# Antithrombotic Protein C Activator for Hemodialysis

> **NIH NIH R44** · ARONORA, INC. · 2020 · $1,493,466

## Abstract

Project Summary
Although potent antithrombotic drugs are available, all inadvertently target vital hemostatic mechanisms,
resulting in dose-limiting hemorrhagic toxicity that restricts their use. Due to a lack of safe thromboprophylaxis,
thrombotic/thromboembolic blood vessel occlusions and vascular device failures remain among the leading
causes of death and severe chronic disability in the U.S. Consequently, there is a significant and urgent unmet
medical need for safe antithrombotic drugs. The safety problem with current antithrombotics is particularly
complicated in end stage renal disease (ESRD) patients on chronic hemodialysis, who are prone to both
bleeding and thromboembolic complications. Moreover, some ESRD patients develop acute heparin induced
thrombocytopenia (HIT), another potentially life threatening complication of heparin use in a small but
significant fraction of ESRD patients, leaving them with few if any options for temporal anticoagulation during
hemodialysis sessions. We will therefore continue clinical development of our first-in-class, FDA Fast Track
designated antithrombotic enzyme, ProCase (E-WE thrombin, AB002), by beginning to explore its safety and
antithrombotic activity during hemodialysis. The product candidate is a hemostatically safe antithrombotic
protein C activator enzyme that has the potential to help this desperately ill patient population. E-WE thrombin
has been designed to act in part by increasing the surface concentration of the anticoagulant, profibrinolytic,
and cytoprotective enzyme, endogenous activated protein C (APC), at the site of developing blood clots via
targeted cellular delivery. This unique mechanism of action allows E-WE thrombin to target cell-rich
pathological blood clots (thrombi) without disabling vital hemostasis. In primates, doses as low as 1 µg/kg are
antithrombotic without significant systemic anticoagulation or measurable antihemostatic effects. This critical
Phase I/II Fast-Track SBIR grant will allow us to continue product development by providing essential support
for an exploratory phase 2a clinical study to evaluate the safety and antithrombotic effect of E-WE thrombin
during hemodialysis in a small group of ESRD patients. The trial will be deemed successful and support further
studies in this and other indications if E-WE thrombin is not associated with an increase in clinically significant
drug-related adverse events versus placebo, while showing evidence of antithrombotic activity in the
hemodialysis device. Successfully achieving our SBIR milestone will lead directly into the next product
development stage: performing subsequent definitive trials in hemodialysis and other important blood clotting
diseases (e.g. ischemic stroke, pulmonary embolism, and acute myocardial infarction) for the benefit of
patients who desperately need safer antithrombotic and thrombolytic therapies.

## Key facts

- **NIH application ID:** 9929002
- **Project number:** 5R44HL147695-02
- **Recipient organization:** ARONORA, INC.
- **Principal Investigator:** Erik Ian Tucker
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,493,466
- **Award type:** 5
- **Project period:** 2019-05-15 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929002

## Citation

> US National Institutes of Health, RePORTER application 9929002, Antithrombotic Protein C Activator for Hemodialysis (5R44HL147695-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9929002. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*