# Engineering a Potent Immune-evading Uricase

> **NIH NIH R43** · STEALTH BIOLOGICS, LLC · 2020 · $299,870

## Abstract

Abstract
The accumulation of uric acid in the urinary tract, blood stream, or tissues causes a pathological condition
known as hyperuricemia, which leads to a variety of acute and chronic diseases including gout. Gout alone
afflicts more than 8 million Americans, causing acute pain and potentially even chronic functional impairment.
While a number of drugs have been developed to treat symptoms and to limit production or increase excretion
of uric acid, these drugs do not suffice for the majority of gout patients. A powerful alternative therapeutic
approach is to directly attack uric acid deposits, using the enzyme uricase to degrade uric acid into products
that are readily excreted. Unfortunately, while one uricase variant (pegloticase, or Krystexxa®) has been
approved for treatment of chronic refractory gout, it suffers from severe immunogenicity-associated problems.
In particular it carries black box warnings for anaphylaxis and other detrimental outcomes, along with a fairly
short period of therapeutic efficacy for many patients, who have to discontinue treatment due to the
development of antidrug antibodies.
Stealth Biologics® has developed a leading-edge immuno engineering platform, integrating computational
protein design, high-throughput protein engineering, and exquisitely sensitive immunoassays. We have a
proven track record of using this platform to render non-human enzymes (among other types of proteins)
“stealth”y, evading immune recognition while still maintaining potent therapeutic function. We propose here to
systematically overcome uricase’s immunogenicity problems by addressing the root sources of immune
recognition, using our platform to develop a high-function, low-immunogenicity candidate. This molecule will
then serve as the basis for a phase II project to further advance the lead candidate towards IND-enabling
studies and ultimately an effective treatment for gout and other hyperuricemia-associated diseases.

## Key facts

- **NIH application ID:** 9908607
- **Project number:** 1R43AI149839-01
- **Recipient organization:** STEALTH BIOLOGICS, LLC
- **Principal Investigator:** Chris Bailey-Kellogg
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $299,870
- **Award type:** 1
- **Project period:** 2019-12-18 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908607

## Citation

> US National Institutes of Health, RePORTER application 9908607, Engineering a Potent Immune-evading Uricase (1R43AI149839-01). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9908607. Licensed CC0.

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