# Novel synthetic TLR4 agonists

> **NIH NIH R44** · INIMMUNE CORPORATION · 2020 · $580,244

## Abstract

Project Summary
 There are currently no approved vaccines for most emerging biological pathogens (Ebola,
Chikungunya, MERS CoV, SARS, Zika), opportunistic infections (S. aureus, Candidiasis, adenovirus) or
potential bioterrorism agents (Y. pestis, B. Pseudomallei, F. tularensis, Bunyaviridae, Flaviviridae), and
therapeutic interventions such as antibiotics and antivirals are only effective for a select few pathogens.
A promising approach for rapidly neutralizing the risk of pathogen exposure is the use of
immunomodulators capable of eliciting a robust innate immune response within hours of administration
that would provide protective resistance against a wide range of infectious diseases.
 Proof-of-principle has been established that a new class of chemically and metabolically more stable
synthetic TLR4 agonists provide safe and effective protection to mice when administered intranasally two
days before a lethal influenza virus challenge. In this Phase II application, we will further optimize these
new synthetic TLR4 agonists and formulations for stability, potency and safety, and optimize an
administration schedule to provide weeks-long non-specific resistance against influenza virus. We will
also assess the potential toxicity of the new TLR4 agonists in mice and develop a scalable cGMP
synthesis of the lead candidate.
 This phase II proposal has the potential to develop a new broad-spectrum immunomodulator that
would provide non-specific protective resistance (NSR) against a wide range of biological pathogens,
and is primarily targeted for preventing upper respiratory tract infections in individuals or populations at
risk for emerging or opportunistic pathogen exposure. Such treatment could reduce morbidity and
mortality associated with seasonal or pandemic influenza viruses as well as other respiratory pathogens
of significant medical concern. The work proposed herein will comprise the pre-clinical basis for IND-filing
and human clinical trials using a safe and effective synthetic TLR4 agonist for individuals or populations
with a high risk of exposure to seasonal and pandemic influenza viruses.

## Key facts

- **NIH application ID:** 10005111
- **Project number:** 5R44AI136081-03
- **Recipient organization:** INIMMUNE CORPORATION
- **Principal Investigator:** Juhienah Khalaf
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $580,244
- **Award type:** 5
- **Project period:** 2018-02-09 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005111

## Citation

> US National Institutes of Health, RePORTER application 10005111, Novel synthetic TLR4 agonists (5R44AI136081-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10005111. Licensed CC0.

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