# Mitigation of Acute Kidney Injury (AKI) using the polymer prodrug, APP-103TM

> **NIH NIH R44** · CELDARA MEDICAL, LLC · 2020 · $998,624

## Abstract

Project Summary
Acute Kidney Injury (AKI) is common in hospitalized patients after severe illness or
following major surgeries, such as cardiovascular surgery. The incidence of AKI in critically
ill patients is greater than 40%. Patients who have an AKI event have poor long-term
outcomes including increased debilitating comorbidities such as chronic kidney disease
and increased mortality. Ischemia/reperfusion injury (IRI), an unavoidable consequence of
cardiovascular surgery, is a known cause of AKI. IRI is partially the result of the formation
of reactive oxygen species (ROS) in the absence of sufficient antioxidative moieties, and
can lead to the induction of inflammation. There is currently no clinically available
therapeutic treatment to prevent or treat AKI, which leaves a large cohort of suffering
patients and a high burden on our healthcare system.
Our product, APP-103™, consists of effective anti-oxidant and anti-inflammatory
copolymer nanoparticles that have previously been demonstrated to be highly effective in
ameliorating damage from oxidative stress in several IRI models of kidney, heart, limb
injury, and renal transplantation. APP-103™ is a dispersion of polyoxalate-vanillyl alcohol
(VA) copolymer particles that is degraded by hydrogen peroxide, thereby reducing the local
concentration of ROS and yielding anti-inflammatory VA. The polymer chemistry and
biology of APP-103 is well understood and indicative of an excellent safety profile. While
easily administered systemically, it offers site-specific anti-oxidative and anti-inflammatory
therapy without expensive and marginally effective targeting molecules. A single 500 nm
diameter APP™ particle provides the ability to mitigate ~1011 ROS molecules, and is
activated only in the presence of ROS, i.e. APP activity is self-limiting.
To date, we have been able to produce APP-103™ at the scale necessary for preclinical
work, and are advancing through IND-enabling studies with no toxicity. We have also
demonstrated efficacy in pre-clinical AKI models. The purpose of this proposal is to
provide mechanistic insight of APP-103 in kidney IRI, demonstrate proof of concept
in a large animal model of AKI, and then advance APP-103™ from lab manufacturing
through completion of IND-enabling studies. The milestone of ultimate success will
be the submission of an IND in order to bring this exceptionally promising therapy
into clinical application.

## Key facts

- **NIH application ID:** 9920348
- **Project number:** 4R44DK117714-02
- **Recipient organization:** CELDARA MEDICAL, LLC
- **Principal Investigator:** Brandy Lynn Houser
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $998,624
- **Award type:** 4N
- **Project period:** 2019-05-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920348

## Citation

> US National Institutes of Health, RePORTER application 9920348, Mitigation of Acute Kidney Injury (AKI) using the polymer prodrug, APP-103TM (4R44DK117714-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9920348. Licensed CC0.

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