# PA21259, SBIR Phase I, Developing a RIG-I agonist to prevent COVID-19

> **NIH ALLCDC R43** · HDT BIO CORPORATION · 2022 · $299,984

## Abstract

Project summary:
Despite widespread availability of vaccines, the SARS-CoV-2 pandemic continues to wreak havoc on our
healthcare system and our economy. High numbers of unvaccinated individuals combined with vaccine
breakthrough cases continues to allow the virus to spread throughout the community and cause morbidity and
mortality at high rates. There continues to be an urgent need for innovative therapeutics to address the current
pandemic, as well as those which will inevitably arise in the future.
Host-directed therapies (HDTs) offer a promising approach in this regard. Rather than targeting the virus itself,
HDTs target the host to either restrict an essential growth factor or upregulate innate defenses. By targeting the
host to attack the virus, traditional mechanisms of antiviral resistance are circumvented. We are developing a
broad-spectrum antiviral RNA molecule targeting retinoic acid inducible gene-I (RIG-I), a host pattern recognition
receptor (PRR) evolved to recognize viral RNA to trigger innate antiviral immune responses, an approach
validated in preclinical studies to protect mice from multiple RNA and DNA viruses. Our preliminary data show
the RIG-I agonist, PAMP105, prevents SARS-CoV-2 replication in vitro and can be effectively delivered to the
lung to completely prevent disease from influenza and SARS-CoV-2 infection. In the proposed studies herein,
we will perform critical formulation optimization to create a final product to be tested for efficacy against SARS-
CoV-2 challenge in vitro and in vivo. We will optimize parameters of four clinically relevant nanoparticle
formulations, including our novel nano-structured lipid carrier, which effectively protects and delivers RNA in
vivo. We will optimize formulation parameters and downselect a final formulation by measuring cytokine release
patterns in vivo from the blood, lung, and liver following innate immune agonist delivery. The lead formulated
PAMP molecule will be tested for efficacy against a SARS-CoV-2 challenge in Syrian hamsters.
To this point, little progress has been made clinically in developing innate immune agonists as therapeutics. Our
expertise formulating agonists and vaccine platforms (including RNA) for preclinical and clinical trials will allow
us to use a variety of nanoparticle formulations to deliver this RNA RIG-I agonist safely and effectively in a
pressurized metered-dose inhaler to treat SARS-CoV-2 infection following exposure or after symptom onset.
With results from this Phase I project, we will advance our formulated host-directed RNA molecule into clinical
development as a as part of our Phase II research. Once developed, our therapeutic can be quickly pivoted for
use against any number of current or emerging viruses, including influenza, Hepatitis B Virus, Hepatitis C Virus,
Dengue Virus, or West Nile Virus, all of which are susceptible to PAMP in preclinical studies.

## Key facts

- **NIH application ID:** 10484777
- **Project number:** 1R43IP001229-01A1
- **Recipient organization:** HDT BIO CORPORATION
- **Principal Investigator:** Bryan Berube
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2022
- **Award amount:** $299,984
- **Award type:** 1
- **Project period:** 2023-09-30 → 2024-07-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10484777

## Citation

> US National Institutes of Health, RePORTER application 10484777, PA21259, SBIR Phase I, Developing a RIG-I agonist to prevent COVID-19 (1R43IP001229-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10484777. Licensed CC0.

---

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