The purpose of this first in human study is to assess safety, pharmacokinetics, pharmacodynamics, and immunogenicity of single ascending doses of HZN-457.

Inclusion Criteria:

• Screening serum uric acid (sUA) ≥ 4 mg/dL (238 µmol/L)
• Screening body mass index (BMI) between 20 to 34.0 kg/m2, inclusive
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECG findings, as deemed by the Investigator.
• Male participants must refrain from donating sperm and either agree to remain abstinent from heterosexual intercourse OR agree to utilize contraception
• Female participants must be non-pregnant, non-lactating postmenopausal woman of non-childbearing potential (WONCBP) with a follicle-stimulating hormone (FSH) level in the postmenopausal range (> 40 IU/L)

Exclusion Criteria:

• History or presence of gout.
• Use of any prescription medication within 14 days or 5 half-lives prior to dosing
• Participation in another investigational clinical study (eg, drug, vaccine, invasive device) within 30 days or 5 half-lives, whichever is longer, prior to Day 1.
• Current liver disease, as determined by alanine transaminase (ALT) or aspartate transaminase (AST) levels > upper limit of normal (ULN) at Screening or Day -1.