# New target and new therapy for severe Covid-19 and viral hyperinflammation damage: renalase and renalase agonists

> **NIH NIH R43** · BESSOR PHARMA, LLC · 2024 · $296,931

## Abstract

Abstract
The SARS-CoV-2 host response is associated with wide-ranging immuno-inflammatory
derangements and tissue injury. We are developing an innovative therapeutic, BP-1002, to both
blunt inflammatory cytokines and protect tissues. BP-1002 has the potential to prevent organ
injury and deaths from COVID-19, regardless of viral variants. BP-1002, is a renalase (RNLS)
agonist - a recently discovered secretory protein that promotes cell survival and downregulates
the inflammatory response by signaling through the plasma-membrane calcium-ATPase,
ATP2B4 (PMCA4b) receptor, and activating growth and survival pathways (protein kinase B,
JAK/STAT, and MAP kinase). This activity is contained in a 20-40 amino acid RNLS site.
Because RNLS is a large protein complex requiring manufacturing, we designed and developed
BP-1002, a proprietary 36−aa RNLS-based (97.3 % amino acid identity) that contains the RNLS
activity site. This RNLS agonist is stable and easily manufactured using chemical synthesis.
Preliminary data show that low plasma RNLS correlates with disease severity hospitalized
COVID-19 patients; or in acute renal injury, cardiac injury, and pancreatitis, which are COVID-
19 complications. Also, BP-1002 blunted inflammatory cytokine production (IL6, TNFα and IL1β)
in human blood exposed ex vivo to the S- and M-proteins of SARS-CoV-2; improved survival by
60% in mouse models of simulated viral disease (poly(I:C) or SARS-CoV-2 infection). BP-1002
or recombinant RNLS reduced cell and tissue injury through modulation of inflammation,
preservation of vascular integrity, and apoptosis prevention. Additionally, in a mouse
inflammation model, single doses of BP-1002 had activity lasting 6 (intravenous) or 10
(subcutaneous) hours. Further, chronic-dosing pharmacology studies in mice show a profile
consistent with a desirable therapeutic index. These studies confirm the strong potential for BP-
1002 as a new therapeutic for COVD-19. BP-1002 may also be useful alone or in combination
with other COVID-19 therapies. A candidate for testing is IL-6 inhibitors, which have shown
varied benefits for COVID-19 therapy. We plan further proof of concept evaluation of BP-1002,
alone or with potentially synergistic IL-6 inhibition, to blunt inflammatory cytokines, prevent
tissue damage and death in several mouse COVID-19 models. In addition, we will compare the
pharmacokinetics after 30-min infusion, the route of administration that will be used in patients,
with those after a dose-response studies after SC admin using a viral mouse model. Lastly,
additional analytical studies will allow specifications to be set for future production.

## Key facts

- **NIH application ID:** 10924059
- **Project number:** 5R43AI170278-02
- **Recipient organization:** BESSOR PHARMA, LLC
- **Principal Investigator:** BARRY A BERKOWITZ
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $296,931
- **Award type:** 5
- **Project period:** 2023-09-07 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924059

## Citation

> US National Institutes of Health, RePORTER application 10924059, New target and new therapy for severe Covid-19 and viral hyperinflammation damage: renalase and renalase agonists (5R43AI170278-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10924059. Licensed CC0.

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