# A Vitamin K analog countermeasure for organophosphate poisoning

> **NIH NIH R43** · NEUROENE THERAPEUTICS INC · 2024 · $299,713

## Abstract

Abstract
Neuroene Therapeutics has discovered a novel class of well-tolerated, brain-penetrating, non-sedating
compounds that are small analogs of Vitamin K (VK) that mimic the form of VK needed for mitochondrial and
neurological health. Our VK analogs are effective in several animal models of pharmacoresistant seizures and
Parkinson's disease. Our lead antiseizure drug (ASD) candidate is fast-acting, has broad-spectrum antiseizure
activity in several pharmacoresistant seizure models, and is mitochondrial protective. Neuroene's clinical
candidate has great potential as a fast-acting rescue agent and long-term chronic therapeutic. VK analogs are
very stable in dry form at room temperature, allowing for long shelf life for stockpiling in the event of a public
health emergency or bio-incident.
Organophosphate agents (OPs) are used widely as pesticides, but are also potent nerve agents for chemical
warfare. Foreign adversaries have stockpiles of chemical weapons and have used these agents in the past. OPs
irreversibly inhibit the enzyme acetylcholinesterase. However, they have also been shown to inhibit other
pathways at low doses where acetylcholinesterase is not inhibited. Oxidative stress and mitochondrial
dysfunction occur at low OP doses, and it has been shown that OP compounds induce changes in mitochondrial
membrane potential and inhibit mitochondrial complexes needed for ATP production. While there are several
treatments for OP exposure, most have undesirable side effects and/or have a very narrow window to administer
their drug. Whereas Neuroene's clinical candidate protects against mitochondrial dysfunction, a major toxicity of
OP exposure, and does not target the mechanisms of the standard of care treatments. Neuroene's clinical
candidate has excellent tolerability in mice, and naturally occurring VK has no upper dose limit/maximum
tolerated dose. Neuroene's clinical candidate could represent a potentially superior alternative to the standard
of care for OP exposure, or as an adjuvant to the standard treatment of care, by targeting an additional
mechanism of action for OP-poisoning. Aim 1. Determine the PK properties of Neuroene's clinical candidate,
safe dosing range and maximum tolerated dose in rats. Aim 2. Determine the ability of Neuroene's clinical
candidate to ameliorate diisopropyl fluorophosphate (DFP) SE in rats. Aim 3. Determine the ability of Neuroene's
clinical candidate to ameliorate soman poisoning in rats. Neuroene's clinical candidate is fast-acting, broad-
spectrum, and protects mitochondria. This compound could immediately stabilize and override cascading effects
due to poisoning by OPs. If successful, Neuroene's drug could be a dual-purpose ASD for acute settings and to
reduce long-term sequela associated with OP poisoning. Neuroene's clinical candidate could be made widely
available commercially to improve the United States' health security posture due our commercial indications for
pharmacoresistant seizures, while be...

## Key facts

- **NIH application ID:** 10843945
- **Project number:** 5R43AI176434-02
- **Recipient organization:** NEUROENE THERAPEUTICS INC
- **Principal Investigator:** SHERINE S CHAN
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $299,713
- **Award type:** 5
- **Project period:** 2023-05-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843945

## Citation

> US National Institutes of Health, RePORTER application 10843945, A Vitamin K analog countermeasure for organophosphate poisoning (5R43AI176434-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10843945. Licensed CC0.

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