# Selective Kv7.2/3 activators for the treatment of neuropathic pain

> **NIH NIH U44** · KNOPP BIOSCIENCES, LLC · 2021 · $2,200,680

## Abstract

Project Summary
The successful management of chronic pain is inadequate in many patients and has contributed to the
abuse of and addiction to opioids, a continuing major public health crisis in the United States and
worldwide. The development of non-addictive pain therapeutics can help counter opioid addiction and
benefit patients, including those who suffer from neuropathic pain, and in particular diabetic neuropathic
pain (DNP). Our project’s goal is to develop a safe, efficacious and non-addictive small-molecule drug
that activates Kv7 voltage-gated potassium channels to address overactive neuronal activity in DNP.
The first specific aim is discover Kv7 activators that favor Kv7 isoforms altered in DNP and found in
dorsal root ganglia, namely the Kv7.2/3 isoforms. Through iterative lead optimization studies on our
novel series of Kv7 activators, we are targeting Kv7.2/3 activation with selectivity over both Kv7.4
channels and another off target of other Kv7.2/3 activators, GABAA receptors. This approach is
expected to decrease off-target side effects observed with the use of earlier non-biased Kv7 activators
including urinary retention (mediated by Kv7.4), and somnolence and dizziness (mediated by
enhancement of GABAA receptor function). This phase also includes optimization of absorption,
distribution, metabolism, excretion, and toxicity profiles and building correlations between in-vitro
activities to in-vivo efficacies in a neuropathic rat DNP model. A second animal model, the L5/L6 spinal
nerve constriction model, will also be used to test the ability of candidate compounds to generalize to
other forms of neuropathic pain. The second specific aim will be to further characterize two to four
advanced compounds by assessing additional pharmacological properties including CYP450
induction/time dependent inhibition and in-vitro safety/selectivity panels. The third aim is to select a
candidate for study in non-GLP toxicology and pharmacokinetic studies in rodent and non-rodent
species. Specific aims four and five involve completing the studies needed to prepare an Investigational
New Drug (IND) application. These studies include Chemical Manufacturing Controls activities such as
formulation studies and Good Manufacturing Practices synthesis of drug candidate followed by
cardiovascular and safety pharmacology studies, and 28-day Good Lab Practices toxicology studies in
two animal species. This screening paradigm is intended to establish a clinic-ready, well-tolerated and
widely effective product to treat neuropathic pain.

## Key facts

- **NIH application ID:** 10450301
- **Project number:** 4U44NS115732-02
- **Recipient organization:** KNOPP BIOSCIENCES, LLC
- **Principal Investigator:** Lynn Resnick
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,200,680
- **Award type:** 4N
- **Project period:** 2021-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450301

## Citation

> US National Institutes of Health, RePORTER application 10450301, Selective Kv7.2/3 activators for the treatment of neuropathic pain (4U44NS115732-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450301. Licensed CC0.

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