥650 pg/mL and ≤5000 pg/mL (i.e.,
≥76.9 pmol/L and 591 pmol/L) or evidence of septal wall thickening >1.2 cm on
echocardiogram

8. Must have a biopsy unless data are available from a previous one. The biopsy may be
taken from any tissue or organ affected by ATTR amyloidosis (eg, abdominal fat pad,
salivary gland), at the Investigator's discretion. Nerve biopsies are not required.

9. Polyneuropathy Disability (PND) Score ≤IIIB

10. Neuropathy Impairment Score (NIS) ≥5 and ≤130

Exclusion Criteria:

1. Amyloid light chain or other non-ATTR amyloidosis

2. Any past history of or present abuse of alcohol, diabetes, B12 or folate deficiencies,
autoimmune diseases, hereditary disorders other than TTR (e.g. Charcot Marie-Tooth),
uncontrolled hypothyroidism or other etiologies for the peripheral neuropathy

3. Received prior liver transplant

4. Planned liver transplant

5. mBMI ≤600 kg/m2 × g/L

6. New York Heart Association (NYHA) Functional Class III-IV

7. LVEF ≤45%

8. Uncontrolled symptomatic orthostatic hypotension

9. Myocardial infarction, unstable or uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6
months prior to the first dose of study drug

10. Uncontrolled infection, or active malignancy with the exception of the following:

• Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in
situ cervical cancer

11. Hospitalized for heart failure within the 12 weeks prior to the first dose of study
drug

12. Treatment with patisiran or inotersen within 30 days or 5 half-lives whichever is
longer) prior to Month 1-Day 1