# Preclinical development of an immunomodulatory agent capable of mitigating SARS-CoV-2 virus related hypercytokinemia

> **NIH NIH R44** · CYTOAGENTS, INC. · 2021 · $1,000,000

## Abstract

Abstract
CytoAgents is developing GP1681 (beraprost-314d) to regulate the uncontrolled inflammatory response that can
result from viral infections. This inflammatory response is associated with increased disease severity, acute lung
injury (ALI), acute respiratory distress syndrome (ARDS), and death. The emergence of novel viruses with
pandemic potential poses a major threat to world health and security. In particular, the emergence of novel
coronaviruses (CoVs) of animal origin in recent decades indicates that these viruses will continue to cross
species boundaries and cause outbreaks in humans. The current outbreak of SARS-CoV-2, a highly pathogenic
CoV that causes lower respiratory tract infections and severe pneumonia, represents a severe public health
emergency and has been declared a global pandemic by the World Health Organization. SARS-CoV-2 has so
far infected nearly 3M individuals in 185 countries, resulting in over 200K deaths, with the greatest number of
confirmed cases in the U.S. While most individuals with COVID-19 report only mild illness, about 14% develop
severe disease requiring hospitalization and oxygen support, and 5% require intensive care. This has resulted
in a significant burden on healthcare systems in several countries, as well as a massive economic burden
globally. Studies have revealed that the severity of viral disease and negative health outcomes are often
associated with an overstimulated cytokine response, rather than the viral load per se. Overactivation of the
inflammatory response results in the uncontrolled release of proinflammatory cytokines, known as
hypercytokinemia, which contributes to the destruction of lung tissue, and in severe cases, leads to ARDS,
multiorgan dysfunction, and death. GP1681 moderates hypercytokinemia and may reduce the duration and
severity of many viral diseases, including COVID-19. Evaluation in mouse models has shown notable efficacy of
GP1681 in the treatment of influenza. Knowledge of the mechanism of action of GP1681 suggests that it may
be equally effective in treating COVID-19. CytoAgents has submitted an Investigational New Drug (IND)
Application to the FDA for an influenza indication and received approval to proceed with a Phase 1 study.
Additional NIH (NIAID)-funded preclinical studies are also underway in influenza models. To assess the potential
of GP1681 for use against COVID-19, the aims of this project are 1) IND-enabling toxicology studies expanding
the initial toxicology screens, as longer treatment may be needed given the typical COVID-19 disease course;
2) Pharmacokinetic (PK) analysis in a non-human primate (NHP) model; and 3) Assessment of the efficacy of
delayed GP1681 treatment in an NHP model of COVID-19, as therapy in the clinic is typically initiated at some
time after viral infection. The outcomes of this project will prepare CytoAgents for an IND application for the use
of GP1681 in the treatment of COVID-19.

## Key facts

- **NIH application ID:** 10155839
- **Project number:** 1R44AI157719-01
- **Recipient organization:** CYTOAGENTS, INC.
- **Principal Investigator:** JODI K CRAIGO
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,000,000
- **Award type:** 1
- **Project period:** 2021-03-06 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155839

## Citation

> US National Institutes of Health, RePORTER application 10155839, Preclinical development of an immunomodulatory agent capable of mitigating SARS-CoV-2 virus related hypercytokinemia (1R44AI157719-01). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/10155839. Licensed CC0.

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